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Biochemia Medica Jun 2024Hairy cell leukemia (HCL) represents 2% of all leukemia cases, with men aged above 55 years being the most affected. The most common symptoms of this type of leukemia... (Review)
Review
Hairy cell leukemia (HCL) represents 2% of all leukemia cases, with men aged above 55 years being the most affected. The most common symptoms of this type of leukemia include splenomegaly, monocytopenia, and neutropenia. In the basic blood count examination, leukopenia with monocytopenia and granulocytopenia, as well as aplastic anemia and/or thrombocytopenia occur. The mutation of β-rapidly accelerated fibrosarcoma () proto-oncogene, which can be found in nearly 100% of patients, is an important feature of HCL. Immunophenotypic analysis of the HCL cells reveals high expression of B-lineage antigens, including CD19, CD20, and CD22. Additionally, CD11c, CD25, CD103, and CD123 belong to specific markers of HCL. Lactate dehydrogenase activity and β-2-microglobulin concentration are also important in the patient's assessment. The differential diagnosis between HCL, hairy cell leukemia variant (HCL-V) and splenic marginal zone lymphoma (SMZL) is of first importance. Currently, the main treatment for HCL involves the use of purine analogues, excluding pregnant women, individuals with severe infections, and those with relapsing HCL.
Topics: Humans; Leukemia, Hairy Cell; Proto-Oncogene Mas; Proto-Oncogene Proteins B-raf; Diagnosis, Differential; Male; Mutation
PubMed: 38882583
DOI: 10.11613/BM.2024.020502 -
Acta Biomaterialia Jun 2024Wound healing is facilitated by biomaterials-based grafts and substantially impacted by orchestrated inflammatory responses that are essential to the normal repair...
Wound healing is facilitated by biomaterials-based grafts and substantially impacted by orchestrated inflammatory responses that are essential to the normal repair process. Tropoelastin (TE) based materials are known to shorten the period for wound repair but the mechanism of anti-inflammatory performance is not known. To explore this, we compared the performance of the gold standard Integra Dermal Regeneration Template (Integra), polyglycerol sebacate (PGS), and TE blended with PGS, in a murine full-thickness cutaneous wound healing study. Systemically, blending with TE favorably increased the F4/80 macrophage population by day 7 in the spleen and contemporaneously induced elevated plasma levels of anti-inflammatory IL-10. In contrast, the PGS graft without TE prompted prolonged inflammation, as evidenced by splenomegaly and greater splenic granulocyte and monocyte fractions at day 14. Locally, the inclusion of TE in the graft led to increased anti-inflammatory M2 macrophages and CD4 T cells at the wound site, and a rise in Foxp3 regulatory T cells in the wound bed by day 7. We conclude that the TE-incorporated skin graft delivers a pro-healing environment by modulating systemic and local tissue responses. STATEMENT OF SIGNIFICANCE: Tropoelastin (TE) has shown significant benefits in promoting the repair and regeneration of damaged human tissues. In this study, we show that TE promotes an anti-inflammatory environment that facilitates cutaneous wound healing. In a mouse model, we find that inserting a TE-containing material into a full-thickness wound results in defined, pro-healing local and systemic tissue responses. These findings advance our understanding of TE's restorative value in tissue engineering and regenerative medicine, and pave the way for clinical applications.
PubMed: 38871204
DOI: 10.1016/j.actbio.2024.06.009 -
Clinical Case Reports Jun 2024When a person has both HS and beta-thalassemia, their clinical symptoms tend to be less severe. This is because these two conditions have contrasting features. If the...
KEY CLINICAL MESSAGE
When a person has both HS and beta-thalassemia, their clinical symptoms tend to be less severe. This is because these two conditions have contrasting features. If the clinical symptoms and laboratory results cannot be solely attributed to hemolytic anemia, it is important to consider the possibility of another form of hemolytic anemia coexisting.
ABSTRACT
We present a 26-year-old woman who has been experiencing abdominal pain, jaundice, and anemia for the past 15 years. Initially, she was diagnosed with gallstones and splenomegaly, but after a thorough hematology examination conducted by expert colleagues, it was discovered that she had both beta-thalassemia and hereditary spherocytosis. The osmotic fragility test confirmed this diagnosis. The patient was advised to undergo both splenectomy and cholecystectomy procedures. It is worth noting that the co-occurrence of these two conditions is rare.
