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Platelets Dec 2024The purpose of this study is to investigate the molecular interactions and potential therapeutic uses of Eltrombopag (EPAG), a small molecule that activates the cMPL...
The purpose of this study is to investigate the molecular interactions and potential therapeutic uses of Eltrombopag (EPAG), a small molecule that activates the cMPL receptor. EPAG has been found to be effective in increasing platelet levels and alleviating thrombocytopenia. We utilized computational techniques to predict and confirm the complex formed by the ligand (EPAG) and the Thrombopoietin receptor (TPO-R) cMPL, elucidating the role of RAS, JAK-2, STAT-3, and other essential elements for downstream signaling. Molecular dynamics (MD) simulations were employed to evaluate the stability of the ligand across specific proteins, showing favorable characteristics. For the first time, we examined the presence of TPO-R in human umbilical cord mesenchymal stem cells (hUCMSC) and human gingival mesenchymal stem cells (hGMSC) proliferation. Furthermore, treatment with EPAG demonstrated angiogenesis and vasculature formation of endothelial lineage derived from both MSCs. It also indicated the activation of critical factors such as RUNX-1, GFI-1b, VEGF-A, MYB, GOF-1, and FLI-1. Additional experiments confirmed that EPAG could be an ideal molecule for protecting against UVB radiation damage, as gene expression (JAK-2, ERK-2, MCL-1, NFkB, and STAT-3) and protein CD90/cMPL analysis showed TPO-R activation in both hUCMSC and hGMSC. Overall, EPAG exhibits significant potential in treating radiation damage and mitigating the side effects of radiotherapy, warranting further clinical exploration.
Topics: Humans; Pyrazoles; Benzoates; Receptors, Thrombopoietin; Hydrazones; Mesenchymal Stem Cells; Hydrazines; Molecular Dynamics Simulation; Angiogenesis
PubMed: 38832545
DOI: 10.1080/09537104.2024.2359028 -
Cureus Apr 2024Cytomegalovirus (CMV) is a DNA virus that can cause widespread, severe infection in immunocompromised patients. While CMV usually leads to a subclinical infection in...
Cytomegalovirus (CMV) is a DNA virus that can cause widespread, severe infection in immunocompromised patients. While CMV usually leads to a subclinical infection in immunocompetent individuals, it can rarely cause severe disease in this population. The SARS-CoV-2 virus is an RNA virus and part of the family. SARS-CoV-2 led to the COVID-19 (coronavirus disease 2019) pandemic. Even though COVID-19 usually presents with signs and symptoms of upper respiratory tract infection in younger adults, viral pneumonia, cytopenia, and neurological symptoms become more apparent with increasing age. Herein, we describe an immunocompetent 73-year-old female patient in whom oxygen demand and pancytopenia developed during hospitalization for post-ablation inguinal access site infection. The thorax CT revealed viral pneumonia, but two subsequent SARS-CoV-2 polymerase chain reaction (PCR) tests and a viral respiratory multiplex PCR panel were negative. The CMV viral load was high in the blood sample, and the patient responded to valganciclovir treatment. Although SARS-CoV-2 should be evaluated in patients with viral pneumonia and cytopenia, other viral etiologies mimicking SARS-CoV-2 infection, such as CMV, should not be overlooked in the era of the COVID-19 pandemic.
PubMed: 38817494
DOI: 10.7759/cureus.59360 -
Cureus Apr 2024Gelatinous transformation of bone marrow (GTBM) is a rare hematologic condition in which hematopoietic cells in the bone marrow are replaced by extracellular gelatinous...
Gelatinous transformation of bone marrow (GTBM) is a rare hematologic condition in which hematopoietic cells in the bone marrow are replaced by extracellular gelatinous substances, often resulting in cytopenias. The true incidence of this condition is presently unknown, as the current body of literature primarily consists of case reports. However, an analysis of a large bone marrow registry suggests that this is a highly rare entity even among a population requiring bone marrow biopsy. We present a case of a 24-year-old man with a history of diffuse large B cell lymphoma and an associated 45-kilogram weight loss, who was later found to have GTBM. The extent of his cytopenias resulted in a prolonged hospitalization with numerous complications, eventually leading to experimental treatment with allogeneic stem cell transplantation (ASCT). To our knowledge, this is the first reported case of GTBM in which ASCT was employed as a potential treatment modality. While our patient did have clinical improvement following ASCT, the permanence of these results is presently unclear. Furthermore, it is uncertain if the ASCT was truly causative of the stabilization of the patient. Given this, we are currently unable to advocate for ASCT as a treatment for GTBM. We report this case to raise awareness of this rare entity in the context of refractory cytopenias.
PubMed: 38817486
DOI: 10.7759/cureus.59354 -
Future Science OA 2024Vitamin B12 deficiency is widely recognized as a common cause of anemia. However, symptoms such as dysphagia, melanoderma, and pancytopenia, although less frequent, can...
