BACKGROUND Anemia derived from immune checkpoint inhibitor (ICI) is recognized as a systemic immune-related adverse event (irAE). However, only a few studies reported regarding pernicious anima (PA) or megaloblastic anemia induced by vitamin B12 (Vit.B12) deficiency after ICI treatment. Vit.B12 deficiency-induced PA remains unclear as an irAE. CASE REPORT We present a case of a 68-year-old man with hepatocellular carcinoma and renal cell carcinoma who developed Vit.B12 deficient megaloblastic anemia after the induction of atezolizumab-containing chemotherapy. Laboratory findings revealed hemoglobin of 6.1 g/dL with signs of hemolysis, gastric parietal cell antibody positivity, and gastrin level elevations. He tested negative for Helicobacter pylori antibodies. Upper gastrointestinal endoscopy showed atrophic mucosa that affected almost the entire stomach. The loss of gastric folds and marked vascular visibility were observed. We defined it as open type (O-3) atrophic gastritis, although histopathological examination was not performed. Based on these findings, the anemia was considered megaloblastic anemia induced by Vit.B12 deficiency (PA). The anemia demonstrated partial recovery (hemoglobin of 9.5 g/dL) with the resolution of hemolytic pattern after mecobalamin administration. We found that PA was associated with parietal cell antibody production triggered by atezolizumab, in which the removal of immune checkpoint brakes by atezolizumab may reveal this pathogenesis. Because PA is recognized as the progressive status of autoimmune gastritis, ICI treatment-induced PA is suggested to emerge at the late phase. CONCLUSIONS PA is indicated as a potential complication of ICI-containing chemotherapy. Measuring Vit.B12 levels is essential when encountering cases of anemia and gastritis during ICI treatment.

Rituximab is employed in the treatment of B-cell non-Hodgkin lymphomas (NHL) and autoimmune disorders of hematological interest (ADHI), such as autoimmune hemolytic anemia (AIHA), acquired hemophilia A (AHA), and immune thrombocytopenia (ITP). Rituximab induces profound B-cell depletion, reducing the titer of immunoglobulins and autoreactive antibodies, but secondary hypogammaglobulinemia increases risk of infections. We performed a retrospective, multicentric study across seven Italian centers to compare two cohorts of patients with either indolent NHL or ADHI treated with rituximab between March 2014 and March 2024. We evaluated the incidence and characteristics of infections and common antimicrobial prophylaxis adopted according to local clinical practice, in the absence of shared guidelines for ADHI. We included 285 patients (52% female; median age 55 years). The ADHI cohort comprised 187 patients (65%; 97 ITP, 78 AIHA, 12 AHA), while the control group included 98 i-NHL patients (34%). We documented 65 infectious events occurring in 65/285 patients (22.8%). Infection-related mortality occurred in 9 patients (4%). When stratified, the cumulative 180-day incidence of infections was 9.4% (IC95% 8.8%-10%) for NHL patients and 13.7% for ADHI (IC95% 12.2%-14.2%). Multivariate analysis identified prophylaxis (OR 2.62, p = 0.014) and post-treatment hypogammaglobulinemia (OR 2.73 p = 0.004) as risk factors. The risk of infection in patients with ADHI is high and comparable to that observed in NHL. Therefore, close monitoring of IgG levels is strongly advised, and mortality can be contained through rigorous antimicrobial stewardship.

Systemic lupus erythematosus can present with varied clinical features, and life-threatening serositis or autoimmune hemolysis may precede more typical findings. We report a 56-year-old woman who presented with progressive dyspnea, pleuritic chest discomfort, hypotension, and tachycardia and was found to have a large pericardial effusion with tamponade physiology requiring urgent pericardiocentesis. During hospitalization, worsening anemia with positive direct antiglobulin testing, peripheral spherocytes, reticulocytosis, hyperbilirubinemia, low haptoglobin, and splenomegaly supported the diagnosis of warm autoimmune hemolytic anemia. Infectious, malignant, and other causes of inflammatory pericardial effusion were excluded. The overall presentation, including serositis, autoimmune hemolysis, and positive lupus serologies, supported the diagnosis of late-onset systemic lupus erythematosus. She was treated with pericardiocentesis, corticosteroids, transfusion support, intravenous immunoglobulin, rituximab, and later hydroxychloroquine, with resolution of the pericardial effusion and improvement in anemia. This case emphasizes that systemic lupus erythematosus should be considered in adults with otherwise unexplained cardiac tamponade accompanied by hemolysis, even when classic mucocutaneous or musculoskeletal manifestations are absent at presentation.