PubMed: 38868122
DOI: 10.1002/ccr3.9080 -
Journal of Infection in Developing... May 2024Tuberculous lymphadenitis (TBLN) is the most common infectious etiology of peripheral lymphadenopathy in adults, in Turkiye. This study aimed to identify the...
INTRODUCTION
Tuberculous lymphadenitis (TBLN) is the most common infectious etiology of peripheral lymphadenopathy in adults, in Turkiye. This study aimed to identify the demographic, clinical, and laboratory variables that differentiate TBLN from non-tuberculous lymphadenitis (NTBLN), as well as the etiology of lymphadenopathy in adults.
METHODOLOGY
Patients who were over 18 years old and were referred to the infectious disease outpatient clinics with complaints of swollen peripheral lymph nodes, and who underwent lymph node biopsy between 1 January 2010 and 1 March 2021, were included in this multicenter, nested case-control study.
RESULTS
A total of 812 patients at 17 tertiary teaching and research hospitals in Turkiye were included in the study. TBLN was the most frequent diagnosis (53.69%). The proportion of patients diagnosed with TBLN was higher among females; and among those who had a higher erythrocyte sedimentation rate, positive purified protein derivative test, and positive interferon-gamma release test result (p < 0.05). However, TBLN was less frequent among patients with generalized lymphadenopathy, bilateral lymphadenopathy, axillary lymphadenopathy, inguinal lymphadenopathy, hepatomegaly, splenomegaly, leukocytosis, and moderately increased C reactive protein levels (p < 0.05).
CONCLUSIONS
Identifying the variables that predict TBLN or discriminate TBLN from NTBLN will help clinicians establish optimal clinical strategies for the diagnosis of adult lymphadenopathy.
Topics: Humans; Tuberculosis, Lymph Node; Female; Male; Adult; Case-Control Studies; Middle Aged; Young Adult; Turkey; Lymph Nodes; Adolescent; Lymphadenopathy; Aged; Interferon-gamma Release Tests
PubMed: 38865395
DOI: 10.3855/jidc.19502 -
Investigative Ophthalmology & Visual... Jun 2024Lupus-like chronic graft-versus-host disease (cGVHD) has been previously described, but the ocular findings have not been elucidated. Recipient mice in a lupus-like...
PURPOSE
Lupus-like chronic graft-versus-host disease (cGVHD) has been previously described, but the ocular findings have not been elucidated. Recipient mice in a lupus-like cGVHD model manifested notable and persistent ocular surface phenotypes. Herein, we further explored immunopathogenic mechanisms underlying these ocular phenotypes.
METHODS
A previously described lupus-like cGVHD model was established by intraperitoneal injection of splenocytes from bm12 mice into C57BL/6J mice. Systemic findings were evaluated for the presence of splenomegaly, proteinuria, and autoantibodies. Comprehensive evaluations were conducted on ocular manifestations and immunopathological features in this model.
RESULTS
The lupus-like cGVHD model was successfully constructed 2 weeks post-transplantation. The recipient mice developed lupus-like phenotypes, including splenomegaly, proteinuria, and increased autoantibodies, and their ocular presentations included corneal epithelial defects and decreased tear secretion. Histological analysis revealed a reduction in corneal nerve fiber density and corneal endothelial cells, along with conjunctival fibrosis and loss of goblet cells. Moreover, cGVHD induced progressive aggravation of immune cell infiltration and fibrosis in the lacrimal glands. RNA-Sequencing (RNA-seq) results of the lacrimal glands demonstrated that the differentially expressed genes (DEGs) between the control and cGVHD groups were associated with GVHD pathways. Immune infiltration analysis using RNA-seq and flow cytometry confirmed that CD8+ T lymphocytes predominantly constituted the inflammatory infiltrating cells within the lacrimal glands.
CONCLUSIONS
This lupus-like cGVHD model (bm12→C57BL/6J) exhibited persistent ocular surface manifestations, characterized by immune infiltration of CD8+ T lymphocytes in the lacrimal glands. Thus, this ocular cGVHD model may be used to explore the underlying mechanisms and discover novel therapeutic interventions.
Topics: Animals; Graft vs Host Disease; Mice; Disease Models, Animal; Mice, Inbred C57BL; Chronic Disease; Lupus Erythematosus, Systemic; Female; Autoantibodies; Bronchiolitis Obliterans Syndrome
PubMed: 38864812
DOI: 10.1167/iovs.65.6.20 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Jun 2024To analyze the clinical data of histiocytic necrotizing lymphadenitis(HNL), comparing the similarities and differences between children and adults, to deepen the...
