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The authors discuss the issues of teenage pregnancy for youth in group homes. They mention the use of the Power Through Choices intervention program for prevention of pregnancy, the recruitment of group homes in which to implement the program, and the problems of tracking participants in the program.

413 Background: Fibrolamellar carcinoma (FLC) is a very rare liver tumor, comprising only 1% of all primary liver tumors in the United Sates. There is no standard of care for unresectable disease. Current practices are based on small retrospective studies and case series. We aim to analyze the clinicopathologic factors and treatment modalities affecting overall survival (OS) in FLC. Methods: Using the National Cancer Data Base (NCDB), we identified 496 patients diagnosed with FLC between 2004 and 2015. Simple descriptive statistics were created for all covariates. Survival data was available on 461 patients. Kaplan Meier Survival analysis was used for unadjusted results, and Cox proportional hazards model was used for multivariable analysis. The objective of the study is to identify predictors of survival in FLC. Results: The median age at diagnosis was 32 (range 18-90) years. Fifty-six percent were males. Stage distribution included 114 (31.2%), 43 (11.8%), 89 (24.3%) and 120 (32.8%) patients for stages I, II, III and IV, respectively. Median follow-up was 24 months. Surgery of the primary site was performed on 282 (56.9%) of patients, 146 (51.2%) of which had regional lymph node dissection. Seventy (47.9%) patients had pN+ disease. Among patients with available serum alpha fetoprotein (AFP) data, 146 (42.5%) had abnormal AFP levels (> 20 ng/mL). Median OS by stage were 78.5, 87.2, 18.6, and 10.6 months for stages I, II, III, and IV, respectively. Multivariate analysis showed that age (HR 1.01, p < 0.0001), pN+ (HR 2.31, p = 0.0003), and abnormal AFP (HR 1.69, p = 0.0003) were negative predictors of survival. Among metastatic patients, 57 (11.4%) had metastatectomy. Metastatectomy improved overall survival in stage IV FLC, HR 0.51 (95% CI 0.29-0.89). Conclusions: Independent predictors of decreased OS in patients with FLC include age, pN+ and abnormal AFP. Metastatectomy improved OS. FLC is a rare disease entity that warrants further investigations to better delineate optimal treatment approaches.

Objectives To determine the frequency of pulmonary involvement in patients with thrombotic thrombocytopenic purpura (TTP). Methods The experience of the Oklahoma TTP-HUS (hemolytic–uremic syndrome) Registry, a population-based cohort of consecutive patients without selection or referral bias, 1995–2012, was analyzed. Evidence for pulmonary involvement in patients with TTP was also documented with a systematic review of published reports. Results Only one of 74 Registry patients with acquired severe ADAMTS13 deficiency (activity

Background: Immunotherapy directed against the PD-1/PDL-1 (programmed cell death protein [ligand] 1) pathway has shown activity across a range of malignancies. Immune-related adverse events have been shown to be associated with the efficacy of PD-1/PDL-1 inhibitors in patients with melanoma and non-small cell lung cancer. Thrombocytopenia has been reported in up to 33% of patients receiving anti PD-1/PDL-1 therapy. Our hypothesis is that immune-mediated thrombocytopenia may be a biomarker for response to anti PD-1/PDL-1 therapy. Methods: We collected data on 250 patients aged 18 years and older who were treated with anti PD-1/PDL-1 therapy at the University of Oklahoma Health Sciences Center between January 2014 and January 2016. Initial platelet count at baseline as well as nadir platelet count during treatment were examined. Patient's clinicopathologic characteristics were analyzed using simple descriptive statistics [median (range) for continuous covariates and n (%) for categorical variables]. Kaplan Meier Analysis was performed to assess how thrombocytopenia was associated with overall survival (OS) and progression free survival (PFS). Patients were grouped according to their nadir platelet count: normal platelets (≥150k), grade 1 (75k-150k), and combined grades 2, 3, 4 ( Results: A total of 250 patients were reviewed in this study. After excluding 27 patients with baseline platelet count Conclusion: Our study shows that in patients treated with anti PD-1/PDL-1 therapy, grade 1 thrombocytopenia appears to be positively correlated with survival outcomes. This survival advantage was not seen with higher grades of thrombocytopenia. PD-L1 was recently shown to be expressed on human platelets; thus, thrombocytopenia is likely immune-mediated. Thrombocytopenia may be a biomarker for efficacy of immune checkpoint therapy. The predictive significance of thrombocytopenia in patients receiving PD-1/PDL-1 therapy warrants further investigations. Disclosures No relevant conflicts of interest to declare.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disorder caused by antibodies directed at self-antigens leading to platelet destruction. Autoantibodies from most patients with ITP are directed to platelet membrane glycoprotein(GP) IIb-IIIa or GPIb-IX. 80% of ITP cases are classified as primary and it's unclear why auto reactive antibodies are formed in these patients. Studies from the United States, Asia and Europe show an increasing incidence of ITP with aging. Thrombopoietin receptor agonists (TPO-RA) interact directly with the TPO receptor on megakaryocytes to stimulate platelet production and can surprisingly produce sustained remissions of chronic ITP in some patients even after discontinuation of treatment. The heterogeneity of the course of ITP and the response to treatment, especially the response to treatment with thrombopoietin receptor agonists (TPO-RA), suggests pathogenic and clinical diversity of ITP. Clonal hematopoiesis is known to occur in elderly patients and has been associated with adverse outcomes including hematologic cancers and cardiovascular disease. We hypothesized that clonal hematopoiesis and associated passenger somatic mutations contribute to loss of immune tolerance in some ITP patients, causing the generation of auto-reactive antibodies and affecting the response to TPO-RA. METHODS: Platelet RNA was extracted from 13 blood samples obtained from 11 ITP patients using Direct-zolTM RNA MicroPrep Kit (Zymo Research). 2 patients provided samples during both relapse and remission. cDNA generation was performed from enriched total RNA using SMARTerR Target RNA Capture for IlluminaR Kit (Clontech). Target-specific biotinylated DNA probes were designed to hybridize to mRNA transcripts for common platelet antigens including (GP) IIb-IIIa and GPIb-IX. cDNA libraries were prepared using the Nextera™ XT DNA Library preparation kit. Following the pooling of libraries they were sequenced on an Illumina Nextseq 500 instrument in Mid-output mode with single-ended reads of 150 bp. RESULTS: In one of the paired patient specimens, we found substantial differences in platelet populations between relapse and remission on a TPO-RA. Different previously-reported non-disease-causing heterozygous single nucleotide variants (SNVs) were detected during relapse and remission. Expression at a level approximating 50% in remission and a reciprocal expression in relapse suggests that 2 point mutations leading to a missense amino acid change (Glu to Lys at amino acid 671) in GPIIb (ITGA2B) and (Thr to Met at amino acid 161) in GPIb (GP1BA) provoke an immune response (Table 1). Further, the reciprocal expression at these levels is consistent with expression of a somatic mutation in a clonal fashion. CONCLUSION: We documented that unique platelet clones were expressed during relapse and remission of ITP. These findings demonstrate that clonal expression of platelets bearing somatic mutations in target glycoproteins are associated with ITP disease course and response to therapy. Such somatic mutations are likely to be passenger mutations acquired prior to clonal expansion. Expression of a somatic mutation in a clonal fashion may drive autoimmune response. Table 1. Table 1. Disclosures No relevant conflicts of interest to declare.

