Oscar Segurado

ASC Therapeutics

To evaluate the efficacy and safety of adalimumab plus methotrexate (MTX) given for up to 4 years in patients with active, longstanding rheumatoid arthritis. Patients responding inadequately to MTX were entered into a 24 week, controlled study (ARMADA) with adalimumab plus MTX or placebo plus MTX, and some were enrolled in a subsequent open label e...

Metastatic renal cell carcinoma (RCC), like melanoma, belongs to the small group of human tumors in which partial or complete remission has been observed in some patients after treatment with various forms of immunotherapy. In contrast to melanoma, CTL showing MHC-restricted lysis of RCC have not been easily found among tumor-infiltrating lymphocyt...

To assess the diversity of T-cell receptor (TCR) gene rearrangements in uncloned lymphocytes we used a three-stage strategy that allows the detection of a restricted TCR repertoire and the identification of the predominant, rearranged sequence(s). We have analyzed in parallel T cells obtained from a renal cell carcinoma infiltrate that specifically...

Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resul...

Introduction : Hemophilia comprises a group of X-linked hemorrhagic disorders that result from a deficiency of coagulation factors. The disorder affects mainly males and leads to chronic pain, joint deformity, reduced mobility, and increased mortality. Current therapies require frequent administration of replacement clotting factors, but the emerge...

Graft versus host disease (GVHD) can occur at any period post allogeneic hematopoietic stem cell transplantation as a common clinical complication contributing to significant morbidity and mortality. Acute GVHD develops in approximately 30-50% of patients receiving transplants from matched related donors. High doses of steroids are used as first-li...

Introduction: Currently, a few in vivo gene replacement therapies are commercially available, with many in clinical development for the treatment of some inherited monogenic diseases. These disorders arise from mutations in genes encoding essential proteins with a well understood biological function. Wide adoption of gene replacement therapies req...

Precision medicine, a medical modality focusing on tailoring medical decision-making to individual patients, is changing the way we think about, prevent, treat, and monitor many diseases, including those requiring gene and cell therapies. Both gene and cell therapies involve the therapeutic transfer of new genetic material into a target cell with t...

Cell therapy requires precise screening and monitoring of patients to ensure that the transfer of either autologous or allogeneic cells to a patient results in a therapeutic effect to targeted organs or tissues. One well-established application of cell therapy is allogeneic hematopoietic stem cell transplantation (allo-HSCT) to treat hematologic co...

Objective Responsive assessment of disease activity in patients who have rheumatoid arthritis (RA) is necessary to evaluate therapeutic efficacy and guide treatment. We compared the utility of the multibiomarker disease activity (MBDA) score in the assessment of RA disease activity with that of the Disease Activity Score in 28 joints using the eryt...

Introduction Comprehensive genomic profiling of solid tumors using circulating tumor DNA (ctDNA) has enabled the detection of all NCCN guideline-recommended somatic genomic classes of alterations from a single, non-invasive blood draw. However, current ctDNA tests still face two major challenges: the inability to reliably identify somatic variants...

Introduction The availability of targeted and immunotherapies has provided NSCLC patients with more effective treatment options. However, this has resulted in an increase in the number and modality of tests required for treatment selection. Given 30-50% of advanced lung cancer patients have insufficient or unavailable tissue for comprehensive genom...

Introduction Circulating Tumor Cells (CTCs) are shed into the blood early by in situ neoplasm and are the mechanism by which cancer metastasizes. CTCs are generally precursors to ctDNA and can be used for early cancer detection. However, to the best of our knowledge, no platform has been analytically validated to detect CTCs in early stage/pre-canc...

Objective To evaluate the analytical performance of a 98-gene NGS panel designed to detect highly- penetrant, rare pathogenic germline variants, strongly linked to predisposition of cancers in Taiwan and USA. Methods This 98-gene panel was developed following an extensive review of genes with a strong clinical and genetic linkage evidence for cance...

Free kindle download: https://www.amazon.com/dp/B07BYRF5XL/ref=cm_sw_em_r_mt_dp_pFkCFbNJH4VDH - - - ANXIETY AND STRESS are epidemic in today’s fast-paced world. In response, many turn to meditation and related practices with limited long-term success. Meditation worked well for thousands of years, but can’t counter the effects of life in the twenty...

La relajación mental y física eran efectivas cuando la vida era más simple, pero no pueden contrarrestar la tensión constante que vivimos en el siglo 21. Necesitamos una nueva forma para controlar la ansiedad, especialmente si pensamos en el devastador efecto de la ansiedad y el estrés en el sistema inmune. La consecuencia son enfermedades graves c...