OBJECTIVE
To analyze the clinical data of histiocytic necrotizing lymphadenitis(HNL), comparing the similarities and differences between children and adults, to deepen the understanding of the disease by clinical physicians, and to improve diagnostic rate and reduce misdiagnosis and mistreatment.
METHODS
The clinical data of hospitalized patients with histiocytic necrotizing lymphadenitis diagnosed by biopsy from January 2010 to August 2023 in Peking University First Hospital were collec-ted, and the clinical features, laboratory examinations, pathological features, treatments with antibiotics and glucocorticoids, and prognosis of histiocytic necrotic lymphadenitis were analyzed. Grouped based on age, the differences of clinical characteristics, laboratory tests, treatment, and prognosis between the children group (< 16 years old) and the adult group (≥16 years old) were compared.
RESULTS
Among the 81 enrolled patients, there were 42 males and 39 females. The median age was 21(14, 29) years, the median duration of disease was 20.0(13.0, 30.0) days, and the median length of hospital stay was 13.0 (10.0, 15.0) days. The first symptoms were fever, lymphadenopathy, and both. All the patients had enlarged lymph nodes with different parts and sizes, 96.3% (78 of 81) of the patients had cervical lymphadenopathy, 50.6% (41 of 81) had bilateral cervical lymphadenopathy, 55.6% (45 of 81) had supraclavicular, axillary or inguinal lymphadenopathy, and the median lymph node diameter was 20.0(20.0, 30.0) mm. Only one patient had no fever, the other 80 patients had fever, the median peak body temperature was 39.0(38.0, 39.8) ℃. Accompanying symptoms: rash (8.6%, 7/81), fatigue (34.6%, 28/81), night sweating (8.6%, 7/81), chills (25.3%, 25/81), muscle soreness (13.6%, 11/81), and joint pain (6.2%, 5/81). There were 17 cases (21.0%, 17/81) of hepatosplenomegaly, of which 12 cases (70.6%, 12/17) were splenomegaly. 68.8%(55/80) of patients had a decrease in white blood cell (WBC) count, with 47.5%(38/80)increased in lymphocyte(LY)proportion, 53.4%(39/73) increased in high-sensitivity C-reactive protein(CRP), 79.2%(57/72) increased in erythrocyte sedimentation rate(ESR), 22.2%(18/81) increased in alanine transaminase(ALT), 27.2%(22/81) elevated in aspartate transaminase(AST), and 81.6%(62/76) elevated in lactate dehydrogenase(LDH). All the 81 patients underwent lymph node biopsy, and 77.8%(63/81) of the patients showed that most of the structures in the lymph nodes were destroyed or disappeared, and 16.0%(13/81) of the lymph nodes were still in existence, hyperplasia and normal lymph node were 1.2%(1/81) respectively, and 3.7%(3/81) had normal lymph node structures. Immunohistochemical staining was performed in 67 cases. The percentages of CD3 and CD68(KP1) were respectively 97.0%(65/67), and MPO were 94.0%(63/67). In the study, 51 patients (63.0%, 51/81) were treated with glucocorticoid therapy after diagnosis. The median time for temperature to return to normal was 1.0(1.0, 4.0) days after glucocorticoid therapy. when the glucocorticoid treatment worked best, the body temperature could drop to normal on the same day. There were significant differences in length of stay, predisposing factors, chills, the rate of increase in high-sensitivity CRP, antibiotic and glucocorticoid treatment between the adults and children groups ( < 0.05).
CONCLUSION
In clinical practice, if there are cases with unexplained fever, superficial lymph node enlargement, and reduced white blood cells as clinical characteristics, and general antibiotics treatment is ineffective, histiocytic necrotic lymphadenitis should be considered. Lymph node biopsy should be performed as early as possible to clarify the diagnosis, reduce misdiagnosis and mistreatment, and symptomatic treatment should be the main treatment. Glucocorticoids therapy has a definite therapeutic effect.
