Partitioning of Chemotherapeutics into Nuclear Condensates-Opening the Door to New Approaches for Drug Development.

Klein et al. (2020) demonstrate for the first time that small-molecule cancer therapeutics are selectively partitioned and concentrated within phase-separated nuclear condensates, providing new insights to drug efficacy and creating the opportunity for enhanced control of therapeutic targeting.

Weakly Bound Complex Formation between HCN and CH3Cl: A Matrix-Isolation and Computational Study.

The matrix-isolated infrared spectrum of a hydrogen cyanide-methyl chloride complex was investigated in a solid argon matrix. HCN and CH3Cl were co-condensed onto a substrate held at 10 K with an excess of argon gas, and the infrared spectrum was measured using Fourier-transform infrared spectroscopy. Quantum chemical geometry optimization, harmonic frequency, and natural bonding orbital calculations indicate stabilized hydrogen- and halogen-bonded structures. The two resulting weakly bound complexes are both composed of one CH3Cl molecule bound to a (HCN)3 subunit, where the three HCN molecules are bound head-to-tail in a ring formation. Our study suggests that─in the presence of CH3Cl─the formation of (HCN)3 is promoted through complexation. Since HCN aggregates are an important precursor to prebiotic monomers (amino acids and nucleobases) and other life-bearing polymers, this study has astrophysical implications toward the search for life in space.

Impact of telehealth visits on hydroxyurea response in sickle cell anemia.

BACKGROUND: It is important to ensure access to hydroxyurea (HU) for patients with sickle cell anemia (SCA) living in rural areas. The University of Alabama at Birmingham (UAB) Pediatric Sickle Cell program's satellite clinics reduce the barrier of transportation to the university-based clinic. However, as compared with the university clinic, these satellite clinics do not offer immediate access to HU dosing laboratory results and a nurse clinician calls families with HU dose adjustments after the clinic visit. This study evaluated the impact of telehealth dosing adjustments on HU laboratory and clinical response as compared with university-based patients. METHODS: A one-year retrospective chart review was performed to evaluate HU laboratory and clinical response based on clinic location and socioeconomic status for patients with SCA. We identified the number of clinic and acute care visits for one year and calculated the mean complete blood count and fetal hemoglobin (HbF) values for each patient. RESULTS: We identified 107 academic center participants with SCA-prescribed HU and 65 satellite clinic participants. The mean age of participants was 11 ± 5 years. We identified no difference in HbF (13.3 ± 0.7 vs 11.7 ± 0.8, P = 0.13), Hb (8.46 ± 1.1 vs 8.55 ± 1.1, P = 0.59), mean corpuscular volume (91.0 ± 10.6 vs 91.7 ± 9.5, P = 0.67), or absolute neutrophil count (4.85 ± 2.3 vs 4.87 ± 2.3, P = 0.95) when comparing Birmingham versus satellite clinics. We also identified no difference in hospital admissions (0.99 ± 0.1 versus 0.85 ± 0.2, P = 0.49), based on clinic location. CONCLUSIONS: The use of telehealth did not negatively impact laboratory response to HU. Future studies should identify novel approaches to improve access to HU among patients with SCA living in rural areas.

Clinical outcomes for pediatric patients receiving radiotherapy for solid tumor central nervous system metastases.

Central nervous system (CNS) metastases are rare, but devastating complications of pediatric solid tumors. Radiotherapy alone or postresection serves as an important treatment; however, data on the use of whole-brain radiotherapy (WBRT) versus focal radiotherapy, including stereotactic radiosurgery or stereotactic radiotherapy, for these indications are limited. We report a single institution experience of 26 pediatric patients treated with radiotherapy for solid tumor CNS metastases without leptomeningeal disease. Focal radiotherapy (n = 10) was well tolerated and survival outcomes did not differ between patients treated with WBRT (n = 16) versus focal radiation, suggesting that focal radiotherapy may be considered for patients with limited CNS metastases.

Novel CUBN Mutation in a Young Child With Megaloblastic Anemia.

