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New Full Length Feature Film about Friendship and Life with Sickle Cell Disease
Spilled Milk A FILM BY FRIENDS ABOUT FRIENDS
Spilled Milk is a film about two lifelong friends – a white guy from Utah and a black guy from New Jersey. Omar is living with Sickle Cell Disease; Jaqai has uprooted his life to make a documentary about him. A first-time filmmaker, Jaqai quickly discovers that he’s underestimated just how physically and emotionally debilitating the disease has been for his friend. Meanwhile, Omar is getting a taste of what it’s like to be a reluctant poster child for Sickle Cell when he’d rather be left to his own devices and seek distraction through video games.
Still, Jaqai gets access that only a best friend could. He takes an intimate look at Omar’s everyday life and explores the harsh realities of Sickle Cell, the effects of which extend beyond the significant physical impact of the disease. Spilled Milk captures straight talk from doctors about the inexperience many hospital staffers have with Sickle Cell, and the consequent stigmas that can plague African Americans seeking treatment for pain.
The challenges that arise during the course of making the film bring Omar and Jaqai even closer, especially as Omar faces a life-threatening health scare and a surprisingly difficult decision about whether to pursue a potential cure.
This is a powerful film that all health care providers should see about daily life with sickle cell disease.
To watch the entire 1 hour 24 minute film free go to spilledmilkmovie.com/watch
Best friends, men document powerful story of life with sickle cell disease
Omar Beach, 43, and Jaqai Mickelsen, 40, have been close since they met at their San Diego high school back in the early 1990’s.
Beach has sickle cell disease, a group of inherited disorders that cause the body’s red blood cells to contort and become sickle-shaped. The cells, which should be round, carry oxygen throughout the body. But, because of their sharp edges, they block blood flow to the joints and organs, triggering severe pain crises and damage. When Mickelsen asked Beach to let him tell the story of his battle with sickle cell disease, Beach initially said no. He didn’t want sickle cell to define him.
“The last thing I want is pity or sadness, and stuff like that,” Beach says.
Free Health Care Provider training video: Reducing the Complications of Blood Transfusion for Sickle Cell Disease
Online videos: http://ghpc.gsu.edu/CME/
Free CME/CNE credit: CDC.GOV/TCEONLINE
Introduction – James Eckman, M.D.
Use of blood transfusion during acute illness – Peter Lane, M.D.
Delayed hemolytic transfusion reactions – Ross Fasano, M.D.
Management of chronic transfusion – James Eckman, M.D.
Transfusion is an established therapy in sickle cell disease that can treat and prevent certain disease complications, reducing morbidity and mortality. But there are unique aspects of transfusing individuals with sickle cell disease that must be taken into consideration to maximize benefits and minimize transfusion complications. The goal of this course is to reduce the burden of transfusion complications in sickle cell disease by increasing the use of evidence-based practices among primary and emergency health care providers who treat these patients.
In 2014, the National Heart Lung and Blood Institute of the National Institutes of Health released an expert panel report on sickle cell disease management, including evidence-based recommendations for transfusion and the avoidance and management of transfusion complications. In addition, guidelines from Great Britain were published in 2017 addressing laboratory and clinical management of transfusion in sickle cell disease. This course presents these and other important aspects of quality, effective care for individuals with sickle cell disease.
The course is intended for providers who make clinical decisions about prescribing transfusion for sickle cell disease patients or managing patients who receive transfusions. Appropriate learners include adult, pediatric, and family general practitioners; surgeons, hospitalists and emergency medicine specialists; physician assistants and clinical nurse practitioners. The Introduction module covers general considerations for transfusion in sickle cell disease and the genetic and biological foundations of the most common transfusion complications. The remaining modules are case-based scenarios addressing specific areas of concern. Each module is a self-contained, stand-alone segment covering essential material. They can be taken individually or in any sequence, but users may find it helpful to take the Introduction module first.
How One Child’s Sickle Cell Mutation Helped Protect the World From Malaria
The genetic mutation arose 7,300 years ago in just one person in West Africa, Its advantage: a shield against rampant malaria. https://www.nytimes.com/2018/03/08/health/sickle-cell-mutation.html
Articles in the Medical Literature
J Pediatr Psychol. 2018 Mar 17. doi: 10.1093/jpepsy/jsy015. [Epub ahead of print]
Sickle cell disease (SCD) predominately affects Black Americans. This is the first study of its kind to describe the racial bias experiences of youth with SCD and their reactions to these experiences.