Introduction: Congenital thrombotic thrombocytopenic purpura (cTTP) is an autosomal recessive disease characterised by acute episodes of thrombotic microangiopathy. cTTP has a clinically heterogeneous course. Currently there are more than 150 disease-causing ADAMTS13 gene mutations reported, though a genotype-phenotype correlation of this ultra-rare disease remains incompletely understood. Characterization of mutations of the ADAMTS13 gene will be useful for carrier detection and genetic counselling. In 2006, the Hereditary TTP Registry (ClinicalTrials.gov NCT01257269; www.ttpregistry.net) was initiated in order to achieve this objective by identifying possible triggers of acute episodes of TTP and to document individual clinical courses and treatment requirements. Methods: The Hereditary TTP Registry is an international cohort study. Individual data were analysed from 121 cTTP patients, who were enrolled between 2006 and the end of 2017. Diagnosis of cTTP was confirmed by a severely deficient ADAMTS13 activity Results: The cTTP cohort consists of 54 and 52 patients from Europe and Asia (90% from Japan), respectively, 13 patients from the Americas and 2 patients from Africa. For 69% of the patients regular treatment was reported, which consisted predominantly of fresh frozen plasma infusion (84%). More compound heterozygous (n=76) than homozygous mutation carriers (n=45) were included. The female to male ratio was 1:1, and the median age at first diagnosis was 25.8 years (range from 0 to 81.3 years). Prior arterial thromboembolic events (mainly myocardial infarction, stroke, TIA) were present in 27% of patients at enrolment and at the age of 50 years more than half of the patients had experienced at least one such event. In the 121 patients, we identified 98 different ADAMTS13 mutations (missense 57; nonsense 12; frameshift due to deletions or insertions 21; splice site 8). The most frequent observed mutations were c.4143_4144dupA (exon 29; p.Glu1382Argfs*6; n=58 alleles), c.3178C>T (exon 24; p.Arg1060Trp; n=13), and c.577C>T (exon 6; p.Arg193Trp; n=11). Nineteen mutations have not been previously reported (8 missense, 3 splice site, 2 nonsense, and 6 frameshift mutations). Mutations are located across the whole ADAMTS13 gene and affect all domains (there was no "hotspot"). We did not find a correlation of the mutations with clinical or laboratory features, except for ADAMTS13 c.4143_4144dupA. For this mutation, the age at initial diagnosis was younger (median age 4.1 years, range 1.8 - 52.1) in compound heterozygous compared to homozygous patients (median 23.3 years, range 0.7 - 47.5,) (p=0.040). Patient numbers were equally distributed (p = 0.51); 16 patients were compound heterozygotes and 21 were homozygotes. All patients were of Scandinavian or Central European ancestry. For the other assessed clinical parameters, no significant difference between compound heterozygotes and homozygotes was observed. Conclusion: At present, the Hereditary TTP Registry is the largest cohort on cTTP, to our knowledge. The large number of different mutations as well as confounding factors, including multi-ethnic and geographical factors in our internationally compiled patient cohort make unravelling the genotype-phenotype correlation in cTTP challenging. Yet, for c.4143_4144dupA, we can conclude that homozygous patients with ADAMTS13 c.4143_4144dupA are clinically less severely affected than compound heterozygotes due to the later onset of the disease in homozygotes, whereas the clinical characteristics are similar between compound heterozygotes and homozygotes. Why homozygous carriers of c.4143_4144dupA, despite having no ADAMTS13 activity in plasma, may have a rather late onset of acute TTP remains to be further elucidated. Disclosures Friedman: Shire: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees. Knöbl:Ablynx: Consultancy, Other: Member of Advisory Board. Schneppenheim:CSL Behring: Consultancy; SHIRE: Consultancy. Kremer Hovinga Strebel:Ablynx: Other: Advisory Board; SHIRE: Other: Advisory Board, Research Funding.