143 Background: The diagnostic confirmation of prostate cancer in patients with a PSA in the gray zone (4–10 ng/ml) is controversial, often leading to unnecessary biopsies. The sensitivity of the PSA test at a 4 ng/mL cut-off can be as low as 21%. We introduce a new test for prostate cancer detection in PSA gray zone patients, with the potential to...

556 Background: Colorectal cancer (CRC) is among the most preventable cancers when precancerous lesions are detected at an early stage. Current screening methods for CRC require bowel prep or stool-based testing that are inconvenient, resulting in low compliance. Stool based tests have limited sensitivity for the detection of precancerous lesions....

Objectives: To examine the association between a multibiomarker disease activity (MBDA) score, CRP and clinical disease activity measures among RA patients with and without concomitant FM. Methods: In an observational cohort of patients with established RA, we performed a cross-sectional analysis comparing MBDA scores with CRP by rank correlatio...

Objective Rheumatoid arthritis (RA) clinical trials often exclude patients with low C-reactive protein (CRP), slowing trial enrollment. We evaluated whether RA patients with a high multi-biomarker disease activity (MBDA) score (>44) among those with low CRP (≤10 mg/L) could complement patients with CRP >10mg/L to enhance patient recruitment without...

Background Dose reduction or stopping of TNF inhibitors (TNFi) appears to be feasible and safe in patients with rheumatoid arthritis (RA), but may lead to flaring. No factors, including DAS28-CRP, have been found to predict successful dose reduction thus far1. The multi-biomarker disease activity (MBDA) score measures disease activity in RA on a sc...

Background A multi-biomarker disease activity (MBDA) score (Vectra® DA) has been validated to assess disease activity, on a scale of 1-100, by measuring 12 serum biomarkers associated with inflammation in RA. Objectives To evaluate the correlation of MBDA score with DAS28-CRP and modified Sharp van der Heijde (mSvdH) progression score in a strategy...

Background Accurate measurement of disease activity is important for optimal management of patients with rheumatoid arthritis (RA). Better understanding of similarities and differences among the available clinical and biomarker-based disease activity measures may improve their use for therapeutic decision-making. Objectives Evaluate the relationshi...

Background The autoantibody positive (AAB+) subset of rheumatoid arthritis (RA) patients is prone to develop bone damage. Since the extent of bone erosion in AAB+ RA shows substantial variation, we hypothesized that, next to AAB, the level of local and systemic inflammation and tissue metabolism is the second factor determining damage. We therefore...

Background Clinical trials in rheumatoid arthritis (RA) often require elevated C-reactive protein (CRP), e.g., >10 mg/L, to enhance detection of clinical and radiographic efficacy. However, this inclusion criterion may limit recruitment by excluding some patients with active disease. The multi-biomarker disease activity (MBDA) score quantifies dise...

Background Clinical assessment of rheumatoid arthritis (RA) patients may be challenging when objective measures, such as C-reactive protein (CRP), do not show elevated disease activity or when patients have concomitant, non-inflammatory pain, as occurs with fibromyalgia (FM). A multi-biomarker disease activity (MBDA) blood test has been developed t...

Hematopoietic stem cell transplantation, which requires accurate enumeration of stem cells, is routinely used in clinical settings. Flow cytometry provides a qualitative and quantitative assessment of CD34+ cells. Precision, linearity, and stability of the novel BD™ Stem Cell Enumeration (SCE) Kit were evaluated on two flow cytometry platforms usin...

Joint damage is related to disease activity in rheumatoid arthritis (RA), but the degree of its progression and the temporal associations between disease activity and joint damage are unclear. The aim of this study was to evaluate whether there is a latency in the effect of disease activity on radiographic progression in patients with RA. Data were...

To estimate the comparative lifetime cost-effectiveness of sequenced therapy with tumor necrosis factor (TNF) antagonists as the initial therapeutic intervention for patients with early rheumatoid arthritis (RA). Because patients with RA switch regimens many times throughout the course of disease, sequenced therapeutic interventions were modeled, c...

Three novel restriction fragment length polymorphisms (RFLPs) have been identified using a pan-HLA class I probe and the endonuclease SstI. This study, in conjunction with previously reported SstI RFLPs, now allows the identification of the HLA-crossreacting antigens Aw19 (A29/30/31/32/w33), A23/24 and A3/11 by specific hybridization patterns with...

To estimate relative efficiencies of the 7 rheumatoid arthritis (RA) Core Data Set measures to distinguish adalimumab from control treatments in 4 clinical trials. Four adalimumab clinical trials were analyzed for arithmetic and percentage changes for each Core Data Set measure from baseline to endpoint: 3 assessor/physician measures -- swollen joi...

