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Biomedical subjects

Javier Zamora

Publications and source records attributed to Javier Zamora.

13 recordsLinked to original sources
PubMed2026

Tumour-infiltrating lymphocytes differ across MammaPrint® classifications in breast cancer.

MammaPrint&#xae; refines risk stratification in early oestrogen receptor-positive, HER2-negative breast cancer, evolving from a binary to a four-tier classification (UltraLow-Risk, Low-Risk, High-Risk 1, and High-Risk 2). The relationship between routine histopathological features, immune infiltration, and genomic risk within this framework remains incompletely characterized in luminal disease. We retrospectively analysed 492 luminal breast carcinomas with available MammaPrint&#xae; results. Clinicopathological variables (including histological subtype, grade, Ki-67, hormone receptor expression, lymphovascular invasion (LVI), and HER2-low status) were recorded. Stromal tumour-infiltrating lymphocytes (TILs) were quantified according to the criteria of Salgado et al. and spatially categorized as immune-deserted, stromal-restricted, immune-excluded, or inflamed patterns. CD4 and CD8 infiltration was assessed by immunohistochemistry on tissue microarrays. Associations with binary and four-tier MammaPrint&#xae; categories were examined using multivariable models. High-Risk tumours (41%) were enriched for increased grade, Ki-67, and LVI and lower PR expression. In High-Risk tumours, inflamed spatial patterns were more frequent and median TIL levels were significantly higher compared with Low-Risk tumours (15% vs 5%, P < 0.001). CD4 and CD8 infiltration increased with genomic risk, and CD4 retained a modest but statistically significant association after adjustment for conventional pathological variables. In the four-tier model, UltraLow-Risk/Low-Risk tumours showed minimal TILs and were enriched for invasive lobular carcinoma, whereas High-Risk 1/High-Risk 2 tumours displayed progressively higher proliferative and immune features. No association was observed between HER2-low status and genomic risk. Immune infiltration parallels proliferative and genomic risk gradients in luminal breast cancer. These findings indicate that immune descriptors align with the genomic risk continuum, although their independent prognostic contribution beyond established genomic assays requires further evaluation.

Humans↗
PubMed2005

Accuracy of B-type natriuretic peptide levels in the diagnosis of left ventricular dysfunction and heart failure: a systematic review.

OBJECTIVES: To evaluate the accuracy of B-type natriuretic peptide levels (BNP) in the diagnosis of heart failure and left ventricular dysfunction. DATA SOURCES: Electronic search in Medline, Embase, Cochrane Library and Medion database, and hand search of reference lists. REVIEW METHODS: We have included published studies on the accuracy of BNP which had both sufficient information to construct the 2x2 diagnostic cross table and an appropriate spectrum of patients. RESULTS: Fifty five studies (16,730 patients) were analyzed. The main determinants of diagnostic accuracy were the reference standard analyzed (clinical heart failure versus left ventricular dysfunction), and the methodological quality of the study. BNP levels were highly accurate for the diagnosis of clinical heart failure (diagnostic OR=41; 95% CI 23-74). The negative likelihood ratios were homogeneous, and useful for excluding the existence of heart failure (pooled negative likelihood ratio=0.11; 95% CI 0.08-0.16). The studies focused on the identification of left ventricular dysfunction were heterogeneous, with indications of publication bias, and showed less overall diagnostic accuracy than studies focused on heart failure. CONCLUSIONS: BNP levels are useful for ruling out heart failure. The accuracy of BNP for identifying patients with systolic dysfunction is more limited.

Cardiac Output, Low↗
PubMed2005

The transition from acute to subacute and chronic low back pain: a study based on determinants of quality of life and prediction of chronic disability.

