Encephalopathy is a heterogeneous clinical syndrome with numerous neurological and systemic etiologies. We report the case of a 67-year-old man, a chronic ethanol consumer, admitted with a one-week history of confusional syndrome. Initial laboratory tests revealed severe hypercalcemia, acute kidney injury, mild anemia, and hyperproteinemia. Serum ammonia levels were within normal limits, reducing the likelihood of hepatic encephalopathy despite the patient's chronic ethanol use. Cerebral imaging excluded acute cerebrovascular events, while abdominal ultrasound demonstrated splenomegaly and normal-sized kidneys. Serum protein electrophoresis and immunofixation identified a monoclonal IgG-kappa component, strongly suggestive of multiple myeloma. The patient's neurocognitive symptoms improved rapidly following systemic corticosteroid therapy and fluid-electrolyte rebalancing, confirming hypercalcemia as the primary mechanism of encephalopathy. Hypercalcemic encephalopathy as an initial manifestation of multiple myeloma is exceedingly rare. This case highlights the diagnostic complexity in elderly patients with multiple potential contributors to altered mental status, including chronic ethanol exposure and renal dysfunction. The presence of normal renal dimensions, unexplained hypercalcemia, and a monoclonal component should prompt evaluation for plasma cell malignancy. Early recognition of hypercalcemia-induced encephalopathy and prompt investigation for underlying hematologic malignancy are essential to prevent irreversible organ damage and to ensure timely initiation of specific therapy.

Patients with compromised immune systems, particularly those living with human immunodeficiency virus (HIV) infection and HIV-related lymphoma, pose multiple challenges for anesthesiologists because of hematologic abnormalities, critically low platelet counts, and potential drug-drug interactions. This report describes a 55-year-old male patient with HIV and Burkitt-type non-Hodgkin lymphoma (NHL) who presented with splenomegaly and severe platelet sequestration. Preoperative hematologic optimization was achieved with two platelet apheresis sessions and tranexamic acid for antifibrinolytic prophylaxis. The patient underwent an elective splenectomy under balanced general anesthesia. Propofol, fentanyl, and rocuronium were used for anesthetic induction, and tracheal intubation was successfully performed using videolaryngoscopy without complications. Following surgery, transversus abdominis plane (TAP) blocks and rectus sheath blocks were performed using ropivacaine, providing adequate analgesia without the need for postoperative opioids. The patient remained hemodynamically stable throughout the procedure, with an uneventful anesthetic recovery and no bleeding or infectious complications. He was discharged on postoperative day 3, with a platelet count of 80,000/µL. Optimal perioperative management of HIV-positive patients with severe thrombocytopenia is essential for safe anesthetic care. Appropriate blood product utilization and regional analgesia techniques may further improve outcomes. Multidisciplinary management is crucial for minimizing perioperative risks and enhancing patient outcomes.

Background/Objectives: Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by epithelial injury and excessive inflammatory responses. J2H-1802 is a newly synthesized hybrid molecule designed to combine the pharmacological properties of mycophenolate mofetil and 5-aminosalicylic acid. This study evaluated the protective and anti-inflammatory effects of J2H-1802 in a dextran sulfate sodium (DSS)-induced colitis mouse model and investigated its underlying mechanisms. Methods: Experimental colitis was induced in mice by administration of 2.5% (w/v) DSS for 7 days, followed by oral treatment with J2H-1802. Body weight, stool consistency, fecal bleeding, and disease activity index were assessed. Colon length and spleen weight were measured to evaluate macroscopic damage. Levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, and myeloperoxidase in colon tissues were quantified, and the expression of phosphorylated nuclear factor-κB and cyclooxygenase-2 was analyzed by Western blotting. Results: J2H-1802 alleviated DSS-induced body weight loss, diarrhea, and fecal bleeding, resulting in reduced disease activity index scores. It also prevented colon shortening and attenuated splenomegaly. In addition, J2H-1802 significantly suppressed the elevated levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, and myeloperoxidase in colon tissues. Western blot analysis further showed that J2H-1802 inhibited the DSS-induced upregulation of phosphorylated nuclear factor-κB and cyclooxygenase-2. Conclusions: J2H-1802 protected against DSS-induced colitis by reducing inflammatory responses and inhibiting the nuclear factor-κB/cyclooxygenase-2 signaling pathway. These findings suggest that J2H-1802 functions as a hybrid anti-inflammatory scaffold with in vivo pharmacological activity and may warrant further optimization and investigation in IBD models.