The HUMIRA (adalimumab) Pen is a novel, integrated, disposable autoinjection delivery system for the subcutaneous injection of adalimumab. Adalimumab is a biological disease modifier for the treatment of rheumatoid arthritis and other chronic debilitating diseases mediated by tumor necrosis factor. Sustaining long-term efficacy with a biological th...

To analyze 2 indices composed of the 3 patient reported outcomes (PRO) in the American College of Rheumatology (ACR) Core Data Set--physical function, pain, and global estimate--without joint count or laboratory data, for capacities to distinguish active from control treatments in 4 pivotal clinical trials. Data from 4 clinical trials involving ada...

Adalimumab is a therapeutic monoclonal antibody for SC administration by 2 single-use injection devices providing bioequivalent amounts of adalimumab: a ready-to-use, prefilled syringe and an integrated, disposable delivery system, the autoinjection Pen. Although pens have been shown to be preferred over syringes by patients requiring long-term SC...

To ask rheumatologists about the likelihood of performing a formal joint count at each visit of a patient with rheumatoid arthritis (RA) in standard clinical care. Direct query of rheumatologists at an international meeting of about 600 rheumatologists from 17 European countries. Overall, 14% of rheumatologists reported performing a formal joint co...

The most useful marker in gynaecological cancer is CA125 for epithelial ovarían malignancy. Although multiple studies have evaluated the potential of CA125 to screen for ovarían cancer in asymptomatic women, an insufficient number of women have so far been investigated to show whether or not early detection improves survival. A randomized trial is...

In this note is recommended a unified nomenclature for allotypes and variants of human complement factor B, which was approved by the Nomenclature Committee of the International Union of Immunological Societies (IUIS).

The wide variances between prostate specific antigen (PSA) values for various assays and the demonstration that many of these differences are due to calibration differences has resulted in efforts to develop standards for PSA. Two major efforts are underway in the USA. The National Committee for Clinical Laboratory Standards (NCCLS) has published p...

The AxSYM Free PSA assay was demonstrated to have good analytical sensitivity and reproducibility. The F/T ratio determinations for 385 men tested during the Prostate Awareness Week who had biopsies due to an elevated total PSA value and/or a suspicious DRE demonstrated that the percentage of free PSA was lower in patients found to have prostate ca...

Several solid tumors, including renal cell carcinoma (RCC), can display pronounced lymphocytic infiltrates which indicate the occurrence of a host antitumor immune response. With the exception of melanoma, the predominant cells that have been cultivated from tumor-infiltrating lymphocytes (TIL) and studied in vitro are nonspecific effector cells [i...

Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all branches of science and how science impacts upon all aspects of society and life.

Metastatic renal cell carcinoma (RCC), like melanoma, belongs to the small group of human tumors in which partial or complete remission has been observed in some patients after treatment with various forms of immunotherapy. In contrast to melanoma, CTL showing MHC-restricted lysis of RCC have not been easily found among tumor-infiltrating lymphocyt...

This note describes the designations for variants of the human complement component C2, which were approved by the Nomenclature Committee of the International Union of Immunological Societies (IUIS).

This note describes the recommended designations for allotypes of human complement component C4, which were approved by the Nomenclature Committee of the International Union of Immunological Societies (IUIS).

Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all branches of science and how science impacts upon all aspects of society and life.

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Several lines of evidence suggest that major histocompatibility complex (MHC)-linked susceptibility to insulin-dependent diabetes mellitus (IDDM) is not restricted to the presence or absence of any single gene product. The existence of population-specific haplotypes associated with IDDM supports the concept that distinct combinations of MHC alleles...

This note describes the recommended designations for allotypes of human complement component C4, which were approved by the Nomenclature Committee of the International Union of Immunological Societies (IUIS).

Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all branches of science and how science impacts upon all aspects of society and life.

The question of HLA susceptibility to Type 1 (insulin-dependent) diabetes mellitus remains unresolved. In the present study, 127 diabetic patients and 177 unrelated control subjects have been analysed for their class I and class II serological antigens, class II (DR, DQ) DNA restriction fragment length polymorphisms and DQA1 and B1 exon-2 nucleotid...

The first inherited combined total deficiency of C7 and C4B complement components associated with SLE is described in a young female. Functional C7 assays showed a homozygous C7 deficiency in the propositus and her sister, and an heterozygous one in their parents. C4 molecular analyses showed that both the propositus and her mother had two HLA hapl...

The combination of the HLA complement allotypes BFS, C2C, C4AQ0 (deleted gene) and C4B1, termed SC01 complotype, usually present in the HLA-B8,DR3,DQw2 diabetogenic haplotype, has also been found in a novel "low frequency" HLA-B49,DR4,DQw8 haplotype associated with Spanish insulin-dependent diabetes mellitus (IDDM). Family studies of C4 antigenic d...

