R2* magnetic resonance imaging (R2*-MRI) can quantify hepatic iron content (HIC) by noninvasive means but is not fully investigated. Patients with iron overload completed 1.5T R2*-MRI examination and liver biopsy within 30 days. Fortythree patients (sickle cell anemia, n ‫؍‬ 32; ␤-thalassemia major, n ‫؍‬ 6; and bone marrow failure, n ‫؍‬ 5) were analyzed: median age, 14 years, median transfusion duration, 15 months, average (؎SD) serum ferritin 2718 plus or minus 1994 ng/mL, and average HIC 10.9 plus or minus 6.8 mg Fe/g dry weight liver. Regions of interest were drawn and analyzed by 3 independent reviewers with excellent agreement of their measurements (intraclass correlation coefficient ‫؍‬ 0.98). Ferritin and R2*-MRI were weakly but significantly associated (range of correlation coefficients among the 3 reviewers, 0.41-0.48; all P < .01). R2*-MRI was strongly associated with HIC for all 3 reviewers (correlation coefficients, 0.96-0.98; all P < .001). This high correlation confirms prior reports, calibrates R2*-MRI measurements, and suggests its clinical utility for predicting HIC using R2*-MRI. This study was registered at www.clinicaltrials.gov as #NCT00675038. IntroductionMonitoring body iron content is critical for clinical management of patients with iron overload. Prior reports of iron measurements by R2 magnetic resonance imaging (MRI) and R2*-MRI relaxometry in the liver have shown good correlations with hepatic iron content (HIC). 1-3 However, MRI calibration varies according to instrumentation and technique. To calibrate the R2*-MRI technique for noninvasive HIC assessment, we conducted a study to estimate the correlation of R2*-MRI with liver biopsy-proven HIC determination in patients with iron overload. Methods PatientsPatients 7 years of age and older with iron overload (ferritin Ͼ 1000 ng/mL within 3 months of enrollment or Ն 18 erythrocyte transfusions) were eligible. All participants underwent nonsedated liver MRI examination and ferritin measurement, followed within 30 days by liver biopsy with HIC determination. The St Jude Children's Research Hospital Institutional Review Board provided continuing approval, and all participants or legal guardians signed informed consent in accordance with the Declaration of Helsinki. Liver biopsiesTwo liver specimens were obtained, the first for liver iron quantitation (Mayo Laboratories, Rochester MN) and the second for pathology review. All histology was reviewed by a single pathologist blinded to clinical status and HIC values. Liver fibrosis was scored from zero (absent fibrosis) to 6 (cirrhosis). 4 MRI techniqueThe single breath-hold R2*-MRI used a 1.5T MRI scanner (Siemens Symphony, Siemens; Malvern, PA) using a multiecho gradient echo sequence to acquire 20 images with increasing echo times (range, 1.1-17.3 ms). Liver images were obtained in transversal slice orientation through the center at the main portal vein origin. Slice thickness measured 10 mm with in-plane resolution of 3.125 mm. Quantitative T2* maps were calculated offline using custom-...

The long-term efficacy and toxicity of hydroxyurea for infants are undefined, and its role in preventing organ dysfunction is unknown. Short-term feasibility of hydroxyurea administration, toxicities, hematologic effects, and effect on spleen function in infants with sickle cell anemia (

Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1β was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD.

Early manifestations of sickle nephropathy include glomerular hyperfiltration and proteinuria, typically microalbuminuria. Over time, a subset of patients develops histologic changes, decreased glomerular filtration, and ultimately renal failure. This cross-sectional study was designed to determine the rate of glomerular hyperfiltration and prevalence of albuminuria in a cross-sectional analysis of untreated children with sickle cell anemia (SCA), and to identify correlates of both complications. Measured glomerular filtration rate (GFR) by plasma clearance of 99-technetium diethylenetriaminepentaacetate was compared to GFR estimates calculated from published formulas. Eighty-five children (mean age 9.4 ± 4.8 years) were studied; 76% had glomerular hyperfiltration with mean GFR = 154 ± 37 mL/min/1.73m2. GFR declined in teenage years and was significantly correlated with increased serum cystatin C levels and higher systolic blood pressure. Measured GFR had only modest correlations with GFR estimates (Pearson correlation coefficients ≤0.5). Albuminuria, usually microalbuminuria, occurred in 15.9% and was associated with higher diastolic blood pressure and lower white blood cell and absolute neutrophil counts. Cystatin C levels inversely reflect GFR changes and are associated with albuminuria; serial monitoring may provide a sensitive and accurate marker of nephropathy in children with SCA.

