Search Results (23)

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

Cytokine storm is a critical driver of acute respiratory distress syndrome and multiple organ failure. Human β-defensin 2 (HBD-2) is the first inducible defensin discovered in human body. Defensin can resist pathogenic microorganisms invading the body through direct bactericidal effect and also modulates acquired immune response. Albumin exhibits immunomodulatory properties and can reduce the level of inflammatory cytokines to improve the systemic inflammatory response. We previously engineered a recombinant fusion protein, DF₂-HSA, comprising two HBD-2 molecules linked to human serum albumin. Here, we evaluated its effect on cytokine storm using a lipopolysaccharide (LPS)-induced cytokine storm murine model (BALB/c athymic mice, female). DF₂-HSA reduced the mortality in cytokine storm murine model and prolonged the retention time of HBD-2 in the body. A Luminex assay showed that DF₂-HSA reduced the production of multiple inflammatory cytokines in cytokine storm murine model. Evans blue staining showed that DF₂-HSA reduced vascular leakage. Transmission electron microscopy showed that DF₂-HSA reduced the lung injury of cytokine storm mice. The pathological results showed that DF₂-HSA alleviated the lung and small intestine damage of cytokine storm mice. In summary, DF₂-HSA effectively inhibits cytokine storms and ameliorates associated tissue damage. Full article

Background: Evans syndrome is a rare autoimmune disease characterized by immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia, typically triggered by an episode of immune dysregulation or multiple other factors. We present what appears to be the first reported case of Evans syndrome developing in a 66-year-old female following respiratory syncytial virus (RSV) vaccination. Case Presentation: A 66-year-old female presented with a petechial rash on her arms, legs, and face. Laboratory tests revealed a platelet count of 1 × 10⁹/L, significantly lower than her historical baseline of >200 × 10⁹/L. On hospital day 4, her hemoglobin declined from 14.3 g/dL to 9.9 g/dL, with laboratory evidence of hemolysis, including elevated bilirubin, low haptoglobin, and increased lactate dehydrogenase (LDH). Bone marrow biopsy revealed megakaryocytic hyperplasia consistent with ITP, along with a small polyclonal B-cell population lacking CD20 expression. Imaging was unremarkable, showing no interval changes aside from stable pre-existing pulmonary nodules and no lymphadenopathy. These findings supported a diagnosis of Evans syndrome. Initial therapy with dexamethasone and intravenous immunoglobulin (IVIG) for presumed ITP was ineffective. Due to refractory thrombocytopenia, the patient initially received one dose of rituximab, followed by one dose of romiplostim. Subsequently, the patient received rituximab infusions every week at a rate of 375 mg/m² for four doses, as well as prednisone at a dose of 1 mg/kg/day. Within five weeks, her blood count returned to normal. Conclusions: This case raises concern for a potential temporal association between RSV vaccination and the onset of Evans syndrome. It underscores the need for heightened clinical awareness and further investigation into immune-mediated hematologic complications following RSV immunization. Full article

Idiopathic normal-pressure hydrocephalus (iNPH) is clinically characterized by the Hakim–Adams triad: gait disturbance, cognitive decline, and urinary incontinence. Cognitive impairment in iNPH predominates as a subcortical syndrome, with deficits in executive functions, psychomotor slowing, and memory inefficiency. However, the cognitive profile is heterogeneous and often overlaps with other neurodegenerative conditions, complicating differential diagnosis. This study investigated the cognitive features of iNPH using the Rey Auditory Verbal Learning Test (RAVLT), comparing 29 iNPH patients to 28 healthy controls. Demographic and neuroimaging parameters—such as Evans Index and Callosal Angle—were assessed. Results indicated significantly lower Montreal Cognitive Assessment (MoCA) and RAVLT scores in iNPH patients compared to controls. Analysis of serial position effects revealed that, whereas healthy individuals exhibited typical primacy and recency effects in verbal memory, iNPH patients demonstrated a selective impairment of the primacy effect, likely reflecting hippocampal dysfunction. These findings underline the importance of detailed neuropsychological evaluation in differentiating iNPH from other dementias and suggest that damage to medial temporal lobe structures plays a prominent role in the verbal memory deficit observed in iNPH. Full article

