Identification of Clinical and Laboratory Parameters Associated with the Development of Acute Chest Syndrome during Vaso-Occlusive Episodes in Children with Sickle Cell Disease: A Preliminary Step before Assessing Specific and Early Treatment Strategies.

This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days, p < 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (p < 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 109/L) and neutrophil (>10 × 109/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74-0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS.

Incidence and predictive score for delayed hemolytic transfusion reaction in adult patients with sickle cell disease.

Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication of transfusion in sickle cell disease (SCD). The frequency of DHTR is underestimated because its symptoms mimic those of vaso-occlusive crisis and antibodies (Abs) are often not detectable. No predictive factors for identifying patients likely to develop DHTR have yet been defined. We conducted a prospective single-center observational study over 30 months in adult sickle cell patients. We included 694 transfusion episodes (TEs) in 311 patients, divided into occasional TEs (OTEs: 360) and chronic transfusion program (CTEs: 334). During follow-up, 15 cases of DHTR were recorded, exclusively after OTEs. DHTR incidence was 4.2% per OTE (95% CI [2.6; 6.9]) and 6.8% per patient during the 30 months of the study (95% CI [4.2; 11.3]). We studied 11 additional DHTR cases, to construct a predictive score for DHTR. The DHTR mortality is high, 3 (11.5%) of the 26 DHTR patients died. The variables retained in the multivariate model were history of DHTR, number of units previously transfused and immunization status before transfusion. The resulting DHTR-predictive score had an area under the ROC curve of 0.850 [95% CI: 0.780-0.930], a negative-predictive value of 98.4% and a positive-predictive value of 50%. We report in our study population, for the first time, the incidence of DHTR, and, its occurrence exclusively in occasionally transfused patients. We also describe a simple score for predicting DHTR in patients undergoing occasional transfusion, to facilitate the management of blood transfusion in SCD patients.

Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease.

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from the consumption of meat products contaminated by the agent causing bovine spongiform encephalopathy. Evidence supporting the presence of a population of silent carriers that can potentially transmit the disease through blood transfusion is increasing. The development of a blood-screening assay for both symptomatic vCJD patients and asymptomatic carriers is urgently required. We show that a diagnostic assay combining plasminogen-bead capture and protein misfolding cyclic amplification (PMCA) technologies consistently detected minute amounts of abnormal prion protein from French and British vCJD cases in the required femtomolar range. This assay allowed the blinded identification of 18 patients with clinical vCJD among 256 plasma samples from the two most affected countries, with 100% sensitivity [95% confidence interval (CI), 81.5 to 100%], 99.2% analytical specificity (95% CI, 95.9 to 100%), and 100% diagnostic specificity (95% CI, 96.5 to 100%). This assay also allowed the detection of silent carriage of prions 1.3 and 2.6 years before the clinical onset in two blood donors who later developed vCJD. These data provide a key step toward the validation of this PMCA technology as a blood-based diagnostic test for vCJD and support its potential for detecting presymptomatic patients, a prerequisite for limiting the risk of vCJD transmission through blood transfusion.

Nursing home admission in elderly subjects with dementia: predictive factors and future challenges.

OBJECTIVES: The aim of this study was to identify factors predictive of nursing home admission (NHA) over a period of 1 year among elderly subjects with dementia. METHODS: The study population was drawn from the SAFES cohort that was formed within a national research program into the recruitment of emergency departments in 9 teaching hospitals. Subjects were to have been hospitalized in a medical ward in the same hospital as the emergency department to which they were initially admitted. Subjects who experienced NHA before emergency department admission were excluded. Those with a confirmed diagnosis of dementia were considered in the present analysis. NHA has been defined as the incident admission into either a nursing home or other long term care facility within the follow-up period. Data obtained from a Comprehensive Geriatric Assessment were used in a Cox model to predict 1-year NHA. RESULTS: The 425 subjects of the study were 86 ± 6 years old, and were mainly women (63%). NHA rate was 40% (n = 172). Four factors were identified to increase NHA risk: age 85 or older (hazard ratio [HR] = 1.5; 95% confidence interval [CI] = 1.1-2.1), inability to use the toilet (HR = 2.5; 95% CI = 1.5-4.2), balance disorders (HR = 1.5; 95% CI = 1.1-2.1), and living alone (HR = 1.5; 95% CI = 1.1-2.1). Three factors decreased this risk significantly: inability to transfer (HR = 0.5; 95% CI = 0.3-0.8), increased number of children (HR = 0.88; 95% CI = 0.96-0.99), and increased initial Mini-Mental State Examination score (HR = 0.97; 95% CI = 0.8-0.9). CONCLUSION: NHA determinants in dementia are strongly linked to the patient's own characteristics but also to his or her physical or social environment. Interventions should target both members of the dyad "patient-caregiver" because both are affected by the disease.