Inherited disorders of cobalamin (Cbl, vitamin B12) metabolism are rare causes of megaloblastic anemia and neurologic abnormalities. More prevalent in certain ethnic groups, these disorders occur despite adequate Cbl intake and usually result from abnormal vitamin cell transport or processing. Cubilin (CUBN, intrinsic factor-cobalamin receptor) is the intestinal receptor for the endocytosis of intrinsic factor-vitamin B12. Its gene is localized to chromosome 10p13 and mutations involving CUBN have been described in patients with congenital megaloblastic anemia. In this report, we describe a novel CUBN pathogenic variant in a child with megaloblastic anemia.

Applying Statistical Design of Experiments To Understanding the Effect of Growth Medium Components on Cupriavidus necator H16 Growth.

Cupriavidus necator H16 is gaining significant attention as a microbial chassis for range of biotechnological applications. While the bacterium is a major producer of bioplastics, its lithoautotrophic and versatile metabolic capabilities make the bacterium a promising microbial chassis for biofuels and chemicals using renewable resources. It remains necessary to develop appropriate experimental resources to permit controlled bioengineering and system optimization of this microbe. In this study, we employed statistical design of experiments to gain understanding of the impact of components of defined media on C. necator growth and built a model that can predict the bacterium's cell density based on medium components. This highlighted medium components, and interaction between components, having the most effect on growth: fructose, amino acids, trace elements, CaCl2, and Na2HPO4 contributed significantly to growth (t values of <-1.65 or >1.65); copper and histidine were found to interact and must be balanced for robust growth. Our model was experimentally validated and found to correlate well (r2 = 0.85). Model validation at large culture scales showed correlations between our model-predicted growth ranks and experimentally determined ranks at 100 ml in shake flasks (ρ = 0.87) and 1 liter in a bioreactor (ρ = 0.90). Our approach provides valuable and quantifiable insights on the impact of medium components on cell growth and can be applied to model other C. necator responses that are crucial for its deployment as a microbial chassis. This approach can be extended to other nonmodel microbes of medical and industrial biotechnological importance.IMPORTANCE Chemically defined media (CDM) for cultivation of C. necator vary in components and compositions. This lack of consensus makes it difficult to optimize new processes for the bacterium. This study employed statistical design of experiments (DOE) to understand how basic components of defined media affect C. necator growth. Our growth model predicts that C. necator can be cultivated to high cell density with components held at low concentrations, arguing that CDM for large-scale cultivation of the bacterium for industrial purposes will be economically competitive. Although existing CDM for the bacterium are without amino acids, addition of a few amino acids to growth medium shortened lag phase of growth. The interactions highlighted by our growth model show how factors can interact with each other during a process to positively or negatively affect process output. This approach is efficient, relying on few well-structured experimental runs to gain maximum information on a biological process, growth.

Identifying the Transcriptional Response of Cancer and Inflammation-Related Genes in Lung Cells in Relation to Ambient Air Chemical Mixtures in Houston, Texas.

Atmospheric pollution represents a complex mixture of air chemicals that continually interact and transform, making it difficult to accurately evaluate associated toxicity responses representative of real-world exposure. This study leveraged data from a previously published article and reevaluated lung cell transcriptional response induced by outdoor atmospheric pollution mixtures using field-based exposure conditions in the industrialized Houston Ship Channel. The tested hypothesis was that individual and co-occurring chemicals in the atmosphere relate to altered expression of critical genes involved in inflammation and cancer-related processes in lung cells. Human lung cells were exposed at an air-liquid interface to ambient air mixtures for 4 h, with experiments replicated across 5 days. Real-time monitoring of primary and secondary gas-phase pollutants, as well as other atmospheric conditions, was simultaneously conducted. Transcriptional analysis of exposed cells identified critical genes showing differential expression associated with both individual and chemical mixtures. The individual pollutant identified with the largest amount of associated transcriptional response was benzene. Tumor necrosis factor (TNF) and interferon regulatory factor 1 (IRFN1) were identified as key upstream transcription factor regulators of the cellular response to benzene. This study is among the first to measure lung cell transcriptional responses in relation to real-world, gas-phase air mixtures.

Management of severe chronic pain with methadone in pediatric patients with sickle cell disease.