Patients with Homologous Recombination Deficits (HRD) have shown increased survival in many cancers. With PARP inhibitors surfacing as a potential therapy for Glioma patients, we aim to explore the existence of HRD and its prognostic value in High-Grade Glioma patients. We conducted a chart review of patients with Gliomas who received Foundation One testing at The University of Oklahoma from 2013 to 2018. We used Foundation Ones Loss of Heterozygosity (LOH) score as a measure for HRD. We analyzed the correlation between the existence of mutated IDH and the LOH score. We then analyzed the significance of receiving Foundation One testing prior to any treatment on LOH score. Finally, we separated the patient population into two groups, High-HRD (>5% LOH or >3% LOH) and Low-HRD (

Many patients with syndromes of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, have been reported to have a drug-induced etiology, and many different drugs have been suspected as a cause of TMA. We established criteria to assess the strength of evidence for a causal association of a drug with TMA and systematically searched for all published reports of drug-induced TMA. We identified 1569 articles: 604 were retrieved for review, 344 reported evaluable data for 586 individual patients, 43 reported evaluable data on 46 patient groups. Seventy-eight drugs were described; 22 had evidence supporting a definite causal association with TMA. Three drugs accounted for 61 of the 104 patient reports with definite evidence (quinine, 34; cyclosporine, 15; tacrolimus, 12). Twenty additional drugs had evidence supporting a probable association with TMA. These criteria and data can provide support for clinicians evaluating patients with suspected TMA.

Recovery from acute episodes of thrombotic thrombocytopenic purpura (TTP) appears complete except for minor cognitive abnormalities and risk for relapse. The Oklahoma TTP-HUS (hemolytic uremic syndrome) Registry enrolled 70 consecutive patients from 1995 to 2011 with ADAMTS13 activity

Objective This study aimed to evaluate the utility of risk stratification of gynecologic oncology patients with neutropenic fever (NF). Methods A retrospective chart review of gynecologic cancer patients admitted with NF from 2007 to 2011 was performed, wherein demographic, oncologic, and NF characteristics (hospitalization length, complications, and death) were collected. The Multinational Association for Supportive Care in Cancer (MASCC) risk index score was calculated; low risk was considered ≥21. SAS 9.2 was used for statistical analyses. Results Eighty-three patients met the study criteria. Most (92%) were Caucasian and had advanced stage disease (71%). Primary tumors were 58% ovary, 35% endometrium, and 6% cervix. All patients were receiving chemotherapy on admission (72% for primary, 28% for recurrent disease). Forty-eight percent had a positive culture, and most (58%) positive cultures were urine. Seventy-six percent of patients were considered low risk. High-risk patients were more likely to have a severe complication (10% versus 50%, p =0.0003), multiple severe complications (3% versus 20%, p =0.0278), ICU admission (2% versus 40%, p p =0.0417), and death due to neutropenic fever (0% versus 15%, p =0.0124). MASCC had a positive predictive value of 50% and negative predictive value of 90%. The median MASCC score for all patients was 22 (range, 11–26), but the median MASCC score for those with death or a severe complication was 17 (range, 11–24). Conclusion Based on this pilot data, MASCC score appears promising in determining suitability for outpatient management of NF in gynecologic oncology patients. Prospective study is ongoing to confirm safety and determine impact on cost.

Background Acute, immune-mediated thrombocytopenia may be caused by many different approved drugs as well as by other substances including vaccines, complementary and alternative medicines, herbal remedies, nutritional supplements, foods and beverages. All causes are described as drug-induced thrombocytopenia (DITP). Often the cause is not recognized, resulting in recurrent thrombocytopenia and inappropriate treatments. Systematic analysis of children (age less than 18 years) with suspected DITP has not been previously reported. Procedures (1) We searched 15 databases to identify articles describing children with thrombocytopenia as an adverse effect of drugs and other substances. Articles were reviewed to assign levels of evidence for an association of the suspected substance with thrombocytopenia. (2) Data from the BloodCenter of Wisconsin were reviewed to identify reports of drug-dependent, platelet-reactive antibodies in children with suspected DITP. Results Of 2,191 articles identified, 242 were selected for review. Seventy-two articles reporting 74 individual patients and nine groups of patients had evaluable data. Eleven individual patients and one group had definite evidence and 40 patients and three groups had probable evidence for an association of the suspected substance with thrombocytopenia. Thirty-two substances had a definite or probable association with thrombocytopenia. During 2008–2012, sera from 91 children with suspected DITP were tested and 21 had drug-dependent, platelet-reactive antibodies involving six substances. Conclusions Drugs and other substances must be considered as potential causes of thrombocytopenia. Evidence from published reports and data for drug-dependent, platelet-reactive antibodies can help clinicians evaluate of children with unexpected thrombocytopenia. Pediatr Blood Cancer 2013;60:1975–1981. © 2013 Wiley Periodicals, Inc.

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) associated with severe, acquired ADAMTS13 deficiency is uncommonly reported in children. The incidence, demographic, and clinical features of these children, compared to adults, have not been described. PROCEDURES This study focused on children (

Long-term follow-up of children with immune thrombocytopenia (ITP) indicates that the majority undergo remission and severe thrombocytopenia is infrequent. Details regarding bleeding manifestations, however, remain poorly categorized. We report here long- term data from the Intercontinental Cooperative ITP Study Group Registry II focusing on natural history, bleeding manifestations, and management. Data on 1345 subjects were collected at diagnosis and at 28 days, 6, 12, and 24 months thereafter. Median platelet counts were 214 × 10(9)/L (interquartile range [IQR] 227, range 1-748), 211 × 10(9)/L (IQR 192, range 1-594), and 215 × 10(9)/L (IQR 198, range 1-598) at 6, 12, and 24 months, respectively, and a platelet count

Using a developmental, social-ecological approach to understand the etiology of health risk behavior and inform primary prevention efforts, we assess the predictive effects of family and neighborhood social processes on youth physical fighting and weapon carrying. Specifically, we focus on relationships among youth and their parents, family communication, and parental monitoring, as well as sense of community and neighborhood informal social control, support, concerns, and disorder. This study advances knowledge through its investigation of family and neighborhood structural factors and social processes together, employment of longitudinal models that estimate effects over adolescent development, and use of self-report and observational measures. Data from 1,093 youth/parent pairs were analyzed from the Youth Assets Study using a Generalized Estimating Equation (GEE) approach; family and neighborhood assets and risks were analyzed as time-varying and lagged. Similar family assets affected physical fighting and weapon carrying, whereas different neighborhood social processes influenced the two forms of youth violence. Study findings have implications for the primary prevention of youth violence, including the use of family-based approaches that build relationships and parental monitoring skills, and community-level change approaches that promote informal social control and reduce neighborhood concerns about safety.

