RESUMEN
Oxidative stress is a major contributor to the pathophysiology of sickle cell disease (SCD) including hemolysis and vaso-occlusive crisis (VOC). L-glutamine is a conditionally essential amino acid with important roles, including the synthesis of antioxidants, such as reduced glutathione and the cofactors NAD(H) and NADP(H), as well as nitric oxide. Given the increased levels of oxidative stress and lower (NADH):(NAD + + NADH) ratio in sickle erythrocytes that adversely affects the blood rheology compared to normal red blood cells, L-glutamine was investigated for its therapeutic potential to reduce VOC. While L-glutamine was approved by the United States (US) Food and Drug Administration to treat SCD, its impact on the redox environment in sickle erythrocytes is not fully understood. The mechanism through which L-glutamine reduces VOC in SCD is also not clear. In this paper, we will summarize the results of the Phase 3 study that led to the approval of L-glutamine for treating SCD and discuss its assumed mechanisms of action. We will examine the role of L-glutamine in health and propose how the extra-erythrocytic functions of L-glutamine might contribute to its beneficial effects in SCD. Further research into the role of L-glutamine on extra-erythrocyte functions might help the development of an improved formulation with more efficacy.
Asunto(s)
Anemia de Células Falciformes , Hemoglobinopatías , Compuestos Orgánicos Volátiles , Anemia de Células Falciformes/tratamiento farmacológico , Glutamina/uso terapéutico , Hemoglobinopatías/tratamiento farmacológico , Humanos , NAD/uso terapéutico , Oxidación-Reducción , Compuestos Orgánicos Volátiles/uso terapéuticoRESUMEN
For more than two decades, hydroxyurea was the only therapeutic agent approved by the Food and Drug Administration (FDA) for sickle cell disease (SCD). Although curative allogeneic hematopoietic stem cell transplants (allo-HSCT) were also available, only very few patients underwent the procedure due to lack of matched-related donors. However, therapeutic options for SCD patients increased dramatically in the last few years. Three new agents, l-glutamine, crizanlizumab, and voxelotor, were approved by the FDA for use in SCD patients. The number of SCD patients who underwent allo-HSCT also increased as a result of advances in the prevention of graft failure and graft-versus-host disease from using mismatched donor HSC. More recently gene therapy was made available on clinical trials. The increased treatment options for SCD have led to a sense of optimism and excitement among many physicians that these new approaches would alter the clinical course and disease burden. Although these newer agents do provide hope to SCD patients, the hyped-up responses need to be evaluated in the context of reality. In this review, we will discuss and compare these new agents and cell-based therapy, evaluate their clinical and economic impacts, and examine their roles in reducing the disease burden.
Asunto(s)
Anemia de Células Falciformes , Trasplante de Células Madre Hematopoyéticas , Adulto , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/etiología , Anticuerpos Monoclonales Humanizados , Benzaldehídos/efectos adversos , Glutamina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Pirazinas , PirazolesRESUMEN
Aim: This study sought to determine breast arterial calcification (BAC) prevalence in a primary care setting and its potential use in guiding further cardiovascular workup. Materials & methods: A radiologist reviewed 282 consecutive mammograms. Characteristics of BAC-positive and negative women were compared. Results: BAC prevalence was 34%. BAC-positive women were older (mean age: 60 vs 52, p < 0.001), had higher mean 10-year cardiac risk (11 vs 6%, p < 0.001), more hypertension (65 vs 40%, p < 0.001) and coronary artery disease (10 vs 2%, p = 0.0041), statin (50 vs 32%, p = 0.006) and aspirin use (28 vs 16%, p = 0.012). Thirty-seven percent (33/96) of BAC-positive women could potentially benefit from further cardiac testing. Conclusion: Mammography identifies BAC-positive women with low traditionally assessed cardiovascular risk who might benefit from further cardiovascular workup.
Asunto(s)
Médicos , Calcificación Vascular , Mama/diagnóstico por imagen , Femenino , Humanos , Mamografía , Persona de Mediana Edad , Atención Primaria de Salud , Factores de Riesgo , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiologíaRESUMEN
INTRODUCTION: Although Coronavirus Disease 2019 (COVID-19) is primarily a disease of the respiratory system in its transmission and clinical manifestations, physicians have also reported a tropism toward the nervous system. METHODS: Neurological symptoms can occur as one of many systemic manifestations of a critical form of the disease or in isolation as the predominant presenting complaint. RESULTS: We report a series of 6 patients who suffered significant cerebrovascular accidents while being treated for critical COVID-19 in the intensive care units of a quaternary care hospital in New York's Hudson valley. CONCLUSIONS: This series demonstrates how a relatively rare but catastrophic neurological complication can occur in patients with COVID-19 while they are being managed for their more common problems such as respiratory and renal failure.
RESUMEN
Paraneoplastic syndromes are most frequently associated with lung cancer. This review considers a variety of paraneoplastic syndromes associated with lung cancer and discusses their pathophysiology, clinical features and management options.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/epidemiología , Infección Hospitalaria/epidemiología , Adolescente , Adulto , Anciano , Infecciones por Clostridium/complicaciones , Infección Hospitalaria/complicaciones , Diarrea/microbiología , Femenino , Hospitalización , Humanos , Incidencia , Masculino , Persona de Mediana Edad , New York , Estudios Retrospectivos , Adulto JovenRESUMEN
Thrombotic microangiopathy (TMA) describes a pathological process of microvascular thrombosis, consumptive thrombocytopenia, and microangiopathic hemolytic anemia, leading to end-organ ischemia and infarction, affecting particularly the kidney and brain. TMA is a pathological feature of a number of clinical disorders including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and atypical hemolytic uremic syndrome. Rare but important, TMA may also occur in malignancy, connective tissue disease, malignant hypertension, and renal transplantation (rejection or drug toxicity). We present a very rare case where the patient developed acute kidney injury from TMA but found to have multiple myeloma as the possible underlying etiology.