Characterization of Hematopoiesis in Sickle Cell Disease by Prospective Isolation of Stem and Progenitor Cells.

The consequences of sickle cell disease (SCD) include ongoing hematopoietic stress, hemolysis, vascular damage, and effect of chronic therapies, such as blood transfusions and hydroxyurea, on hematopoietic stem and progenitor cell (HSPC) have been poorly characterized. We have quantified the frequencies of nine HSPC populations by flow cytometry in the peripheral blood of pediatric and adult patients, stratified by treatment and control cohorts. We observed broad differences between SCD patients and healthy controls. SCD is associated with 10 to 20-fold increase in CD34dim cells, a two to five-fold increase in CD34bright cells, a depletion in Megakaryocyte-Erythroid Progenitors, and an increase in hematopoietic stem cells, when compared to controls. SCD is also associated with abnormal expression of CD235a as well as high levels CD49f antigen expression. These findings were present to varying degrees in all patients with SCD, including those on chronic therapy and those who were therapy naive. HU treatment appeared to normalize many of these parameters. Chronic stress erythropoiesis and inflammation incited by SCD and HU therapy have long been suspected of causing premature aging of the hematopoietic system, and potentially increasing the risk of hematological malignancies. An important finding of this study was that the observed concentration of CD34bright cells and of all the HSPCs decreased logarithmically with time of treatment with HU. This correlation was independent of age and specific to HU treatment. Although the number of circulating HSPCs is influenced by many parameters, our findings suggest that HU treatment may decrease premature aging and hematologic malignancy risk compared to the other therapeutic modalities in SCD.

HIV portends a poor prognosis in myelodysplastic syndromes.

Even though HIV is associated with worse prognosis in many malignancies, the clinical course of myelodysplastic syndrome (MDS) in HIV + patients has not been well studied. Determining the clinical presentation and outcomes of MDS in these patients would be important for future diagnostic strategies, as anemia and other cytopenias are commonly seen in HIV + patients. Unique data mining software was used to identify cases of MDS or AML in adult patients who were also HIV + at Albert Einstein/Montefiore Medical Center between 1 January 2003 and 1 January 2017. Using Chi-Square and Fisher's exact test, characteristics of the HIV + MDS patients were compared to 135 HIV - MDS patients from the same institution diagnosed between 1997 and 2011. Fourteen biopsy proven MDS patients were identified with concomitant HIV. HIV + MDS patients presented at a younger age (59 vs. 71 yrs, p = .001) had higher risk disease, faster progression to acute leukemia, and worse overall survival (median survival 11.2 vs. 69.1 mo, p < .001) compared to HIV - MDS controls. Additionally, there was a higher prevalence of clonal-hematopoiesis related mutations (ASXL1, DNMT3A) and a higher proportion of patients with high risk cytogenetics. Analysis of the largest single center cohort of HIV + MDS patients demonstrated that these individuals present at a significantly younger age and with higher risk disease than their HIV - counterparts.

Sickle Cell Crisis Complicated by Synthetic Cannabinoid Abuse: A Case Report.

We describe a case of delirium occurring in a hospitalized sickle cell patient. Following admission for a typical pain crisis, the patient continued to report unrelieved pain with marked agitation for several days, despite escalating doses of opioid analgesia, and ultimately required intubation following development of acute chest syndrome (ACS). After some delay, it was discovered that he had been using a synthetic cannabinoid (K2) which may have precipitated his pain crisis and, with hindsight, explained his prolonged period of delirium. Delayed recognition was due to multiple factors, notably the absence of an index of suspicion for this novel drug, the presence of alternate explanations for the patient's altered mental status, and the fact that reliable laboratory screening for synthetic cannabinoids is currently not widely available.

Pain management practices by internal medicine residents--a comparison before and after educational and institutional interventions.

We aimed to improve internal medicine residents' deficiencies in pain management and evaluate the effectiveness of our intervention, which included an interactive conference series, e-mail vignettes, and didactic sessions. An anonymous survey was administered at the beginning and at the end of an academic year, before and after the intervention, respectively. We analyzed 65 preintervention and 63 postintervention surveys. Self-perception of competency in pain management increased from 40% to 60% (P = .02). Perception of adequacy of training increased from 38.5% to 55.6% (P = .05). Opioid conversion skills improved by 25% (P = .02). Overall, knowledge did not change significantly, except in the subgroup of residents who had completed the oncology rotation from 0.60 to 0.72 (P = .003). "Opiophobia'' improved by 20% (P = .05). Documentation of pain improved (rank correlation = 21; P = .02). We concluded that educational and institutional interventions administered over an academic year improved pain management skills and documentation and reduced "opiophobia'' among residents.

Use of a comprehensive survey as a first step in addressing clinical competence of physicians-in-training in the management of pain.

Deficiencies in practice, knowledge, and competence among physicians are important contributing factors to the unsatisfactory level of analgesic care in hospitalized patients. By way of a comprehensive survey, we characterized these deficiencies within an internal medicine residency program as an initial step in designing remedial educational strategies. To do so, an anonymous 43-item survey was administered to residents in an internal medicine program. A total of 61 residents (69 percent) responded. The results indicated that patient-controlled analgesia (PCA), a standardized pain scale, and an opioid equivalence table were underused. Competence in opioid conversion was suboptimal, but completion of an oncology rotation and familiarity with the opioid equivalence table predicted greater competence in this area (p = 0. 00 7 and p = 0.001, respectively). Self-perceptions of adequacy of training and pain-management competence were predictors of knowledge (p = 0.026 andp = 0.038, respectively). Attitudes regarding opioid analgesia were generally satisfactory (i.e., low "opiophobia " score), although the risk of addiction was still overestimated. The characterization of deficiencies in pain management in a residency program is an essential step in the design and implementation of educational interventions. Administration of a comprehensive survey is a simple and effective method of gathering this data and has the additional benefit of promoting awareness of pain management issues. Our experience served to establish, among other findings, the didactic value of experience on an oncology floor; this result substantiates the value of practical experience in the gaining of clinical competence in pain management. Interventions that capitalize on the findings of the survey and the interest in pain management generated by its administration are currently ongoing at our institution.