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British Journal of Haematology Jun 2024Sickle cell disease (SCD) includes a group of heterogenous disorders that result in significant morbidities. HbSS is the most common type of SCD and HbSC is the second...
Sickle cell disease (SCD) includes a group of heterogenous disorders that result in significant morbidities. HbSS is the most common type of SCD and HbSC is the second most common type of SCD. The prevalence of HbSC disease in the United States and United Kingdom is ~1 in 7174 births and 1 in 6174 births respectively. Despite its frequency, however, HbSC disease has been insufficiently studied and was historically categorized as a more 'mild' form of SCD. We conducted this study of HbSC disease as part of the NHLBI funded Sickle Cell Disease Implementation Consortium (SCDIC). The SCDIC registry included 2282 individuals with SCD, ages 15-45 years of whom 502 (22%) had HbSC disease. Compared with people with sickle cell anaemia (SCA), the study found that people with HbSC disease had a higher frequency of splenomegaly (n (%) = 169 (33.7) vs. 392 (22.1)) and retinopathy (n (%) = 116 (23.1) vs. 189 (10.6)). A Many people with HbSC also had avascular necrosis (n (%) = 112 (22.3)), pulmonary embolism (n (%) = 43 (8.6)) and acute chest syndrome (n (%) = 228 (45.4)) demonstrating significant disease severity. HbSC disease is more clinically severe than was previously recognized and deserves additional evaluation and targeted treatments.
PubMed: 38898714
DOI: 10.1111/bjh.19523 -
Colloids and Surfaces. B, Biointerfaces Jun 2024Prussian blue (PB) is authenticated in clinical treatment, while it generally exhibits unfavorable chemodynamic therapy (CDT) performance. Herein, we developed...
Prussian blue (PB) is authenticated in clinical treatment, while it generally exhibits unfavorable chemodynamic therapy (CDT) performance. Herein, we developed manganese-doped prussian blue (PBM) nanoparticles to significantly enhance both CDT and photothermal therapy (PTT) effect. The lower redox potential of Mn (0.088 V) in PBM against that of Fe (0.192 V) in PB leads to favorable electron transfer of PBM with respect to PB. Besides, PBM has a lower charge-transfer resistance (Rct) of 2.98 Ω than 4.83 Ω of PB. Once PBM entering the tumor microenvironment (TME), Mn may be readily reduced by glutathione (GSH) and therein to enhance intracellular oxidative stress. Meanwhile, the superoxide dismutase (SOD)-like activity of PBM facilitates the conversion of endogenous superoxide (O) into HO. Mn subsequently catalyzes HO to generate toxic hydroxyl radicals (•OH). Notably, the PBM plus laser irradiation can effectively trigger a robust immunogenic cell death (ICD) due to the combination therapy of CDT and PTT. Additionally, the mice treated by PBM followed by laser irradiation efficiently avoided splenomegaly and lung metastasis, along with significant up-regulation of the Stimulator of Interferon Genes (STING) expression. Overall, PBM significantly inhibits tumor growth and metastasis, making it a promising multifunctional nanoplatform for cancer treatment.
PubMed: 38897024
DOI: 10.1016/j.colsurfb.2024.114045 -
Frontiers in Veterinary Science 2024This study marks the first occasion that has been isolated, identified, and characterized as the causative pathogen in spotted sea bass (). Infected fish exhibited a...
This study marks the first occasion that has been isolated, identified, and characterized as the causative pathogen in spotted sea bass (). Infected fish exhibited a range of external symptoms, including scale loss, bleeding from the jaw, anus, and tail, among other signs, as well as internal manifestations such as congested liver, splenomegaly, branchial anemia, yellow fat syndrome, and intestinal edema. Notably, exophthalmia and meningoencephalitis-typical symptoms associated with previous infections-were not observed. A predominant bacterial isolate (designated 10S01) was recovered from the pure culture of spleen of a diseased spotted sea bass in Zhuhai, China. The strain was then subjected to Gram staining, biochemical profiling, and molecular confirmation through 16S rRNA and gene, corroborating its identity as . Pathogenicity was assessed by intraperitoneal injection challenge in spotted sea bass weighing approximately 13 g/fish, revealing a LD50 of 74 cfu/g-fish. The 10S01 strain demonstrated the ability to colonize various organs, including the spleen, liver, kidney, and brain, with a relatively higher affinity for the spleen. Furthermore, antimicrobial susceptibility testing indicated that the 10S01 strain was sensitive to 14 tested antibiotics, particularly chloramphenicol, ciprofloxacin, clarithromycin, florfenicol, ofloxacin, rifampicin, and trimethoprim/sulfamethoxazole, highlighting these as preferred treatments for infections in spotted sea bass. These findings contribute significantly to our understanding of pathogenesis and inform the prompt and appropriate antibiotic treatment of infections.