Vasocclusive pain crises are common among pediatric patients with sickle cell disease (SCD). Some patients with repeated pain crises develop chronic pain. We performed a retrospective cohort study of pediatric patients with SCD with chronic pain treated with methadone. We identified a significant reduction in pain hospitalizations following methadone treatment (0.35 ± 0.19 vs. 0.19 ± 0.17 hospitalizations/month, P = 0.016). In addition, we did not observe overt organ toxicity nor symptoms of opioid withdrawal during methadone wean. We suggest that methadone is safe and has some clinical benefit, which should be proven in prospective randomized trials for pediatric patients with SCD and chronic pain.

Impact of early analgesia on hospitalization outcomes for sickle cell pain crisis.

BACKGROUND: Painful events are the leading cause of hospitalizations for patients with sickle cell disease. Individualized pain plans targeting patient-specific maximum opioid dosing may shorten hospitalization length and are recommended by national guidelines. Prior to implementing individualized sickle cell pain plans, we tested the hypothesis that a shorter time to achieve a maximum opioid dose would improve hospitalization outcomes. PROCEDURE: Two-year IRB-approved, retrospective study of pediatric patients admitted for vaso-occlusive crisis (VOC). We recorded the emergency department admission time, order entry time for the maximum opioid dose during the hospitalization, and time of discharge orders.  We categorized patients as infrequent if they required <3 admissions for VOC over two years and patients as frequent if they required ≥3 admissions for VOC over two years. To account for multiple admissions, generalized linear modeling was performed. RESULTS: We identified 236 admissions for acute pain observed in 108 patients. Achieving an earlier maximum opioid dose was significantly associated with shorter length of hospitalization for frequent and infrequent pain patients (both P ≤ 0.0001). As total hospitalization length can be impacted by the time a maximum opioid order was placed, we also analyzed hospitalization length after the maximum opioid order was placed. Frequent pain patients who achieved earlier analgesia had a significantly shorter hospitalization from the time the maximum opioid order was placed (P = 0.03) while no association was found for infrequent pain patients (P = 0.84). CONCLUSIONS: Early achievement of maximum analgesia improved hospitalization outcomes and warrant further investigation in prospective studies of individualized pain plans.

Red blood cell transfusion therapy for sickle cell patients with frequent painful events.

BACKGROUND: Recurrent pain events or chronic pain are among the most common complications of sickle cell disease. Despite attempts to maximize adherence to and dosing of hydroxyurea, some patients continue to suffer from pain. Our institution developed a program to initiate chronic red blood cell transfusions for one year in patients clinically deemed to have high healthcare utilization from sickle cell pain, despite being prescribed hydroxyurea. PROCEDURE: An institutional review board approved retrospective study to evaluate the health outcomes associated with a one-year red blood cell transfusion protocol in sickle cell patients experiencing recurrent pain events as compared with the health outcomes for these patients in the one year prior to receiving transfusion therapy. We performed a matched-pair analysis using a Wilcoxon signed rank to determine the impact of transfusion therapy on clinic visits, emergency department visits, hospital admissions, hospitalization days, and opioid prescriptions filled. RESULTS: One year of transfusion therapy significantly reduced the number of total emergency department visits for pain (6 vs 2.5 pain visits/year, P = 0.005), mean hospitalizations for pain (3.4 vs 0.9 pain admissions/year), and mean hospital days per year for pain crisis (23.5 vs 4.5, P = 0.0001), as compared with the one year prior to transfusion therapy. We identified no significant difference in opioid prescriptions filled during the year of transfusion therapy. CONCLUSION: Patients with frequent pain episodes may benefit from one year of transfusion therapy.

Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia.

BACKGROUND: Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care. METHODS: In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct. RESULTS: A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04). CONCLUSIONS: Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).

Elective cholecystectomy reduces morbidity of cholelithiasis in pediatric sickle cell disease.

