Immune checkpoint inhibitors have transformed the treatment of hematolymphoid malignancies by enhancing antitumor immunity. These agents are associated with immune-related adverse events (irAEs), including hematologic toxicities such as autoimmune hemolytic anemia, immune-related thrombocytopenia (irTCP), and neutropenia. Although rare, hematologic irAEs (hem-irAEs) may reflect systemic immune activation and could serve as biomarkers of treatment response. Emerging evidence, particularly from observational studies and meta-analyses, suggests that patients who experience hem-irAEs may have lower rates of disease recurrence and improved survival outcomes. This manuscript reviews the mechanisms, incidence, and prognostic implications of hem-irAEs in patients with hematolymphoid malignancies, emphasizing their hypothesis-generating potential as predictive markers that warrant prospective validation.

Spur cell anemia (SCA) is a rare but severe form of acquired hemolytic anemia seen in advanced cirrhosis and carries a poor prognosis in the absence of liver transplantation. We report the case of a middle-aged man with alcohol-related cirrhosis who developed profound anemia requiring recurrent transfusions. An extensive workup was performed to rule out other causes of anemia, including gastrointestinal bleeding, microangiopathic hemolytic anemia, and autoimmune hemolytic anemia. Peripheral smear confirmed the presence of acanthocytes, consistent with SCA. Given that he was not a transplant candidate, supportive transfusions were provided, but his condition deteriorated rapidly, and he died within one month of diagnosis. This case highlights the aggressive course of SCA in non-transplant candidates and underscores the need for further research into alternative therapies.

Leptospirosis is a globally prevalent zoonotic infection caused by pathogenic spirochaetes of the genus Leptospira Although typically associated with mild flu-like symptoms or Weil's disease (characterised by jaundice, renal failure and haemorrhagic manifestations), atypical and severe presentations can mimic other systemic disorders. A man in his 40s presented with fever, myalgia along with rapidly progressive jaundice, thrombocytopenia, microangiopathic haemolytic anaemia and acute kidney injury, preceded by a short episode of diarrhoea. The initial working diagnosis was haemolytic uraemic syndrome (HUS) secondary to Shiga toxin-producing Escherichia coli and he was treated with plasma exchange, transfusions and renal replacement therapy. However, stool examinations were negative for Shiga toxin and bacterial pathogens. Subsequent investigations confirmed leptospirosis. He improved significantly after treatment with doxycycline alongside supportive therapy. This case highlights the importance of considering leptospirosis as a differential diagnosis in patients with HUS, particularly in endemic regions, to avoid delays in targeted treatment.

Anemia is a public health issue affecting people of all ages worldwide. 43% of children under five in Egypt are suffering from anemia. Hemolytic anemia (HA), characterized by the premature destruction of red blood cells, is often associated with oxidative stress. Phenylhydrazine (PHZ) is a chemical substance frequently used to induce HA in experimental animal models. Studies indicate that niacin (nicotinic acid) activates antioxidant pathways through nuclear factor erythroid 2-related factor 2 (Nrf2). This study aimed to evaluate the anti-anemic effects of niacin in PHZ-induced hemolytic anemia in rats. Twenty-four rats were divided into four groups (n=6). The control group received saline for two days, then 5% CMC. The anemia group received PHZ (40 mg/kg/day, i.p.) for two days, followed by 5% CMC. The low- and high-dose niacin groups received PHZ for two days, then niacin (100 or 360 mg/kg/day, orally) for six days. Niacin-treated groups showed hematological parameters close to normal levels, affected the expression of Nrf2/ARE genes, preserved histological architecture, and reduced caspase-3 protein expression. Niacin protected rats from hemolytic anemia by restoring blood parameters and promoting red blood cell survival. It may serve as a potential treatment by reducing oxidative stress, ferroptosis, and inflammation, while supporting erythropoiesis.