Participants were 20 youth with SCD (ages 13-21 years) who were asked to describe any racial bias events they experienced, as recorded on the Perception of Racism in Children and Youth measure (PRaCY). Interviews were recorded, transcribed, and analyzed by two independent raters using a conventional content analysis approach.
All participants reported at least one incident of racial bias. Content analysis of racial bias events (n = 104) yielded 4 categories and 12 subcategories as follows: Perpetrator (Peers, Authority Figures, and General Public), Type of Racial Bias (Explicit, Implicit), Behavioral Reaction (Approach, Avoidant), and Emotional Response (Dysphoria, Anger, Unconcerned, Inferior, Anxious).
This study provides a description of racial bias experiences within community and medical settings and highlights the need for further evaluation of the impact of racial bias among youth with SCD.
West J Emerg Med. 2018 Mar;19(2):311-318. doi: 10.5811/westjem.2017.9.35422. Epub 2018 Feb 12.
Use of alternative venues to manage uncomplicated vaso-occlusive crisis (VOC), such as a day hospital (DH) or ED observation unit, for patients with sickle cell anemia, may significantly reduce admission rates, which may subsequently reduce 30-day readmission rates.
In the context of a two-institution quality improvement project to implement best practices for management of patients with sickle cell disease (SCD) VOC, we prospectively compared acute care encounters for utilization of 1) emergency department (ED); 2) ED observation unit; 3) DH, and 4) hospital admission, of two different patient cohorts with SCD presenting to our two study sites. Using a representative sample of patients from each institution, we also tabulated SCD patient visits or admissions to outside hospitals within 20 miles of the patients’ home institutions.
Over 30 months 427 patients (297 at Site 1 and 130 at Site 2) initiated 4,740 institutional visits, totaling 6,627 different acute care encounters, including combinations of encounters. The range of encounters varied from a low of 0 (203 of 500 patients [40.6%] at Site 1; 65 of 195 patients [33.3%] at Site 2), and a high of 152 (5/month) acute care encounters for one patient at Site 2. Patients at Site 2 were more likely to be admitted to the hospital during the study period (88.4% vs. 74.4%, p=0.0011) and have an ED visit (96.9% vs. 85.5%, p=0.0002). DH was used more frequently at Site 1 (1.207 encounters for 297 patients at Site 1, vs. 199 encounters for 130 patients at Site 2), and ED observation was used at Site 1 only. Thirty-five percent of patients visited hospitals outside their home academic center.
In this 30-month assessment of two sickle cell cohorts, healthcare utilization varied dramatically between individual patients. One cohort had more hospital admissions and ED encounters, while the other cohort had more day hospital encounters and used a sickle cell disease observation VOC protocol. One-third of patients sampled visited hospitals for acute care outside of their care providers’ institutions.
J Thromb Thrombolysis. 2018 Mar 19. doi: 10.1007/s11239-018-1637-y. [Epub ahead of print]
Patients with sickle cell disease (SCD) experience initial and recurrent venous thromboembolism (VTE) more commonly and at a younger age than the general population, and it confers a higher mortality for patients with SCD. However, limited evidence is available to guide anticoagulant use for VTE treatment in this population. The primary objective of this study is to characterize the effectiveness and safety of direct oral anticoagulants (DOAC) and warfarin for VTE treatment among patients with SCD. This single-center retrospective study includes adult patients with SCD who were diagnosed with VTE. Data was obtained from review of electronic health records for the 6 months after VTE diagnosis. Among the 22 patients treated initially with a DOAC, 6 (27%) developed recurrent VTE, none experienced major bleeding, and 3 (14%) experienced clinically relevant non-major bleeding (CRNMB). Similarly, of 15 patients initially treated with warfarin, 3 (20%) developed a recurrent VTE, 1 (7%) experienced major bleeding, and 2 (13%) experienced CRNMB. Twelve patients received more than one oral anticoagulant during the study period, most commonly due to a recurrent VTE, concern for non-adherence, or subtherapeutic INR. Overall, the incidence of VTE recurrence and bleeding events were similar between groups, but occurred at a higher rate than those found in major clinical trials of anticoagulant agents. Prescribers should continue to individualize therapeutic decision-making regarding oral anticoagulant therapy for VTE treatment for individuals with SCD based on patient-specific factors and anticipated ability to adhere to the drug regimen or required monitoring.