BACKGROUND: Cholelithiasis is a frequent complication in pediatric sickle cell disease (SCD). Though it is standard practice to perform a cholecystectomy in pediatric SCD patients with symptoms of cholelithiasis, the use of elective cholecystectomy for asymptomatic patients remains controversial. PROCEDURE: Records of 191 pediatric sickle cell patients with cholelithiasis who underwent cholecystectomy were retrospectively reviewed. Patients classified as follows: (i) elective-no preoperative symptoms, cholelithiasis on screening ultrasound, comprehensive preoperative plan; (ii) symptomatic-preoperative symptoms of cholelithiasis on diagnostic ultrasound, comprehensive preoperative plan; or (iii) emergent-hospitalization for acute cholecystitis symptoms, cholelithiasis on diagnostic ultrasound, limited preoperative preparation. We compared the morbidity of cholecystectomy by examining pre- and post-cholecystectomy hospital admission days, length of stay for cholecystectomy, and surgical complications. RESULTS: Patients with SCD underwent a total of 191 cholecystectomies over a 10-year period: 51 elective, 110 symptomatic, and 30 emergent. Patients who required emergent cholecystectomy had a longer postoperative hospitalization time than elective or symptomatic cholecystectomy (7.3 vs 4.3, P < 0.001). Baseline values for total bilirubin and aspartate aminotransferase (AST) were significantly elevated (P < 0.02 and P < 0.07, respectively) in patients requiring emergent cholecystectomy. CONCLUSIONS: This represents the largest reported retrospective review of pediatric cholelithiasis and cholecystectomy in SCD to date. These data strongly suggest that elective cholecystectomy decreases morbidity associated with emergent cholecystectomy. The overall outcomes for symptomatic and elective patients are favorable. However, our study indicates the need for prospective studies to identify clinical indicators for those emergent patients.

Acute kidney injury during a pediatric sickle cell vaso-occlusive pain crisis.

BACKGROUND: Patients who develop sickle cell disease (SCD) nephropathy are at a high risk for mortality. The pathophysiology of vaso-occlusive pain crisis may contribute to acute kidney injury (AKI). Non-steroidal anti-inflammatory drugs, known inducers of AKI, are used to treat pain crises. Multiple gaps exist in the knowledge about the impact of AKI in SCD. METHODS: We conducted a 2-year retrospective review of AKI events in patients admitted for vaso-occlusive crisis. AKI was defined by an increase of ≥0.3 mg/dL or 50% in serum creatinine from baseline. Laboratory values and ketorolac administration by days and dose (mg/kg) were identified from hospital records. A generalized mixed effects model for binary outcomes evaluated AKI based on laboratory variables and ketorolac administration. A generalized mixed Poisson effects model analyzed the association of AKI with hospital length of stay. RESULTS: Thirty-three out of 197 admissions for vaso-occlusive pain crisis (17%) were associated with AKI. Fifty-two percent of the cases presented to the Emergency Room (ER) with AKI. Every one unit decrease in hemoglobin from baseline to admission increased the risk of AKI by 49%. Among patients who received ketorolac for pain, both total days and doses of ketorolac were associated with AKI. Finally, patients with pain and AKI required longer periods of hospitalization than patients without AKI. CONCLUSION: Acute kidney injury during sickle cell pain crisis is common and may be an important modifiable risk factor for developing chronic kidney disease (CKD). Further studies are needed to determine the impact of nephrotoxic medications on progressive SCD nephropathy.

Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia.

BACKGROUND: Patients with sickle cell anemia (SCA) have an increased prevalence of nephropathy and mortality from chronic kidney disease (CKD). METHODS: We evaluated the association of hyperuricemia and nocturnal hypertension with lower estimated glomerular filtration rate (eGFR) using cystatin-C in patients aged 10-21 years with the HbSS or HbSB0 form of the disease during a non-acute clinic visit. eGFR and uric acid measurements were obtained in 83 and 81 participants, respectively, and 24-h ambulatory blood pressure monitoring (ABPM) was performed in 44 participants. Annual testing included vital signs, complete blood count, comprehensive metabolic panel, medications, urine microalbumin/creatinine, and lactate dehydrogenase measurements. Hyperuricemia was defined as a uric acid level of ≥5.5 mg/dL. Nocturnal hypertension was defined as >25% of nocturnal readings at >95th percentile according to norms established by the American Heart Association Statement on ABPM in children and adolescents. RESULTS: The mean eGFR was statistically significantly lower in patients with hyperuricemia than in those with normal uric acid levels (143 vs. 161 mL/min/1.73 m2, respectively). Of the 44 participants for whom ABPM data were available, 14 (32%) had systolic nocturnal hypertension and 12 (27%) had diastolic nocturnal hypertension. The mean eGFR was statistically significantly lower in participants with nocturnal systolic and diastolic hypertension than in those with normal nocturnal blood pressure. In a regression model, nocturnal hypertension and hyperuricemia were associated with a lower eGFR. CONCLUSIONS: Two risk factors for CKD, i.e., nocturnal hypertension and hyperuricemia, were associated with lower eGFR in older children and adolescent patients with SCA. Long-term studies on their association with progression to CKD in this population are warranted. KEY POINT: Nocturnal hypertension and hyperuricemia are established risk factors for nephropathy in other diseases and may play a role in SCA nephropathy.