We describe an infant whose peripheral blood mononuclear cells were unable to proliferate or synthesize IL-2 in response to a mitogenic combination of antibodies directed against CD2 and CD28. This peculiar defect, which has been stable to date, was attributed to an impairment in CD28-mediated T cell activation, because further comitogenic combinat...

A T cell line termed DIL2 has been derived from an infant with a polyclonal T cell receptor (TCR)/CD3 cell surface expression defect. Indirect immunofluorescence showed that the expression of certain TCR/CD3 epitopes (like those detected by WT31 and BMA031 monoclonals) was strongly reduced (around five-fold) on DIL2, whereas other epitopes (like th...

A novel TaqI restriction fragment length polymorphism (RFLP) of 4.15 kb is reported using a DR beta probe (pRTV1). This fragment corresponds to the DRB1 locus and allows the subdivision at the DNA level of the DRB1*0301 allele (DR3 antigen), which had not previously been reported. Both splits also distinguish each of the two DR3-bearing extended ha...

HLA-DR5 and DRw8 are not significantly linked to juvenile rheumatoid arthritis (JRA) in the Spanish population. However, we have found restriction fragment length polymorphisms (RFLPs) beta DR-2.9-kb-EcoRI and C4-14.3-kb-EcoRI, that correlate significantly with JRA. Eighty-six percent of our patients present either HLA-DR5 or the beta DR-2.9-kb-Eco...

Three novel restriction fragment length polymorphisms (RFLPs) have been identified using a pan-HLA class I probe and the endonuclease SstI. This study, in conjunction with previously reported SstI RFLPs, now allows the identification of the HLA-crossreacting antigens Aw19 (A29/30/31/32/w33), A23/24 and A3/11 by specific hybridization patterns with...

A simple and highly sensitive analytical isoelectric focusing (IEF) technique using immunofixation with anti-C2 serum followed by silver staining has been developed in order to study simultaneously the structural polymorphism of both native C2 and C2 activation fragments (C2a MW 74,000 and C2b MW 34,000). Structural C2 polymorphism of C2*B and C2*C...

When studied by immunoelectrophoresis the factor B (BF)*F allele is a monomorphic protein, but by using isoelectric focusing (IEF), it turns out to be polymorphic. Two BF*F allelic subdivisions, BF*FA and BF*FB, were detected in samples from unrelated Spanish donors; *FA and *FB are in Hardy-Weinberg equilibrium, segregate as autosomal codominant a...

When studied by immunoelectrophoresis the factor B (BF)*F allele is a monomorphic protein, but by using isoelectric focusing (IEF), it turns out to be polymorphic. Two BF*F allelic subdivisions, BF*FA and BF*FB, were detected in samples from unrelated Spanish donors; *FA and *FB are in Hardy-Weinberg equilibrium, segregate as autosomal codominant a...

An anti-Purkinje cell antibody (APCA) was found in serum and CSF of 2 patients with paraneoplastic cerebellar degeneration (PDC) and breast carcinoma. Integrity of the blood-brain barrier (BBB) was normal in one patient and slightly damaged in the other. In both patients CSF IgG index was normal, but CSF/serum APCA ratio and CSF IgG APCA index were...

Es wird die diagnostische Bedeutung der Serum und Liquorbefunde bei 235 Patienten mit primär entzündlichen Neuropathien dargestellt. Das Gesamtkollektiv enthält 100 Patienten mit einem Guillain-Barré-Syndrom (GBS), 10 Patienten mit einem Fisher-Syndrom (FS), 25 Patienten mit chronisch-entzündlichen Polyradikuloneuritiden (CEP), und 100 Patienten mi...

Es wird die diagnostische Bedeutung der Serum- und Liquorbefunde bei 235 Patienten mit primär entzündlichen Neuropathien dargestellt. Das Gesamtkollektiv enthält 100 Patienten mit einem Guillain-Barré-Syndrom (GBS). 10 Patienten mit einem Fisher-Syndrom (FS), 25 Patienten mit chronisch-entzündlichen Polyradikuloneuritiden (CEP), und 100 Patienten m...

Clinical data and the serum and cerebrospinal fluid (CSF) findings of 71 patients with Guillain-Barré syndrome (GBS), 7 with Fisher syndrome and 24 with chronic inflammatory polyradiculoneuropathy (CIP), were analysed. Isoelectric focusing of serum and CSF together with different formulae and diagrams were applied to study blood-CSF barrier (BCB) f...