scholarly journals Parvovirus B19 Infection Associated with Silent Cerebral Infarcts: A Secondary Analysis of the Silent Cerebral Infarct Trial Cohort

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3410-3410 ◽  
Author(s):  
Foluso Joy Ogunsile ◽  
Michael R. DeBaun ◽  
Kelli Currie ◽  
Mark J. Rodeghier

Abstract Introduction: Silent cerebral infarcts (SCI) are the major cause of neurological injury occurring in almost 40% of the population in children with sickle cell anemia (SCA); and are associated with a Full-Scale IQ decrease of approximately 5 points. Acute anemic events, defined as hemoglobin< 6.0 g/dl, is associated with an increase odds ratio (OR) of SCI (OR 2.72; 95% CI, 1.13-6.54; P = .025; Bernaudin et al. Blood. 2015 Mar 5; 125(10):1653-61). Infection with parvovirus B19 (B19V) causes a transient reticulocytopenia and an acute drop in hemoglobin levels in children with SCA. We tested the hypothesis that a history of B19V infection was associated with increased odds ratio of SCIs. Methods: In this retrospective cross-sectional study design, we performed a secondary analysis on the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial). Children with SCA between 5 and 15 years of age, with no history of overt strokes or seizures, were screened for SCIs with MRIs of the brain. Research personnel reviewed medical records to determine a history of B19V infection. Based on prior evidence from the SIT Trial cohort demonstrating that lower hemoglobin levels divided into tertiles are associated with an increase odds of SCI (DeBaun et al. Blood. 2012 Apr 19;119(16):3684-90), three analyses were performed. We stratified by hemoglobin levels into tertiles (<7.6g/dL, ³7.6 and ²8.4 g/dL, and >8.4 g/dL), to determine an association between SCI status and history of B19V infection. Chi squared statistic was used as the measure of association. As a secondary analysis of the original SIT trial cohort, the level of strong significance associated with an increased odds ratio of SCI was determined to be <0.01, with values <0.05 considered moderate significance. Results: A total of 814 of the SIT Trial participants had their SCI status adjudicated (present or absent) and a recorded history of B19V status (yes or no). In the cohort, 30% had a SCI and 17% had a history of B19V infection. Prior B19V infection with baseline hemoglobin levels <7.6 g/dL were associated with increase OR of SCI (OR 2.20; 95% CI, 1.22 to 3.97; p=0.008). Prior B19V infection with a baseline hemoglobin levels in the middle (³7.6 to²8.4 g/dL) and upper tertiles (> 8.4 g/dl) were not associated with an increased OR of SCI (OR 0.88; 95% CI, 0.47 to 1.66; p=0.695; and ³8.5 g/dL OR 1.39; 95% CI, 0.72 to 2.69; p=0.328; respectively). Conclusion: Children with SCA, a history of B19V and a low baseline hemoglobin level <7.6 g/dL have an increased OR of SCIs. Future efforts in developing a vaccine for B19V may provide an opportunity for decreasing the incidence of SCIs in children with SCA. Disclosures No relevant conflicts of interest to declare.

2017 ◽  
Vol 65 (1) ◽  
pp. e26767 ◽  
Author(s):  
Foluso J. Ogunsile ◽  
Kelli L. Currie ◽  
Mark Rodeghier ◽  
Adetola Kassim ◽  
Michael R. DeBaun ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2254-2254
Author(s):  
Allison A. King ◽  

Abstract Background: Among students with sickle cell anemia (SCA), cerebral infarcts are an established risk factor for poor cognition and academic achievement. We tested the hypothesis that in children with SCA, lower socioeconomic status (SES) is associated with grade failure. Methods: We evaluated the association between the SES as measured by annual income per person in household per year, age of student, gender, medical history and grade failure in children with SCA in 24 sites participating in the Silent Cerebral Infarct Multi-Center Clinical Trial. Results: A total of 404 students were evaluable. The mean age was 9.2 years (range 6–13), 37% had a silent infarct, 15% failed a grade, and 18% had an Individualized Education Plan. SES was divided in tertiles based on annual income/person in the household/year &lt; $5000, $5000–$9999, &gt; $10,000. After adjustment for covariates, the risk of grade failure was 1.4 (95% CI 1.2, 1.6) for each increasing year of age, and 1.9 (95% CI 1.03, 3.5) for male gender. Children from households of the lowest tertile were 4 times more likely to fail a grade than children from the top tertile. A silent cerebral infarct was not associated with grade failure 1.4 (95% CI 0.8, 2.6). No student with a history of grade failure was hospitalized &gt; 3 times per year over the past three years. Conclusion: Among students with SCA, poverty is the greatest risk factor for grade failure; whereas the presence of silent cerebral infarct is not. Targeted strategies to improve educational attainment in students with SCA are needed.


