Implementation of a High-Accuracy Targeted Gene Expression Panel for Clinical Care.

This study describes the validation of a clinical RNA expression panel with evaluation of concordance between gene copy gain by a next-generation sequencing (NGS) assay and high gene expression by an RNA expression panel. The RNA Salah Targeted Expression Panel (RNA STEP) was designed with input from oncologists to include 204 genes with utility for clinical trial prescreening and therapy selection. RNA STEP was validated with the nanoString platform using remnant formalin-fixed, paraffin-embedded-derived RNA from 102 patients previously tested with a validated clinical NGS panel.

RET splice site variants in medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is an aggressive cancer that is often caused by driver mutations in . Splice site variants (SSV) reflect changes in mRNA processing, which may alter protein function. SSVs have been described in thyroid tumors in general but have not been extensively studied in MTC.

Comparing Three Methods for Reducing Psychotropic Use in Older Demented Spanish Care Home Residents.

Background/objective: In nursing homes across the world, and particularly in Spain, there are concerns that psychotropic medications are being overused. For older Spanish nursing home residents who had dementia, we sought to evaluate the association between applying interventions designed to reduce inappropriate psychotropic medication use and subsequent psychotropic use.

Design: Retrospective, propensity score-matched, controlled, patient-level observational analysis.

Effect of nonpermissive HLA-DPB1 mismatches after unrelated allogeneic transplantation with in vivo T-cell depletion.

We investigated the impact of donor-recipient HLA-DPB1 matching on outcomes of allogeneic hematopoietic stem cell transplantation with in vivo T-cell depletion using antithymocyte globulin (ATG) for patients with hematological malignancies. All donor-recipient pairs had high-resolution typing for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DRB3/4/5 and were matched at HLA-A, HLA-B, HLA-C, and HLA-DRB1. HLA-DPB1 mismatches were categorized by immunogenicity of the DPB1 matching using the DPB T-cell epitope tool.

In Vitro Studies of Chromone-Tetrazoles against Pathogenic Protozoa, Bacteria, and Fungi.

In vitro studies to fourteen previously synthesized chromone-tetrazoles and four novel fluorine-containing analogs were conducted against pathogenic protozoan (Entamoeba histolytica), pathogenic bacteria (Pseudomonas aeruginosa, and Staphylococcus aureus), and human fungal pathogens (Sporothrix schenckii, Candida albicans, and Candida tropicalis), which have become in a serious health problem, mainly in tropical countries.

Synthesis of 3-tetrazolylmethyl-4H-chromen-4-ones via Ugi-azide and biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis.

The synthesis of novel 3-tetrazolylmethyl-4H-chromen-4-ones via an Ugi-azide multicomponent reaction and their biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis are described. Reported yields are moderate to good and biological results show that these compounds could be considered as candidates to anti-parasitic drugs, especially against G. lamblia.

[Relevance of CYP2C19 2 regarding platelet reactivity in patients with acute coronary syndrome treated with clopidogrel].

Background And Objective: Previous studies have shown that the metabolism of P2Y12 receptor blockers is influenced not only by CYP2C19 2 but also by PON1-Q192R alelles. We aimed to evaluate the impact of CYP2C19 2 and PON1-Q192R polymorphisms carriage in platelet reactivity and clinical outcome in patients with ischemic heart disease undergoing cardiac catheterization.

Patients And Method: We recruited prospectively patients with acute coronary syndrome undergoing cardiac catheterization (n=247).

Multiple mismatches at the low expression HLA loci DP, DQ, and DRB3/4/5 associate with adverse outcomes in hematopoietic stem cell transplantation.

A single mismatch in highly expressed HLA-A, -B, -C, and -DRB1 loci (HEL) is associated with worse outcomes in hematopoietic stem cell transplantation, while less is known about the cumulative impact of mismatches in the lesser expressed HLA loci DRB3/4/5, DQ, and DP (LEL). We studied whether accumulation of LEL mismatches is associated with deleterious effects in 3853 unrelated donor transplants stratified according to number of matches in the HEL. In the 8/8 matched HEL group, LEL mismatches were not associated with any adverse outcome.

Characteristics of culprit atheromatous plaques obtained in vivo by intravascular ultrasound radiofrequency analysis: results from the CULPLAC study.

Objectives: We used virtual histology-intravascular ultrasound (VH-IVUS) to investigate the characteristics of culprit lesions in acute coronary syndromes (ACS).

Background: Autopsy studies of patients who died of ACS have shown that culprit atheromatous plaques almost always contain a large lipid-necrotic core covered by a ruptured thin fibrous cap. There are no studies of sufficient size that have assessed the in vivo characterization of plaques responsible for ACS.

Psychotropic medications and falls in nursing homes: a cross-sectional study.

Background: Psychotropic medications are very frequently used in nursing homes and have been associated with falls. Little is known on the potential differences between types and subtypes of these medications, and also regarding different prescription patterns.

Methods: Data from 4502 residents living in 41 nursing homes belonging to a Spanish private chain were collected during a study period of 1 month and analyzed.

HLA population genetics: a Lebanese population.

