-
Cureus Jul 2023Introduction Thrombocytopenia is a commonly observed condition in clinical practice, and its diagnosis is often challenging due to numerous aetiologies and variations in...
Introduction Thrombocytopenia is a commonly observed condition in clinical practice, and its diagnosis is often challenging due to numerous aetiologies and variations in clinical presentation. Early identification of thrombocytopenia and its causes can help prevent life-threatening haemorrhagic manifestations. Methodology A prospective observational study was conducted at a tertiary care hospital from February 2019 to January 2020. This evaluation aimed to determine the causes and prevalence of thrombocytopenia in a tertiary care setting. Patients aged 15 or older with a platelet count of fewer than 150,000/ µL were eligible for inclusion in this evaluation. Investigations for aetiology detection were recommended. Results During the one-year study period, a total of 100 patients, including 58 males and 42 females, with thrombocytopenia were selected for the study. The most common age group affected by thrombocytopenia in this study was between 46 and 55 years old. The most common clinical manifestations observed were generalised weakness (70%), haemorrhagic manifestations (60%), fever (50%), joint pain (37%), splenomegaly (35%), headache (30%), breathlessness (23%), lymphadenopathy (22%), hepatomegaly (24%), and abdominal pain (12%). The most prevalent causes of thrombocytopenia were megaloblastic anaemia (19 cases), dengue fever (15 cases), malaria (11 cases), enteric fever (nine cases), immune thrombocytopenia (ITP) (eight cases), and leukaemia (seven cases). Bleeding was reported as a symptom of thrombocytopenia in 60% of individuals in this study. Conclusion In the study, thrombocytopenia was more common in people aged 46-55 years, and males were more commonly affected than females. Megaloblastic anaemia and infectious disease were the most common causes of thrombocytopenia. Bleeding manifestations were found in 60% of patients with thrombocytopenia.
PubMed: 37551236
DOI: 10.7759/cureus.41511 -
Cureus Oct 2023Background and objective Vitamin B1 deficiency can cause a variety of abnormalities in the neuropsychiatric, cardiovascular, and other systems. This condition can be...
Background and objective Vitamin B1 deficiency can cause a variety of abnormalities in the neuropsychiatric, cardiovascular, and other systems. This condition can be rapidly corrected and prevented from progressing to irreversible sequelae through vitamin B1 supplementation. Therefore, early detection of and intervention in vitamin B1 deficiency are essential. We have previously demonstrated an association between vitamin B1 deficiency and appetite loss in hospitalized older adult patients in rural Japan. This study aimed to examine the additional predictors of vitamin B1 deficiency in patients with appetite loss and other symptoms suggestive of vitamin B1 deficiency. Material and methods This cross-sectional study involved 519 patients admitted to a rural hospital between April 2020 and March 2022. Data on vitamin B1 levels, age, sex, BMI, albumin levels, functional independence measure (FIM), hemoglobin levels, Charlson Comorbidity Index (CCI), and medications were collected from electronic medical records. Vitamin B1 deficiency was defined as serum vitamin B1 level <20 µg/dL. Data were analyzed using the Mann-Whitney U test, Student's t-test, and chi-square test, followed by multivariate logistic regression to examine the predictors of vitamin B1 deficiency. Results A total of 113 patients (21.5%) were found to be vitamin B1-deficient. Multivariate logistic regression showed that anemia was significantly associated with vitamin B1 deficiency [adjusted odds ratio (AOR): 1.71, 95% confidence interval (CI): 1.07-2.73, p<0.05]. Conclusion Based on our findings, anemia is significantly associated with vitamin B1 deficiency in hospitalized Japanese patients living in rural areas. Therefore, physicians should be mindful of the possibility of vitamin B1 deficiency in hospitalized patients with anemia.
PubMed: 38021762
DOI: 10.7759/cureus.47173 -
BMC Pulmonary Medicine Mar 2024Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is... (Review)
Review
BACKGROUND
Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed.
CASE DESCRIPTION
Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia.
CONCLUSIONS
This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.
Topics: Humans; Female; Middle Aged; Erlotinib Hydrochloride; Anemia; Anemia, Megaloblastic; Adenocarcinoma of Lung; ErbB Receptors; Lung Neoplasms; Vitamin B 12
PubMed: 38448889
DOI: 10.1186/s12890-024-02935-9 -
Molecular Genetics & Genomic Medicine Mar 2024Although proteinuria is long recognized as an independent risk factor for progressive chronic kidney diseases, not all forms of proteinuria are detrimental to kidney...