Background: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are critical conditions lacking effective pharmacologic therapies. Lipopolysaccharide (LPS), a bacterial endotoxin, is a well-established trigger of ALI. Emerging evidence suggests that heparin derivatives may attenuate lung injury, but their mechanisms remain unclear. Methods: This study evaluated the protective effects of 2-O, 3-O desulfated heparin (ODSH) in a murine model of LPS-induced ALI. Mice received LPS intratracheally with or without ODSH pre-treatment. Lung injury was assessed by bronchoalveolar lavage fluid (BALF) analysis, Evans blue dye albumin EBDA) extravasation, and histopathology. Results: ODSH treatment significantly reduced BALF protein concentration, inflammatory cell infiltration, and EBDA leakage. ODSH preserved endothelial barrier function in vitro, as evidenced by transendothelial electrical resistance (TER) measurements in human lung microvascular endothelial cell (HLMVEC) monolayers. Histological assessment (H&E staining) and myeloperoxidase (MPO) staining demonstrated reduced lung injury and neutrophil infiltration in the ODSH group. ODSH also downregulated pro-inflammatory mediators (NF-κB, IL-6, p38 MAPK) and upregulated the anti-inflammatory cytokine IL-10. Conclusions: ODSH mitigates LPS-induced ALI by reducing vascular permeability, neutrophilic inflammation, and pro-inflammatory signaling while enhancing IL-10 expression. These findings suggest ODSH may offer a novel therapeutic approach for treating ALI. Full article

Background/Objetives: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Nutritional disorders, particularly cachexia, significantly impact morbidity and mortality in IPF but remain under-investigated. This study aimed to characterize cachexia phenotypes in IPF through morphofunctional assessment (MFA) and to evaluate their prognostic relevance, including the role of mitochondrial biomarkers. Methods: In this prospective bicenter study, 85 IPF patients underwent MFA including bioelectrical impedance vector analysis (BIVA), nutritional ultrasound (NU), and T12-level computed tomography (T12-CT) for body composition. Functional and strength assessments included timed up and go test (TUG) and handgrip strength (HGS), respectively. Cachexia was defined by Evans’ criteria, Martin’s CT-based criteria, and our IPF-specific proposed definition. Serum GDF-15 and PGC-1α levels were also measured. Results: Cachexia prevalence varied by definition: 24.71% (Evans), 29.5% (Martin) and 42.4% (IPF Cachexia Syndrome). Cachectic patients showed significantly lower muscle mass, function, and quality (measured by reduced muscle attenuation at T12-CT), along with higher GDF-15 and lower PGC-1α levels. The presence of IPF Cachexia syndrome (HR 2.56; 95% CI, 1.08–6.07; p = 0.033), GDF-15 > 4412.0 pg/mL (HR 3.21; 95% CI, 1.04–9.90; p = 0.042) and impaired TUG (>8 s) (HR 3.77; 95% CI, 1.63–8.71; 0.002) were all independently associated with increased 24-month mortality. Conclusions: Cachexia is prevalent in IPF and showed strong concordance between the three diagnostic criteria. The IPF Cachexia syndrome, based on comprehensive morphofunctional phenotyping, demonstrated superior discriminatory capacity. The addition of mitochondrial biomarkers may improve early detection and support personalized interventions to improve patient outcomes. Full article

Immune cytopenias, such as autoimmune hemolytic anemia, immune thrombocytopenia, and Evans syndrome, are characterized by autoantibodies targeting various blood cells, initiating their destruction. Interactions between T cells, B cells, their ultimate maturational plasma cell descendants, dendritic cells, and macrophages result in antibody production, including the autoreactive ones. Autoimmune phenomena can be idiopathic or associated with various immune dysregulation conditions or malignancies. Interventions disrupting this complex network at different levels have been used to treat immune cytopenias with certain levels of success. Some cases are known to be refractory to many different therapeutic approaches, including the ones eliminating B cells. In some such cases, targeting plasma cells resulted in disease control. Among plasma cell compartments, unique long-lived plasma cells (LLPCs) residing primarily in the bone marrow, are specialized antibody-producing cells with an extended lifespan, capable of persistently secreting antibodies. LLPCs can evade conventional therapeutic strategies designed to target often-proliferating cells. Research focusing on the role of LLPCs in autoimmune phenomena including immune cytopenias has provided evidence for their role, characterized by the sustained production of autoantibodies. Frequent genetic mutations and progression to other immune dysregulation entities have been reported in a group of children with immune cytopenias. This might provide new insights focusing on the potential underlying genetic and epigenetic mechanisms leading to generation and maintenance of LLPCs in autoimmune disorders. We provide a brief review of LLPC biology and evidence for their role in immune cytopenias with potential future implications in this article. Full article