The growing influence of practice guidelines has increased concern for potential sources of bias. Two recent guidelines for primary immune thrombocytopenia (ITP) provided a unique opportunity for a systematic comparison of different methods of practice guideline development. One guideline (International Consensus Report [ICR]) was supported by pharmaceutical companies that produce products for ITP. The ICR panel members were selected for expertise in ITP; 16 (73%) reported associations with pharmaceutical companies. The other guideline was sponsored by the American Society of Hematology (ASH); panel members were selected for lack of conflicts and for expertise in guideline development as well as for ITP. Discrepancies were conspicuous when the guidelines addressed treatment. In contrast to the ASH guideline, the ICR gave stronger recommendations for agents manufactured by companies from which the ICR or its panel members received support. These data provide direct evidence that differences in financial support and methods of evidence evaluation can influence recommendations.

Research has identified factors (assets) that protect youth from engaging in risk behaviors including alcohol use. Very little research has examined asset/nonuse of alcohol associations by youth gender or determined if asset/nonuse of alcohol associations are influenced by the neighborhood environment. The purpose of the study was to determine if multiple youth assets and neighborhood factors are differentially associated with youth nonuse of alcohol by gender. Method: Five waves of data were collected annually from households (N = 1111) randomly selected to participate in the Youth Asset Study. Seventeen assets and 6 neighborhood factors assessed at waves 1 - 4 were analyzed longitudinally using marginal logistic regression to predict nonuse of alcohol at waves 2 - 5. Results: Sample mean age was 14.3 years, 52% female; 39% white, 28% Hispanic, 23% African-American, and 9% other. Numerous assets were prospec- tively associated with alcohol nonuse for females (12 assets) and males (16 assets). Three assets were significantly more protective from alcohol use for males compared to females. Final modeling indicated that three assets were protective from alcohol use for both genders and that one asset was protective only for males. There were no significant associations between the neighborhood variables and nonuse of alcohol, and the neighborhood variables did not influence the asset/nonuse of alcohol associations. Conclusions: Youth assets appear to protect both genders from future alcohol use but males may benefit even more from asset-building prevention programming. Youth alcohol use and alcohol nonuse/asset associations may not be influenced by the neighborhood environment.

Clinical assessment of bone marrow is limited by an inability to evaluate the marrow space comprehensively and dynamically and there is no current method for automatically assessing hematopoietic activity within the medullary space. Evaluating the hematopoietic space in its entirety could be applicable in blood disorders, malignancies, infections, and medication toxicity. In this paper, we introduce a CT/PET 3D automatic framework for measurement of the hematopoietic compartment proliferation within osseous sites. We first perform a full-body bone structure segmentation using 3D graph-cut on the CT volume. The vertebrae are segmented by detecting the discs between adjacent vertebrae. Finally, we register the bone marrow CT volume with its corresponding PET volume and capture the spinal bone marrow volume. The proposed framework was tested on 17 patients, achieving an average accuracy of 86.37% and a worst case accuracy of 82.3% in automatically extracting the aggregate volume of the spinal marrow cavities.

Drinking and driving among adolescents and young adults remains a significant public health burden. Etiological research is needed to inform the development and selection of preventive interventions that might reduce alcohol- involved crashes and their tragic consequences. Youth assets—that is, skills, competencies, relationships, and opportunities—can help youth overcome chal- lenges, successfully transition into adulthood, and reduce problem behavior. We examined the predictive influence of individual, relationship, and community assets on drinking and driving (DD) and riding with a drinking driver (RDD). We assessed prospective relationships through analysis of data from the Youth Assets Study, a community-based longitudinal study of socio-demographically diverse youth. Results from calculation of marginal models using a Generalized Estimating Equation approach revealed that parent and peer relationship and school connect- edness assets reduced the likelihood of both drinking and driving and riding with a drinking driver approximately 1 year later. The most important and consistent asset that influenced DD and RDD over time was parental monitoring, highlighting the role of parental influence extending beyond the immediate teen driving context into young adulthood. Parenting-focused interventions could influence factors that place youth at risk for injury from DD to RDD, complementing other evidence-based strategies such as school-based instructional programs and zero tolerance Blood Alcohol Concentration laws for young and inexperienced drivers.

Publisher's Note: There is an [Inside Blood Commentary][1] on this article in this issue. To the editor: Recent systematic reviews assessing the role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura (TTP)[1][2],[2][3] identified 2 major observational

Current noninvasive evaluation of bone marrow proliferation in leukemia treatment is limited to manually examining marrow tissue in multiple regions of interest (ROIs). The statistics extracted from these ROIs often fail to provide an accurate global characterization of the patient's marrow. We propose an automatic framework for segmenting spinal marrow compartments to characterize the bone marrow from full-body joint PET/CT scans acquired subsequent to bone marrow transplantation. We first apply a graph-cut algorithm to the CT volume to obtain a 3D full-body bone map. We then isolate the spinal column in a single sagittal plane where connected components labeling and iterative thresholding are used to segment the vertebral bodies. This fully automated approach achieves an average accuracy of 91.7% and a worst case accuracy of 80.4% in testing on 51 scans of 17 patients. Finally, we outline a method for rejecting the cortical bone in transverse planes that can be combined with the sagittally segmented vertebral bodies to obtain a 3D map of the vertebral body medullary cavities for the entire spine.