Blood Cells Mol Dis. 2018 Mar 7. pii: S1079-9796(17)30470-9. doi: 10.1016/j.bcmd.2018.03.001. [Epub ahead of print]
Acute chest syndrome (ACS) is a leading cause of mortality in patients with sickle cell disease (SCD). Systemic corticosteroids decrease ACS severity, but the risk of readmission for vaso-occlusive crises (VOC) has limited their use. The efficacy of inhaled corticosteroids (ICS) as a safer alternative is currently unknown. An observational, historic cohort study compared patients with SCD with ACS who received ICS at admission (ICS) to those who did not (non-ICS). Outcome measures included rates of transfusion, oxygen requirement, BiPAP initiation, PICU transfer, intubation, readmission, hospital cost, and length of stay. One hundred twenty patients with SCD (55 non-ICS, 65 ICS) were included. A significantly higher proportion of the non-ICS group had bilateral infiltrates, but fewer had asthma. More children in the ICS group had BiPAP initiated, however transfer to the PICU, intubation, transfusion rates, oxygen requirement, hospital cost, length of stay, and readmission rates did not differ between groups. Regression analysis did not reveal any differences in outcomes, nor were outcomes changed when patients were separated based on the presence or absence of asthma. In this observational cohort study, ICS did not demonstrate a significant reduction in ACS morbidity, though ICS use should be studied in a prospective manner.
Cochrane Database Syst Rev. 2018 Mar 16;3:CD011130. doi: 10.1002/14651858.CD011130.pub3. [Epub ahead of print]
Sickle cell disease (SCD) is a group of disorders that affects haemoglobin, which causes distorted sickle- or crescent-shaped red blood cells. It is characterized by anaemia, increased susceptibility to infections and episodes of pain. The disease is acquired by inheriting abnormal genes from both parents, the combination giving rise to different forms of the disease. Due to increased erythropoiesis in people with SCD, it is hypothesized that they are at an increased risk for folate deficiency. For this reason, children and adults with SCD, particularly those with sickle cell anaemia, commonly take 1 mg of folic acid orally every day on the premise that this will replace depleted folate stores and reduce the symptoms of anaemia. It is thus important to evaluate the role of folate supplementation in treating SCD.
To analyse the efficacy and possible adverse effects of folate supplementation (folate occurring naturally in foods, provided as fortified foods or additional supplements such as tablets) in people with SCD.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also conducted additional searches in both electronic databases and clinical trial registries.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register: 17 November 2017.
Randomised, placebo-controlled trials of folate supplementation for SCD.
DATA COLLECTION AND ANALYSIS:
Four review authors assessed We used the standard Cochrane-defined methodological procedures.Four review authors independently assessed the eligibility and risk of bias of the included trials and extracted and analysed the data included in the review. The quality of the evidence was assessed using GRADE.