Disease eponyms can be confusing, difficult to remember, scientifically non-robust, and lacking in implications on and relationships with cell lineage, histogenesis, and pathogenesis. This review is geared toward revisiting hematolymphoid diseases with eponyms in light of recent advances in technology and science by searching the past fifty years of the literature using Scopus and Google Scholar with the keywords “eponyms, hematolymphoid, diseases, lymphoma, benign, malignant, lymph node, spleen, liver, bone marrow, leukemia”. With advances in science and technology, there is accumulation of information on the morphologic nuances and immunologic, immunophenotypic, and genetic features of various hematolymphoid eponymic diseases, thus shedding light on important issues of etiology and pathogenesis with implications on therapy in various non-neoplastic (Castleman, Evans syndrome Kikuchi–Fujimoto, IgG4-related diseases) and neoplastic (Hodgkin, Burkitt, NK/T-cell lymphomas, dendritic/histiocytic neoplasms, and Sezary syndrome) diseases. This contributes to modern nomenclature, classification, subtyping, prognostication, and discoveries on new treatment strategies of hematolymphoid eponymic diseases. Full article

Background/Objectives: Evans’ syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous or sequential onset of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Given its rarity, available data concerning the clinical course and optimal management in pregnancy are limited. Methods: We present the case of a 32-year-old woman who experienced ES during her first pregnancy. She had been previously diagnosed with childhood-onset SLE at the age of 14 but had been in treatment-free remission since the age of 24. The treatment of both AIHA and ITP included intravenous immunoglobulins, cyclosporine-A, high dosage oral corticosteroids, and, in the second trimester, rituximab. The delivery was planned at 34 + 6 weeks of gestation (GW); no immunological alterations or infectious complications were detected in the newborn. The post-delivery period was uncomplicated, and the mother was discharged with a normal blood count. A narrative review of available ES cases during pregnancy is also presented. Results: A total of 16 patients with ES in pregnancy were reported, including the one we described. None of them developed major bleedings during gestation, while a case of abruptio placentae with delayed postpartum hemorrhage occurred. ITP was difficult to treat in 4/16 women after delivery; 4/16 patients also developed gestational hypertensive disorders. Perinatal outcomes include 13/17 healthy newborns and 4/17 stillbirths (2 of them were twins), of which 1 was due to fetal AIHA. Gestational age at birth was before 37 GW in 8/17. In 15/16 women, ES resolved after delivery. Conclusions: The occurrence of ES during pregnancy has been rarely reported; it constitutes a clinical challenge due to the need for multiple treatments, including conventional immunosuppressants and/or biologic drugs as steroid-sparing agents. After delivery, ES appeared to be less resistant to treatment than it was during pregnancy. Full article

Evans Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger’s Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal–tibioperoneal artery bypass surgery and the subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach to managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD. Full article

Neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) that usually results in poor clinical outcomes and may be accompanied by paraneoplastic syndromes (PNS). NEPC is becoming more frequent. It can initially manifest as PNS, complicating diagnosis. Therefore, we reviewed the literature on the different PNS associated with NEPC. We systematically reviewed English-language articles from January 2017 to September 2023, identifying 17 studies meeting PRISMA guidelines for NEPC and associated PNS. A total of 17 articles were included in the review. Among these, Cushing’s Syndrome (CS) due to ectopic Adrenocorticotropic hormone (ACTH) secretion was the most commonly reported PNS. Other PNS included syndrome of inappropriate Anti-Diuretic Hormone secretion (SIADH), Anti-Hu-mediated chronic intestinal pseudo-obstruction (CIPO), limbic encephalitis, Evans Syndrome, hypercalcemia, dermatomyositis, and polycythemia. Many patients had a history of prostate adenocarcinoma treated with androgen deprivation therapy (ADT) before neuroendocrine features developed. The mean age was 65.5 years, with a maximum survival of 9 months post-diagnosis. NEPC is becoming an increasingly more common subtype of PCa that can result in various PNS. This makes the diagnosis and treatment of NEPC challenging. Further research is crucial to understanding these syndromes and developing standardized, targeted treatments to improve patient survival. Full article

The municipality of Salvador, situated in Brazil, distinguished itself as the epicenter of the emergence of microcephaly related to congenital manifestations of Zika syndrome. Despite the anticipated significant developmental setbacks in these children, research has indicated a varied range of outcomes, with certain instances even reflecting minimal developmental delay. Our objective was to pinpoint determinants that could forecast developmental anomalies in children diagnosed with microcephaly associated with congenital Zika syndrome (CZS). Methodology: A forward-looking clinical and neurodevelopmental examination was conducted focusing on neonates diagnosed with microcephaly with CZS, birthed between September 2015 and April 2016 at the Hospital Geral Roberto Santos, in Salvador city. That infants were monitored up to their third year by a multiprofessional team. Child development was assessed using the composite Bayley III score. Undertaken by two blinded experts, cranial CT scan analysis was performed during the neonate period for the detection of brain abnormalities and to quantify ventricle enlargement, measured by Evans’ index (EI). Results: Fifty newborns were evaluated with a median head circumference of 28 cm (interquartile range 27–31 cm). EI was associated with neurodevelopmental delay at three years and remained significant after adjustment for head circumference. A 0.1-point increase in EI was associated with a delay of 3.2 months in the receptive language (p = 0.016), 3.4 months in the expressive language (p = 0.016), 3.4 months in the cognitive (p = 0.016), 2.37 months in the gross motor (p = 0.026), and 3.1 months in the fine motor (p = 0.021) domains. Conclusions: EI predicted neurodevelopmental delay in all Bayley domains in children with microcephaly associated with CZS. Full article