PubMed: 38895715
DOI: 10.3389/fvets.2024.1404054 -
Cureus May 2024Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the immune system erroneously attacking healthy tissues and organs. SLE has a wide variety...
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the immune system erroneously attacking healthy tissues and organs. SLE has a wide variety of clinical presentations. The signs and symptoms of SLE are very well-known, though rare presentations could occur that require early clinical attention. Macrophage activation syndrome (MAS) is a severe and life-threatening condition in which the immune system becomes overactive, leading to the excessive stimulation and proliferation of immune cells. MAS can occur as a primary immune disorder, which is not very common. It can also happen secondary to a wide variety of pathological conditions, which include infections, malignancies, autoimmune, and rheumatologic disorders. In rare cases, SLE can present with overlapping features of MAS, further complicating the clinical picture, and may require specialized management. Early recognition and intervention of this overlap are essential for improving outcomes, as delayed diagnosis and treatment can lead to significant morbidity and mortality. Here, we present a case of a young adult female who was diagnosed with SLE with the initial presentation of MAS in the form of fever, splenomegaly, cytopenia, and hemophagocytosis.
PubMed: 38894758
DOI: 10.7759/cureus.60567 -
Diagnostics (Basel, Switzerland) May 2024Shear wave elastography (SWE) has become popular in clinical practice for many diseases. However, there is not adequate research on spleen-related diseases. This study...
Shear wave elastography (SWE) has become popular in clinical practice for many diseases. However, there is not adequate research on spleen-related diseases. This study aimed to investigate the potential of quantitative values obtained through SWE in evaluating spleen pathologies in the pediatric population and to demonstrate its performance to differentiate splenomegaly-related diseases. The research group retrospectively included children with pathological diagnoses related to the spleen from November 2016 to April 2021, and they were categorized into three groups, including portal hypertension (PH), benign lymphoid hyperplasia (BLH), and malignant infiltration (MI). Spleen sizes and parenchymal stiffness were also calculated for each group. Subsequently, mean spleen stiffness in each group was compared with normal values within the same age group. In total, 2781 children (1379 children for the study group; 1402 children for the control group) were enrolled in the study. The highest stiffness was observed in the PH group, which is statistically higher than others ( < 0.05). Although the mean spleen stiffness in the group with BLH was higher than the control and MI group, the difference was not statistically significant ( = 0.08). The mean stiffness in the group with MI was significantly lower than both the control group ( = 0.005) and PH ( = 0.01). In conclusion, using SWE in the differential diagnosis of etiologies causing splenomegaly could make an important contribution.
PubMed: 38893668
DOI: 10.3390/diagnostics14111142 -
International Journal of Molecular... May 2024Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by the uncontrolled activation of cytotoxic T lymphocytes, NK cells, and... (Review)
Review
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by the uncontrolled activation of cytotoxic T lymphocytes, NK cells, and macrophages, resulting in an overproduction of pro-inflammatory cytokines. A primary and a secondary form are distinguished depending on whether or not it is associated with hematologic, infectious, or immune-mediated disease. Clinical manifestations include fever, splenomegaly, neurological changes, coagulopathy, hepatic dysfunction, cytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis. In adults, therapy, although aggressive, is often unsuccessful. We report the case of a 41-year-old man with no apparent history of previous disease and an acute onset characterized by fever, fatigue, and weight loss. The man was from Burkina Faso and had made trips to his home country in the previous five months. On admission, leukopenia, thrombocytopenia, increased creatinine and transaminases, LDH, and CRP with a normal ESR were found. The patient also presented with hypertriglyceridemia and hyperferritinemia. An infectious or autoimmune etiology was ruled out. A total body CT scan showed bilateral pleural effusion and hilar mesenterial, abdominal, and paratracheal lymphadenopathy. Lymphoproliferative disease with HLH complication was therefore suspected. High doses of glucocorticoids were then administered. A cytologic analysis of the pleural effusion showed anaplastic lymphoma cells and bone marrow aspirate showed hemophagocytosis. An Epstein-Barr Virus (EBV) DNA load of more than 90000 copies/mL was found. Bone marrow biopsy showed a marrow localization of peripheral T lymphoma. The course was rapidly progressive until the patient died. HLH is a rare but usually fatal complication in adults of hematologic, autoimmune, and malignant diseases. Very early diagnosis and treatment are critical but not always sufficient to save patients.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Male; Adult; Macrophage Activation Syndrome
PubMed: 38892108
DOI: 10.3390/ijms25115921 -
Frontiers in Immunology 2024This study aims to discuss the clinical manifestations and treatment of Familial hemophagocytic lymphohistiocytosis (FHL) caused by a mutation in the UNC13D gene. (Review)
Review
OBJECTIVES
This study aims to discuss the clinical manifestations and treatment of Familial hemophagocytic lymphohistiocytosis (FHL) caused by a mutation in the UNC13D gene.