One trial, undertaken in 1983, was eligible for inclusion in the review. This was a double-blind placebo-controlled quasi-randomised triaI of supplementation of folic acid in people with SCD. A total of 117 children with homozygous sickle cell (SS) disease aged six months to four years of age participated over a one-year period (analysis was restricted to 115 children).Serum folate measures, obtained after trial entry at six and 12 months, were available in 80 of 115 (70%) participants. There were significant differences between the folic acid and placebo groups with regards to serum folate values above 18 µg/L and values below 5 µg/L (low-quality evidence). In the folic acid group, values above 18 µg/L were observed in 33 of 41 (81%) compared to six of 39 (15%) participants in the placebo (calcium lactate) group. Additionally, there were no participants in the folic acid group with serum folate levels below 5 µg/L, whereas in the placebo group, 15 of 39 (39%) participants had levels below this threshold. Haematological indices were measured in 100 of 115 (87%) participants at baseline and at one year. After adjusting for sex and age group, the investigators reported no significant differences between the trial groups with regards to total haemoglobin concentrations, either at baseline or at one year (low-quality evidence). It is important to note that none of the raw data for the outcomes listed above were available for analysis.The proportions of participants who experienced certain clinical events were analysed in all 115 participants, for which raw data were available. There were no statistically significant differences noted; however, the trial was not powered to investigate differences between the folic acid and placebo groups with regards to: minor infections, risk ratio (RR) 0.99 (95% confidence interval (CI) 0.85 to 1.15) (low-quality evidence); major infections, RR 0.89 (95% CI 0.47 to 1.66) (low-quality evidence); dactylitis, RR 0.67 (95% CI 0.35 to 1.27) (low-quality evidence); acute splenic sequestration, RR 1.07 (95% CI 0.44 to 2.57) (low-quality evidence); or episodes of pain, RR 1.16 (95% CI 0.70 to 1.92) (low-quality evidence). However, the investigators reported a higher proportion of repeat dactylitis episodes in the placebo group, with two or more attacks occurring in 10 of 56 participants compared to two of 59 in the folic acid group (P < 0.05).Growth, determined by height-for-age and weight-for-age, as well as height and growth velocity, was measured in 103 of the 115 participants (90%), for which raw data were not available. The investigators reported no significant differences in growth between the two groups.The trial had a high risk of bias with regards to random sequence generation and incomplete outcome data. There was an unclear risk of bias in relation to allocation concealment, outcome assessment, and selective reporting. Finally, There was a low risk of bias with regards to blinding of participants and personnel. Overall the quality of the evidence in the review was low.There were no trials identified for other eligible comparisons, namely: folate supplementation (fortified foods and physical supplementation with tablets) versus placebo; folate supplementation (naturally occurring in diet) versus placebo; folate supplementation (fortified foods and physical supplementation with tablets) versus folate supplementation (naturally occurring in diet).
One doubIe-blind, placebo-controlled triaI on folic acid supplementation in children with SCD was included in the review. Overall, the trial presented mixed evidence on the review’s outcomes. No trials in adults were identified. With the limited evidence provided, we conclude that, while it is possible that folic acid supplementation may increase serum folate levels, the effect of supplementation on anaemia and any symptoms of anaemia remains unclear.If further trials were conducted, these may add evidence regarding the efficacy of folate supplementation. Future trials should assess clinical outcomes such as folate concentration, haemoglobin concentration, adverse effects and benefits of the intervention, especially with regards to SCD-related morbidity. Such trials should include people with SCD of all ages and both sexes, in any setting. To investigate the effects of folate supplementation, trials should recruit more participants and be of longer duration, with long-term follow-up, than the trial currently included in this review. However, we do not envisage further trials of this intervention will be conducted, and hence the review will no longer be regularly updated.
Nat Rev Dis Primers. 2018 Mar 15;4:18010. doi: 10.1038/nrdp.2018.10.
Sickle cell disease (SCD) is a group of inherited disorders caused by mutations in HBB, which encodes haemoglobin subunit β. The incidence is estimated to be between 300,000 and 400,000 neonates globally each year, the majority in sub-Saharan Africa. Haemoglobin molecules that include mutant sickle β-globin subunits can polymerize; erythrocytes that contain mostly haemoglobin polymers assume a sickled form and are prone to haemolysis. Other pathophysiological mechanisms that contribute to the SCD phenotype are vaso-occlusion and activation of the immune system. SCD is characterized by a remarkable phenotypic complexity. Common acute complications are acute pain events, acute chest syndrome and stroke; chronic complications (including chronic kidney disease) can damage all organs. Hydroxycarbamide, blood transfusions and haematopoietic stem cell transplantation can reduce the severity of the disease. Early diagnosis is crucial to improve survival, and universal newborn screening programmes have been implemented in some countries but are challenging in low-income, high-burden settings.
Blood Adv. 2018 Mar 13;2(5):575-585. doi: 10.1182/bloodadvances.2017012500.