2019 ◽  
Vol 37 (12) ◽  
pp. 1223-1227 ◽  
Author(s):  
Jennifer Hyer ◽  
Claire Ulrickson ◽  
Elise Yerelian ◽  
Torri D. Metz ◽  
Amanda A. Allshouse ◽  
...  

Abstract Objective Substance use disorders often coexist with depression. The objective of this study was to establish whether pregnant women who report depressive symptomatology were more likely to report use of alcohol, tobacco, and marijuana during pregnancy. Study Design This was a secondary analysis of prospectively collected data from the Maternal-Fetal Medicine Units Network Preterm Prediction Study. Self-reported history of alcohol, tobacco, and marijuana use was compared between pregnant women with and without depressive symptomatology with adjustment for demographic factors. Results After adjustment for demographic factors, women with depressive symptomatology were more likely to report: any alcohol use (odds ratio [OR]: 1.4, 95% confidence interval [CI]: 1.1–1.8), >1 drink per week (OR: 1.3, 95% CI: 1.0–1.8), and >1 drink per day (OR: 2.2, 95% CI: 1.5–3.4). Women with depressive symptomatology were also more likely to report use of marijuana (OR: 1.8, 95% CI: 1.2–2.6) and cigarettes (OR: 1.4, 95% CI: 1.1–1.7). Conclusion Depressive symptomatology was associated with an increase in self-reported the use of alcohol, tobacco, and marijuana during pregnancy. These data reveal the importance of targeted screening of pregnant women with depressive symptomatology for substance use.


2018 ◽  
Vol 36 (06) ◽  
pp. 624-631 ◽  
Author(s):  
Cande Ananth ◽  
Kathleen Jablonski ◽  
Leslie Myatt ◽  
James Roberts ◽  
Alan Tita ◽  
...  

Objective To assess the risk of ischemic placental disease (IPD) including preeclampsia, small for gestational age (SGA), and abruption, in relation to preeclampsia in maternal grandmother, mother, and sister(s). Study Design We performed a secondary analysis of data from a randomized trial of vitamins C and E for preeclampsia prevention. Data on family history of preeclampsia were based on recall by the proband. The associations between family history of preeclampsia and the odds of IPD were evaluated from alternating logistic regressions. Results Of the 9,686 women who delivered nonmalformed, singleton live births, 17.1% had IPD. Probands provided data on preeclampsia in 55.5% (n = 5,374) on all three family members, 26.5% (n = 2,562) in mother and sister(s) only, and 11.6% (n = 1,125) in sister(s) only. The pairwise odds ratio (pOR) of IPD was 1.16 (95% confidence interval [CI]: 1.00–1.36) if one or more of the female relatives had preeclampsia. The pORs of preeclampsia were 1.54 (95% CI: 1.12–2.13) and 1.35 (95% CI: 1.03–1.77) if the proband's mother or sister(s) had a preeclamptic pregnancy, respectively, but no associations were seen for SGA infant or abruption. Conclusion This study suggests that IPD may share a predisposition with preeclampsia, suggesting a familial inheritance.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1531-1531
Author(s):  
Alvin H. Schmaier ◽  
Alona Merkulova ◽  
Haley Gittleman ◽  
Omar Alhalabi ◽  
Evi Stavrou ◽  
...  

