Search

Despite the availability of hydroxyurea, the clinical use of the medication among patients with sickle cell disease (SCD) remains low in the United States. Given the high healthcare utilization cost, SCD requires new therapeutic approaches. Recent studies demonstrated bacterial overgrowth and dysbiosis-related intestinal pathophysiological changes in SCD. Intestinal microbes regulate neutrophil ageing. Aged and activated neutrophils contribute to the pathogenesis of vaso-occlusive crisis (VOC) in SCD. In this paper, we will review the pre-clinical and clinical data on how antibiotics might reduce the intestinal microbial density and influence the course of VOC. Based on these observations, we will discuss rationales for and potential challenges to antibiotic-based therapeutic approaches that may modify the clinical course of VOC in SCD., (Copyright © 2021. Published by Elsevier Ltd.)

Painful vaso-occlusive crisis (VOC) remains the most common reason for presenting to the Emergency Department and hospitalization in patients with sickle cell disease (SCD). Although two new agents have been approved by the Food and Drug Administration for treating SCD, they both target to reduce the frequency of VOC. Results from studies investigating various approaches to treat and shorten VOC have so far been generally disappointing. In this paper, we will summarize the complex pathophysiology and downstream events of VOC and discuss the likely reasons for the disappointing results using monotherapy. We will put forward the rationale for exploring some of the currently available agents to either protect erythrocytes un-involved in the hemoglobin polymerization process from sickling induced by the secondary events, or a multipronged combination approach that targets the complex downstream pathways of VOC., (© 2021. The Author(s).)

Obesity and diabetes mellitus are prevalent among the African-American/Black population. They result in multiple chronic conditions that impact the quality and lifespan of the patients. Their occurrence in patients with sickle cell disease (SCD) will increase the risks for multimorbidity in these patients. We have carried out a chart survey of a cohort of 449 patients with SCD to determine the prevalence rates of obesity and diabetes mellitus in these patients. SCD patients were less likely to develop obesity and diabetes mellitus, compared to their peers of the same race/ethnicity. The lower prevalence rates were observed in those over the age of 6 years, irrespective of the gender of the patients. Their life-time probabilities for obesity and diabetes mellitus were also low. Within this group of SCD patients, obesity was associated with significantly higher prevalence of diabetes mellitus. The underlying reasons for our observed results of low prevalence rate of obesity in SCD remain speculative but may be related to reduced calorie intake, increased calorie use due to hypermetabolism, reduced intestinal absorption, or intestinal dysbiosis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hematopoietic stem cell transplant (HSCT) is the only cure for patients with sickle cell disease (SCD). Although most SCD patients experience progressive end-organ damage and shortened lifespans, not all patients follow the same disease course, tempo, or outcome. Therefore, the dilemma facing physicians is weighing the selection of patients and timing for the procedure against donor type and transplant-related mortality and morbidity that go up with increasing age. On the other hand, the dilemma facing the patients and families is how acceptable HSCT that carries some mortality risks to them. We have analyzed the chronic conditions due to SCD in 449 patients to determine whether SCD-related multiple chronic conditions (MCC) can be risk-stratified to identify the group of patients predicted to not only have shortened lifespans but also functional limitation and poor quality of life so that these at-risk patients can be offered HSCT early and before MCC develops. We identified that the age of onset of the first SCD-related chronic conditions strongly predicted for the risks for disease-related MCC. SCD patients who suffered their first disease-related chronic condition before age 30 years developed MCC at a rate of 19.1 times faster than those at a later age. These patients are therefore high-risk patients and should be offered HSCT early in the course of their disease before multiple organ damage intervenes, even if matched-related donors are not available. This patient selection and timing approach provides a forum for an easy-to-understand and real-time discussion, including the choice of donor type, with SCD patients and families when considering HSCT.