BackgroundSickle cell disease is an inherited blood disorder that affects over 100,000 Americans. Sickle cell disease–related complications lead to significant morbidity and early death. Evidence supporting the feasibility, acceptability, and efficacy of self-management electronic health (eHealth) interventions in chronic diseases is growing; however, the evidence is unclear in sickle cell disease.ObjectiveWe systematically evaluated the most recent evidence in the literature to (1) review the different types of technological tools used for self-management of sickle cell disease, (2) discover and describe what self-management activities these tools were used for, and (3) assess the efficacy of these technologies in self-management.MethodsWe reviewed literature published between 1995 and 2016 with no language limits. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and other sources. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two independent reviewers screened titles and abstracts, assessed full-text articles, and extracted data from articles that met inclusion criteria. Eligible studies were original research articles that included texting, mobile phone–based apps, or other eHealth interventions designed to improve self-management in pediatric and adult patients with sickle cell disease.ResultsOf 1680 citations, 16 articles met all predefined criteria with a total of 747 study participants. Interventions were text messaging (4/16, 25%), native mobile apps (3/16, 19%), Web-based apps (5/16, 31%), mobile directly observed therapy (2/16, 13%), internet-delivered cognitive behavioral therapy (2/16, 13%), electronic pill bottle (1/16, 6%), or interactive gamification (2/16, 13%). Interventions targeted monitoring or improvement of medication adherence (5/16, 31%); self-management, pain reporting, and symptom reporting (7/16, 44%); stress, coping, sleep, and daily activities reporting (4/16, 25%); cognitive training for memory (1/16, 6%); sickle cell disease and reproductive health knowledge (5/16, 31%); cognitive behavioral therapy (2/16, 13%); and guided relaxation interventions (1/16, 6%). Most studies (11/16, 69%) included older children or adolescents (mean or median age 10-17 years; 11/16, 69%) and 5 included young adults (≥18 years old) (5/16, 31%). Sample size ranged from 11 to 236, with a median of 21 per study: <20 in 6 (38%), ≥20 to <50 in 6 (38%), and >50 participants in 4 studies (25%). Most reported improvement in self-management–related outcomes (15/16, 94%), as well as high satisfaction and acceptability of different study interventions (10/16, 63%).ConclusionsOur systematic review identified eHealth interventions measuring a variety of outcomes, which showed improvement in multiple components of self-management of sickle cell disease. Despite the promising feasibility and acceptability of eHealth interventions in improving self-management of sickle cell disease, the evidence overall is modest. Future eHealth intervention studies are needed to evaluate t...

(1) Many patients hold misconceptions about IBS being caused by dietary habits, developing into cancer, colitis, causing malnutrition, or worsening with age; (2) patients most often seek information about dietary changes; and (3) educational needs may be different for persons using the internet for medical information.

Background Donors other than matched siblings and low-intensity conditioning regimens are increasingly used in haematopoietic stem cell transplantation. We aimed to compare the relative risk of donor type and conditioning regimen intensity on the transplantation outcomes of in patients with sickle cell disease. Methods For this retrospective cohort study, we collected data from 90 US centres reported to the Center for International Blood and Marrow Transplant Research. Eligible patients were younger than 50 years, had genetically confirmed sickle cell disease (Hb SS) or sickle beta thalassemia (Hb Sβ), and underwent allogeneic haematopoietic cell transplantation between Jan 15, 2008, and Dec 28, 2017. We considered transplants from donor-recipient pairs matched at the allele-level (HLA-A, HLA-B, HLA-C, and HLA-DRB1), including HLA-matched sibling donors, haploidentical related donors, matched unrelated donors, or mismatched unrelated donors. The main outcome was event-free survival. The effect of donor type, conditioning regimen intensity (myeloablative, non-myeloablative, and reduced-intensity regimens), age (≤12 or 13-49 years), sex, performance score, comorbidity index, recipient cytomegalovirus serostatus, graft type (bone marrow, peripheral blood, or umbilical cord blood), and transplantation period (2008-12 and 2013-17) on outcomes was studied using Cox regression models. Findings Of 996 patients with sickle cell disease and who underwent transplantation in 2008-17, 910 (91%) were included (558 [61%] patients had HLA-matched sibling donors, 137 [15%] haploidentical related donors, 111 [12%] matched unrelated donors, and 104 [11%] mismatched unrelated donors). The median follow-up was 36 months (IQR 18-60) after transplantation from HLA-matched siblings, 25 months (12-48) after transplantation from haploidentical related donors, 37 months (23-60) after transplantation from HLA-matched unrelated donors, and 47 months (24-72) after transplantation from mismatched unrelated donors. Event-free survival was worse in recipients aged 13 years or older than in those younger than 13 years (hazard ratio 1•74, 95% CI 1•24-2•45; p=0•0014) and in those who received a transplant from haploidentical related donors (5•30, 3•17-8•86; p<0•0001), matched unrelated donors (3•71, 2•39-5•75; p<0•0001), and mismatched unrelated donors (4•34, 2•58-7•32; p<0•0001) than in patients who received a transplant from matched siblings. There was no significant difference in event-free survival between recipients of transplants from non-sibling donors: haploidentical related donors (1•43, 0•81-2•50; p=0•21) or mismatched unrelated donors (1•17, 0•67-2•05; p=0•58) versus HLA-matched unrelated donors, or mismatched unrelated donors versus haploidentical related donors (1•22, 0•65-2•27; p=0•98). Event-free survival was also worse in patients conditioned with reduced-intensity regimens (1•97, 1•15-3•36; p=0•013) than in those conditioned with non-myeloablative regimens, but did not differ between those who received myeloablative compared with n...

SIMON® was feasible and improved hematologic parameters in children with SCA receiving hydroxyurea at a MTD. Future work will include extension of this technology to children with other chronic medical conditions who require daily use of medication.