The frequency of epstein-barr virus infection and associated lymphoproliferative syndrome after transplantation and its manifestations in children

Twenty cases of Epstein-Barr virus (EBV)-associated lymphoproliferative syndrome (LPS), defined by the presence of EBV nuclear antigen and/or EBV DNA in tissues, were diagnosed in 1467 transplant recipients in Pittsburgh from 1981—1985. The frequency of occurrence in pediatric transplant recipients was 4% (10/ 253), while in adults it was 0.8% (10/1214) (P < .0005). The frequency of LPS in adults declined after 1983 coincidental with the introduction of cyclosporine monitoring. However there was no apparent decline of LPS in children. We describe these ten pediatric cases and one additional case of LPS in a child who received her transplant before 1981. The frequency of EBV infection in 92 pediatric liver recipients was 63%. Of these subjects, 49% were sero-negative and 77% of those acquired primary infection. Of 11 cases of pediatric EBV-associated LPS, 10 were in children who had primary infection shortly before or after transplantation. These results reinforce the impor-tance of primary EBV infection in producing LPS, which was previously shown in adults. Children are at greater risk because they are more likely to be seronegative for EBV and to acquire primary infection. Three clinical types of LPS were recognized in children. The first (5 cases) was a self-limited mononucleo-sislike syndrome. The second syndrome (4 cases) began similarly, but then progressed over the next two months to widespread lymphoproliferation in internal organs and death. The third type (2 cases) was an extranodal intestinal monoclonal B cell lymphoma, occurring late after primary infection. © 1988 by The Williams and Wilkins Co

Infection with human immunodeficiency virus in the pittsburgh transplant population: A study of 583 donors and 1043 recipients, 1981-1986

We performed a retrospective serologic survey of 583 organ donors and 1043 transplant recipients for antibodies to human immunodeficiency virus type 1 (HIV- 1). Two (0.34%) of the 583 donors and 18 (1.7%) of the 1043 recipients had HIV-1 antibodies by enzyme immunoassay and by Western blot. Two of 5 seropositive recipients tested also had blood cultures positive for HIV-1. Seven (0.7%) of the 1043 transplant recipients had antibodies to HIV-1 before transplantation; 2 of these had hemophilia A, and 5 had previous transfusions. Eleven (1.3%) of 860 recipients followed for 45 days or more seroconverted to HIV-1 a mean of 96 days after transplantation. Likely sources of HIV-1 infection for 3 of these 11 recipients included a seropositive organ donor in 1 patient and high-risk blood donors in 2 patients. A definite source of HIV-1 infection was not found for the other 8 recipients, 3 of whom seroconverted to HIV-1 after institution of blood donor screening for HIV-1 antibodies. Seroconversion to HIV-1 was less common in kidney recipients than in liver, heart, or multiple-organ recipients (P<0.02). Nine (50%) of the 18 HIV-1 seropositive transplant recipients died a mean of 6 months after transplant surgery, and 9 (50%) are still alive a mean of 43 months after transplantation. AIDS-like illnesses occurred in 3 of the dead and 1 of the living patients and included pneumocystis pneumonia (3 cases), miliary tuberculosis (1 case), and recurrent cytomegalovirus infection (1 case). These data suggest that the course of HIV-1 infection is not more severe in transplant recipients receiving cyclosporine than in other hosts and that, despite screening of blood and organ donors, a small number of transplant recipients will become infected with HIV-1. © 1989 by The Williams and Wilkins Co

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care

Ideas in the Hispanic Caribbean in the nineteenth century: The antillanismo as emancipatory and integration ideal

En la compleja y conflictiva realidad del Caribe hispano del siglo XIX, emerge un conjunto de ideas que se organizan en torno de la voluntad de independencia, de libertad y autoafirmación política y cultural, de integración antillana y nuestroamericana. Ideas que pueden ser sintetizadas en el término antillanismo. Fueron esgrimidas en oposición al colonialismo y al imperialismo y fundamentadas desde posiciones filosóficas que abarcaron un amplio espectro, desde la ilustración al positivismo y el krausismo. Su originalidad radica en haber constituido una trama discursiva ligada dialécticamente a los acontecimientos de la situación social e histórica que buscaba comprender y transformar.In the Spanish Caribbean complex and conflicting realities of nineteenth–century, grows a set of ideas that are organized around the desire for independence, freedom, political and cultural self–assertion and integration. These ideas can be summarized in the term antillanismo. They were put forward in opposition to colonialism and imperialism and reasoned from philosophical positions that covered a wide spectrum, from illustration to positivism and krausism. Its originality lies in having formed a discursive frame dialectically linked to the events of the socio–historical situation that sought to understand and transform.Fil: Arpini, Adriana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentin

Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma

Objective Long-term safety of pembrolizumab in melanoma was analyzed in KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006. Patients and methods Analysis involved patients who received ≥1 pembrolizumab dose. Lead-time bias was addressed via landmark analyses in patients who were progression-free before day 147. Results Adverse events (AEs) were analyzed for 1567 patients (median follow-up, 42.4 months). Most AEs were mild/moderate; grade 3/4 treatment-related AEs occurred in 17.7% of patients. Two pembrolizumab-related deaths occurred. Any-grade immune-mediated AEs (imAEs) occurred in 23.0%, most commonly hypothyroidism (9.1%), pneumonitis (3.3%), and hyperthyroidism (3.0%); grade 3/4 imAEs occurred in 6.9% of patients. Most imAEs occurred within 16 weeks of treatment. In landmark analysis, patients who did (n = 79) versus did not (n = 384) develop imAEs had similar objective response rates (ORRs) (64.6% versus 63.0%); median time to response (TTR), 5.6 months for both; median duration of response (DOR), 20.0 versus 25.3 months; median progression-free survival (PFS), 17.0 versus 17.7 months; median overall survival (OS), not reached (NR) versus 43 months (p = 0.1104). Patients who did (n = 17) versus did not (n = 62) receive systemic corticosteroids had similar ORRs (70.6% vs. 62.9%) and median TTR (6.4 vs. 5.6 months) but numerically shorter median PFS (9.9 vs. 17.0 months); median DOR, 14.2 months versus NR; median OS, NR for both. Conclusions These results enhance the knowledge base for pembrolizumab in advanced melanoma, with no new toxicity signals after lengthy follow-up of a large population. In landmark analyses, pembrolizumab efficacy was similar regardless of imAEs or systemic corticosteroid use. Clinical trial registry NCT01295827, NCT01704287, NCT01866319

Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling

Although melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression

Developing the Social Skills of Young Adult Special Olympics Athletes

The purpose of the study was to determine if young adult Special Olympics participants could develop, generalize, and maintain target social skills (eye contact, contributing relevant information, and turn taking) as a result of a 14-week Social Skills and Sports (S3) Program that combined classroom instruction with soccer activities. Data were collected through direct observation during soccer practices, parent interviews, and parent rating forms. Visual analysis and qualitative methodology were applied to analyze the four case studies. All of the participants increased their ability to demonstrate at least one of the targeted skills, generalized the skill(s) to other settings, and maintained the skill(s) five weeks after completing the intervention. Participants also developed social skills that were not targeted in S 3