Tick-borne haemoparasite Babesia gibsoni has been detected rarely in cats, in surveys of apparently healthy animals. In stored blood from a 6-year-old male-neutered domestic shorthair cat in Hong Kong, B. gibsoni DNA was detected retrospectively using PCR for Babesia spp. 18S rRNA and mitochondrial cytochrome B genes, followed by sequencing and basic local alignment search tool (BLAST) analysis. The cat presented with severe haemolytic anaemia and thrombocytopenia. The cat responded to supportive care and glucocorticoids and was clinically normal despite persistent subclinical thrombocytopenia until six months after presentation, when it succumbed to a fatal haemorrhagic episode. Necropsy revealed severe intestinal and pulmonary haemorrhage and hypocellular bone marrow with megakaryocytosis but no other causes of immune-mediated thrombocytopenia (IMTP) or immune-mediated haemolytic anaemia (IMHA). Blood stored on days 158 and 180 tested PCR negative for Babesia spp. This report demonstrates that geographic range of B. gibsoni detection in cats includes Hong Kong. The exclusion of other causes suggests that B. gibsoni might have potentially played a role in triggering immune-mediated disease in this case. Full article

Background: Hepatopulmonary syndrome (HPS) is a pulmonary vasculature complication in the setting of liver disease that is characterized by pathological vasodilation resulting in arterial oxygenation defects. We investigated the role of extracellular vesicles (EV) in cirrhosis patients with HPS, as well as the functional effect of EV administration in a common bile duct ligation (CBDL) HPS mouse model. Methods: A total of 113 cirrhosis patients were studied: 42 (Gr. A) with HPS and 71 (Gr. B) without HPS, as well as 22 healthy controls. Plasma levels of EV associated with endothelial cells, epithelial cells, and hepatocytes were measured. The cytokine cargoes were estimated using ELISA. The effect of EV administered intranasally in the CBDL mouse model was investigated for its functional effect in vascular remodeling and inflammation. Results: We found endothelial cells (EC) associated EV (EC-EV) were elevated in cirrhosis patients with and without HPS (p < 0.001) than controls. EC-EV levels were higher in HPS patients (p = 0.004) than in those without HPS. The epithelial cell EVs were significantly high in cirrhosis patients than controls (p < 0.001) but no changes found in patients with HPS than without. There was a progressive increase in EC-EV levels from mild to severe intrapulmonary shunting in HPS patients (p = 0.02 mild vs. severe), and we were able to predict severe HPS with an AUROC of 0.85; p < 0.001. An inverse correlation of EC-EVs was found with hemoglobin (r = −0.24; p = 0.031) and PaO2 (r = 0.690; p = 0.01) and a direct correlation with MELD (r = 0.32; p = 0.014). Further, both TNF-α (p = 0.001) and IL-1β (p = 0.021) as cargo levels were significantly elevated inside the EVs of HPS patients than without HPS. Interestingly, upon administration of intranasal EVs, there was a significant decrease in Evans blue accumulation and lung wet–dry ratio (p = 0.042; 0.038). A significant reduction was also noticed in inflammation and cholestasis. Conclusion: High levels of plasma EC-EV levels were found in patients with HPS with elevated pro-inflammatory cytokine cargoes. EC-EVs were indicative of severe HPS condition. In the CBDL HPS model, we were able to prove the beneficial effects of improving vascular tone, inflammation, and liver pathogenesis. Full article

Recently, Brentuximab Vedotin (BV) has emerged as an important therapy not only for Hodgkin’s Lymphoma, but also for CD30-positive T cell lymphomas. Although anemia and thrombocytopenia are common myelosuppressive side effects, to our knowledge, this is the first described case of Evans Syndrome associated with BV therapy. We present the case of a 64-year-old female, diagnosed with relapsed Peripheral T Cell Lymphoma Not Otherwise Specified (PTCL-NOS), who, after receiving six cycles of BV, developed authentic severe autoimmune hemolytic anemia with strong positive direct anti-globulin (Coombs) test, simultaneously associated with severe immune thrombocytopenia. The patient was unresponsive to systemic corticotherapy, but fully recovered after a course of IV immunoglobulin. Full article