STUDY DESIGN: Follow-up study. OBJECTIVES: To document differences between acute and subacute low back pain (LBP) based on the risk of developing chronic disability and on the correlation between pain, disability, and quality of life. SUMMARY OF BACKGROUND DATA: The subacute stage should identify the time in which the risk of developing chronic disability increases and specific measures should be considered, but its definition is currently inconsistent. METHODS: 366 patients were given Visual Analog Scales (VAS) for LBP and referred pain (RP), Roland-Morris questionnaires (RMQs), and EuroQol (EQ) questionnaires on their first visit and 14 and 59 days later. RESULTS: Median duration of pain when entering the study was 4 days (P25, P75: 2,10). Simple correlations among LBP, VAS, and RMQ were r = 0.407 (day 1), 0.688 (day 15), and 0.739 (day 60). Among LBP, VAS, and EQ, r = -0.523, r = -0.701, and r = -0.760. Among RP, VAS, and RMQ, r = 0.280, r = 0.561, and r = 0.583. Between RP, VAS, and EQ, r = -0.306, r = -0.534 and r = -0.600. Between RMQ and EQ, r = -0.650, r = -0.765 and r = -0.815. In 42 patients, disability did not improve throughout the study period, and a prestudy duration of > or = 14 days was the only independent predictor. All these models were significant at the P < 0.007 level. Improvement in quality of life was more likely to occur in patients in which disability improved [odds ratio (OR), 18.29; 95% CI; 8.64, 38.73; P < 0.001]. As opposed to acute patients, in those with a prestudy duration of pain of > or = 14 days, on day 60 RP had no influence on disability, and LBP had no influence on quality of life. CONCLUSION: LBP influences disability and quality of life more than RP. Disability is predicted by pain duration and quality of life is predicted by disability, but pain severity predicts neither one of them. Changes related to determinants of disability and quality of life, and to the prediction of chronic disability, appear 14 days after the onset of pain, supporting that cutoff point for considering a patient as being subacute.

Acute Disease↗
PubMed2004

Steroid withdrawal in renal transplant patients on triple therapy with a calcineurin inhibitor and mycophenolate mofetil: a meta-analysis of randomized, controlled trials.

BACKGROUND: Two previous meta-analyses of randomized, controlled trials of steroid withdrawal after renal transplantation have shown significant increases in acute rejection (both analyses) and graft failure rates (the last analysis). A new examination of this topic including only randomized, controlled trials based on currently used, new, potent therapy with calcineurin inhibitors and mycophenolate mofetil (MMF), avoiding early trials with azathioprine, is justified. METHODS: Steroid withdrawal in patients on triple therapy including a calcineurin inhibitor and MMF was assessed through meta-analysis of randomized, controlled trials in which intention-to-treat rates of acute rejection and renal allograft failure were established after steroid withdrawal or continuation. RESULTS: Six trials were included, four in patients receiving cyclosporine and two in patients receiving tacrolimus. The risk ratio (RR) for acute rejection was 2.28 (95% confidence interval [CI], 1.65-3.16; P < 0.00001) and the pooled risk difference (RD) was 0.08 (95% CI, 0.05-0.11; P < 0.001), indicating that the proportion of patients with acute rejection after prednisone withdrawal was significantly higher compared with controls. The RR for graft failure was 0.73 (95% CI, 0.42-1.28; P = 0.27) and the RD was -0.01 (95% CI, -0.03-0.01; P = 0.28), indicating that the proportion of patients with graft failure after withdrawal was not significantly different from that observed in controls. Total cholesterol was significantly lower after steroid withdrawal (weighted mean difference, -0.53 microM (95% CI, -0.70 to -0.36; P < 0.0001). CONCLUSIONS: Renal allograft recipients on triple therapy with a calcineurin inhibitor, MMF, and steroids are at low but significant risk of acute rejection after steroid withdrawal but do not suffer an increased risk of early graft failure. It is necessary to extend controlled follow-up to confirm graft function stabilization.

Adrenal Cortex Hormones↗
PubMed2004

CD4 cell recovery during successful antiretroviral therapy in naive HIV-infected patients: the role of intravenous drug use.

