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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 -
The Journal of the Association of... Apr 2024A 21-year-old female patient presented to us with severe low back pain for 4 months. On examination, patient was afebrile, with severe pallor, and tenderness in both...
HISTORY AND EXAMINATION
A 21-year-old female patient presented to us with severe low back pain for 4 months. On examination, patient was afebrile, with severe pallor, and tenderness in both sacroiliac (SI) joints. Patient was being admitted and evaluated, and during the course of evaluation, developed severe headache, which was severe in intensity and associated with nausea and projectile vomiting. Initial investigations: An X-ray of the bilateral SI joints revealed inflammation, and the antinuclear antibody (ANA) turned out to be 4+ with pancytopenia and raised lactate dehydrogenase (LDH), but the liver function tests were normal. Rest of the rheumatological profile was unremarkable. During the course of the evaluation, she developed a severe headache, which, on imaging, showed presence of cerebral edema with chronic subdural hematoma, and a concomitant coagulopathy workup revealed evidence of disseminated intravascular coagulation (DIC).
DISCUSSION
Taking the whole picture into consideration, a malignant process in the body was suspected, and serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) were sent, all of which were raised. Validating the clinical clue was the bone marrow biopsy done for pancytopenia, which revealed malignant epithelial infiltration. A contrast-enhanced computed tomography (CECT) thorax and whole abdomen were done to find out the primary, which showed a neoplastic mass at the gastroesophageal junction along with bony metastases in the vertebrae and left adrenal. Tissue from the primary lesion was taken for histopathological examination (HPE) through upper gastrointestinal endoscopy. Although HPE revealed grade III poorly differentiated stomach adenocarcinoma, the patient had succumbed to the disease process by the time the diagnosis came to light.
CONCLUSION
In short, this case perfectly illustrates how solid organ malignancies might be a mimicker of multisystem disorders, thereby delaying diagnosis and worsening the prognosis even further.
Topics: Humans; Female; Pancytopenia; Disseminated Intravascular Coagulation; Young Adult; Autoimmunity
PubMed: 38881089
DOI: 10.59556/japi.72.0497 -
International Journal of Rheumatic... Jun 2024
Topics: Humans; Osteochondrodysplasias; Congenital Bone Marrow Failure Syndromes; Male; Female; Treatment Outcome; Pancytopenia; Cytopenia; Anemia, Refractory
PubMed: 38873830
DOI: 10.1111/1756-185X.15220 -
The Lancet. Gastroenterology &... Jun 2024There is an unmet need for effective therapies in pretreated advanced biliary tract cancer. We aimed to evaluate the efficacy of nanoliposomal irinotecan and...
Nanoliposomal irinotecan and fluorouracil plus leucovorin versus fluorouracil plus leucovorin in patients with cholangiocarcinoma and gallbladder carcinoma previously treated with gemcitabine-based therapies (AIO NALIRICC): a multicentre, open-label, randomised, phase 2 trial.
BACKGROUND
There is an unmet need for effective therapies in pretreated advanced biliary tract cancer. We aimed to evaluate the efficacy of nanoliposomal irinotecan and fluorouracil plus leucovorin compared with fluorouracil plus leucovorin as second-line treatment for biliary tract cancer.
METHODS
NALIRICC was a multicentre, open-label, randomised, phase 2 trial done in 17 German centres for patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0-1, metastatic biliary tract cancer, and progression on gemcitabine-based therapy. Patients were randomly assigned (1:1) to receive intravenous infusions of nanoliposomal irinotecan (70 mg/m), fluorouracil (2400 mg/m), and leucovorin (400 mg/m) every 2 weeks (nanoliposomal irinotecan group) or fluorouracil (2400 mg/m) plus leucovorin (400 mg/m) every 2 weeks (control group). Randomisation was by permutated block randomisation in block sizes of four, stratified by primary tumour site. Investigator-assessed progression-free survival was the primary endpoint, which was evaluated in all randomly assigned patients. Secondary efficacy outcomes were overall survival, objective response rate, and quality of life. Safety was assessed in all randomly assigned patients who received at least one dose of the study treatment. Enrolment for this trial has been completed, and it is registered with ClinicalTrials.gov, NCT03043547.