Sickle-cell disease (SCD) leads to recurrent vaso-occlusive crises, chronic end-organ damage, and resultant physical, psychological, and social disabilities. Although hematopoietic stem-cell transplantation (HSCT) is potentially curative for SCD, this procedure is associated with well-recognized morbidity and mortality and thus is ideally offered only to patients at high risk of significant complications. However, it is difficult to identify patients at high risk before significant complications have occurred, and once patients experience significant organ damage, they are considered poor candidates for HSCT. In turn, patients who have experienced long-term organ toxicity from SCD such as renal or liver failure may be candidates for solid-organ transplantation (SOT); however, the transplanted organs are at risk of damage by the original disease. Thus, dual HSCT and organ transplantation could simultaneously replace the failing organ and eliminate the underlying disease process. Advances in HSCT conditioning such as reduced-intensity regimens and alternative donor selection may expand both the feasibility of and potential donor pool for transplantation. This review summarizes the current state of HSCT and organ transplantation in SCD and discusses future directions and the clinical feasibility of dual HSCT/SOT.
PMCID: PMC5851417 Free PMC Article
Am J Hum Genet. 2018 Mar 7. pii: S0002-9297(18)30048-X. doi: 10.1016/j.ajhg.2018.02.003. [Epub ahead of print]
Five classical designations of sickle haplotypes are made on the basis of the presence or absence of restriction sites and are named after the ethno-linguistic groups or geographic regions from which the individuals with sickle cell anemia originated. Each haplotype is thought to represent an independent occurrence of the sickle mutation rs334 (c.20A>T [p.Glu7Val] in HBB). We investigated the origins of the sickle mutation by using whole-genome-sequence data. We identified 156 carriers from the 1000 Genomes Project, the African Genome Variation Project, and Qatar. We classified haplotypes by using 27 polymorphisms in linkage disequilibrium with rs334. Network analysis revealed a common haplotype that differed from the ancestral haplotype only by the derived sickle mutation at rs334 and correlated collectively with the Central African Republic (CAR), Cameroon, and Arabian/Indian haplotypes. Other haplotypes were derived from this haplotype and fell into two clusters, one composed of Senegal haplotypes and the other composed of Benin and Senegal haplotypes. The near-exclusive presence of the original sickle haplotype in the CAR, Kenya, Uganda, and South Africa is consistent with this haplotype predating the Bantu expansions. Modeling of balancing selection indicated that the heterozygote advantage was 15.2%, an equilibrium frequency of 12.0% was reached after 87 generations, and the selective environment predated the mutation. The posterior distribution of the ancestral recombination graph yielded a sickle mutation age of 259 generations, corresponding to 7,300 years ago during the Holocene Wet Phase. These results clarify the origin of the sickle allele and improve and simplify the classification of sickle haplotypes.
Am J Hematol. 2018 Mar 9. doi: 10.1002/ajh.25085. [Epub ahead of print]
Jordan LC1, Williams DOR2, Rodeghier MJ3, Covert B2, Ponisio MR4, Casella JF5, McKinstry RC6, Noetzel MJ7, Kirkham FJ8, Meier ER9, Fuh B10, McNaull M11, Sarnaik S12, Majumdar S13, McCavit TL14, DeBaun MR2.
In a prospective cohort study, we tested the hypothesis that children with sickle cell anemia (SCA) with normal transcranial Doppler ultrasound (TCD) velocities and without silent cerebral infarcts (SCIs) would have a lower incidence rate of new neurological events (strokes, seizures or transient ischemic attacks) compared to children with normal TCD measurements and SCIs, not receiving regular blood transfusions. Non-randomized participants from the Silent Cerebral Infarct Transfusion (SIT) Trial who had screening magnetic resonance imaging (MRI) of the brain and normal TCD measurements were included. Follow-up ended at the time of first neurological event, start of regular blood transfusion, or loss to follow-up, whichever came first. The primary endpoint was a new neurological event. Of 421 participants included, 68 had suspected SCIs. Mean follow-up was 3.6 years. Incidence rates of new neurological events in non-transfused participants with normal TCD values with SCIs and without SCIs were 1.71 and 0.47 neurological events per 100 patient-years, respectively, p=0.065. The absence of SCI(s) at baseline was associated with a decreased risk of a new neurological event (hazard ratio 0.231, 95% CI 0.062 – 0.858; p=0.029). Local pediatric neurologists examined 67 of 68 participants with suspected SCIs and identified 2 with overt strokes classified as SCIs by local hematologists; subsequently one had a seizure and the other an ischemic stroke. Children with SCA, without SCIs, and normal TCD measurements have a significantly lower rate of new neurological events when compared to those with SCIs and normal TCD measurements. Pediatric neurology assessment may assist risk stratification. This article is protected by copyright. All rights reserved.