We evaluated the impact of HIV risk practice on immune reconstitution in a prospective cohort of 288 patients (176 former injecting drug users) who maintained complete virus suppression for more than 24 months. Significant differences in CD4 cell counts at 6 and 24 months were detected. Multivariate analysis showed that drug use was an independent predictor of poor immunological recovery. Injection drug abuse impairs short and long-term CD4 cell recovery in HIV-positive patients initiating successful highly active antiretroviral therapy.

Adult↗
PubMed2004

Influence of biologic markers on the outcome of Hodgkin's lymphoma: a study by the Spanish Hodgkin's Lymphoma Study Group.

PURPOSE: Current therapies fail to cure a significant proportion of patients with Hodgkin's lymphoma (HL). Predictive systems for stratification of the disease and selection of treatment based on sets of clinical variables, such as the international prognostic score (IPS), are of relatively small practical value. The predictive use of biologic parameters has so far provided limited and inconsistent results. Here we explore the influence of a set of molecular markers on the outcome of HL. PATIENTS AND METHODS: Forty molecular markers involved in B-cell differentiation and activation, signal transduction, cell cycle, and apoptosis control were analyzed in 259 classic HL patient cases by using tissue microarrays. Univariate analysis was performed to evaluate the influence of markers on favorable outcome (complete remission of > 12 months). Significant variables were included in a multivariate logistic regression analysis, and the probability of favorable outcome was estimated. RESULTS: Univariate analysis revealed four molecular markers that predicted outcome, and the multivariate analysis showed p53, Bcl-X(L), and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) to have independent significance. The combination of these factors determined two groups of patients (group I, zero to one factor; group II, two to three factors) with a probability of a favorable outcome of.948 and.687, respectively. A multivariate Cox's model shows that these biologic risk groups have special predictive power in low-IPS patients. CONCLUSION: The data from this exploratory study suggest that the accumulation of molecular events seems to influence the outcome of HL, particularly in the low-IPS group.

Adolescent↗
PubMed2004

Correlation between pain, disability, and quality of life in patients with common low back pain.

STUDY DESIGN: Correlation among previously validated questionnaires. OBJECTIVES: To determine the correlation between pain, disability, and quality of life in patients with low back pain. SUMMARY OF BACKGROUND DATA: The Visual Analogue Scale (VAS), and the Roland-Morris (RMQ), Oswestry (OQ), and EuroQol (EQ) Questionnaires are validated instruments to assess pain, low back pain-related disability, and quality of life. METHODS: The study was done in the primary care setting, in Mallorca, with 195 patients who visited their physician for LBP. Individuals were given the VAS, RMQ, OQ, and EQ on their first visit and 14 days later. RESULTS: Median duration of pain when entering the study was 10 days (P25,P75: 3, 40). On day 1, simple correlation was r = 0.347 between VAS and RMQ, r = -0.422 between VAS and EQ, and r = -0.442 between RMQ and EQ. On day 15, simple correlation was r = 0.570 between VAS and RMQ, r = -0.672 between VAS and EQ, and r = -0.637 between RMQ and EQ. Multiple linear regression models showed that, on day 1, the VAS score explains 12% of the RMQ score and the VAS and RMQ scores explain 27% of the EQ score. On day 15, the VAS score explains 33% of the RMQ score, and the VAS and RMQ scores explain 58% of the EQ score. On day 1, a 10% increase in VAS worsens disability by 3.3% and quality of life by 2.65%. On day 15, a 10% increase in VAS worsens disability by 4.99% and quality of life by 3.80%. Prestudy duration of pain had no influence on any model. All these correlation coefficients and models are significant at the P < 0.001 level. The OQ had lower correlation values with the other three scales, and only two of them were significant. CONCLUSION: Clinically relevant improvements in pain may lead to almost unnoticeable changes in disability and quality of life. Therefore, these variables should be assessed separately when evaluating the effect of any form of treatment for low back pain. The influence of pain and disability on quality of life progresses while they last, and doubles in 14 days. In acute and subacute patients, this increase is not dependent on the previous duration of pain.

