L-glutamine for sickle cell disease: more than reducing redox.

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.

l-glutamine, crizanlizumab, voxelotor, and cell-based therapy for adult sickle cell disease: Hype or hope?

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.

The potential impact of mammographic breast arterial calcification on physician practices in a primary care setting.

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.

Stroke in critical COVID-19 patients: a cautionary tale from the frontlines.

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.

Paraneoplastic syndromes in lung cancer and their management.

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.

Multiple Myeloma as the Underlying Cause of Thrombotic Microangiopathy Leading to Acute Kidney Injury: Revisiting a Very Rare Entity.

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.