BACKGROUND
Although proteinuria is long recognized as an independent risk factor for progressive chronic kidney diseases, not all forms of proteinuria are detrimental to kidney function, one of which is isolated proteinuria caused by cubilin (CUBN)-specific mutations. CUBN encodes an endocytic receptor, initially found to be responsible for the Imerslund-Gräsbeck syndrome (IGS; OMIM #261100) characterized by a combined phenotype of megaloblastic anemia and proteinuria.
METHODS
After analyzing their clinical and pathological characterizations, next-generation sequencing for renal disease genes or whole-exome sequencing (WES) was performed on four patients with non-progressive isolated proteinuria. CUBN biallelic pathogenic variants were identified and further analyzed by cDNA-PCR sequencing, immunohistochemistry, minigene assay, and multiple in silico prediction tools, including 3D protein modeling.
RESULTS
Here, we present four patients with isolated proteinuria caused by CUBN C-terminal biallelic pathogenic variants, all of which showed no typical IGS symptoms, such as anemia and vitamin B12 deficiency. Their urine protein levels fluctuated between +~++ and estimated glomerular filtration rate (eGFR) were normal or slightly higher. Mild mesangial hypercellularity was found in three children's renal biopsies. A homozygous splice-site variant of CUBN (c.6821+3 (IVS44) A>G) was proven to result in the exon 44 skipping and premature translation termination by cDNA sequencing and immunohistochemistry. Compound heterozygous mutations were identified among the other three children, including another novel splice-site variant (c.10764+1 (IVS66) G>A) causing the retention of first 4 nucleotides in intron 66 by minigene assay, two unreported missense mutations (c.4907G>A (p.R1636Q); c. 9095 A>G (p.Y3032C)), and two reported missense mutations in China (c.8938G>A (p.D2980N); c. 9287T>C (p.L3096P)), locating behind the vitamin B12-binding domain, affecting CUB11, CUB16, CUB22, CUB23, and CUB27 domains, respectively.
CONCLUSION
These results demonstrate that above CUBN mutations may cause non-progressive and isolated proteinuria, expanding the variant spectrum of CUBN and benefiting our understanding of proteinuria and renal function.
Topics: Child; Humans; DNA, Complementary; Proteinuria; Receptors, Cell Surface
PubMed: 38488435
DOI: 10.1002/mgg3.2353 -
Indian Journal of Pathology &... Sep 2023Rogers syndrome is an extremely rare autosomal recessive syndrome of which only 100 cases are known worldwide. It is characterized by thiamine-responsive megaloblastic...
Rogers syndrome is an extremely rare autosomal recessive syndrome of which only 100 cases are known worldwide. It is characterized by thiamine-responsive megaloblastic anaemia, diabetes mellitus and sensorineural deafness. It results from the deficiency of a thiamine transporter protein. We herein report a 16-year-old Indian male referred to our centre with complaints of refractory anaemia, deafness, diabetes pulmonary arterial hypertension and tricuspid regurgitation. Based on the clinical features and haematologic picture and dramatic response of anaemia to thiamine therapy the possibility of a TRMA was considered. Sequencing analysis for TRMA revealed a homozygous c.242dup (p.Tyr81Ter) mutation of the SLC19A2 gene.
PubMed: 38391342
DOI: 10.4103/ijpm.ijpm_287_23 -
Cureus Feb 2024The pediatric ICU (PICU) is a specialized area where critically sick children are managed. The mortality rates in PICUs are higher in developing countries as compared to...
BACKGROUND
The pediatric ICU (PICU) is a specialized area where critically sick children are managed. The mortality rates in PICUs are higher in developing countries as compared to developed nations. Many of these deaths could be prevented if very sick children were identified soon after they arrived at the health facility. Hematological indices like platelet lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) have been frequently used in adults as indicators of mortality. However, their use in the pediatric population is limited due to a lack of validated reference intervals.
OBJECTIVE
The objective of the study is to assess the role of hematological indices in identifying adverse outcomes in terms of mortality in children admitted to the PICU.
MATERIALS AND METHODS
It is a prospective, observational study done at a tertiary care hospital. All children aged one year to 12 years admitted to the PICU were enrolled in the study. A sample for complete blood count was taken within one hour of admission to the PICU. Children who had received blood products in the last two months, those on chronic medications (>two weeks) that can affect bone marrow cellularity, and known cases of hematological disorders such as megaloblastic anemia, hematological malignancies, immune thrombocytopenia, and aplastic anemia were excluded from the study. PLR, NLR, and platelets to mean platelet volume ratio (PLT/MPV) were determined and compared among the survivors and non-survivors.
RESULTS
Out of 275 enrolled patients, 119 (43.3%) patients expired during the study period. While PLR had high sensitivity and NLR had high specificity (85.71% and 92.31%, respectively) for predicting mortality, none of these parameters had a good area under the curve (AUC) in our study. PLT/MPV of ≥32 had a sensitivity of 39.5% and a specificity of 56.41% for predicting mortality.
