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Cureus Feb 2024Bradycardia, renal failure, atrioventricular (AV) block, shock, and hyperkalemia (BRASH) syndrome is a rare clinical entity that poses challenges for healthcare...
Bradycardia, Renal Failure, Atrioventricular Block, Shock, and Hyperkalemia (BRASH) Syndrome Emergence in a Unique Intersection of COVID-19 and End-Stage Renal Disease: A Case Report.
Bradycardia, renal failure, atrioventricular (AV) block, shock, and hyperkalemia (BRASH) syndrome is a rare clinical entity that poses challenges for healthcare practitioners. It is characterized by bradycardia, renal failure, atrioventricular (AV) obstruction, shock, and hyperkalemia. This case is an interesting instance of BRASH syndrome in the setting of COVID-19 infection and end-stage renal disease (ESRD). Initial laboratory results revealed macrocytic anemia, renal dysfunction, acidosis, and mild hyponatremia, along with hyperkalemia. An electrocardiogram (EKG) and telemonitoring showed dopamine-resistant persistent bradycardia until transvenous temporary pacemaker placement was done, which resolved the bradycardia. Anti-hyperkalemic therapy, avoiding AV nodal-blocking medication, and temporary pacemaker placement were all part of the management. After receiving hemodialysis, the patient gradually recovered. Bradycardia improved and potassium normalized. The intricate interaction between hyperkalemia and AV nodal obstruction that causes BRASH syndrome results in severe bradycardia and shock. To the best of our knowledge, this is the first case of BRASH syndrome in a patient with an active COVID-19 infection in a previously vaccinated patient. Even though case reports make up the majority of the material currently in publication, to fully comprehend the mechanisms underlying this illness, more research is required, as early detection of this syndrome is crucial for better patient outcomes.
PubMed: 38524089
DOI: 10.7759/cureus.54695 -
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 -
Journal of Ayub Medical College,... 2023Thiamine-responsive megaloblastic anaemia (TRMA) is characterized by the classic trio of diabetes mellitus, sensorineural hearing loss, and megaloblastic anaemia,...
Thiamine-responsive megaloblastic anaemia (TRMA) is characterized by the classic trio of diabetes mellitus, sensorineural hearing loss, and megaloblastic anaemia, typically emerging subtly between infancy and adolescence. Administration of high-dose thiamine often yields improvements in anaemia and occasionally in diabetes. Uncommon manifestations include optic atrophy, congenital heart defects, short stature, and stroke. In this specific case, a 5-year-old diagnosed with insulin-dependent diabetes mellitus (IDDM) since the age of one presented with symptoms such as polyuria, fever, and vomiting, revealing an HbA1c of 10.64. Further examinations disclosed compromised hearing and vision. A negative antibody workup and a thyroid profile indicating hypothyroidism prompted additional investigations, including Brainstem Evoked Response Audiometry (BERA) and retinal examination, confirming bilateral sensorineural hearing loss and maculopathy, respectively. A comprehensive blood count unveiled megaloblastic anaemia. Genetic profiling confirmed a homozygous mutation in the SLC19A2 gene, thus diagnosing TRMA. An early diagnosis, coupled with genetic confirmation, enables timely intervention, with patients responding positively to high-dose thiamine. Genetic counselling plays a pivotal role in enlightening families about the disease and its inheritance patterns, fostering awareness and understanding.
Topics: Humans; Child, Preschool; Thiamine Deficiency; Thiamine; Anemia, Megaloblastic; Hearing Loss, Sensorineural; Hypothyroidism; Diabetes Mellitus; Membrane Transport Proteins
PubMed: 38406914
DOI: 10.55519/JAMC-S4-12486 -
MedRxiv : the Preprint Server For... Feb 2024encodes Feline leukemia virus subgroup C receptor 1 (FLVCR1), a solute carrier (SLC) transporter within the Major Facilitator Superfamily. FLVCR1 is a widely expressed...
