Knowledge of fertility and perception of fertility treatment among adults with sickle cell disease (KNOW FERTILITY)

IntroductionThis study assessed fertility knowledge in adults with sickle cell disease using the Cardiff Fertility Knowledge Scale and Fertility Treatment Perception Survey and compared knowledge scores in respondents with sickle cell disease to previously reported unaffected cohorts.MethodsThis cross-sectional study surveyed adults over age 18 with sickle cell disease at an adult sickle cell disease center using a 35-question survey addressing infertility risk factor knowledge and perceptions of fertility treatment. Analyses included summary statistics for continuous and categorical variables, univariate linear regression, and Mann-Whitney U tests for group comparisons of Fertility Knowledge Scale scores. Fertility Treatment Perception Survey scores were measured by medians of the two positive statements and four negative statements to generate separate positive and negative treatment belief scores. Statistical significance was set at p < 0.05 for all analyses.ResultsNinety-two respondents (71 female, 21 male) with median age of 32 years (IQR: 25.0, 42.5) completed the survey between October 2020-May 2021. Sixty-five percent of respondents reported taking sickle cell disease treatment and 18% reported refusing at least one sickle cell disease treatment due to fertility concerns. The mean Fertility Knowledge Score was 49% (SD: 5.2), lower than reported in an international cohort (57% vs. 49%, p = 0.001), and higher than in a cohort of reproductive-aged Black women in the USA (49% vs. 38%, p = 0.001). Less than 50% of respondents correctly identified common infertility risk factors including sexually transmitted infections, advanced age, and obesity. Mean positive fertility perception score was 3 (IQR 3, 4), and negative fertility perception score was 3.5 (IQR 3, 4). Factors associated with agreement with negative fertility perception statements included: trying to conceive, refusing sickle cell disease treatment, and undergoing fertility treatment.DiscussionOpportunities exist to improve knowledge of infertility risk factors among adults with sickle cell disease. This study raises the possibility that nearly one in five adults with sickle cell disease refuse SCD treatment or cure due to infertility concerns. Education about common infertility risks factors needs to be addressed alongside disease- and treatment- associated fertility risks

Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom

Background: The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial. Methods and Results: We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death. Conclusions: A TRV≥ 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable. The study is registered in ClinicalTrials.gov with identifier: NCT00492531

Hypoxia-Induced Mitogenic Factor (HIMF/FIZZ1/RELMα) Recruits Bone Marrow-Derived Cells to the Murine Pulmonary Vasculature

. and localized to the media layer of the vessels. This finding suggests that these cells are of mesenchymal origin and differentiate toward myofibroblast and vascular smooth muscle. Structural location in the media of small vessels suggests a functional role in the lung vasculature. To examine a potential mechanism for HIMF-dependent recruitment of mesenchymal stem cells to the pulmonary vasculature, we performed a cell migration assay using cultured human mesenchymal stem cells (HMSCs). The addition of recombinant HIMF induced migration of HMSCs in a phosphoinosotide-3-kinase-dependent manner.These results demonstrate HIMF-dependent recruitment of BMD mesenchymal-like cells to the remodeling pulmonary vasculature

Pharmacological Inhibition of Caspase and Calpain Proteases: A Novel Strategy to Enhance the Homing Responses of Cord Blood HSPCs during Expansion

Background: Expansion of hematopoietic stem/progenitor cells (HSPCs) is a well-known strategy employed to facilitate the transplantation outcome. We have previously shown that the prevention of apoptosis by the inhibition of cysteine proteases, caspase and calpain played an important role in the expansion and engraftment of cord blood (CB) derived HSPCs. We hypothesize that these protease inhibitors might have maneuvered the adhesive and migratory properties of the cells rendering them to be retained in the bone marrow for sustained engraftment. The current study was aimed to investigate the mechanism of the homing responses of CB cells during expansion. Methodology/Principal Findings: CB derived CD34 + cells were expanded using a combination of growth factors with and without Caspase inhibitor-zVADfmk or Calpain 1 inhibitor- zLLYfmk. The cells were analyzed for the expression of homingrelated molecules. In vitro adhesive/migratory interactions and actin polymerization dynamics of HSPCs were assessed. In vivo homing assays were carried out in NOD/SCID mice to corroborate these observations. We observed that the presence of zVADfmk or zLLYfmk (inhibitors) caused the functional up regulation of CXCR4, integrins, and adhesion molecules, reflecting in a higher migration and adhesive interactions in vitro. The enhanced actin polymerization and the RhoGTPase protein expression complemented these observations. Furthermore, in vivo experiments showed a significantly enhanced homing to the bone marrow of NOD/SCID mice

Routine Paediatric Sickle Cell Disease (SCD) Outpatient Care in a Rural Kenyan Hospital: Utilization and Costs

More than 70% of children with sickle cell disease (SCD) are born in sub-Saharan Africa where the prevalence at birth of this disease reaches 2% or higher in some selected areas. There is a dearth of knowledge on comprehensive care received by children with SCD in sub-Saharan Africa and its associated cost. Such knowledge is important for setting prevention and treatment priorities at national and international levels. This study focuses on routine care for children with SCD in an outpatient clinic of the Kilifi District Hospital, located in a rural area on the coast of Kenya.To estimate the per-patient costs for routine SCD outpatient care at a rural Kenyan hospital.We collected routine administrative and primary cost data from the SCD outpatient clinic and supporting departments at Kilifi District Hospital, Kenya. Costs were estimated by evaluating inputs - equipment, medication, supplies, building use, utility, and personnel - to reflect the cost of offering this service within an existing healthcare facility. Annual economic costs were similarly calculated based on input costs, prorated lifetime of equipment and appropriate discount rate. Sensitivity analyses evaluated these costs under different pay scales and different discount rate.We estimated that the annual economic cost per patient attending the SCD clinic was USD 138 in 2010 with a range of USD 94 to USD 229.This study supplies the first published estimate of the cost of routine outpatient care for children born with SCD in sub-Saharan Africa. Our study provides policy makers with an indication of the potential future costs of maintaining specialist outpatient clinics for children living with SCD in similar contexts

Association of Sickle Cell Trait With Chronic Kidney Disease and Albuminuria in African Americans

The association between sickle cell trait (SCT) and chronic kidney disease (CKD) is uncertain

Dental infections increase the likelihood of hospital admissions among adult patients with sickle cell disease

The objective: To determine if dental infections increase the likelihood of hospital admission among adult patients with sickle cell disease (SCD). Basic Research Design: Cross-sectional analysis of data from the Nationwide Emergency Department Sample (NEDS) pooled for the years 2006 through 2008. Prevalence ratios (PR) for the effects of interest were estimated using Poisson regression with robust estimates of the variance. Participants: Adults, aged 18 and over, diagnosed with SCD using ICD-9-CM codes excluding participants discharged with a code for sickle cell trait. Main outcome measure: Emergency department (ED) visit disposition, dichotomised to represent whether or not the ED visit ended in admission versus being treated and released. Results: Among patients having a sickle cell crisis, those with dental infections were 72% more likely to be admitted compared to those not having dental infections (PR=1.72, 95%CI 1.58-1.87). No association was observed among adult SCD patients not having a sickle crisis event. Based on preliminary data from this analysis, prevention of dental infection among patients with SCD could result in an estimated cost saving of $2.5 million dollars per year. Conclusions: Having a dental infection complicated by a sickle cell crisis significantly increases the likelihood of hospital admission among adult SCD patients presenting to the ED. © BASCD 2013