Although studies have shown that smoking is detrimental to the health of patients with systemic lupus erythematosus (SLE), studies regarding barriers and motivators for smoking cessation are lacking. The purpose of this study was to generate hypotheses regarding the barriers and motivators for smoking cessation in SLE patients.This study was based on the theoretical framework of the stages of change model. All participants met SLE classification criteria. Interviews were conducted with 16 current and 10 former smokers.Motivators included: medical reasons, readiness, and concern for others. Barriers included: enjoyment, coping mechanism, and an emotional connection. Participants were unsure of the impact of smoking on their medication and disease, and had mixed feelings regarding the impact on pain.The main motivator for cessation in this population was concern for one's health. Rheumatologists need to include disease specific harms and assess pain management strategies as part of cessation counseling.

Quinine is a common cause of drug-induced thrombocytopenia and the most common cause of drug-induced thrombotic microangiopathy. Other quinine-induced systemic disorders have been described. To understand the complete clinical spectrum of adverse reactions to quinine we searched 11 databases for articles that provided sufficient data to allow evaluation of levels of evidence supporting a causal association with quinine. Three reviewers independently determined the levels of evidence, including both immune-mediated and toxic adverse reactions. The principal focus of this review was on acute, immune-mediated reactions. The source of quinine exposure, the involved organ systems, the severity of the adverse reactions, and patient outcomes were documented. One hundred-fourteen articles described 142 patients with definite or probable evidence for a causal association of quinine with acute, immune-mediated reactions. These reactions included chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, acute kidney injury, rhabdomyolysis, liver toxicity, cardiac ischemia, respiratory failure, hypoglycemia, blindness, and toxic epidermal necrolysis. One hundred-two (72%) reactions were caused by quinine pills; 28 (20%) by quinine-containing beverages; 12 (8%) by five other types of exposures. Excluding 41 patients who had only dermatologic reactions, 92 (91%) of 101 patients had required hospitalization for severe illness; 30 required renal replacement therapy; three died. Quinine, even with only minute exposure from common beverages, can cause severe adverse reactions involving multiple organ systems. In patients with acute, multi-system disorders of unknown origin, an adverse reaction to quinine should be considered.

Plasma exchange (PEX) treatment for patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) has risk for major complications.

Background Severe ADAMTS13 deficiency is a critical component of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura but is found only in about 60% of patients clinically diagnosed with this disease. Design and Methods Over a period of 8 years and six episodes of thrombotic thrombocytopenic purpura we studied the evolution of the anti-ADAMTS13 antibody response in a patient using different ADAMTS13 assays and epitope mapping. Results Anti-ADAMTS13 autoantibodies were found in all episodes but were inhibitory only in the last two episodes. In a flow-based assay, normal ADAMTS13 activity was found only during the first disease episode, while ADAMTS13 activity was normal using a static assay in episodes 1 and 3, and severely deficient in the last two episodes. Fluorescence evolution in a modified fluorescence resonance energy transfer assay using a von Willebrand factor A2 domain peptide substrate was linear in episodes 1, 5 and 6, but increased exponentially in episodes 3 and 4. Despite the variable functional characteristics of the anti-ADAMTS13 autoantibodies, their principal epitope was the ADAMTS13 spacer domain in all episodes. Conclusions The patient is unique as he displayed features of maturation or shaping of the anti-ADAMTS13 autoantibody response during the course of multiple episodes of thrombotic thrombocytopenic purpura. Anti-ADAMTS13 autoantibodies may be important in vivo despite normal ADAMTS13 activity in routine assays. Consequently, treatment decisions should not be based solely on activity assay results.

The absence of specific diagnostic criteria, the urgency to begin plasma exchange treatment, and the risk for complications from plasma exchange make the initial evaluation of patients with suspected thrombotic thrombocytopenic purpura (TTP) difficult. Systemic infections may mimic the presenting clinical features of TTP. In the Oklahoma TTP-HUS (hemolytic-uremic syndrome) Registry, 1989-2010, 415 consecutive patients have been clinically diagnosed with their first episode of TTP; in 31 (7%) the presenting clinical features were subsequently attributed to a systemic infection. All 31 patients had diagnostic criteria for TTP; 16 (52%) had the complete "pentad" of microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, renal failure, and fever. Four (16%) of 25 patients who had ADAMTS13 measurements had

BACKGROUND: Coated platelets (PLTs), a subpopulation of PLTs observed upon dual agonist stimulation with collagen and thrombin, are known to retain several procoagulant a-granule proteins on their surface. By formation of a highly active membrane-bound prothrombinase complex, these PLTs represent an important step in the coagulation cascade as a consequence of their ability to generate thrombin at the site of vascular injury. Various clinical observations suggest that higher levels of coated PLTs are associated with thrombosis while a deficiency of coated PLTs results in a bleeding diathesis. Current quality control guidelines for in vitro PLT storage measure PLT viability but no routine evaluation of the hemostatic function of stored PLTs and particularly no estimation of coated PLT potential is performed. Our primary objective was to evaluate if the process of apheresis and storage of PLT units alters the levels of coated PLTs. In addition, we sought to determine how transfusion of stored PLTs into patients with thrombocytopenia affects the patient’s coated PLT levels. STUDY DESIGN AND METHODS: Coated PLT levels were analyzed in 13 voluntary PLT donors before donation, in the fresh apheresis product (Trima, CaridianBCT) and in the stored apheresis product just before transfusion. In addition, 10 patients with thrombocytopenia were analyzed for coated PLTs before and after transfusion of a stored PLT product. RESULTS: Coated PLT levels were significantly decreased after the process of apheresis (17% relative decline; p < 0.01) and with prolonged storage (1 to 5 days; 53% relative decline; p < 0.001). Transfusion of stored PLT units did not result in significant increment of coated PLT levels in patients with thrombocytopenia as expected considering the low level of coated PLTs in stored PLT units. Furthermore, there was no suggestion of regeneration of coated PLT potential upon reinfusion. CONCLUSIONS: Isolation and storage of apheresis PLTs by standard blood bank procedures results in a significant decline in coated PLT potential. Reinfusion of stored apheresis PLTs into patients with thrombocytopenia resulted in a predictable change in coated PLT potential with no suggestion of regeneration of lost coated PLT potential. P latelets (PLTs) have two critical roles in promoting hemostasis at the site of vascular injury. The firstisprimaryhemostasisinvolvingplugformation resulting from PLT adhesion to the subendothelial membrane and subsequent PLT aggregation. The other role is to provide a negatively charged membrane surface for formation of an active prothrombinase complex, resulting in thrombin generation for propagation of fluid-phase coagulation, often referred to as secondary hemostasis. Although all PLTs have an inherent capacity to satisfy the aggregation function, it is observed that a subpopulation of PLTs has an enhanced ability to form prothrombinase complexes and may, therefore, play an especially critical role in hemostasis. 1

