bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse Events in Sickle Cell Patients with Nocturnal Hypoxia.
Authors: Campbell Andrew D. , Okumura Megumi , Unaka Ndidi , Hutchinson Sally , Onyekwere Onyinye 
Published: April 2020

Abstract
The relationship between hemoglobin dexoygenation and sickling is well known. However, the relationship between hypoxia and severity of disease in sickle cell patients has not been well established. Recently, nocturnal hypoxemia has been associated with higher incidence of CNS events including strokes, and elevated TCDs. We present our case series on 13 patients(12 SS, 1 SC) with sickle cell disease (SCD) who have nocturnal hypoxia. Approximately 75 patients were screened at the University of Michigan Sickle Cell clinic for nocturnal hypoxia either by symptoms of obstructive sleep apnea or by longitudinal baseline clinic 02 saturations (02 Sat &lt;92%). Of the 13 hypoxic pts, median baseline O2 Sat 90%(n=13, mean 90) and the median nocturnal O2sat (Nctnl 02 sat) 84%(n=13, mean 80%) with 10/13 with moderate-severe nocturnal hypoxia (O2sats&lt;85%)based on sleep studies. Multiple adverse events noted in the cohort were pulmonary hypertension (PHTN TRJV&gt;2.5, n=9, median 2.74/mean 2.74,) frequent pain episodes(&gt;3visits to ER or hospitalizations/year, n=7, with 5 pts &gt;5/year ), recurrent acute chest syndrome( ≥ 3 episodes, n= 10), CNS events (n=3 silent infarcts, vascular stenosis), priapism( (n=4, among 6 males ). Also reported were possible causes of the underlying hypoxia including obstructive sleep apnea(OSA)(n=7 of 11 pts), asthma(n= 10 of 13 pts), and chronic lung disease( n=8). In conclusion, the persistence of nocturnal hypoxia in pediatric sickle cell disease could possibly contribute to the development of severe complications of sickle cell disease. Treatment of underlying hypoxia (ie nighttime oxygen, maximize asthma treatment, T&A for OSA)may help prevent complications and lead to the improvement clinical symptoms. Further, chronic nocturnal hypoxia may complicate pulmonary disease and accelerated the development of PHTN. More studies are needed to clarify the mechanism of hypoxia in SCD.
Table I. Clinical &Demographic Data of 13 SCD Patients with Nocturnal Hypoxia. Age:(6–22y/o, mean 15) Sex: M=6 F=7 Clinical: Total Mild Mod Sev. Genotype: SS=12, SC=1 Mean Range Nctnl Hypoxia(&lt;%) 13 3 5(&lt;85) 5(&lt;80) Baseline O2 Sat(%) 90 +3.0 86–97 Obstr Sleep Apnea 7 3 3 1 Nctnl 02 sat (%) 80+8.4 59–87 Pulm HTN 9 4 4 1 Total #Apneic Events(11) 65.6+80 6–256 Rest. Lung Ds. 8 2 5 1 Obstr. Apneic Events(7) 27+68.5 0–221 # of Episodes &lt;3 3–4 &gt;4 Hypopneic Events(9) 32.5+38 0–132 ACS 2 5 5 TRJet Velocity 2.74+.42 2–3.5 Severe Pain Crises/yr 1 2 5
Mortality Trends in People with Sickle Cell Disease in North Carolina.
Authors: Redding-Lallinger Rupa 
Published: April 2020