Disability Evaluation↗
PubMed2004

The role of angiotensin receptor blockers and/or angiotensin converting enzyme inhibitors in the prevention of atrial fibrillation in patients with cardiovascular diseases: meta-analysis of randomized controlled clinical trials.

UNLABELLED: The inhibition of the renin-angiotensin system has demonstrated both experimental and clinical effects in preventing atrial fibrillation. However, there is still uncertainty about the role of these drugs in clinical practice. The objective of this review has been to assess the effects of angiotensin II type-1 receptor blockers (ARBs) and/or angiotensin converting enzyme inhibitors (ACEIs) for preventing atrial fibrillation. We searched the Cochrane controlled Trials Register (Cochrane Library Issue 4, 2002), MEDLINE (January 1980 to November 2003), EMBASE (January 1980 to November 2003) and reference list of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: We conducted a meta-analysis of all randomized controlled clinical trials that compared ARBs and/or ACEIs with either placebo or conventional therapy in patients with either hypertension, heart failure, ischemic heart disease, or diabetes mellitus. The pooled outcome was the development of new onset atrial fibrillation. Two reviewers independently assessed trial quality and extracted data. In some cases, the study authors were contacted for additional information. Seven trials involving a total of 24,849 patients were included (11,328 randomized to active therapy and 13,521 to control). There was a significant statistical difference in the pooled development of atrial fibrillation between the treatment and control group. (OR, 0.57; 95% CI, 0.39 to 0.82); test for overall effect z = 2.98 P = 0.003). Treatment with ACEIs/ARBs markedly reduces the risk of development or recurrence of atrial fibrillation.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

[Usefulness of brain natriuretic peptide to evaluate patients with heart failure treated with cardiac resynchronization].

INTRODUCTION AND OBJECTIVES: The aim of the present study was to document the evolution of the blood levels of brain natriuretic peptide (BNP) in patients with heart failure and their correlation with the clinical course after implantation of a biventricular pacemaker. PATIENTS AND METHOD: Twenty-eight patients with heart failure associated to left bundle branch block and left ventricular systolic dysfunction were included in the study. In each patient we performed laboratory tests, chest X-ray, electrocardiogram and echocardiogram, and measured blood levels of BNP. RESULTS: During follow-up (10 [6] months) functional capacity improved, decreasing from 3.3 (0.6) to 2.10 (0.4) (P=.03). The rate of hospitalizations for heart failure decreased from an average of 1.8 (0.7) (6 months before the procedure) to 0.8 (0.3) (6 months after the procedure; P=.04). The basal value of BNP decreased from 193 (98) pg/mL to 52 (14) at the end of the follow-up in the responder group (22 patients) and increased from 564 (380) to 650 (80) pg/mL in the nonresponder group (6 patients). Patients who responded showed significant clinical improvement and decreasing levels of BNP, which reached a plateau an average of 6 months after implantation. Multivariate logistic regression analysis identified lower levels of BNP, idiopathic dilated cardiomyopathy, and functional class as independent predictors of response to therapy. Age, QRS width and left ventricular ejection fraction were not predictors of response. CONCLUSIONS: Brain natriuretic peptide concentrations allowed us to monitor, in an objective manner, the clinical course of patients with biventricular resynchronization therapy.

Aged↗
PubMed2004

Immunosuppressive treatment for idiopathic membranous nephropathy: a systematic review.