encodes Feline leukemia virus subgroup C receptor 1 (FLVCR1), a solute carrier (SLC) transporter within the Major Facilitator Superfamily. FLVCR1 is a widely expressed transmembrane protein with plasma membrane and mitochondrial isoforms implicated in heme, choline, and ethanolamine transport. While knockout mice die with skeletal malformations and defective erythropoiesis reminiscent of Diamond-Blackfan anemia, rare biallelic pathogenic variants are linked to childhood or adult-onset neurodegeneration of the retina, spinal cord, and peripheral nervous system. We ascertained from research and clinical exome sequencing 27 individuals from 20 unrelated families with biallelic ultra-rare missense and predicted loss-of-function (pLoF) variant alleles. We characterize an expansive phenotypic spectrum ranging from adult-onset retinitis pigmentosa to severe developmental disorders with microcephaly, reduced brain volume, epilepsy, spasticity, and premature death. The most severely affected individuals, including three individuals with homozygous pLoF variants, share traits with knockout mice and Diamond-Blackfan anemia including macrocytic anemia and congenital skeletal malformations. Pathogenic missense variants primarily lie within transmembrane domains and reduce choline and ethanolamine transport activity compared with wild-type with minimal impact on FLVCR1 stability or subcellular localization. Several variants disrupt splicing in a mini-gene assay which may contribute to genotype-phenotype correlations. Taken together, these data support an allele-specific gene dosage model in which phenotypic severity reflects residual FLVCR1 activity. This study expands our understanding of Mendelian disorders of choline and ethanolamine transport and demonstrates the importance of choline and ethanolamine in neurodevelopment and neuronal homeostasis.
PubMed: 38405817
DOI: 10.1101/2024.02.09.24302464 -
Practical Laboratory Medicine Mar 2024To compare the laboratory tests conducted in real-life settings for patients with anemia with the expected prescriptions derived from an optimal checkup.
OBJECTIVE
To compare the laboratory tests conducted in real-life settings for patients with anemia with the expected prescriptions derived from an optimal checkup.
METHODS
A panel of experts formulated an "optimal laboratory test assessment" specific to each anemia profile. A retrospective analysis was done of the laboratory tests conducted according to the type of anemia (microcytic, normocytic or macrocytic). Using an algorithmic system, the laboratory tests performed in real-life practice were compared with the recommendations suggested in the "optimal laboratory test assessment" and with seemingly "unnecessary" laboratory tests.
RESULTS
In the analysis of the "optimal laboratory test assessment", of the 1179 patients with microcytic anemia, 269 (22.8%) had had one of the three tests recommended by the expert system, and only 33 (2.8%) had all three tests. For normocytic anemia, 1054 of 2313 patients (45.6%) had one of the eleven recommended tests, and none had all eleven. Of the 384 patients with macrocytic anemia, 196 (51%) had one of the four recommended tests, and none had all four. In the analysis of "unnecessary laboratory tests", one lab test was unnecessarily done in 727/3876 patients (18.8%), i.e. 339 of 1179 (28.8%) microcytic, 171 of 2313 (7.4%) normocytic, and 217 of 384 (56.5 %) macrocytic anemias.
CONCLUSION
Laboratory investigations of anemia remain imperfect as more than half of the cases did not receive the expected tests. Analyzing other diagnostic domains, the authors are currently developing an artificial intelligence system to assist physicians in enhancing the efficiency of their laboratory test prescriptions.
PubMed: 38404528
DOI: 10.1016/j.plabm.2024.e00357 -
Journal of Clinical Medicine Feb 2024VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized systemic autoinflammatory disease caused by somatic mutations in...
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized systemic autoinflammatory disease caused by somatic mutations in hematopoietic progenitor cells. This case series of four patients with VEXAS syndrome and comorbid myelodysplastic syndrome (MDS) aims to describe clinical, imaging, and hematologic disease presentations as well as response to therapy. Four patients with VEXAS syndrome and MDS are described. A detailed analysis of imaging features, hemato-oncological presentation including bone marrow microscopy and clinical-rheumatological disease features and treatment outcomes is given. All patients were male; ages ranged between 64 and 81 years; all were diagnosed with MDS. CT imaging was available for three patients, all of whom exhibited pulmonary infiltrates of varying severity, resembling COVID-19 or hypersensitivity pneumonitis without traces of scarring. Bone marrow microscopy showed maturation-disordered erythropoiesis and pathognomonic vacuolation. Somatic mutation in the codon 41 were found in all patients by next-generation sequencing. Therapy regimes included glucocorticoids, JAK1/2-inhibitors, nucleoside analogues, as well as IL-1 and IL-6 receptor antagonists. No fatalities occurred (observation period from symptom onset: 18-68 months). Given the potential underreporting of VEXAS syndrome, we highly recommend contemporary screening for mutations in patients presenting with ambiguous signs of systemic autoinflammatory symptoms which persist over 18 months despite treatment. The emergence of cytopenia, especially macrocytic hyperchromic anemia, should prompt early testing for mutations. Notably conspicuous, pulmonary alterations in CT imaging of patients with therapy-resistant systemic autoinflammatory symptoms should be discussed in interdisciplinary medical teams (Rheumatology, Hematology, Radiology and further specialist departments) to facilitate timely diagnosis during the clinical course of the disease.