Human leukocyte antigen (HLA) typing was done in 426 Lebanese subjects of 88 families, in which 347 haplotypes were identified. The A, B, C, DRB1, DRB3/4/5, DQB1 and DPB1 loci were typed at high resolution. This study shows that information theory, as originally developed by Claude Shannon in 1948, provides a promising theoretical foundation to study the population genetics of a genetic system like HLA.

Cytokine gene polymorphisms affect reactivation of cytomegalovirus in patients with cancer.

Reactivation of cytomegalovirus (CMV) in the bloodstream may occur upon severe immune defect or suppression during lifetime. We performed a case controlled study to probe the effects of the host cytokine gene single nucleotide polymorphisms (SNPs) on CMV reactivation. The study subjects were patients with cancer but without stem cell transplantation.

Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations.

The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products.

Exploiting antitumor immunity to overcome relapse and improve remission duration.

Cancer survivors often relapse due to evolving drug-resistant clones and repopulating tumor stem cells. Our preclinical study demonstrated that terminal cancer patient's lymphocytes can be converted from tolerant bystanders in vivo into effective cytotoxic T-lymphocytes in vitro killing patient's own tumor cells containing drug-resistant clones and tumor stem cells. We designed a clinical trial combining peginterferon α-2b with imatinib for treatment of stage III/IV gastrointestinal stromal tumor (GIST) with the rational that peginterferon α-2b serves as danger signals to promote antitumor immunity while imatinib's effective tumor killing undermines tumor-induced tolerance and supply tumor-specific antigens in vivo without leukopenia, thus allowing for proper dendritic cell and cytotoxic T-lymphocyte differentiation toward Th1 response.

Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation.

Anti-HLA donor-specific Abs (DSAs) have been reported to be associated with graft failure in mismatched hematopoietic stem cell transplantation; however, their role in the development of graft failure in matched unrelated donor (MUD) transplantation remains unclear. We hypothesize that DSAs against a mismatched HLA-DPB1 locus is associated with graft failure in this setting. The presence of anti-HLA Abs before transplantation was determined prospectively in 592 MUD transplantation recipients using mixed-screen beads in a solid-phase fluorescent assay.

Mismatches outside exons 2 and 3 do not alter the peptide motif of the allele group B*44:02P.

Sequence variations outside exons 2 and 3 do not appear to affect the function of human leukocyte antigen (HLA) class I alleles. HLA-B*44:02:01:01 and -B*44:27 are considered functionally identical because they differ by a single amino acid substitution of Val > Ala at position 199, which is located in the α3 domain. To validate that HLA-B*44:02:01:01 and -B*44:27 represent functionally identical alleles that might reflect a permissive mismatch in hematopoetic stem cell transplantation (HSCT), we determined their peptide-binding features.

Altered decamer and nonamer from an HLA-A0201-restricted epitope of Survivin differentially stimulate T-cell responses in different individuals.

Survivin is a universal tumor antigen that is being currently targeted in vaccine approaches against cancer. Our study here examined the immunogenicity of a novel variant of an HLA-A0201-binding decamer peptide from region 95 to 104 of Survivin (ELMLGEFLKL) with a T→M modification at position 3 in the peptide. We found that this new modified 10-mer peptide had enhanced HLA-A0201 binding and induced a stronger T-cell response over its wild type counterpart peptide (ELTLGEFLKL) in select HLA-A0201(+) normal donors.

Results of HLA antibody testing using ELISA vs the fluorescent bead method and retrospective review of data for recipients of packed RBCs and platelets from male HLA-immunized donors.

We reviewed HLA antibody testing results using an enzyme-linked immunosorbent assay (ELISA) for all male blood donors at our institution during a 3.5-month period to look for HLA immunization. Confirmatory testing of 33 blood samples positive for HLA class I and/or II antibodies was performed using the fluorescent bead method.

Prophylaxis of graft-versus-host disease in unrelated donor transplantation with pentostatin, tacrolimus, and mini-methotrexate: a phase I/II controlled, adaptively randomized study.

Purpose: Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after matched unrelated, related, or mismatched related donor hematopoietic stem-cell transplantation (HSCT). Improved GVHD prevention methods are needed. Pentostatin, an adenosine deaminase inhibitor, leads to lymphocyte depletion with low risk of myelosuppression.

Outcomes of patients with myeloid malignancies treated with allogeneic hematopoietic stem cell transplantation from matched unrelated donors compared with one human leukocyte antigen mismatched related donors using HLA typing at 10 loci.

Most candidates for hematopoietic stem cell transplantation (HSCT) lack a human leukocyte antigen (HLA)-identical sibling donor. Some patients may have a related donor with whom they are mismatched at 1 antigen/allele. It is not known whether such a match is preferable to a matched unrelated donor (MUD).

High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation.

BACKGROUND.: Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been implicated in graft rejection in solid organ transplantation, their role in hematopoietic stem-cell transplantation remains unclear. METHODS.

Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease.

The polymorphic products of major histocompatibility complex class I-related chain A (MICA) genes are important in solid organ transplantation rejection. MICA expression is limited to gut epithelium and may play a role in triggering acute graft-versus-host disease (aGVHD). A total of 236 recipients of unrelated donor transplantation were studied.