Abstract
Background. Using data from the Cooperative Study of Sickle Cell Disease which ran from 1978 -19**, published figures for median life expectancy for men with sickle cell disease is 42 years and for women 46 years. Recent data from Texas show a declining childhood mortality rate, compared to the CSSCD data, in a cohort who have been followed from infancy. However, despite the strides made in reducing childhood mortality and improving length and quality of life in some adults, there is still very significant morbidity and mortality from cumulative damage to organs, especially the lungs and the kidneys.
Aims. The purpose of this investigation is to analyze the numbers and causes of death in individuals with sickle cell disease over the past several years in North Carolina. The information gathered may suggest areas in which health services to people with sickle cell disease may be improved.
Methods. The North Carolina State Center for Health Statistics provided the following data for the years 1997–2003. Total number of SCD deaths for each of those years, and the age, county of residence, place of death, the ICD codes for the underlying and contributing cause of death as listed on the death certificates of the decedents.
Results. There were 277 deaths over the 7 year period. Fifty-three percent of these deaths occurred during the earlier half of this period. Overall, 49% of the deaths occurred in people from age 30 to age 49, and this proportion remained quite stable during the 7 years. Deaths of people 20 years and younger made up 14% of total deaths; there were fewer in the second half of the time period than in the first half—40% of the total deaths in this age group occurred from late 2000 through 2003 vs 60% from 1997 through early 2000. Deaths in the youngest age group (0–5) were only 4.3% of the total deaths for the period. For the individuals who died between birth and 20 years of age, the underlying cause of death from the death certificates were grouped as “sickle cell disease with or without complications” in 50%, congenital heart disease in 11%, bacterial infection in 17%, gastroenteritis in 9.5%, UTI in 6% and other in 4%. For those who died between 30 and 40 years of age the underlying cause of death as listed on the death certificates were grouped as: sickle cell anemia, with and without crisis—58%, pulmonary complications—12%, cardiovascular problems—10%, CNS problems—5%, hepatic disorders and infections—each &lt;5%, and other—10%.
Conclusions. Mortality in the youngest children appears to have lessened in comparison with historical data, and this age group no longer leads in mortality rates. Deaths in the young adult age range of 30–49 years have showed no downward trend over 7 years. The cause of death from death certificates do not match well with the clinical problems typically seen in people in this age group. The lack of precise diagnoses on death certificates may reflect a lack of understanding of sickle cell complications among doctors in the community.
Increased Chromosomal Breaks in Sickle Cell Disease as Evidenced by the Presence of Micronuclei in Erythrocytes.
Authors: Lal Ashutosh , Bhagat Amrita , Atamna Wafa , Offer Tal , Vichinsky Elliott P. , Kuypers Frans A. , Ames Bruce N. 
Published: April 2020

Abstract
Double-stranded DNA breaks are serious lesions that contribute to the pathogenesis of cancer and chronic illnesses. Free radical injury is an important mechanism for the production of DNA modifications that eventually lead to chromosomal breaks. The generation of free radicals is increased in sickle cell disease (SCD) owing to the presence of the relatively unstable HbS and recurrent ischemia-reperfusion events. In the present study, a sensitive reticulocyte micronucleus assay was used to determine the frequency of chromosomal breaks in patients with SCD (Offer et al. FASEB J. 2005;19:485). A micronucleus is a piece of a chromosome left behind in a reticulocyte as a consequence of DNA double-stranded break after the nucleus is extruded. Blood samples were obtained from patients with SCD (n=33) and healthy volunteers (n=23). After immunomagnetic enrichment of CD71+ reticulocytes (Trf-Ret), RNA was removed with RNAse, and the cells were stained for miconuclei using the DNA dye 7-aminoactinomycin D (7-AAD) followed by flow cytometric evaluation. The appearance of reactive oxygen species in cytosol and membrane lipid oxidation in RBCs were measured by flow cytometry using the fluorescent markers 2, 7-dichlorofluorescin diacetate (DCF) and C11-BODIPY, respectively. The frequency of micronucleated Trf-Ret was significantly higher (p&lt;.0001) in patients with SCD (mean 3.061/10,000 Trf-Ret, range 0.256 to 9.779) as compared with normal controls (mean 0.750/10,000 Trf-Ret, range 0.043 to 2.659). Mean DCF (125.1%) and C11-BODIPY (117.6%) fluorescence intensities were significantly greater than the mean control value (100%, p 0.0001). Our data indicate that patients with sickle cell disease have increased double stranded DNA-breaks compared with healthy controls, and suggest that elevated production of oxidants could contribute to the development of genetic damage in these patients.
Results of Arthroplasty for Avascular Necrosis of the Humeral Head in Sickle Cell Patients.
Authors: Lau Michelle W. , Galatz Leesa M. , Williams Kimberly , Blinder Morey A. 
Published: April 2020