Red blood cell (RBC) clearance by macrophages maintains blood homeostasis and is dysregulated in the hemolytic disorder sickle cell disease (SCD) and the lysosomal storage disorder Gaucher disease (GD), where biophysical and biochemical alterations promote premature phagocytosis. We develop a multiscale hybrid modeling framework integrating signaling dynamics, biophysical simulations, and machine learning to investigate the mechanisms governing RBC phagocytosis in these diseases. Our approach couples a systems biology model of macrophage-RBC signaling with Dissipative Particle Dynamics (DPD) simulations of molecular diffusion and membrane interactions, and leverages Physics-Informed Neural Networks (PINNs) for robust parameter inference. The DPD framework provides mechanistic insight into antibody diffusion, receptor engagement, and membrane-level interactions during macrophage-RBC contact, generating spatially resolved trajectories of CD47-SIRP α signaling and antibody-receptor binding that serve as intermediate observables constraining the signaling model. The model accurately captures differential phagocytic responses between healthy and altered RBCs, revealing diminished inhibitory signaling and changes in SHP1-mediated pathways in both SCD and GD. Identifiability analysis combining Fisher Information Matrix diagnostics and profile likelihood confirms that parameters governing the CD47-SIRP α -SHP1 axis are among the most robustly recoverable, and simulations of therapeutic perturbations with anti-SIRP α antibodies demonstrate modulation of engulfment outcomes. We further employ Physics-Informed Kolmogorov-Arnold Networks (PIKANs) as an alternative to standard PINNs, demonstrating improved robustness under noise and sampling variability. More broadly, our multiscale platform linking biophysical simulation with systems-level inference is generalizable, offering mechanistic insights and computational tools for therapeutic exploration in diseases involving dysregulated phagocytosis.

Complement dysregulation is frequently implicated in the thrombotic microangiopathy (TMA) known as atypical hemolytic uremic syndrome (aHUS). Diacylglycerol kinase epsilon (DGKE) mutations encode a non-complement regulatory protein, and pathogenic variants in DGKE define a distinct form of aHUS. Indeed, the DGKEgene encodes a key enzyme involved in intracellular signaling. While eculizumab and other anti-C5 monoclonal antibodies are widely used in complement-related aHUS, their relevance in DGKE-associated forms remains controversial. We report a case of a patient followed from the age of eight months for suspected aHUS. Genetic testing, performed only at the age of 13 years, revealed a homozygous DGKE mutation (c.412T>C; p.C138R), despite a typical presentation, including hemolytic anemia, thrombocytopenia, and acute kidney injury. Due to severe disease progression and a fatal family history, empirical eculizumab therapy was initiated. Although the treatment resulted in a stable overall clinical status, relapses manifested as isolated nephrotic-range proteinuria (without hemolysis) on two occasions during treatment interruptions. Complement C3 levels remained consistently within the normal range. In this case, eculizumab did not prevent disease relapses, which occurred in the absence of complement activation. The persistence of proteinuria despite C5 blockade further highlights this distinction. The lack of genetic testing options has led to overtreatment in this patient with that type of mutation, with additional costs associated with the drug (eculizumab) and an increased risk of life-threatening infectious complications for the patient.

Epstein-Barr virus (EBV) typically causes infectious mononucleosis, but in rare cases, it may lead to complications such as autoimmune hemolytic anemia (AIHA) and hepatitis. We report the case of an 18-year-old previously healthy female who presented with jaundice, red urine, and arthralgia. Laboratory workup revealed direct hyperbilirubinemia, elevated transaminases, and a direct antiglobulin test positive for IgG (negative for C3d), consistent with warm autoimmune hemolytic anemia in the context of EBV infection. Imaging ruled out biliary obstruction. The patient was managed conservatively, with cautious steroid use, and demonstrated clinical improvement without progression to hepatic failure. This case underscores the importance of recognizing atypical hepatic presentations of EBV and carefully managing overlapping autoimmune complications.

Phage-encoded Shiga toxin (Stx) released by Shiga toxin-producing E. coli (STEC) can kill multiple eukaryotic bacterial predators, including Acanthamoeba castellanii, Tetrahymena thermophila and Caenorhabditis elegans. However, the impact of Stx type, Stx amount, and the serogroup of the E. coli on the effectiveness of this exotoxin are poorly understood. These factors impact the severity of Stx-mediated disease in humans and therefore, by studying their role in modulating predator-prey interactions, we may gain insight into how these virulence factors evolved to contribute to human pathogenicity. Herein, we investigated the effects of these factors on predator killing by measuring the efficiency with which five different hemolytic uremic syndrome (HUS)-causing STEC strains consume and/or kill A. castellanii and C. elegans. These strains express various combinations of Stx types and amounts and O-antigens. We found that variations in Stx types and amounts significantly affect the ability of a given bacterial strain to kill predator A. castellanii and C. elegans, with higher Stx1 titers (HUSEC 31 vs. 19) and the presence of Stx2 alone (HUSEC 20) correlating with significantly greater predator killing. These attributes also affect STEC pathogenicity in humans, suggesting that ecological selective pressures for anti-predator defense inadvertently drive the evolution of strains with higher virulence potential in humans.