FINDING
Between Dec 4, 2017, and Aug 2, 2021, 49 patients were randomly assigned to the nanoliposomal irinotecan group and 51 patients to the control group. Median age was 65 years (IQR 59-71); 45 (45%) of 100 patients were female. Median progression-free survival was 2·6 months (95% CI 1·7-3·6) in the nanoliposomal irinotecan group and 2·3 months (1·6-3·4) in the control group (hazard ratio [HR] 0·87 [0·56-1·35]). Median overall survival was 6·9 months (95% CI 5·3-10·6) in the nanoliposomal irinotecan group and 8·2 months (5·4-11·9) in the control group (HR 1·08 [0·68-1·72]). The objective response rate was 14% (95% CI 6-27; seven patients) in the nanoliposomal irinotecan group and 4% (1-14; two patients) in the control group. The most common grade 3 or worse adverse events in the nanoliposomal irinotecan group were neutropenia (eight [17%] of 48 vs none in the control group), diarrhoea (seven [15%] vs one [2%]), and nausea (four [8%] vs none). In the control group, the most common grade 3 or worse adverse events were cholangitis (four [8%] patients vs none in the nanoliposomal irinotecan group) and bile duct stenosis (four [8%] vs three [6%]). Treatment-related serious adverse events occurred in 16 (33%) patients in the nanoliposomal irinotecan group (grade 2-3 diarrhoea in five patients; one case each of abdominal infection, acute kidney injury, pancytopenia, increased blood bilirubin, colitis, dehydration, dyspnoea, infectious enterocolitis, ileus, oral mucositis, and nausea). One (2%) treatment-related serious adverse event occurred in the control group (worsening of general condition). Median duration until deterioration of global health status, characterised by the time from randomisation to the initial observation of a score decline exceeding 10 points, was 4·0 months (95% CI 2·2-not reached) in the nanoliposomal irinotecan group and 3·7 months (2·7-not reached) in the control group.
INTERPRETATION
The addition of nanoliposomal irinotecan to fluorouracil plus leucovorin did not improve progression-free survival or overall survival and was associated with higher toxicity compared with fluorouracil plus leucovorin. Further research is necessary to define the role of irinotecan-based combinations in second-line treatment of biliary tract cancer.
FUNDING
Servier and AIO-Studien.
PubMed: 38870977
DOI: 10.1016/S2468-1253(24)00119-5 -
Cureus May 2024We present a case of an adult male who presented with pancytopenia accompanied by symptomatic anemia, necessitating chronic transfusions. He was diagnosed with systemic...
We present a case of an adult male who presented with pancytopenia accompanied by symptomatic anemia, necessitating chronic transfusions. He was diagnosed with systemic mastocytosis with an associated hematologic neoplasm. Following an inadequate response to midostaurin therapy, the patient was initiated on the newly approved avapritinib. The patient showed significant improvements in all three blood cell lines; however, he developed leg edema, blepharedema, and gum bleeding on this medication. This case underscores the intricacies of managing a patient with advanced systemic mastocytosis, the emerging role of highly selective KIT inhibition in its treatment, and the practical management of adverse medication effects.
PubMed: 38868249
DOI: 10.7759/cureus.60161 -
Cureus May 2024Nutritional optic neuropathy is a rare and often overlooked factor leading to bilateral, symmetrical, and gradual visual impairment. This condition falls within the...
Nutritional optic neuropathy is a rare and often overlooked factor leading to bilateral, symmetrical, and gradual visual impairment. This condition falls within the category of metabolic neuropathies. We documented a case involving bilateral nutritional optic neuropathy attributed to pancytopenia associated with vitamin B12 deficiency. A healthy 65-year-old Indian woman reported a bilateral, progressive, painless decline in vision over the past six months. She had a history of reduced oral intake for the preceding year and denied experiencing any gastrointestinal or constitutional symptoms. Bilateral visual acuity was 1/60. Examination revealed pale optic discs with attenuated vessels in both eyes and a cup-disc ratio of 0.3. The blood analysis showed low indices and a deficiency in serum vitamin B12. Despite undergoing treatment, her vision remained impaired due to the chronic nature of the condition. This case highlights the importance of identifying visual symptoms in an elderly woman experiencing malnutrition caused by inadequate dietary habits, which leads to bilateral nutritional optic neuropathy.