Abstract BACKGROUND: Prolylcarboxypeptidase (PRCP) is a membrane-associated serine protease that regulates biologic peptides bradykinin, angiotensin II, α-melanocyte stimulating hormone, and activates prekallikein. PRCP and its variants have been associated with metabolic syndrome in males, hypertension in preeclampsia, resistance to ACE inhibitors, and embryonic angiogenesis. Recent studies on PRCPgt/gt mice that have 25% normal PRCP levels show that these animals are hypertensive, have higher risk for arterial thrombosis, increased vascular inflammation, and reduced angiogenic repair after ischemia and injury (Blood 117:3929, 2011; Blood 122:1522, 2013). The hypothesis of this investigation is that polymorphisms in PRCP are associated with cardiovascular disease (CVD). METHODS: DNA from 2,243 subjects from the PEACE Trial (NEJM 351:2058, 2004) were genotyped at 2 PRCP SNPs (rs7104980, rs2298668) and 3 KLKB1 (prekallikrein) SNPs (rs4253252, rs3733402, rs3087505). These subjects were 82% female and had a history of (in decreasing frequency) angina (71%), angiographic coronary disease (66%), heart attack (58%), PTCA (44%), hypertension (42%), CABG (36%), diabetes (15%), stroke (4%), and TIA (3%). The association between single SNP alleles and different cardiovascular related phenotypes was assessed using logistic regression models. These models were adjusted for age, weight, gender, history of hypertension, and history of diabetes. RESULTS: When the logistic regression model was adjusted for age, weight, and gender, SNP rs710980 in PRCP had a 21% increased odds [odds ratio=1.211; 95% CI=(1.008, 1.454)] of having a history of PTCA if carrying the G allele (frequency of 66%) as compared to not having the G allele (frequency 34%). Additionally, adjusting the logistic regression model for history of hypertension and diabetes did not alter the odds ratio for PTCA history. However when the logistic regression model included history of hypertension and diabetes, the odds of having a history of a MI if carrying the same allele also is increased by 21% [odds ratio=1.21; 95% CI=(1.001, 1.455)]. In summary, the rs710980 intronic PRCP SNP conferred risk for CVD, while the PRCP exonic SNP rs2298668 showed no relationship in this population. Alternatively, the exonic KLKB1 SNP rs3733402 of Apple Domain 2 where high molecular weight kininogen binds conferred reduced odds of 24% [odds ratio=0.76; 95% CI=(0.622, 0.928)] of having a history of angiographic coronary disease if carrying the G allele (frequency 67%) as compared to not having the G allele (frequency of 33%). The other two KLKB1 SNPs showed no associations. DISCUSSION: These combined data on PRCP suggest that it is a risk factor for CVD. The present genetic data are consistent with biochemical, cell culture, and in vivo investigations showing that PRCP levels influence vascular biology, renal function, and metabolism. The extent of the genetic associations of PRCP polymorphisms with CVD may be resultant of the database interrogated. The PEACE trial consisted of individuals not severely ill with CVD. Its hypothesis to show that administration of ACE inhibitors leads to increased protection from mild CVD was not met. However, the present investigation showing several positive odds ratios with a certain PRCP SNP for CVD suggests that PRCP is a stronger risk factor for CVD than can be demonstrated in the PEACE subject population. PRCP should be interrogated in additional populations of subjects with CVD. Funding Support: NIH HL052779-17, HL112666-2 Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 259-259 ◽  
Author(s):  
John J. Strouse ◽  
Michael Kraut ◽  
Lisa M. Williams ◽  
Michael R. DeBaun ◽  
James F. Casella