Abstract
Avascular necrosis (AVN) of the humeral head is a debilitating complication of sickle cell disease (SCD) estimated to occur in ~5% of patients for which the optimal therapy is not well defined. Although shoulder replacement is often used for AVN in other settings, little information is available about the outcome of shoulder arthroplasty in this population. In this study, medical records, radiographs, and pre-operative assessment scores of eight adult patients with sickle cell disease were reviewed. Post-operative assessment scores and radiographs were prospectively collected by an independent observer at follow-up appointments. All eight patients had &gt;2 years of follow up. The mean age of the patients at the time of surgery was 37 years old and there were 4 males and 4 females. Six of the patients had Hgb SS, one had Hgb SC and one had Hgb Sβ+ thalassemia. The average duration of symptoms prior to surgery was 26 months. Based on pre-operative shoulder radiographs, 5 of 7 evaluable patients had grade 3 or greater disease. Seven of eight patients had a hemiarthroplasty and one patient had a total arthroplasty. The mean follow up was 51 months. Complications included two episodes of sickle cell crises in the immediate post-operative period, and one intraoperative rotator cuff tear. One patient developed stiffness that required arthroscopic capsular release 22 months after his initial surgery. No infections were seen in the operated shoulder and no shoulder revisions were performed. At the most recent follow-up, the average American Shoulder and Elbow Society (ASES) score improved 31 points, indicating substantial functional improvement (J Shoulder Elbow Surg. 3(6):347–352, 1994). However, only 25% of the patients reported improvement in pain as assessed by a visual analog scale. While two patients had dramatic improvements in all aspects of our outcome measures, two other patients had decreased functional capacity with no improvement in pain. Radiographs at the most recent follow up revealed slight loosening of the prosthetic stem in one patient but no other radiographic complications. In conclusion, shoulder arthroplasty provides improvements in range of motion and joint function in the majority of patients. However, pain relief is less predictable, suggesting that other causes of sickle cell related pain are occuring. Nevertheless, given the limited options available for the treatment of AVN in sickle cell patients who have failed conservative approaches, shoulder arthroplasty is a reasonable treatment option.
Mean Platelet Volume in Children with Sickle Cell Disease on Chronic Transfusion Therapy.
Authors: Lakshminarayanan Sonali , Aygun Banu 
Published: April 2020

Abstract
The symptoms in sickle cell disease are related to ischemic/vaso-occlusive episodes involving the bones, spleen, brain and lungs. One of the possible mechanisms for vaso-occlusion is platelet activation and increased platelet reactivity which is demonstrated by increased platelet volume resulting in an elevated platelet distribution width. We hypothesized that chronic transfusion therapy given to patients with recurrent severe ischemic episodes and/or stroke may lower mean platelet volume (MPV) in addition to decreasing hemoglobin S. We performed a retrospective chart analysis of all patients with sickle cell disease who were on a chronic transfusion regimen at Schneider Children’s Hospital between January 1995 and March 2005. Out of 60 eligible patients, only 42 were eligible for this study. The remaining patients were excluded for less than 3 transfusions in total or incomplete records. The data retrieved included age and sex of the patient, type of sickle cell disease, indication for chronic transfusion therapy, duration of transfusions and blood count variables during the three phases, i.e. prior to, during and after transfusion therapy. The variables included hemoglobin, mean cellular volume, platelet count, reticulocyte count and MPV for each patient with a minimum of one value in each phase. As many values were recorded based on the availability in the records, with at least an interval of 3 months between each blood count and at least 3 months apart from a transfusion.
Results: Sixty-four percent were males and 95% had HbSS genotype. The major indication for transfusion therapy (85%) was stroke. Mean values of each variable and their ranges were compared across the 3 periods using the Kruskal Wallis test. Although the platelet count decreased significantly during transfusions compared to pre-transfusion period, the mean value of MPV did not differ across the 3 periods with a range between 5.9 and 11.3 in all the 3 periods. Furthermore, using the Anacova method proposed by Bland and Altman, there was an overall significant negative correlation between MPV and platelet count, while no correlation at all was present between MPV, reticulocyte count and hemoglobin in any of the 3 periods. Our findings suggest that multiple transfusions do not alter platelet size or volume, which indirectly may indicate that there is no change in platelet function or activity in these patients on chronic transfusion therapy. The changes in MPV values seen in this study are real, as they follow the natural thrombokinetics by maintaining a negative correlation with the platelet count during all 3 periods.
Magnetic Ressonance Imaging (MRI) in the Evaluation of Iron Overload in Patients with Beta Thalassaemia. The Brazilian National Program Preliminary Results.
Authors: Hamerschlak Nelson , Rosemberg Laercio , Parma Alexandre , Assir Fernanda F. , Moreira Frederico R. , Parga Jose R. , Amaro Edson , Samira Morrhy , Edgar Lira , Claudio Fisher , Sandra Loggeto , Monica Verissimo , Aderson Araujo , Giorgio Baldanzi , Antonio Fabron , Claudia Velloso , Merula Steagall A. , Fernando Tricta , Alexandre Cury , Marcelo Vieira , Marcelo Funari G. , Fernanda Magao S. , Joice Nogueira C. 
Published: April 2020