Purpose. Evaluate youth assets or potential strengths and sexual intercourse associations by household income. Design. Data consisted of youth and parent responses from randomly selected households from a cross-sectional study and wave one of a longitudinal extension of that study. Youth assets and sexual intercourse were compared for four income categories. Setting. Midwestern racially diverse, inner-city neighborhoods. Subjects. One adolescent (12–19 years) and one parent (2335 pairs). Measures. Adjusted odds ratios (ORs) were calculated using logistic regression. Variables assessed included parent and youth demographics, youth sexual intercourse, and youth assets (adult and peer role models, family communication, use of time [religion or sports], community involvement, future aspirations, responsible choices, and health practices). Results. Youths' mean age was 14.9 (6 1.8) years, and 52% were female; 44% of respondents were white. Use of time (religion) was significantly associated with never having sex for all but the lowest income youth (OR range = 1.79-2.64). The variable peer role models was significant for the lowest income (OR = 2.01) and two upper income groups (ORs = 2.52 and 4.27, respectively). The variable future aspirations was significant for the lowest income youth (OR = 1.77). Conclusion. The youth asset variable future aspirations was critical for the lowest income households. Other asset variables, such as peer role models and use of time (religion) were critical regardless of income. (Am J Health Promot 2011;25[5]:301-309.)

BACKGROUND It has been postulated that blood group O subjects may be partially protected against thrombotic thrombocytopenic purpura (TTP) because they have lower plasma levels of von Willebrand factor (VWF).

Background: Patients with primary immune thrombocytopenia (ITP) commonly describe symptoms of fatigue. However, hematologists rarely consider fatigue a manifestation of ITP. Objectives: To document the prevalence of fatigue among patients with ITP and to determine the patient characteristics that are associated with fatigue. Methods: Using a cross-sectional design, we surveyed 1871 members of the UK ITP Support Association [585 (31%) responded], and 93 patients enrolled in the Oklahoma (US) ITP Registry [68 (73%) responded] with questions about their ITP and with validated symptom assessment scales for fatigue, daytime sleepiness, and orthostatic symptoms. Results: The prevalence of fatigue among both UK (39%) and US (22%) patients was significantly greater than expected compared with normal subjects (P

Purpose. Improve and expand an existing youth asset scale. Design. Consisted of seven steps: (1) review of poorer-performing items and constructs, (2) literature review for relevant new asset constructs/items, (3) review of revised instrument by panel of experts, (4) qualitative review through focus group research, (5) pilot-test of instrument, (6) evaluation of the performance of the instrument in a longitudinal study, and (7) conduct of test-retest analysis. Subjects/Setting. Youth (N = 1111) recruited through canvassing of randomly selected census tracts and blocks. Measures. Youth Asset Survey (YAS). Analysis. Factor analysis was conducted on 50% of the baseline data and repeated on the second half of the baseline data. Correlations were computed for the test-retest analysis. Results. Following modifications to the YAS based upon qualitative research, the survey was administered to youth (mean age, 14.3years; 53% female; 39% white, 28% Hispanic, 23% African-American, 9% other). Cronbach α = .55–.92. A majority (27 of 34) of α ≥ .65. All items loaded on one construct at α ≥ .40. The final results yielded 17 constructs assessed via 61 items. Spearman correlations and intraclass correlations ranged from .60 to .82 and .58 to .87, respectively. Conclusion. The results generally suggest that the expanded YAS is a reliable and valid measure of assets.

11525Background: Response to neoadjuvant chemotherapy correlates with a positive outcome in localized osteosarcoma patients. However, there are no reliable predictors of chemotherapy response. We i...

PurposePrevious research has shown that religion plays a role in the lives of many youths. This paper aims to extend previous research and examine attendance at religious services and involvement in religious/church activities as separate items to determine if one aspect was more strongly associated with never having had sexual intercourse among youth in the USA. It also aims to consider the effect of other youth assets, and analyze all by gender.Design/methodology/approachCross‐sectional data were examined to assess youth assets and risk behaviors. Multivariate regression was used to determine whether the assets or religion questions were significant in the presence of the other assets/religion questions. The eight assets examined, in addition to church attendance and involvement in religious groups were adult role models, peer role models, family communication, involvement in sports and groups, community involvement, aspirations for the future, responsible choices, and good health – diet and exercise.FindingsInvolvement in church/religious activities, but not attendance at religious services, was associated with never having had sexual intercourse among males and females. Analysis also determined that several of the other youth assets were protective of sexual intercourse among males and among females.Research limitations/implicationsFindings from this study may be limited by the validity of the self‐reported measures. The data were cross‐sectional, making it impossible to draw inferences about the causal directions of the relationships found in this study. Future research should focus on developing interventions to strengthen youth assets.Practical implicationsDeveloping gender and culturally specific interventions to promote youth assets may reduce the number of young people engaging in sex.Originality/valueThe paper extends previous research and examines attendance at religious services and involvement in religious/church activities as separate items to determine if one aspect was more strongly associated with never having had sexual intercourse.