CONCLUSIONS
Hematological parameters have been used across the world to predict ICU mortality. PLR and NLR are simple hematological biomarkers, easy to calculate, and cost-effective, and ratios are better than individual parameters. More studies and stratified samples are required to evaluate the role of hematological markers in identifying the risk of mortality in children admitted to PICUs.
PubMed: 38465050
DOI: 10.7759/cureus.53744 -
International Journal of... Jul 2023Since December 2019 and the global epidemic of COVID-19 different countries have focused on vaccines, and one of the inactivated produced vaccines was the Sinopharm...
Since December 2019 and the global epidemic of COVID-19 different countries have focused on vaccines, and one of the inactivated produced vaccines was the Sinopharm COVID-19 vaccine. Some side effects of this vaccine were reported previously, including pain at the vaccination site, fatigue, lethargy, headache, and tenderness, which were more prevalent among individuals <49 years old. Herein, we reported two patients aged 45 and 51 years old. Both patients have different signs and symptoms after receiving the second dose of the vaccine. None had a history of chronic disease. On examination and following labs and other diagnostic investigations, we found megaloblastic anemia due to atrophic gastritis and low intrinsic factor. These cases showed an autoimmune side effect of the Sinopharm COVID-19 vaccine that was previously reported with an exact mechanism but other features called Covid Arm, Guillain-Barré syndrome, and thrombocytopenia. The mechanism of this reaction is unclear yet.
PubMed: 37817969
DOI: 10.18502/ijhoscr.v17i3.13312 -
Cureus Feb 2024Objective The objectives of this study were to determine the frequency of the clinical spectrum of diseases in patients with macrocytosis and to summarize the diagnostic...
Objective The objectives of this study were to determine the frequency of the clinical spectrum of diseases in patients with macrocytosis and to summarize the diagnostic evaluation of patients found to have macrocytosis on laboratory testing. Background This was a cross-sectional study that took place at the Department of Medicine in Combined Military Hospital, Rawalpindi, Pakistan, from January to June 2023. Methodology One hundred and five patients with macrocytosis with mean corpuscular volume (MCV) values > 100 fL (80 to 100 fL) were inducted as per inclusion and exclusion criteria. Informed consent was obtained from all patients. Complete blood counts (CBC), peripheral blood film, serum vitamin B12 levels, serum folate levels, renal function tests (RFTs), liver function tests (LFTs), and thyroid function tests (TFTs) were performed during the assessment. Results The commonest cause of macrocytosis was vitamin B12 deficiency followed by folate deficiency, combined vitamin B12 and folate deficiency, and other causes were also found in a few cases. Conclusion Serum vitamin B12 and folate deficiency are the most common preventable causes of macrocytosis.
PubMed: 38524035
DOI: 10.7759/cureus.54702 -
Immunologic Research Dec 2023The effects of specific cytokines produced by T cell subsets (such as Th1, Th2, and newly discovered Th17, Treg, Tfh, or Th22) are diverse, depending on interactions...
The effects of specific cytokines produced by T cell subsets (such as Th1, Th2, and newly discovered Th17, Treg, Tfh, or Th22) are diverse, depending on interactions with other cytokines, distinct signaling pathways, phase of the disease, or etiological factor. The immunity equilibrium of the immune cells, such as the Th1/Th2, the Th17/Treg, and the Th17/Th1 balance is necessary for the maintenance of the immune homeostasis. If the balance of the T cells subsets is damaged, the autoimmune response becomes enhanced which leads to autoimmune diseases. Indeed, both the Th1/Th2 and the Th17/Treg dichotomies are involved in the pathomechanism of autoimmune diseases. The aim of the study was to determine the cytokines of Th17 lymphocytes as well as the factors modulating their activity in patients with pernicious anemia. The magnetic bead-based immunoassays used (Bio-Plex) allow simultaneous detection of multiple immune mediators from one serum sample. In our study, we showed that patients suffering from pernicious anemia develop the Th1/Th2 imbalance with a quantitative advantage of cytokines participating in Th1-related immune response, the Th17/Treg imbalance with a quantitative advantage of cytokines participating in Treg-related response, as well as the Th17/Th1 imbalance with a quantitative predominance of cytokines participating in Th1-related immune response. Our study results indicate that T lymphocytes and their specific cytokines play an role in the course of pernicious anemia. The observed changes may indicate the immune response to pernicious anemia or be an element of the pernicious anemia pathomechanism.
Topics: Humans; Cytokines; Anemia, Pernicious; T-Lymphocytes, Regulatory; Th17 Cells; Autoimmune Diseases; Th1 Cells; Th2 Cells
PubMed: 37269464
DOI: 10.1007/s12026-023-09399-9