METHODS
A 6-year-old female child presented with unexplained febricity, splenomegaly, pancytopenia, hemophagocytic lymphohistiocytosis in bone marrow, decreased NK cell activity, soluble CD25 levels > 44000ng/ml. Genetic sequencing revealed a mutation in the UNC13D gene. Additionally, the patient experienced intermittent fever with seizures characterized by involuntary twitching of the left upper limb. Head magnetic resonance imaging (MRI) showed white matter lesions.
RESULTS
According to the HLH-2004 diagnostic criteria revised by the International Society of Histiocytosis the patient was diagnosed with FHL. Despite receiving HLH-2004 treatment, the disease relapsed. However, after a salvage allogeneic Hematopoietic Stem Cell Transplant (HSCT), febricity, abnormal blood cells, and neurological symptoms significantly improved.
CONCLUSIONS
Prompt performance of allogeneic HSCT is crucial upon diagnosis of FHL, especially when neurological involvement is present.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Hematopoietic Stem Cell Transplantation; Female; Child; Transplantation, Homologous; Mutation; Membrane Proteins; Treatment Outcome
PubMed: 38887297
DOI: 10.3389/fimmu.2024.1391074 -
BMC Medical Genomics Jun 2024Haemochromatosis is a genetic disease characterized by the excessive deposition of iron in various tissues and organs, eventually results in organ damage including... (Review)
Review
BACKGROUND
Haemochromatosis is a genetic disease characterized by the excessive deposition of iron in various tissues and organs, eventually results in organ damage including cirrhosis, diabetes, cardiomyopathy, etc. SLC40A1-related haemochromatosis is associated with gain-of-function mutations in the SLC40A1 gene, which encodes ferroportin. While sporadic reports of this condition exist in mainland China, the understanding of the phenotype and genetic pattern associated with the SLC40A1 p.Y333H mutation remains incomplete.
CASE PRESENTATION
We report a pedigree with heterozygous p.Y333H mutation in Chinese Han population. The proband is a 64-year-old man complaining of persistent abnormality of liver enzyme levels for 1 year, with a history of knee joint pain, diabetes and skin pigmentation. He displayed markedly elevated serum ferritin level and transferrin saturation. Magnetic resonance imaging showed iron deposition in the liver, spleen, and pancreas, along with cirrhosis and splenomegaly. Whole exome sequencing identified a heterozygous allelic variant c.997T > C (p.Y333H). Genetic screening of family members identified four first-degree relatives and three second-degree relatives having the same mutation. Additional cases with this mutation from two published studies were included. Among the probands and screened relatives, all eight males aged over 30 y had ferritin level > 1000 µg/L, transferrin saturation > 90%. Four patients with organ damage in the present study received therapeutic phlebotomy, alleviating clinical symptoms and improving in transferrin saturation and serum ferritin.
CONCLUSIONS
This study reports the largest pedigree with heterozygous SLC40A1 p.Y333H mutation in the Chinese population to date. In Chinese families, males over 30 years old with hemochromatosis due to SLC40A1 p.Y333H mutation exhibit severe iron overload phenotypes.
Topics: Humans; Hemochromatosis; Male; Pedigree; Middle Aged; China; Cation Transport Proteins; Mutation; Female
PubMed: 38886778
DOI: 10.1186/s12920-024-01929-0 -
Cureus May 2024A 78-year-old woman with liver cirrhosis due to chronic hepatitis C visited our department for treatment of a thoracic aortic aneurysm. Her Child-Pugh classification was...
A 78-year-old woman with liver cirrhosis due to chronic hepatitis C visited our department for treatment of a thoracic aortic aneurysm. Her Child-Pugh classification was class A, and her model for end-stage liver (MELD) disease score was 8. As she also had thrombocytopenia associated with splenomegaly and esophageal varices, endoscopic injection sclerotherapy and partial splenic embolization were performed before total arch replacement surgery for treating esophageal varices to reduce the bleeding risk during transesophageal echocardiography and for thrombocytopenia, respectively. After endoscopic injection sclerotherapy and partial splenic embolization, the platelet count increased; hence, total arch replacement surgery was performed. By combining partial splenic embolization and endoscopic injection sclerotherapy, we were able to safely perform transesophageal echocardiography and total arch replacement surgery in the perioperative period.
PubMed: 38882984
DOI: 10.7759/cureus.60365 -
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; Male; Diagnosis, Differential; Leukemia, Hairy Cell; Mutation; Proto-Oncogene Mas; Proto-Oncogene Proteins B-raf; Sex Factors
PubMed: 38882583
DOI: 10.11613/BM.2024.020502