Topics: Humans; Male; Histiocytic Necrotizing Lymphadenitis; Female; Adolescent; Adult; Young Adult; Child; Anti-Bacterial Agents; Glucocorticoids; Prognosis; Fever; Lymph Nodes; Lymphadenopathy
PubMed: 38864141
DOI: 10.19723/j.issn.1671-167X.2024.03.022 -
PLoS Neglected Tropical Diseases Jun 2024Leishmania donovani surface glycoprotein 63 (GP63) is a major virulence factor involved in parasite escape and immune evasion. In this study, we generated virus-like...
Leishmania donovani surface glycoprotein 63 (GP63) is a major virulence factor involved in parasite escape and immune evasion. In this study, we generated virus-like particles (VLPs) expressing L. donovani GP63 using the baculovirus expression system. Mice were intramuscularly immunized with GP63-VLPs and challenged with L. donovani promastigotes. GP63-VLP immunization elicited higher levels of L. donovani antigen-specific serum antibodies and enhanced splenic B cell, germinal center B cell, CD4+, and CD8+ T cell responses compared to unimmunized controls. GP63-VLPs inhibited the influx of pro-inflammatory cytokines IFN-γ and IL-6 in the livers, as well as thwarting the development of splenomegaly in immunized mice. Upon L. donovani challenge infection, a drastic reduction in splenic parasite burden was observed in VLP-immunized mice. These results indicate that GP63-VLPs immunization conferred protection against L. donovani challenge infection by inducing humoral and cellular immunity in mice.
Topics: Animals; Leishmania donovani; Mice; Vaccines, Virus-Like Particle; Mice, Inbred BALB C; Female; Leishmaniasis, Visceral; Antibodies, Protozoan; Leishmaniasis Vaccines; Vaccine Efficacy; Immunity, Cellular; Spleen; CD8-Positive T-Lymphocytes; B-Lymphocytes; Immunity, Humoral; Membrane Glycoproteins; Cytokines; Metalloendopeptidases
PubMed: 38857253
DOI: 10.1371/journal.pntd.0012229 -
Cureus May 2024Wilson's disease (WD), or "hepato-lenticular degeneration," is a rare genetic disorder of autosomal recessive inheritance causing toxic tissue accumulation of copper,...
Wilson's disease (WD), or "hepato-lenticular degeneration," is a rare genetic disorder of autosomal recessive inheritance causing toxic tissue accumulation of copper, mainly in the liver, brain, and cornea. Its phenotypic and genotypic heterogeneity characterizes it. This study aimed to clarify the clinical features and spectrum of Wilson's disease in children from the eastern region of Morocco and to study the evolutionary profile and survival in this population while discussing and highlighting the various diagnostic and therapeutic difficulties encountered in the management of WD in our context. This retrospective study encompassed 24 children diagnosed with Wilson's disease, selected from the gastroenterology-hepatology and pediatric nutrition units at Mohamed VI University Hospital in Oujda, Morocco, over a span of nine years, from January 2015 to November 2023. Our series results show 14 boys and 10 girls; the median age of discovery was 11 years, with extremes ranging from 18 months to 15 years. The consanguinity was found in 13 patients. Clinically, the edemato-ascitic syndrome was noted in 14 patients with an alteration of the general state; icterus was found in 13 patients; signs of portal hypertension were present in six patients; and neurological signs in seven cases. Skin manifestations occurred in three cases, and arthralgia in three cases. Six children were diagnosed on the occasion of a family screening. Biologically, hepatic cytolysis was found in 20 patients, with signs of hepatocellular failure in 15 cases. Hemolytic anemia was present in nine patients. Ceruloplasminemia was decreased in 21 patients and cupremia in 19 patients. Cupruria was increased in 22 cases. The Kayser-Fleicher ring was found in 10 cases. Abdominal ultrasound showed ascites in 16 patients, hepatomegaly in 1, splenomegaly in two cases, hepatosplenomegaly in five cases, and cirrhosis in two. MRI showed signal abnormalities in 11 patients. Therapeutically, D-penicillamine was initially introduced in 18 patients and zinc acetate in 6 patients. The evolution was favorable for 15 patients still followed up in the department. Three patients died of hepatocellular failure, and two died of hepatic encephalopathy. Four patients were lost to follow-up.
PubMed: 38854322
DOI: 10.7759/cureus.60023 -
Journal of Hematology & Oncology Jun 2024Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific...
BACKGROUND
Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils.