Youth internal assets and external resources are protective factors that can help youth avoid potentially harmful behaviors. This study investigates how the relationship between youth assets or resources and two sexual risk behaviors (ever had sex and birth control use) varied by gender. Data were collected through in-home interviews from parent—adolescent dyads, including 1,219 females and 1,116 males. Important differences exist between male and female adolescents. Females with the nonparental role models or the family communication resource were more likely to report never having had sexual intercourse than were females without the resources. Among males, the aspirations for the future and responsible choices assets were associated with never having had sexual intercourse. Males and females had two assets or resources in common that were protective of never having had sex: peer role models and use of time (religion). Considering which youth assets and resources are more likely to positively influence sexual behaviors of males and females may be important when planning prevention programs with youth.

Objectives: The purpose of this study was to examine hematologist and patient perspectives about the side-effects of the corticosteroid treatment of immune thrombocytopenic purpura (ITP) and their perspectives about the patient’s risk for bleeding. The specific aim was to compare patient and hematologist perspectives and, if a difference was documented, the implications of that difference. We hypothesized that patients with ITP may have more concern about corticosteroid side-effects and less concern about serious bleeding than hematologists. Methods: We surveyed 80 patients in the Oklahoma ITP Registry and all 83 hematologists in Oklahoma about the occurrence and severity of 18 corticosteroid side-effects and risks for serious bleeding. Results: Response rates were 80% (patients) and 71% (hematologists). Responses of patients and hematologists were significantly different from each other regarding both the frequency of severe corticosteroid side-effects and the risk of serious bleeding. For 13 of the 18 corticosteroid side-effects, patients reported more frequent occurrence of severe symptoms than hematologists (P

BACKGROUND: Patients with apparent complete recovery from thrombotic thrombocytopenic purpura (TTP) often complain of problems with memory, concentration, and fatigue. STUDY DESIGN AND METHODS: Twenty-four patients who were enrolled in the Oklahoma TTP-HUS Registry for their initial episode of TTP, 1995-2006, and who had ADAMTS13 activity of less than 10 percent were evaluated for a broad range of cognitive functions 0.1 to 10.6 years (median, 4.0 years) after their most recent episode. At the time of their evaluation, they had normal physical and Mini-Mental State Examinations and no evidence of TTP. RESULTS: The patients, as a group, performed significantly worse on 4 of the 11 cognitive domains tested than standardized US data from neurologically normal individuals adjusted for age, sex, and education (p < 0.05). These four domains measured complex attention and concentration skills, information processing speed, rapid language generation, and rote memorization. Twenty-one (88%) patients performed below expectations on at least 1 of the 11 domains. No clear patterns were observed between cognitive test results and patients' characteristics or features of the preceding TTP, including age, occurrence of severe neurologic abnormalities, multiple episodes, and interval from an acute episode. CONCLUSION: Patients who have recovered from TTP may have persistent cognitive abnormalities. The abnormalities observed in these patients are characteristic of disorders associated with diffuse subcortical microvascular disease. Studies of larger patient groups will be required to confirm these preliminary observations and to determine patient characteristics that may contribute to persistent cognitive abnormalities.

Reports of deterioration and death after platelet (PLT) transfusions in patients with thrombotic thrombocytopenic purpura (TTP) have led to recommendations that they should not be given except for life-threatening hemorrhage.Published reports of PLT transfusions in patients with TTP were systematically reviewed and data from the Oklahoma TTP-HUS Registry, an inception cohort of 382 consecutive patients, 1989 through 2007, were analyzed.A systematic review identified 34 publications describing outcomes of patients with TTP after PLT transfusions: 9 articles attributed complications to PLT transfusions, 4 suggested that they may be safe, and 21 articles did not comment about a relation between PLT transfusions and outcomes. Fifty-four consecutive patients from the Oklahoma TTP-HUS Registry were prospectively analyzed. ADAMTS13 activity was less than 10 percent in 47 patients; also included were 7 patients whose activity was not measured but who may have been deficient. Thirty-three (61%) patients received PLT transfusions. The frequency of death was not different between the two groups (p = 0.971): 8 (24%) patients who received PLT transfusions died (thrombosis, 5; hemorrhage, 1; sepsis, 2) and 5 (24%) patients who did not receive PLT transfusions died (thrombosis, 4; hemorrhage, 1). The frequency of severe neurologic events was also not different (p = 0.190): 17 (52%) patients who received PLT transfusions (in 5 of these 17 patients, neurologic events only occurred before PLT transfusions) and 7 (33%) patients who did not receive PLT transfusions.Evidence for harm from PLT transfusions in patients with TTP is uncertain.

BACKGROUND: Case series of patients with a diagnosis of thrombotic thrombocytopenic purpura (TTP) have reported different frequencies of human immunodeficiency virus (HIV) infection; some series suggest that HIV infection may cause TTP. METHODS: We systematically reviewed all reports of HIV infection in case series of patients with TTP. We analyzed data from the Oklahoma TTP-HUS (hemolytic uremic syndrome) Registry, an inception cohort of 362 consecutive patients, for 1989-2007. RESULTS: Nineteen case series reported the occurrence of HIV infection at the time of diagnosis of TTP in 0%-83% of patients; individual patient data were rarely described. The Oklahoma TTP-HUS Registry determined the HIV status at the time of diagnosis of TTP in 351 (97%) of 362 patients. HIV infection was documented in 6 (1.84%; 95% CI, 0.68%-4.01%) of 326 adult patients (age, 26-51 years); follow-up data were complete for all 6 patients. The period prevalence of HIV infection among all adults in the Oklahoma TTP-HUS Registry region for 1989-2007 was 0.30%. One patient had typical features of TTP with 5 relapses. Five patients had single episodes; in 4, the clinical features that had initially suggested the diagnosis of TTP were subsequently attributed to malignant hypertension (in 3 patients) and disseminated Kaposi sarcoma (in 1 patient). CONCLUSIONS: HIV infection, similar to other inflammatory conditions, may trigger acute episodes of TTP in susceptible patients. More commonly, acquired immunodeficiency syndrome-related disorders may mimic the clinical features of TTP. If the diagnosis of TTP is suggested in a patient with HIV infection, there should be careful evaluation for alternative diagnoses and cautious consideration of plasma exchange, the required treatment for TTP.