Background and Objectives: Pulmonary hypertension (PH) is a major contributor to morbidity and mortality in sickle cell disease (SCD), yet reliable and accessible biomarkers for cardiopulmonary risk stratification remain limited. This study aimed to evaluate whether the platelet-to-neutrophil ratio (PNR) is independently associated with echo-estimated PH (ePH) in adolescents and adults with SCD and to compare its predictive value with hemoglobin composition and genotype. Materials and Methods: A retrospective cohort study was conducted at King Fahd Hospital of the University, Al Khobar, Saudi Arabia (January 2019-January 2025). Clinical, laboratory, and echocardiographic data from 114 patients with confirmed SCD who underwent transthoracic echocardiography (TTE) were analyzed. ePH was defined as tricuspid regurgitant velocity (TRV) ≥ 2.5 m/s or pulmonary artery acceleration time (PAAT) ≤ 105 ms. Multivariable logistic and linear regression models were used to assess associations between PNR, hemoglobin fractions, genotype, and pulmonary pressure estimates. Results: Overall, 43% of patients met the criteria for ePH. PNR was not independently associated with ePH or TRV in adjusted analyses. In contrast, higher fetal hemoglobin (HbF) levels were independently associated with lower odds of ePH (adjusted OR 0.92 per 1% increase, 95% CI 0.86-0.98) and lower TRV values. The HbS/β[0] genotype was significantly associated with increased odds of ePH (adjusted OR 5.44, 95% CI 1.37-24.0). Exploratory analyses demonstrated an inverse association between PNR and lactate dehydrogenase, suggesting that PNR reflects hemolytic activity rather than pulmonary vascular involvement. Conclusions: In this retrospective cohort of patients with SCD, PNR was not independently associated with ePH or TRV after multivariable adjustment. In contrast, hemoglobin composition and genotype, particularly higher HbF and the HbS/β[0] genotype, were significantly associated with pulmonary pressure estimates.

Rapid, reagent-free screening tools for sickle-cell disease (SCD) are urgently needed in low-resource regions where carrier frequency is high and laboratory infrastructure is scarce. We demonstrate digital holographic microscopy (DHM) as a label-free SCD tool in Colombia, imaging 885 individual erythrocytes (443 cells from venous blood of six SCD patients and 442 cells from 5 healthy donors). Two direct optical observables were extracted: phase difference (Δφ) relative to the surrounding medium and projected circularity index (CI), defined as the aspect ratio between the erythrocyte's minor and major axes. Healthy cells are characterized by Δφ = 1.72 ± 0.30 (mean ± std) rad and CI = 0.94 ± 0.04, whereas SCD cells are distributed around Δφ = 3.00 ± 0.96 rad and CI = 0.70 ± 0.19. Despite some minimal overlap between both distributions, SCD cells are statistically distinguishable from healthy ones based on both Δφ and CI (p < 0.001). A simple rule (Δφ > 2.2 radians ∧ CI < 0.85) classified individual cells with 97.40% accuracy, 94.81% sensitivity, and 100% specificity. While sophisticated classifiers can further optimize boundaries and enable anemia sub-typing, the distinctive contribution of this work is its deliberately minimalist rule - requiring no model training or engineered features - offering immediate and interpretable triage well-suited for low-resource workflows.

Sickle cell disease (SCD) care includes pharmacologic disease-modifying therapies (pDMTs) and chronic blood transfusion therapy (CBT). Using Optum Labs Data Warehouse (2014-2021), we identified individuals with SCD and classified yearly treatment as pDMT only, CBT only, combined pDMT + CBT, or no disease-modifying therapy. Among 4,100 patients, 26% used pDMT only, 3% received CBT only, 1% received both, and 70% received no DMT in a given year. pDMT uptake rose steadily while CBT remained low (3%-4%). In multinomial models (reference: no DMT), older age was associated with lower odds of pDMT and CBT, while prior vaso-occlusive crises and severe organ complications were associated with higher odds across categories. Men had higher odds of pDMT and combined therapy. These findings suggest treatment intensification in routine practice follows accumulating morbidity rather than preceding it, and that substantial implementation gaps persist, particularly among older adults and for CBT, which depends on specialized capacity. Expanding CBT capacity and improving pDMT uptake may narrow gaps and better align real-world care with guideline intent.