BACKGROUND: This study aims to assess whether immunosuppression is beneficial in the treatment of idiopathic membranous nephropathy (IMN). METHODS: We reviewed randomized controlled trials (RCTs) addressing the effect of immunosuppression on histologically proven IMN in adults with nephrotic syndrome followed up for at least 6 months. The literature was searched according to Cochrane Collaboration guidelines. Four therapeutic classes were considered: (1) steroids (alone), (2) alkylating agents (alone or in combination with steroids), (3) calcineurin inhibitors (alone or in combination with steroids), and (4) antiproliferative agents (alone). RESULTS: Eighteen RCTs were selected (1,025 patients). Overall, no differences were found between immunosuppressive treatment and placebo or no treatment. For oral glucocorticoid therapy, no beneficial effect was observed. For alkylating agents, a beneficial effect was observed on complete remission (relative risk [RR], 2.37; 95% confidence interval [CI], 1.32 to 4.25; P = 0.004). Excluding patients with particularly well-preserved renal function, there was no significant difference in complete remission. Cyclophosphamide therapy resulted in a lower rate of adverse-event discontinuations compared with chlorambucil (8 versus 21 discontinuations, respectively; RR, 2.34; 95% CI, 1.25 to 4.39; P = 0.008). For calcineurin inhibitors, no difference was observed. For antiproliferative agents, a paucity of data did not allow a conclusion. CONCLUSION: The meta-analysis failed to show a long-term effect of treatment on patient and/or renal survival. There is weak evidence that the immunosuppressive regimen increased the remission rate. The review of safety showed a higher number of discontinuations for adverse events in immunosuppressive-treatment groups and that cyclophosphamide had fewer side effects than chlorambucil.

Alkylating Agents↗
PubMed2003

Effect of firmness of mattress on chronic non-specific low-back pain: randomised, double-blind, controlled, multicentre trial.

BACKGROUND: A firm mattress is commonly believed to be beneficial for low-back pain, although evidence supporting this recommendation is lacking. We assessed the effect of different firmnesses of mattresses on the clinical course of patients with chronic non-specific low-back pain. METHODS: In a randomised, double-blind, controlled, multicentre trial, we assessed 313 adults who had chronic non-specific low-back pain, but no referred pain, who complained of backache while lying in bed and on rising. Mattress firmness is rated on a scale developed by the European Committee for Standardisation. The H(s) scale starts at 1.0 (firmest) and stops at 10.0 (softest). We randomly assigned participants firm mattresses (H(s)=2.3) or medium-firm mattresses (H(s)=5.6). We did clinical assessments at baseline and at 90 days. Primary endpoints were improvements in pain while lying in bed, pain on rising, and disability. FINDINGS: At 90 days, patients with medium-firm mattresses had better outcomes for pain in bed (odds ratio 2.36 [95% CI 1.13-4.93]), pain on rising (1.93 [0.97-3.86]), and disability (2.10 [1.24-3.56]) than did patients with firm mattresses. Throughout the study period, patients with medium-firm mattresses also had less daytime low-back pain (p=0.059), pain while lying in bed (p=0.064), and pain on rising (p=0.008) than did patients with firm mattresses. INTERPRETATION: A mattress of medium firmness improves pain and disability among patients with chronic non-specific low-back pain.

Adult↗
PubMed2002

Interkinetic nuclear movement may provide spatial clues to the regulation of neurogenesis.

During the transition from S phase to mitosis, vertebrate neuroepithelial cells displace their nuclei and subsequently migrate from the basal membrane to the apical surface of the neuroepithelium, a phenomenon termed interkinetic nuclear movement (INM). Here we provide evidence that cycling neuroepithelial cells pass through a neurogenic state in which they are situated apically, as defined by the capacity to express Notch1, Delta1, and Neurogenin2 (Ngn2). Based on this scenario, we have developed a mathematical model to analyze the influence of INM on neurogenesis. In the absence of INM, the model predicted an increase in the rate of neurogenesis due to the reduction in the influence of inhibitory signals on cells in the neurogenic state. This exacerbation in neurogenesis led to the diminished growth of the neuroepithelium and a reduction in the later production of neurons. Pharmacological perturbation of the stereotypical distribution of precursors along the orthogonal axis of the neuroepithelium resulted in an excess of neurogenesis, as seen by the expression of Ngn2, and of the neuronal marker RA4 in the retina. These findings suggest that INM might be important for the efficient and continued production of neurons in G0, since it is involved in defining a proneural cluster in the ventricular part of the neuroepithelium that contains precursors at stages of the mitotic cycle compatible with neuronal differentiation.

Animals↗