Blood. 2018 Mar 8. pii: blood-2017-10-811505. doi: 10.1182/blood-2017-10-811505. [Epub ahead of print]
Antoniani C1, Meneghini V2, Lattanzi A3, Felix T2, Romano O4, Magrin E5, Weber L6, Pavani G3, El Hoss S7, Kurita R8, Nakamura Y8, Cradick TJ9, Lundberg AS9, Porteus M10, Amendola M3, El Nemer W11, Cavazzana M12, Mavilio F4, Miccio A13.
Naturally occurring, large deletions in the β-globin locus result in hereditary persistence of fetal hemoglobin, a condition that mitigates the clinical severity of sickle-cell disease (SCD) and β-thalassemia. We designed a CRISPR/Cas9 strategy to disrupt a 13.6-kb genomic region encompassing the δ- and β-globin genes and a putative γ-δ intergenic fetal hemoglobin (HbF) silencer. Disruption of just the putative HbF silencer results in a mild increase in γ-globin expression, whereas deletion or inversion of a 13.6-kb region causes a robust re-activation of HbF synthesis in adult erythroblasts, associated with epigenetic modifications and changes in the chromatin contacts within the β-globin locus. In primary, SCD patient-derived hematopoietic stem/progenitor cells, targeting the 13.6-kb region results in high proportion of γ-globin expression in erythroblasts, increased HbF synthesis, and amelioration of the sickling cell phenotype. Overall, this study provides clues for a potential genome editing approach to the therapy of β-hemoglobinopathies.
Pediatr Blood Cancer. 2018 Mar 7. doi: 10.1002/pbc.27027. [Epub ahead of print]
Youth with sickle cell disease (SCD) are at risk for recurrent pain and depressive symptoms, both of which contribute to poorer health outcomes. Furthermore, youth and family coping with child pain, including pain catastrophizing, is known to be associated with poorer psychosocial adjustment and greater functional disability among youth with SCD. In particular, child catastrophizing about pain and parent catastrophizing about their child’s pain have been linked to increased pain and depressive symptoms in youth with chronic pain conditions. Despite this, the impact of child and parent pain catastrophizing on depressive symptoms remains unexplored in pediatric SCD.
The current study evaluated the predictive value of child and parent pain catastrophizing on child depressive symptoms in a sample of 100 youth with SCD. Differences in child and parent pain catastrophizing across youth with and without clinically elevated depressive symptoms were also examined.
Pain frequency and parent and child pain catastrophizing accounted for 35.9% of variance in child depressive symptoms, with only pain frequency and parent pain catastrophizing emerging as unique predictors of clinically elevated depressive symptoms. Additionally, parents of youth with clinically elevated depressive symptoms showed increased helplessness relative to parents of youth with minimal to mild depressive symptoms.
Findings support the value of depression screening and interventions to promote parent self-efficacy in managing childhood SCD pain.
© 2018 Wiley Periodicals, Inc.
Sickle Cell Conferences and Events
Hemoglobinopathy Counselor Training Course will be held on April 11 – 12, 2018
The two-day course, presented by the Cincinnati Comprehensive Sickle Cell Center, will be held at Cincinnati Children’s Hospital Medical Center. The course registration fee is $250. The deadline to register is March 31, 2018 and registration is limited. For more information, including a course brochure, please email: SCDEvents@cchmc.org Registration is also available online at https://www.regonline.com/2018SCDCounselorCourse
12TH ANNUAL SICKLE CELL DISEAE RESEARCH AND EDUCATIONAL SYMPOSIUM!
June 15 -17
WASHINGTON MARRIOTT WARDMAN PARK
2660 WOODLEY ROAD NW WASHINGTON, DC 20008
The 4th Annual Sickle Cell Disease Symposium for Carolinas Healthcare System
Atrium Health will be held on Saturday, October 27, 2018 at the Speedway Club in Charlotte, NC. The theme this year is: “4th Annual SCD Symposium: Racing to Improve the Access to Care & Outcomes for SCD.”