Vitamin B12 deficiency is widely recognized as a common cause of anemia. However, symptoms such as dysphagia, melanoderma, and pancytopenia, although less frequent, can also be associated with this deficiency. We report the case of a 47-year-old Caucasian man presented with dysphagia to solids associated to high heart rate, dyspnea and melanoderma. He was diagnosed with severe anemia (hemoglobin 4 g/dl) in association with pancytopenia. Further investigation confirmed that the underlying cause was severe vitamin B12 deficiency secondary to pernicious anemia. Subsequent treatment with vitamin B12 supplements led to a significant improvement in all symptoms. A review of the existing literature corroborated the rarity of severe anemia occurring in conjunction with dysphagia and melanoderma due to B12 deficiency.
PubMed: 38817371
DOI: 10.2144/fsoa-2023-0176 -
Cureus Apr 2024Dengue fever, an arboviral illness, exhibits a broad range of symptoms, ranging from flu-like symptoms to serious hemorrhagic complications. Hemophagocytic...
Dengue fever, an arboviral illness, exhibits a broad range of symptoms, ranging from flu-like symptoms to serious hemorrhagic complications. Hemophagocytic lymphohistiocytosis (HLH) is an uncommon pathological state caused by excessive activation of the immune system, culminating in organ dysfunction. HLH can be primary or secondary, with infection being the most common cause. The association between dengue fever and dengue-induced HLH is becoming widely acknowledged as a lethal complication. We present the case of a two-year-old male child referred for the management of dengue infection. The patient's condition failed to ameliorate despite appropriate treatment. On further investigation, he was diagnosed with HLH. Following the initiation of steroid therapy, the patient demonstrated gradual improvement with normalization of laboratory parameters. Differentiating between HLH and severe dengue hemorrhagic fever poses a significant challenge, emphasizing the importance of prompt diagnosis for favorable outcomes. Early identification and commencement of corticosteroid therapy are imperative for successful management.
PubMed: 38803771
DOI: 10.7759/cureus.59165 -
Cureus Apr 2024Platelet count and its associated indices like mean platelet volume (MPV) and platelet distribution width (PDW) are cost-effective biomarkers that are easily accessible...
BACKGROUND
Platelet count and its associated indices like mean platelet volume (MPV) and platelet distribution width (PDW) are cost-effective biomarkers that are easily accessible and have a potent role in the diagnosis and management of thrombocytopenia. Since anaemia and thrombocytopenia often go together in pregnancy, it is advisable to utilise these indices for feto-maternal benefit.
MATERIAL AND METHODS
The study was conducted in the Department of Obstetrics and Gynaecology at a tertiary care centre in New Delhi from July 2022 to December 2023 wherein pregnant women of age 18-40 years, period of gestation >28 weeks with thrombocytopenia or abnormal platelet indices were enrolled. Women with pancytopenia, bone marrow suppression or past or current SARS-CoV-2 positive status were excluded.
RESULTS
A total of 150 women were enrolled in the study. The mean age of study population was 25.33 ± 2.90 (range 19-34) years. Subjects were divided into three groups - Group A (mild thrombocytopenia) 24.6%, Group B (moderate thrombocytopenia) 64.6% and Group C (severe thrombocytopenia) 10.6% based on thrombocytopenia severity. Analysing the risk factors, Group C was found to have a significantly higher number of patients with anaemia (p=<0.001), fever (p=0.031), abnormal liquor volumes (p=0.004) and need for blood and platelet transfusion (p=0.077). On correlation of thrombocytopenia with abnormal platelet indices, it was observed that manual platelet count (MPC) and MPV were indirectly correlated (p=0.027). PDW was found to be directly associated with severe thrombocytopenia and indirectly associated with moderate thrombocytopenia. Conclusion: Thrombocytopenia in pregnancy is directly correlated to factors like maternal fever and anaemia, fetal growth restriction, abnormal liquor, blood products and platelet transfusions. It was also concluded that platelet indices like PDW and MPV play an important role in predicting the feto-maternal outcome and hence timely interventions can be done to improve the same.
PubMed: 38803765
DOI: 10.7759/cureus.59156 -
Case Report: Visceral Leishmaniasis Falsely Diagnosed as Viral Hepatitis C Without Febrile Symptoms.Infection and Drug Resistance 2024Visceral leishmaniasis (VL), also known as kala-azar, is caused by an intracellular parasite transmitted to humans by the bite of a sand fly, and with the source of the...
BACKGROUND
Visceral leishmaniasis (VL), also known as kala-azar, is caused by an intracellular parasite transmitted to humans by the bite of a sand fly, and with the source of the infection mainly being dogs. The main features of the disease are irregular fever, weight loss, hepatosplenomegaly and anaemia. Diagnosis relies mainly on bone marrow aspiration tests to find Leishman-Donovan(LD) bodies. And we report the case without febrile symptoms and hepatitis C virus antibody was probably false positive.
CASE PRESENTATION
The case was a 74-year-old male residing in Yangquan City, Shanxi Province, a VL endemic area. He presented with generalised malaise, hepatosplenomegaly and scarring pigmentation on the skin as a result of scratching. Laboratory tests showed pancytopenia, positive hepatitis C virus antibody (HCV-Ab), positive direct anti-human globulin test (DAT), positive anti-cardiolipin antibody IgG, IgM (+), and increased immunoglobulin IgG. Symptomatic treatments such as hepatoprotection and blood transfusion were given, but the patient's symptoms still persisted and his spleen and liver further enlarged. Further repeat tests were performed and found to be negative for hepatitis C virus antibodies and antigens. The patient was eventually found to be infected with by rk39 rapid diagnostic test and metagenomic next-generation sequencing(mNGS). And the patient quickly relieved after one course of treatment with sodium stibogluconate.