Patients agedor = 80 years who are diagnosed with advanced ovarian cancer (OC) have been reported to have a poor prognosis. In the current study, chemotherapy-related toxicity data were evaluated between patients agedor = 80 years and those aged80 years.Patients with OC who underwent cytoreductive surgery with chemotherapy were included. Self-reported toxicity data were obtained from National Cancer Institute Common Toxicity Criteria (CTC) forms. Objective indicators of status including albumin level, weight, and creatinine clearance were abstracted both before and after therapy. Data were compared between patients by decade of age.A total of 246 patients were included. A presenting Karnofsky performance status2 was recorded in 17% of patients agedor = 80 years versus 0% to 4% of patients aged80 years (P = .002). Platinum-based chemotherapy was used in all patients. For patients aged80 years, combination chemotherapy was used in90% versus 69% in those agedor = 80 years (P.0001). Standard-dose combination therapy was used in 72% to 86% of patients aged80 years versus 28% of patients agedor =80 years (P.0001). Patients agedor =80 years completedor =6 cycles of therapy approximately 57% of the time versus 84% to 97% of the time for those aged80 years (P = .0001). CTC forms identified no self-reported toxicities to be more common among patients agedor =80 years. Multivariate logistic regression identified creatinine clearance65 mL/minute (odds ratio [OR] of 4.6), 5% weight loss (OR of 2.5), prechemotherapy albumin level of2 g/dL (OR of 3.65), and initiation of therapy with a single agent (OR of 3.9) as independent predictors of failure to complete chemotherapy.Despite initial treatment modifications as well as toxicity assessment, only 57% of patients agedor =80 years completed planned chemotherapy. It was confirmed that further studies into the pharmacokinetics of chemotherapy in the elderly and more sensitive assessment of therapy-related toxicity are required.

Cross-sectional studies suggest that assets are associated with youth abstinence, but whether these relationships are constant across developmental age groups has not been shown. Data for this study were obtained from two independent datasets collected across a 2-year period using in-person, in-home interviews of youth (52% female; 44% Caucasian, 23% Hispanic, 23% African-American, 10% other) and their parents (N = 2163 youth/parent pairs). Eighty-eight percent of teens aged 12-14 and 58% of teens aged 15-17 reported no sexual intercourse. Individual logistic regression models for assets and abstinence found 5 youth assets with significant adjusted odds ratios for both age groups: Non-Parental Adult Role models; Family Communication; Use of Time (Religion); Responsible Choices; and Peer Role Models. Community Involvement was associated with abstinence for young teens only and Aspirations for the Future and Good Health Practices only for middle teens. These findings can inform policies and programs targeting youth sexual decision-making.

After recovery from thrombotic thrombocytopenic purpura (TTP), patients commonly describe persistent problems with memory, concentration, and endurance.The Oklahoma TTP-HUS Registry, an inception cohort of 364 patients, January 1, 1989, through June 30, 2007, has annually evaluated health-related quality-of-life since 1998 with the Short Form (SF)-36, a widely used questionnaire that assesses eight domains of physical and mental health.A total of 128 patients were eligible for this study (ageor= 18 years, alive in January 1998 without prior relapse, survival and no relapseor=1 year after recovery, no overt disability or additional disorders); 118 (92%) completed the SF-36. At their initial assessment, these patients had significantly worse functioning and well-being than the US population for all domains (p0.05). Forty-nine patients who had their initial assessment more than 2 years after recovery had better scores for three domains than 69 patients who had their initial assessment 2 years or less after recovery (p0.05). Among these 69 patients, there was no difference between subgroups: 1) idiopathic versus other categories of TTP, 2) the presence or absence of severe ADAMTS13 deficiency, 3) the presence or absence of severe neurologic abnormalities during the episode of TTP, and 4) less than 10 or 10 or more plasma exchange treatments required to achieve remission (p0.05). Analysis of serial assessments in 72 (61%) of the 118 patients who had two or more assessments within 5 years of recovery and no intervening relapses demonstrated no significant improvement in any of the domains.After recovery from TTP, patients may have persistent cognitive and physical difficulties.

Objectives: Thrombotic thrombocytopenic purpura (TTP) was initially described as an uncommon and usually fatal disorder. With effective treatment it is more frequently diagnosed, the clinical presentations are more diverse, and long-term sequelae are becoming recognized. Methods: Patient data are from The Oklahoma TTP-hemolytic uremic syndrome (HUS) Registry, an inception cohort of 348 consecutive patients with their first episode of clinically diagnosed TTP or HUS, 1989‐2006. The Registry enrolls all patients in a defined region who are diagnosed with TTP or HUS and for whom plasma exchange treatment is requested. ADAMTS13 activity has been analyzed on 235 (93%) of 254 patients since 1995 at the University of Berne, Switzerland. Patients are described by clinical categories, related to their associated conditions and clinically apparent etiologies, and by the presence of severe ADAMTS13 deficiency. Results and conclusions: The clinical spectrum of syndromes described as TTP is variable with multiple etiologies. Advances in clinical and laboratory investigation have provided better understanding of the pathogenesis of these syndromes, their clinical evaluation and management, and their long-term outcomes. In addition to new information about TTP, these studies provide a model for translational research to define the complete community spectrum of uncommon disorders.