Abstract
Magnetic Ressonance Imaging (MRI) using T2 star (T2*) tecnique appears to be a very useful method for monitoring iron overload and iron chelation therapy in thalassaemia. In Brazil, we have around 400 thalassaemic major patients all over the country. They were treated with hipertransfusion protocols and desferroxamine and/or deferiprone chelation. We developed a cooperative program with the Brazilian Thalassaemic Patients Association (ABRASTA) in order to developT2* tecnique in Brazil to submit brazilian patients to an annual iron overload monitoring process with MRI.. We performed the magnetic ressonance T2* using GE equipment (GE, Milwaukee USA), with validation to chemical estimation of iron in patients undergoing liver biopsy. Until now, 60 patients were scanned, median age=23,2 (12–54); gender: 18 male (30%) and 42 female (70%). The median ferritin levels were 2030 ng/ml (Q1=1466; Q3=3296). As other authors described before, there was a curvilinear inverse correlation between iron concentration by biopsy, liver T2*(r=0,92) and also there were a correlation with ferritin levels. We also correlated myocardial iron measured by T2* with ventricular function.. As miocardial iron increased, there was a progressive decline in ejection fraction and no significant correlation was found between miocardial T2* and the ferritin levels.
Liver iron content can be predicted by ferritin levels. On the other hand, cardiac disfunction is the most important cause of mortality among thalassaemic patients. Since Miocardio iron content cannot be predicted from serum ferritin or liver iron, and ventricular function can only detect those with advance disease, intensification and combination of chelation therapy, guided by T2* MRI tecnique should reduce mortality from the reversible cardiomyopathy among thalassaemic patients.
Variability of the Iron Specific Magnetic Susceptibility of Spleen Tissue in β-Thalassemia and β-Thalassemia/Hb E Patients.
Authors: Hackett Sara L. , Chua-anusorn Wanida , St Pierre Timothy G. , Pootrakul Pensri 
Published: April 2020

Abstract
Patients with β-Thalassemia major are transfusion dependent and become iron loaded owing to the large number of blood transfusions they receive. Patients with β-Thalassemia/Hb E become iron loaded even in the absence of regular blood transfusions because of increased erythropoeisis and stimulated dietary iron absorption. In both cases, iron accumulates in tissues such as the liver, spleen, and heart in the form of insoluble iron(III) oxyhydroxide nanoparticles found in ferritin and hemosiderin. The body iron burden is usually estimated by measurement of the liver iron concentration (LIC). Non-invasive techniques for measuring LIC often exploit the large magnetic susceptibility of tissue iron, taken to be 1600 x 10−9 m3/kgFe at body temperature. The current study examined spleen tissue samples from Australian β-Thalassemia major patients (n = 7) who had undergone chelation and transfusion therapy and Thai β-Thalassemia/Hemoglobin E disease patients (n = 11) who had received very few transfusions and no chelation therapy. Magnetometry measurements of the iron specific magnetic susceptibility of the spleen tissue samples ranged from 800 x 10−9 m3/kgFe to 1800 x 10−9 m3/kgFe. The mean iron specific magnetic susceptibility for the β-Thal major spleen tissue was approximately 25% lower than that for the β-Thal/Hb E samples (p = 0.007 Student’s t test). To investigate the underlying cause of this variability the physico-chemical properties of the tissue iron deposits were probed using cryogenic 57Fe Mössbauer spectroscopy. Spectra recorded at 78K showed that the β-Thal major tissues contained iron with a greater fraction in the form of a more crystalline chemical species of iron oxyhydroxide than the β-Thal/Hb E tissues (p =0.01 Wilcoxon-Mann-Whitney test). Significant correlations (Spearman rank correlation tests) were identified between the iron specific magnetic susceptibility measured at body temperature and the Mössbauer spectral parameters recorded at both 5 K (p = 0.02) and at 78 K (p = 0.03). This relationship between the iron specific magnetic susceptibility and the chemical speciation of iron oxyhydroxide tissue deposits implies that the magnetic behaviour of tissue iron deposits is determined by the physical and chemical nature of the iron deposits. Variability in the iron specific magnetic susceptibility of tissues could impact on the precision of non-invasive techniques of tissue iron measurement based on magnetic susceptibility measurements.
Filamin Binding to Glycoprotein Ibα Signals Talin-Directed α IIbβ 3 Activation.
Authors: Feng Shuju , Lu Xin , Kroll Michael H. 
Published: April 2020