Shiga toxin type 2 (Stx2)-producing Escherichia coli O157H7 has become a global risk to public health. The study aimed to investigate the emergence of antimicrobial resistance patterns in the clinical isolates of E. coli. The isolates revealed a pattern of strong resistance to the majority of the common antibiotics. Most E. coli isolates were susceptible to gentamicin and were classified as MDR. The Stx2 determinant was screened in E. coli O157:H7 isolates through the PCR technique, and the Stx2 was purified by cation exchange and gel filtration chromatography. The purification yielded 5.2 milligrams of pure Stx2. Nigella sativa oil's obtained by the mechanical expression of seeds at room temperature was evaluated for its antibacterial activity against 16 E. coli O157:H7 isolates at different concentrations. The oil induced inhibition zone diameter of 9.83, 16.71, and 27.48 mm at the concentration of 16, 32, and 64 μg/mL, respectively. Minimum inhibitory concentration (MIC) of N. sativa seed oil (NSSO) and gentamicin-treated biofilm-forming different isolates ranged from 64-502 and 32-256 μg/mL, respectively. Optical density (O.D.) and viable counts showed significant differences before and after the treatment with sub-MIC. The injections of Stx2 caused microangiopathy in mice, including hemolytic anemia, thrombocytopenia, and renal impairment. The Stx2 also caused microvascular thrombosis and other histologic damage in the kidney, spleen, and liver, as well as a significant reduction in the splenic size of the infected mice. The results showed that the variance in the values of the complete blood count, as well as histopathological alteration in the spleen, occurred in mice treated with Nigella sativa oil, which was improved compared with the control. This study is the first report on NSSO exhibiting inhibitory activity on E. coli and its Shiga toxin, which can also inhibit virulence in E. coli, thereby suggesting it as an alternative for therapy.

Hemoglobin Evans is a rare, unstable α-chain variant resulting from a valine-to-methionine substitution at codon 62 (E11) of the α-globin gene, previously reported only in HBA2. We describe the first documented case involving the HBA1 gene (HBA1:c.187G > A), identified in a 3-year-old boy who was evaluated for persistent anemia. Laboratory findings revealed hemolytic anemia with low haptoglobin, a negative Coombs test, anisopoikilocytosis, basophilic stippling, and Heinz bodies. The isopropanol instability test was positive in the patient, his father, and his sister, while molecular analysis confirmed heterozygosity for the HBA1:c.187G > A variant in all three family members. This substitution, located in the heme crevice, likely disrupts heme binding and reduces hemoglobin stability, leading to hemolysis. The clinical phenotype was consistent with mild chronic hemolytic anemia, potentially related to the lower transcriptional activity of HBA1 compared with HBA2. This report expands the molecular spectrum of unstable hemoglobins and underscores the importance of α-globin gene analysis in the evaluation of unexplained hemolytic anemia.

In December 2023, the U.S. Food and Drug Administration approved gene-editing therapies as sickle cell disease treatments. Such approvals for gene-editing not only mark radical scientific innovations for populations living with sickle cell disease (SCD) across the United States but also generate an expectation of a potential cure-the end or eradication of an illness and its effects. This essay, however, cautions against framing gene-editing therapy as a "cure" for SCD. Our argument illustrates that, even if gene editing is proven to permanently normalize the hematologic function of the body, there are other painful aspects of SCD that gene editing is unable to transform. Scientific researchers and health care practitioners could benefit from further bioethical consideration of the effects of using curative language with regards to SCD. The curative framing can easily generate misunderstandings in patient-provider communication and elicit unrealistic expectations. Raising awareness about the importance of how gene-editing therapies for SCD are described and about the need to discuss their limitations can prevent further harm.

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.