PubMed: 38398362
DOI: 10.3390/jcm13041049 -
Cureus Jan 2024Vitamin deficiency is common in the geriatric population and is responsible for majorly imbalanced hematological, neurological, and neuropsychiatric functioning....
Vitamin deficiency is common in the geriatric population and is responsible for majorly imbalanced hematological, neurological, and neuropsychiatric functioning. Methylcobalamin deficiency or vitamin B deficiency can be underestimated in some cases and be misdiagnosed as other illnesses, such as thalamic syndrome. Timely diagnosis of this deficiency is essential, especially in the geriatric population, as it might cause irreversible structural brain damage. This is also presented as elevated levels of homocysteine and methylmalonic acid. Clinically, it presents with the following symptoms: lower sensitivity levels to touch and light, psychosis, paresthesia, anemia, imbalance, fatigue, cognitive disturbances, difficulty remembering, and confusion. Symptoms are usually progressive and worsen over a period of time. In this case report, we present the case of a 62-year-old male with clinical symptoms of numbness and tingling in the right side of the body. The neurological presentations resembled left thalamic infarct, but the underlying reason was methylcobalamin deficiency.
PubMed: 38389590
DOI: 10.7759/cureus.52761 -
Respirology Case Reports Feb 2024In cases of Sweet's syndrome with pulmonary involvement, fever of unknown origin, and macrocytic anaemia, VEXAS syndrome can be considered in the differential diagnosis....
Steroid reduction-resistant pulmonary involvement with Sweet's syndrome suspected of being vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome: A case report.
In cases of Sweet's syndrome with pulmonary involvement, fever of unknown origin, and macrocytic anaemia, VEXAS syndrome can be considered in the differential diagnosis. A 67-year-old man who was taking prednisolone for a fever of unknown origin and Sweet's syndrome was referred to us because of an abnormal chest shadow. Computed tomography revealed a nonfibrotic hypersensitivity pneumonitis-like opacity, and blood test results indicated macrocytic anaemia. His pulmonary symptoms spontaneously improved but again exacerbated approximately 1 month later. Methylprednisolone pulse therapy improved his condition, but he had recurring fever flare and pulmonary involvement post-treatment. A peripheral blood gene test planned at a specialized institution was not performed, making the diagnosis difficult. We attempted careful tapering of methylprednisolone, but his macrocytic anaemia led to pancytopenia and he unfortunately died of sepsis due to neutropenia.
PubMed: 38384745
DOI: 10.1002/rcr2.1288 -
Scientific Reports Feb 2024We investigated the clinical implications of the mean corpuscular volume (MCV) in patients with major trauma. This single-center retrospective review included 2021...
We investigated the clinical implications of the mean corpuscular volume (MCV) in patients with major trauma. This single-center retrospective review included 2021 trauma patients admitted to the intensive care unit between January 2016 and June 2020. We included 1218 patients aged [Formula: see text] 18 years with an injury severity score [Formula: see text] 16 in the final analysis. The clinical and laboratory variables were compared between macrocytosis (defined as MCV [Formula: see text] 100 fL) and non-macrocytosis groups. Cox regression analysis was performed to calculate the hazard ratios (HRs) of variables for 30-day mortality, with adjustment for other potential confounding factors. The initial mean value of MCV was 102.7 fL in the macrocytosis group (n = 199) and 93.7 fL in the non-macrocytosis group (n = 1019). The macrocytosis group showed a significantly higher proportion of initial hypotension, transfusion within 4 and 24 h, and 30-day mortality than the non-macrocytosis group. Age ([Formula: see text] 65 years), hypotension (systolic blood pressure [Formula: see text] 90 mmHg), transfusion (within 4 h), anemia (Hb < 12 g/day in women, < 13 g/day in men), and macrocytosis were significantly associated with 30-day mortality (adjusted HR = 1.4; 95% confidence interval 1.01-1.94; p = 0.046) in major trauma patients. Thus, initial macrocytosis independently predicted 30-day mortality in patients with major trauma at a Level I trauma center.
Topics: Male; Humans; Female; Aged; Erythrocyte Indices; Retrospective Studies; Prognosis; Anemia; Anemia, Macrocytic; Folic Acid Deficiency; Hypotension
PubMed: 38365858
DOI: 10.1038/s41598-024-54057-1