Abstract
von Willebrand factor (VWF) binding to platelet glycoprotein (Gp) Ib-IX-V triggers platelet activation. Under conditions of pathologically elevated arterial wall shear stress, VWF-dependent platelet adhesion is coupled to aggregation and thrombus formation principally through GpIbα-induced signaling to α IIbβ 3. To elucidate the mechanism of GpIbα signaling to α IIbβ 3, we have examined molecular interactions involving structural proteins that bind to the cytoplasmic domains of GpIbα and β 3. In CHO cells co-expressing human GpIb-IX and α IIbβ 3, the activation of α IIbβ 3 as reported by monoclonal antibody PAC-1 binding is stimulated by ristocetin (1 mg/ml) + purified human VWF(5 μg/ml). When filamin binding to the cytoplasmic domain of GpIbα is eliminated by deleting GpIbα residues 560-570, PAC-1 binding is eliminated. When human platelets in reconstituted whole blood are treated with a peptide that interferes with filamin binding to GpIbα (as reported in Blood2003;102:2122–2129), shear-dependent (1500 sec−1 shear rate or 60 dynes/cm2 shear stress) platelet deposition onto bovine type I collagen is inhibited. In washed resting platelets and platelets activated by 120 dynes/cm2 shear stress, filamin co-immunoprecipitates with both GpIbα and α IIbβ 3; only its association with β 3 is eliminated by DNaseI (1 mg/ml), demonstrating that filamin binds indirectly to α IIbβ 3 through other cytoskeletal elements. One such element is observed to be talin, which co-immunoprecipitates with filamin, α IIbβ 3 and small amounts of GpIbα in resting platelets. When platelets are sheared for two minutes at 120 dynes/cm2, talin’s DNaseI-resistant association with filamin is decreased and its DNaseI-sensitive association with α IIbβ 3 is increased. These changes are prevented when shear-dependent VWF binding to GpIb-IX-V is blocked by monoclonal antibody AK2. Shear-dependent VWF binding to GpIb-IX-V also results in the proteolysis of talin, which is considered to be one mechanism by which the N-terminal head domain of talin regulates α IIbβ 3 activation. Shear-dependent talin proteolysis is not affected by blocking VWF binding to α IIbβ 3 with a RGD peptide. These results demonstrate that the cytoplasmic domain of GpIbα transduces signals to activate α IIbβ 3 through its interactions with filamin. These signals depend only on VWF binding to GpIb-IX-V. Under pathologically elevated wall shear stress in vitro, the mechanism of signaling may be the release of talin by filamin, thus permitting the proteolysis of talin and enhancing talin’s interaction with α IIbβ 3.
Elevated Hemoglobin F in an African American Girl with HbS/β Thalassemia: Unraveling the Mechanism.
Authors: Fond Aaron M. , Prchal Josef T. , Ou Ching-Nan , Rognerud Cheryl L. , Mahoney Donald , Mims Martha P. 
Published: April 2020

Abstract
Factors controlling hemoglobin F production beyond the neonatal period are poorly understood; however, unraveling the mechanisms underlying hereditary persistence of fetal hemoglobin (HPFH) could lead to therapies for β-thalassemia and sickle cell disease. We identified a non-anemic 5 year old girl with Hbs S, F, and A. Investigation revealed elevated HbF in the mother and paternal sickle trait. More than 90% of the gamma globin chains in the daughter were Gγ. Mother and daughter share the common -29 β thalassemia mutation, but have normal MCVs.
Mother Father Child HbA 77.6% 54% 8.7% HbA2 3.6% 3% 2.7% HbF 18.8% 0% 32.4% HbS 0% 43% 56.2% Hemoglobin 11.4 15.3 13.3 MCV 85.7 82.4 78.2
We set out to determine:
Whether a thalassemia trait explains the MCVs in the mother and child. Whether increased HbF is due to γ globin promoter mutations linked to the −29 β thalassemia mutation.
A duplex PCR strategy was used to genotype family members for the common African −3.7 kb α-thalassemia deletion. Our studies show that the mother is heterozygous for the a globin −3.7 kb deletion while the father and child are homozygous for the wild type α globin locus. The upstream region (−627 to −5) of the Gγ-globin genes of each family member were amplified and the PCR products were digested with the Xmn1 restriction enzyme to determine whether the Xmn1 polymorphism ( C→T at position −158) contributed to the increased fetal hemoglobin. None of the family members had this polymorphism. Sequencing of the upstream region of the Gγ gene revealed that the patient is homozygous for a novel mutation (A →G) at position −309 for which both parents are heterozygous. In summary we describe a novel Gγ gene −309 A →G mutation in association with elevated HbF; further research is in progress to determine if this polymorphism contributes to the patient’s elevated fetal hemoglobin.