CONCLUSION
Patients with VL may cause abnormalities in the immune system, leading to false positives for various antibodies without clear febrile symptoms, resulting in misdiagnosis or delayed diagnosis. It is important to consider VL in cases where there is a significant hepatosplenomegaly with a relevant epidemiological history. If the diagnosis cannot be confirmed through bone marrow aspiration and the patient is not suitable for splenic aspiration, the rk39 test can be used for initial exclusion and further verified through mNGS.
PubMed: 38800583
DOI: 10.2147/IDR.S456984 -
Cureus Apr 2024A 48-year-old woman presented to the hospital with acute pulmonary embolism in the setting of presumed apixaban failure and was transitioned to heparin. Rapidly...
A 48-year-old woman presented to the hospital with acute pulmonary embolism in the setting of presumed apixaban failure and was transitioned to heparin. Rapidly progressive pancytopenia prompted workup with suspicion for heparin-induced thrombocytopenia (HIT) as well as peripheral blood smear concerning for acute promyelocytic leukemia (APL). She was emergently started on non-heparin anticoagulation and transferred to start APL-directed treatment. Both HIT and APL were confirmed with serotonin release assay (SRA) and promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) fusion assay, respectively. We present this case to remark on the novelty of these two acute diseases occurring together. Each of these entities is a hematologic emergency requiring immediate treatment before disease confirmation. We explore the mechanisms by which HIT occurs and outline the parameters for managing APL in the acute setting. Furthermore, this case serves to examine the treatment considerations for needing to carefully balance the thrombotic and hemorrhagic risk of both HIT and APL, which are clinically well-known for coagulopathy. Fortunately, HIT in this patient recovered on anticoagulation without bleeding or worsening thrombosis. Furthermore, following induction and consolidation treatment for APL, she remained negative for residual disease.
PubMed: 38800206
DOI: 10.7759/cureus.58927 -
Cureus Apr 2024Tuberculosis (TB), caused by the bacteria , is a highly infectious and prevalent disease. It is the leading cause of death among communicable diseases and the fifth...
Tuberculosis (TB), caused by the bacteria , is a highly infectious and prevalent disease. It is the leading cause of death among communicable diseases and the fifth leading cause of all diseases in India. The diagnosis can be challenging due to the disease's unique appearance and various presentations. Disseminated TB is characterized by the involvement of two or more non-contiguous sites resulting from hematogenous extension of the disease. Clinical confirmation of the diagnosis of disseminated TB is based on bacteriological or histological evidence. Based on various studies, there is evidence that satisfactory results are obtained from treatment with first-line anti-tubercular drugs. When there is a delay in diagnosis and treatment, it can become a life-threatening condition. We present a case of a 38-year-old alcoholic male who presented with generalized edema, pain, and distension of the abdomen. According to the initial presentation, the provisional diagnosis made was alcoholic liver disease, but it was later diagnosed as disseminated TB with sputum-positive pulmonary TB with abdominal involvement in the form of ascites and hepatosplenomegaly along with hematological involvement as pancytopenia. The patient started showing drastic improvement after the initiation of anti-tubercular therapy.
PubMed: 38800156
DOI: 10.7759/cureus.58902 -
Cureus Apr 2024While Pyoderma gangrenosum (PG) is commonly associated with hematological disorders such as acute myeloid leukemia (AML), it typically presents concurrently with the...
While Pyoderma gangrenosum (PG) is commonly associated with hematological disorders such as acute myeloid leukemia (AML), it typically presents concurrently with the hemopathy, mostly in its bullous form, among middle-aged individuals. Here, we report the unusual case of a young female patient who presented with PG in its ulcerative form, three weeks before the onset of AML. A 31-year-old female presented with a one-week history of painful perianal papulopustule that evolved into an irregular ulceration with violaceous borders, mucopurulent serosity, and erythematous surrounding skin. Laboratory work-up demonstrated elevated inflammatory markers and hyperleukocytosis, with no cytopenia, and normal peripheral blood smear. Two weeks later, the ulcer growth was noted with a similar ulceration at a venipuncture site. A complete blood count revealed pancytopenia, with 45% blasts on the peripheral blood smear. Skin biopsies showed an aseptic neutrophilic infiltrate in favor of PG. Intravenous methylprednisolone was administered with rapid resolution of the lesions. However, the patient died shortly after. The post-mortem results of bone marrow aspirate revealed AML, with immunohistochemistry of the skin lesions confirming the clonality of neutrophils derived from the leukemic clone. This case highlights a distinctive clinical presentation, illustrating the manifestation of PG three weeks before the onset of AML in its ulcerative rather than bullous form, in a young female patient.
PubMed: 38784334
DOI: 10.7759/cureus.58838