PubMed: 38864050
DOI: 10.7759/cureus.60113 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Mar 2024This case report summarizes the experience from diagnosis and treatment of a patient with repeated high fever, hepatosplenomegaly and pancytopenia. Following exclusion...
This case report summarizes the experience from diagnosis and treatment of a patient with repeated high fever, hepatosplenomegaly and pancytopenia. Following exclusion of bacterial, viral, fungal infections and hematological diseases, metagenomic next-generation sequencing of the patient's peripheral blood revealed infection, and rK39 rapid diagnostic test showed positive for anti- antibody, while microscopic examination of bone marrow smears identified amastigotes. Therefore, the case was definitively diagnosed as visceral leishmaniasis, and given anti-infective treatment with sodium antimony gluconate and hormone, hepatoprotection, elevation of white blood cell counts and personalized nursing. Then, the case was cured and discharged from hospital. Metagenomic next-generation sequencing is of great value in etiological detection of fever patients with unknown causes, which deserves widespread clinical applications.
Topics: Humans; Leishmaniasis, Visceral; High-Throughput Nucleotide Sequencing; Male; Metagenomics; Adult; Middle Aged
PubMed: 38857969
DOI: 10.16250/j.32.1374.2023212 -
Molecular and Biochemical Parasitology Sep 2024Malaria, a parasitic infection caused by the genus Plasmodium, results to over 20 million reported cases annually worldwide. Most individuals exhibit various symptoms,... (Review)
Review
Malaria, a parasitic infection caused by the genus Plasmodium, results to over 20 million reported cases annually worldwide. Most individuals exhibit various symptoms, and blood analysis plays a crucial role in determining the appropriate treatment approach. This study discusses various hematologic complications associated with different Plasmodium species. A review of scientific databases including PubMed, Science Direct, Web of Science, Scopus, EMBASE, Magiran, SID, IranMedex was conducted using standard keywords such as Plasmodium, malaria, anemia and blood disorders (hematologic disorder) between 2000 and 2024. The review focused on articles pertaining to clinical trials, prospective cohort, retrospective, cross-sectional and case-control studies. Articles evaluating the effects of malaria on blood cells and indices, with target groups including human and animals, were included. Articles not written in English or Farsi were excluded. Our review revealed that, apart from iron deficiency anemia and vascular dysfunction contributed in part by adhesion of infected RBC to endothelium, decreases in hematocrit and hemoglobin levels, as part of pancytopenia and thrombocytopenia, are characteristic of Plasmodium infection. Additionally, the occurrence of inflammation due to the release of inflammatory cytokines and complement activation can complicate the clinical features of malaria in individuals with hematologic conditions.
Topics: Humans; Malaria; Animals; Plasmodium; Hematologic Diseases; Anemia
PubMed: 38857772
DOI: 10.1016/j.molbiopara.2024.111635 -
Cureus May 2024Methotrexate is an anti-inflammatory and immunomodulatory drug, widely used for moderate to severe psoriasis and other rheumatological conditions such as rheumatoid...
Methotrexate is an anti-inflammatory and immunomodulatory drug, widely used for moderate to severe psoriasis and other rheumatological conditions such as rheumatoid arthritis, besides some types of malignancies. Side effects are more prevalent in high acute doses but can also be seen in low-dose chronic use, especially in cases of drug-dosing errors. Possible symptoms of toxicity include gastrointestinal, hepatic, hematologic and renal dysfunctions, but may also include mucositis and worsening of the psoriatic lesions. Here, we describe a case involving methotrexate toxicity in an elderly patient with psoriasis, detailing the management.
PubMed: 38854245
DOI: 10.7759/cureus.60008