Abstract Abstract 259 Background: Cerebral infarct is a frequent complication in children and adults with sickle cell disease (SCD). About 10% of children with sickle cell anemia (HbSS) will have an overt stroke by 18 years of age and another 22% will have “silent” cerebral infarcts by 14 years of age. There is a second peak in the incidence of overt ischemic stroke in adults with SCD. Both silent and overt stroke can be accompanied by cognitive impairment and thereby increased risk of academic failure. Several laboratory parameters have been associated with these complications, including low hematocrit or hemoglobin, high white blood cell count (WBC), and high platelet count, while lactate dehydrogenase (LDH) and apolipoprotein A1 have been associated with pulmonary vasculopathy in adults with SCD. Elevated C-reactive protein (CRP) and the ratio of apolipoprotein B/A1 are associated with increased stroke risk in the general population. We hypothesized that these and other biomarkers might also be important in children with silent cerebral infarction. Methods: We prospectively measured potential biomarkers, including complete blood count, reticulocytes, fetal hemoglobin (HbF), LDH, CRP, and apolipoprotein A1 and B in 73 children with HbSS and 3 with sickle-β0-thalassemia (HbSβ0), in addition to performing brain magnetic resonance imaging (MRI), in a single center ancillary study of the Silent Infarct Transfusion Trial. MRIs were interpreted for the presence or absence of silent cerebral infarcts (FLAIR hyperintensities ≥3 mm in diameter seen in at least two imaging planes without corresponding symptoms or signs of stroke). Groups were compared by Student's t-test or Wilcoxon rank-sum test and associations evaluated by univariate and multivariate logistic regression. Results: Twenty-seven participants (35.5%, 1 with HbSβ0) had silent cerebral infarcts (age 8.9 ± 2.4 years, 59% male) and 49 (65.2%) had normal brain MRIs (age 8.7 ± 2.1, 53% male). The group with SCD and silent cerebral infarcts had significantly lower hemoglobin concentration and apolipoprotein A1 (P=0.01 for both) than children with SCD without silent cerebral infarcts. Apolipoprotein B and the ratio of apolipoprotein B to A1 were similar between groups. By univariate logistic regression, both apolipoprotein A1 [Odds ratio (OR) 0.95 per mg/dl increase, P<0.05] and hemoglobin (OR 0.52 per g/L increase, P<0.05) were associated with silent cerebral infarct; however, in a multivariate model, apolipoprotein A1 (OR 0.96 per mg/dl, P<0.05), but not hemoglobin (OR 0.78 per g/L, P=0.5), was significantly associated with silent cerebral infarct. Discussion and Conclusions: These data suggest a role of apolipoprotein A1 in the pathogenesis of silent cerebral infarct in children with SCD. Apolipoprotein A1 is a plausible marker or risk factor for cerebrovascular disease in SCD, given the association of lower levels with pulmonary hypertension in SCD and increased risk for cererbrovascular and cardiac disease in the general population. This marker should be studied in a larger longitudinal cohort of children at risk for cerebral infarcts. Disclosures: Strouse: General Electric: Equity Ownership. Casella:Boehringer Ingelheim: Honoraria; Cytrex: Research Funding; Ikaria: Research Funding.


1997 ◽  
Vol 77 (03) ◽  
pp. 444-451 ◽  
Author(s):  
José Mateo ◽  
Artur Oliver ◽  
Montserrat Borrell ◽  
Núria Sala ◽  
Jordi Fontcuberta ◽  
...  

SummaryPrevious studies on the prevalence of biological abnormalities causing venous thrombosis and the clinical characteristics of thrombotic patients are conflicting. We conducted a prospective study on 2,132 consecutive evaluable patients with venous thromboembolism to determine the prevalence of biological causes. Antithrombin, protein C, protein S, plasminogen and heparin cofactor-II deficiencies, dysfibrinoge-nemia, lupus anticoagulant and antiphospholipid antibodies were investigated. The risk of any of these alterations in patients with familial, recurrent, spontaneous or juvenile venous thrombosis was assessed. The overall prevalence of protein deficiencies was 12.85% (274/2,132) and antiphospholipid antibodies were found in 4.08% (87/2,132). Ten patients (0.47%) had antithrombin deficiency, 68 (3.19%) protein C deficiency, 155 (7.27%) protein S deficiency, 16 (0.75%) plasminogen deficiency, 8 (0.38%) heparin cofactor-II deficiency and 1 had dysfib-rinogenemia. Combined deficiencies were found in 16 cases (0.75%). A protein deficiency was found in 69 of 303 (22.8%) patients with a family history of thrombosis and in 205/1,829 (11.2%) without a history (crude odds ratio 2.34, 95% Cl 1.72-3.17); in 119/665 (17.9%) patients with thrombosis before the age of 45 and in 153/1,425 (10.7%) after the age of 45 (crude odds ratio 1.81, 95% Cl 1.40-2.35); in 103/616 (16.7%) with spontaneous thrombosis and in 171/1,516 (11.3%) with secondary thrombosis (crude odds ratio 1.58, 95% Cl 1.21-2.06); in 68/358 (19.0%) with recurrent thrombosis and in 206/1,774 (11.6%) with a single episode (crude odds ratio 1.78,95% Cl 1.32-2.41). Patients with combined clinical factors had a higher risk of carrying some deficiency. Biological causes of venous thrombosis can be identified in 16.93% of unselected patients. Family history of thrombosis, juvenile, spontaneous and recurrent thrombosis are the main clinical factors which enhance the risk of a deficiency. Laboratory evaluation of thrombotic patients is advisable, especially if some of these clinical factors are present.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maiko Maruyama-Inoue ◽  
Tatsuya Inoue ◽  
Shaheeda Mohamed ◽  
Yoko Kitajima ◽  
Shoko Ikeda ◽  
...  