Influence of wheel size on muscle activity and tri-axial accelerations during cross-country mountain biking.

This study aimed to investigate the influence of different mountain bike wheel diameters on muscle activity and whether larger diameter wheels attenuate muscle vibrations during cross-country riding. Nine male competitive mountain bikers (age 34.7 ± 10.7 years; stature 177.7 ± 5.6 cm; body mass 73.2 ± 8.6 kg) participated in the study. Riders performed one lap at race pace on 26, 27.5 and 29 inch wheeled mountain bikes. sEMG and acceleration (RMS) were recorded for the full lap and during ascent and descent phases at the gastrocnemius, vastus lateralis, biceps brachii and triceps brachii. No significant main effects were found by wheel size for each of the four muscle groups for sEMG or acceleration during the full lap and for ascent and descent (P > .05). When data were analysed between muscle groups, significant differences were found between biceps brachii and triceps brachii (P < .05) for all wheel sizes and all phases of the lap with the exception of for the 26 inch wheel during the descent. Findings suggest wheel diameter has no influence on muscle activity and vibration during mountain biking. However, more activity was observed in the biceps brachii during 26 inch wheel descending. This is possibly due to an increased need to manoeuvre the front wheel over obstacles.

The effect of mountain bike wheel size on cross-country performance.

The purpose of this study was to determine the influence of different wheel size diameters on indicators of cross-country mountain bike time trial performance. Nine competitive male mountain bikers (age 34.7 ± 10.7 years; stature 177.7 ± 5.6 cm; body mass 73.2 ± 8.6 kg) performed 1 lap of a 3.48 km mountain bike (MTB) course as fast as possible on 26″, 27.5″ and 29″ wheeled MTB. Time (s), mean power (W), cadence (revs · min-1) and velocity (km · h-1) were recorded for the whole lap and during ascent and descent sections. One-way repeated measure ANOVA was used to determine significant differences. Results revealed no significant main effects for any variables by wheel size during all trials, with the exception of cadence during the descent (F(2, 16) = 8.96; P = .002; P2 = .53). Post hoc comparisons revealed differences lay between the 26″ and 29″ wheels (P = .02). The findings indicate that wheel size does not significantly influence performance during cross-country when ridden by trained mountain bikers, and that wheel choice is likely due to personal choice or sponsorship commitments.

Prevalence of acute kidney injury during pediatric admissions for acute chest syndrome.

BACKGROUND: Patients with sickle cell disease are at risk for developing chronic kidney disease (CKD). Acute kidney injury (AKI) has been linked to progression to CKD, but limited data exist to determine its role in acute complications of sickle cell disease. We hypothesized that AKI occurs in pediatric patients admitted for acute chest syndrome (ACS) and prolongs hospitalization. METHODS: We conducted a 6-year retrospective review of pediatric patients with ACS admitted to a single medical institution. RESULTS: Of the 149 pediatric patients admitted for ACS during the 6-year study period, 12 (8 %) developed AKI. Comparison of patients with and without AKI revealed a significant association between AKI and a larger drop in hemoglobin value from baseline (2.7 vs. 1.4 g/dL; p = 0.003), a lower hemoglobin value at admission (6.4 vs. 7.5 g/dL; p = 0.03), and an increased white blood cell count at admission (33.1 vs. 19.8 × 10(9)/L; p < 0.0001), respectively. AKI (p < 0.0001) together with need for advanced respiratory support (biphasic positive airway pressure or mechanical ventilation) (p < 0.0001) and need for exchange transfusion (p < 0.0001) were associated with prolonged hospitalization. CONCLUSIONS: Clinicians should monitor pediatric patients hospitalized for ACS for the development of AKI as a potentially modifiable risk factor for prolonged hospitalization.