METHODS
Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated. MPN parameters as blood counts, splenomegaly and bone marrow histology were compared to wild-type mice. Megakaryocyte differentiation was investigated using lineage-negative bone marrow cells upon in vitro incubation with TPO/IL-1β. Cytokine concentrations in serum of mice were determined by Mouse Cytokine Array. IL-1α expression in various hematopoietic cell populations was determined by intracellular FACS analysis. RNA-seq to analyse gene expression of inflammatory cytokines was performed in isolated neutrophils from JAK2-V617F and CALR-mutated mice and patients. Bioenergetics of neutrophils were recorded on a Seahorse extracellular flux analyzer. Cell motility of neutrophils was monitored in vitro (time lapse microscopy), and in vivo (two-photon microscopy) upon creating an inflammatory environment. Cell adhesion to integrins, E-selectin and P-selection was investigated in-vitro. Statistical analysis was carried out using GraphPad Prism. Data are shown as mean ± SEM. Unpaired, two-tailed t-tests were applied.
RESULTS
Strikingly, neutrophil-specific expression of JAK2-V617F, but not CALRdel, was sufficient to induce pro-inflammatory cytokines including IL-1 in serum of mice. RNA-seq analysis in neutrophils from JAK2-V617F mice and patients revealed a distinct inflammatory chemokine signature which was not expressed in CALR-mutant neutrophils. In addition, IL-1 response genes were significantly enriched in neutrophils of JAK2-V617F patients as compared to CALR-mutant patients. Thus, JAK2-V617F positive neutrophils, but not CALR-mutant neutrophils, are pathogenic drivers of inflammation in MPN. In line with this, expression of JAK2-V617F or CALRdel elicited a significant difference in the metabolic phenotype of neutrophils, suggesting a stronger inflammatory activity of JAK2-V617F cells. Furthermore, JAK2-V617F, but not CALRdel, induced a VLA4 integrin-mediated adhesive phenotype in neutrophils. This resulted in reduced neutrophil migration in vitro and in an inflamed vessel. This mechanism may contribute to the increased thrombotic risk of JAK2-V617F patients compared to CALR-mutant individuals.
CONCLUSIONS
Taken together, our findings highlight genotype-specific differences in MPN-neutrophils that have implications for the differential pathophysiology of JAK2-V617F versus CALR-mutant disease.
Topics: Animals; Neutrophils; Janus Kinase 2; Mice; Myeloproliferative Disorders; Humans; Inflammation; Calreticulin; Mice, Transgenic; Mice, Inbred C57BL; Cytokines
PubMed: 38853260
DOI: 10.1186/s13045-024-01562-5 -
International Journal of Surgery Case... Jun 2024Hydatid disease is widespread in agricultural regions and globally. Tunisia is notably affected in the Mediterranean. Although liver involvement is common, splenic...
INTRODUCTION AND IMPORTANCE
Hydatid disease is widespread in agricultural regions and globally. Tunisia is notably affected in the Mediterranean. Although liver involvement is common, splenic hydatidosis is rare, with incidence worldwide ranging from 0.5 % to 4 %. Surgery, particularly total or partial splenectomy, remains the primary treatment. We present a unique case of isolated splenic hydatid cyst successfully managed by total splenectomy.
CASE REPORT
A 40-year-old Tunisian farmer presented with persistent pain in the left hypochondrium for 4 months, accompanied by a sensation of heaviness. Physical examination revealed splenomegaly, and laboratory tests showed a positive Indirect Hemagglutination test for Echinococcus sp. (titer >160). Thoracoabdominal CT scan revealed a 10 cm splenic hydatid cyst. Surgery involved total splenectomy via an extended left subcostal approach. Postoperative recovery was uneventful, with successful albendazole therapy and vaccination following splenectomy. During biannual follow-up, the patient remained asymptomatic and did not present with any other hydatid localization.
CLINICAL DISCUSSION
Splenic hydatid cyst is rare. Diagnostic and therapeutic advancements are crucial for its management. Therapeutic options include total splenectomy, spleen preservation, and percutaneous interventions. However, these approaches carry unique risks and benefits. Close monitoring and individualized management are essential to ensure optimal outcomes.
CONCLUSION
Diagnosis of splenic hydatid cysts is challenging due to their often asymptomatic nature and lack of specific signs. With no standardized management protocols available, personalized treatment strategies are essential. Further research is crucial to improve treatment approaches and outcomes for this rare yet clinically important condition.
PubMed: 38851067
DOI: 10.1016/j.ijscr.2024.109869