Background: Brucellosis is a global zoonosis caused by Brucella. Histidine biosynthesis is essential for bacterial growth, but its role in Brucella melitensis virulence remains unclear. HisD catalyzes the final two steps of histidine synthesis and is absent in mammals, making it a potential drug target. Results: We constructed a hisD deletion mutant (ΔhisD) and complemented strain (ChisD) via homologous recombination. ΔhisD failed to grow in medium without histidine supplementation. It showed reduced survival under polymyxin B and SDS stress, and impaired outer membrane integrity under polymyxin B challenge, though no defect was observed under non-stressed conditions. Intracellularly, ΔhisD replicated poorly in HeLa and RAW264.7 cells, and this defect was rescued by exogenous histidine. In a mouse model, ΔhisD exhibited lower bacterial loads in liver and spleen, reduced splenomegaly, and attenuated hepatic granuloma formation. Conclusions: Histidine biosynthesis deficiency attenuates Brucella virulence by restricting nutritional acquisition and conditionally compromising outer membrane stability. HisD is a promising target for anti-brucellosis drug development, and ΔhisD holds potential as a live attenuated vaccine candidate.

Visceral leishmaniasis (VL) is a rare but increasingly recognized parasitic infection in non-endemic European regions, including Romania. We report two cases of VL diagnosed in Timiș County, Western Romania, in 2020: a 57-year-old male presenting with fever, massive splenomegaly, and severe pancytopenia, and a 51-year-old male presenting atypically with fatigue, bicytopenia, and absence of organomegaly. Both patients were diagnosed through bone marrow aspirate examination revealing Leishmania amastigotes. Both cases were classified as imported VL, with exposure linked to endemic regions of eastern Spain (Castellón and València). These cases highlight the importance of maintaining a high index of clinical suspicion for VL in patients presenting with unexplained cytopenias and elevated inflammatory markers, even in the absence of classic features such as hepatosplenomegaly. The present report underscores the relevance of travel history in non-endemic regions such as Romania and the need for clinical awareness of imported VL in patients returning from endemic areas of southern Europe.

Splenic angiosarcoma is a rare aggressive tumor originating from vascular endothelial cells of the spleen,typically presenting with splenomegaly,fatigue,and weight loss.Patients accompanied by anemia,thrombocytopenia,and bone marrow biopsy showing fibrosis are prone to be misdiagnosed with primary myelofibrosis.This article retrospectively analyzes the clinical characteristics of two cases initially diagnosed as primary myelofibrosis but negative for common driver gene mutations (JAK2,CALR,and MPL).One case was confirmed through splenectomy due to progressive splenomegaly,while the other was identified via bone marrow biopsy indicating angiosarcoma invasion.Both cases were ultimately pathologically confirmed as primary splenic angiosarcoma after splenectomy.Through literature review,we aim to enhance awareness of this rare disease,emphasizing that primary splenic tumors secondary to myelofibrosis should be differentially diagnosed in the cases of driver gene mutation-negative myelofibrosis.

Dysregulation of galectins and global protein glycosylation have been reported in various cancers, but their role in myeloproliferative neoplasms (MPNs) have remained incompletely understood. We performed single-cell RNA sequencing (scRNA-seq) which revealed significant enrichment of galectin genes in MPN monocytes. Cell-cell communication analysis predicted monocytes as a pivotal mediator of cell interactions and galectin signaling as a robust input/output pathway for monocytes. We identified elevated expression of galectin-1 (Gal-1, LGALS1) in monocytes from both human MPN samples and mouse models. Mass cytometry (CyTOF) profiling of MPN blood samples demonstrated that recombinant galectin-1 (rGal-1) significantly increased levels of multiple inflammatory cytokines in monocytes without affecting other cell types. Incubation of CD14+ monocytes from MPN patients with rGal-1 led to markedly increased transcription and secretion of inflammatory cytokines. Mechanistically, we uncovered crosstalk between the TLR4 and Gal-1 signaling pathways, as evidenced by protein 3D modeling and co-immunoprecipitation. Notably, TLR4 inhibition abrogated Gal-1 mediated proinflammatory effects in monocytes. We further identified NF-κB-dependent signaling as a key downstream effector of Gal-1, as reporter assays demonstrated rGal-1 mediated activation of NF-κB signaling in a TLR4-dependent manner. We corroborated these findings in vivo in a murine model driven by MPLW515L in which genetic abrogation of Lgals1 ameliorated key MPN disease features, including leukocytosis and splenomegaly. Additionally, Gal-1 inhibition suppressed carrageenan-induced thrombosis and inflammation in vivo. In summary, we identify Gal-1 enrichment in MPN monocytes as a driver of monocyte-mediated inflammation through TLR4 and NF-κB activation and uncover a novel therapeutic avenue for MPNs.