Synthesis of customized petroleum-replica fuel molecules by targeted modification of free fatty acid pools in Escherichia coli.

Biofuels are the most immediate, practical solution for mitigating dependence on fossil hydrocarbons, but current biofuels (alcohols and biodiesels) require significant downstream processing and are not fully compatible with modern, mass-market internal combustion engines. Rather, the ideal biofuels are structurally and chemically identical to the fossil fuels they seek to replace (i.e., aliphatic n- and iso-alkanes and -alkenes of various chain lengths). Here we report on production of such petroleum-replica hydrocarbons in Escherichia coli. The activity of the fatty acid (FA) reductase complex from Photorhabdus luminescens was coupled with aldehyde decarbonylase from Nostoc punctiforme to use free FAs as substrates for alkane biosynthesis. This combination of genes enabled rational alterations to hydrocarbon chain length (Cn) and the production of branched alkanes through upstream genetic and exogenous manipulations of the FA pool. Genetic components for targeted manipulation of the FA pool included expression of a thioesterase from Cinnamomum camphora (camphor) to alter alkane Cn and expression of the branched-chain α-keto acid dehydrogenase complex and ß-keto acyl-acyl carrier protein synthase III from Bacillus subtilis to synthesize branched (iso-) alkanes. Rather than simply reconstituting existing metabolic routes to alkane production found in nature, these results demonstrate the ability to design and implement artificial molecular pathways for the production of renewable, industrially relevant fuel molecules.

Application of a utility analysis to evaluate a novel assessment tool for clinically oriented physiology and pharmacology.

Multiple-choice questions are a gold-standard tool in medical school for assessment of knowledge and are the mainstay of licensing examinations. However, multiple-choice questions items can be criticized for lacking the ability to test higher-order learning or integrative thinking across multiple disciplines. Our objective was to develop a novel assessment that would address understanding of pathophysiology and pharmacology, evaluate learning at the levels of application, evaluation and synthesis, and allow students to demonstrate clinical reasoning. The rubric assesses student writeups of clinical case problems. The method is based on the physician's traditional postencounter Subjective, Objective, Assessment and Plan note. Students were required to correctly identify subjective and objective findings in authentic clinical case problems, to ascribe pathophysiological as well as pharmacological mechanisms to these findings, and to justify a list of differential diagnoses. A utility analysis was undertaken to evaluate the new assessment tool by appraising its reliability, validity, feasibility, cost effectiveness, acceptability, and educational impact using a mixed-method approach. The Subjective, Objective, Assessment and Plan assessment tool scored highly in terms of validity and educational impact and had acceptable levels of statistical reliability but was limited in terms of acceptance, feasibility, and cost effectiveness due to high time demands on expert graders and workload concerns from students. We conclude by making suggestions for improving the tool and recommend deployment of the instrument for low-stakes summative assessment or formative assessment.

The evaluation of a new apheresis device for automated red blood cell exchange procedures in patients with sickle cell disease.

BACKGROUND: The Spectra Optia apheresis system (SO), a blood component separator, can be used to perform red blood cell exchange (RBCX) procedures for the transfusion management of sickle cell disease (SCD) in adults and children. This study was designed to evaluate the performance of the SO RBCX protocols (exchange and depletion/exchange) in patients with SCD. STUDY DESIGN AND METHODS: Patients with SCD and a need for an RBCX procedure as part of a chronic program or as a single procedure were enrolled in this multicenter, single-arm, open-label study. The primary goal of the study was to confirm that the predicted percentage of the patient's original RBCs remaining at the end of the procedure (FCRp) reflects the actual cell fraction remaining, as measured by %HbS (FCRa). Secondary endpoints included ability of the SO to achieve the desired final hematocrit (Hct) and device-related serious adverse events (SAEs). RESULTS: Seventy-two patients 12 years of age or older were enrolled in the study; 60 were evaluable. The ratio of FCRa to FCRp after the RBCX procedure was 0.90, well within the prespecified range of 0.75 to 1.25. The SO was able to achieve the desired final Hct in the evaluable population. The safety profile was favorable, and no patients had an SAE or unexpected adverse device effect or withdrew from the procedure or treatment due to an adverse event. CONCLUSION: The SO performed effectively and safely for both the RBCX procedure and the RBCX depletion/exchange procedure.