AbstractThe purpose of this study was to report the incidence of elevated intraocular pressure (IOP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in Japanese patients with age-related macular degeneration (AMD). A retrospective study of chart review of patients who underwent ≥ 10 intravitreal anti-VEGF injections between April 2009 and December 2019 was conducted. Elevated IOP was defined as IOP ≥ 25 mmHg at one visit. Cases with elevated IOP resulting from IVI were identified. Furthermore, the association between elevated IOP and some parameters, as the risk factors that influence elevated IOP, was investigated. A total of 402 eyes of 370 patients were included in this study. Twenty-eight eyes of 26 patients (7.0%) were identified as cases with elevated IOP after IVI. The mean time of elevation after baseline was 50.6 ± 26.5 months. History of glaucoma (p = 0.021; odds ratio, 5.85), treatment modality (p = 0.019; odds ratio, 6.32), and total number of injections (p = 0.003; odds ratio, 1.03) were significantly associated with elevated IOP. A late complication of elevated IOP is associated with IVI in patients with AMD. Particularly, history of glaucoma and treat and extend regimen with frequent injections were found to be risk factors of elevated IOP.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Felicitas Söhner ◽  
Nils Hansson

Abstract Background Scholars agree that Torbjörn Caspersson’s lab at the Institute of Medical Cell Research and Genetics at the Karolinska Institute, Sweden, played a key role in the first description of the so-called Q-banding technique. It laid the foundation for a new era of cytogenetic diagnostics and had a lasting impact in several areas of biology and medicine. Methods Based on a mixed-method approach, essential aspects of the history of human cytogenetics are considered via primary and secondary analysis of biographical interviews as well as the qualitative evaluation of bibliometrics. Drawing on interviews with colleagues of lab member Lore Zech (1923–2013) and contemporary publications, this paper illuminates the role of and contribution by Zech: To what extent is the discovery attached to her and what does her legacy look like today? Results The analysis of the contemporary witness interviews with colleagues, students and junior researchers shows that Lore Zech was a committed member of Caspersson's research group. In addition, memoirs by contemporary colleagues describe her outstanding skills in microscopy. The different sources paint a multifaceted picture. In addition to the historians' patterns of interpretation, different legacies can also be found within the peer group. Conclusions We argue that Zech represent the type of scientist who, although her research was acknowledged with several prizes, so far has not been part of the canon of pioneers of international cytogenetics.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Seok-Jin Hong ◽  
Byoung-Eun Yang ◽  
Dae-Myoung Yoo ◽  
Sung-Jae Kim ◽  
Hyo-Geun Choi ◽  
...  

Abstract Background Chronic periodontitis is a multifactorial inflammatory disease resulting in patients exhibiting high levels of inflammatory factors causing systemic inflammatory bone destruction that may lead to osteoporosis development. The association between periodontitis and osteoporosis has been documented; however, the findings remain unclear. This study aimed to identify the association between periodontitis and osteoporosis using a cross-sectional study design and Korean Genome and Epidemiology Study (KoGES) health examinee data. Methods This cross-sectional study used epidemiological data from the KoGES during 2004–2016. Of 125,324 participants (age, 40–79 years), 9969 with periodontitis and 115,332 controls (without periodontitis) were selected. We analyzed the history of osteoporosis and fractures of all participants. All participants were examined according to age, sex, income group, obesity, smoking habits, alcohol consumption, and food intake. To analyze the odds ratio (OR) of periodontitis for those with osteoporosis and fractures, a logistic regression model was used. Results The adjusted odds ratio (aOR) of periodontitis for osteoporosis was 2.16 (95% confidence interval [CI], 2.01–2.31; P < 0.001). The aOR of periodontitis for any fracture was 1.54 (95% CI 1.46–1.62; P < 0.001). Conclusion Osteoporosis and fractures are associated with periodontitis. Performing regular oral hygiene and examinations of bone mineral density are recommended to prevent aggravation of osteoporosis and periodontitis.


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