Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: results of a multicenter study after 12 months.

BACKGROUND AND AIMS: infliximab has changed the natural history of inflammatory bowel disease (IBD). The advent of biosimilar treatments such as CT-P13 will hopefully improve the availability of biological therapies. Data with regard to drug switching are currently limited. The objective of the study was to assess the effectiveness and safety of switching from the reference product (RP), infliximab, to CT-P13 in patients with IBD. METHODS: this was a multicenter prospective observational study in patients with Crohn's disease (CD) and ulcerative colitis (UC). All patients had switched from infliximab RP (Remicade®) to CT-P13 treatment and were followed up for 12 months. The efficacy endpoint was the change in clinical remission assessed at 0 and 12 months, according to the Harvey-Bradshaw score and partial Mayo score for patients with CD and UC, respectively. Adverse events were monitored and recorded throughout the study. RESULTS: a total of 167 patients (116 CD/51 UC) were included; 88.8% (103/116) of patients with CD were in remission at the time of the drug switch and 69.7% were in remission at 12 months. The Harvey-Bradshaw (HB) score significantly changed at 12 months (p = 0.001); 84.3% (43/51) of patients with UC were in remission at the time of the drug switch and 76.7% were in remission at 12 months. No significant changes in the median partial Mayo score (p = 0.87) were observed at 12 months. Serious adverse events related to medication were reported in 12/167 (7.2%) cases. CONCLUSION: switching from infliximab RP to CT-P13 is safe and effective at 12 months. The loss of efficacy at 12 months was 15.7%.

Potential clinical biomarkers in rheumatoid arthritis with an omic approach.

OBJECTIVE: To aid in the selection of the most suitable therapeutic option in patients with diagnosis of rheumatoid arthritis according to the phase of disease, through the review of articles that identify omics biological markers. METHODS: A systematic review in PubMed/Medline databases was performed. We searched articles from August 2014 to September 2019, in English and Spanish, filtered by title and full text; and using the terms "Biomarkers" AND "Rheumatoid arthritis". RESULTS: This article supplies an exhaustive review from research of objective measurement, omics biomarkers and how disease activity appraise decrease unpredictability in treatment determinations, and finally, economic, and clinical outcomes of treatment options by biomarkers' potential influence. A total of 122 articles were included. Only 92 met the established criteria for review purposes and 17 relevant references about the topic were included as well. Therefore, it was possible to identify 196 potential clinical biomarkers: 22 non-omics, 20 epigenomics, 33 genomics, 21 transcriptomics, 78 proteomics, 4 glycomics, 1 lipidomics and 17 metabolomics. CONCLUSION: A biomarker is a measurable indicator of some, biochemical, physiological, or morphological condition; evaluable at a molecular, biochemical, or cellular level. Biomarkers work as indicators of physiological or pathological processes, or as a result of a therapeutic management. In the last five years, new biomarkers have been identified, especially the omics, which are those that proceed from the investigation of genes (genomics), metabolites (metabolomics), and proteins (proteomics). These biomarkers contribute to the physician choosing the best therapeutic option in patients with rheumatoid arthritis.

Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistant Enterobacterales (ASTARTÉ): protocol for a randomised, pragmatic trial.

INTRODUCTION: Alternatives to carbapenems are needed in the treatment of third-generation cephalosporin-resistant Enterobacterales (3GCR-E). Temocillin is a suitable candidate, but comparative randomised studies are lacking. The objective is to investigate if temocillin is non-inferior to carbapenems in the targeted treatment of bacteraemia due to 3GCR-E. METHODS AND ANALYSIS: Multicentre, open-label, randomised, controlled, pragmatic phase 3 trial. Patients with bacteraemia due to 3GCR-E will be randomised to receive intravenously temocillin (2 g three times a day) or carbapenem (meropenem 1 g three times a day or ertapenem 1 g once daily). The primary endpoint will be clinical success 7-10 days after end of treatment with no recurrence or death at day 28. Adverse events will be collected; serum levels of temocillin will be investigated in a subset of patients. For a 10% non-inferiority margin, 334 patients will be included (167 in each study arm). For the primary analysis, the absolute difference with one-sided 95% CI in the proportion of patients reaching the primary endpoint will be compared in the modified intention-to-treat population. ETHICS AND DISSEMINATION: The study started after approval of the Spanish Regulatory Agency and the reference institutional review board. Data will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04478721.

Pericarditis purulenta por mycobacterium tuberculosis y streptococcus pneumoniae: revisión del tema, a propósito de un caso / Purulent pericarditis due to mycobacterium tuberculosis and streptococcus pneumoniae: case report and review

La pericarditis purulenta es una patología poco frecuente pero que conlleva alta mortalidad. En la era pre antibióticos, se observaba en pacientes con neumonía complicada y las cocáceas gram positivas eran los gérmenes frecuentemente involucrados. Por otro lado, la pericarditis tuberculosa representa el 1% del total de casos de tuberculosis, aunque es frecuente zonas endémicas, principalmente asociada a la infección por el virus de la inmunodeficiencia humana (VIH). Presentamos el caso de un paciente de 19 años, en situación calle, infectado con VIH, con diagnóstico de pericarditis purulenta, donde se demostró la co-infección de Mycobacterium tuberculosis y Streptecoccus pneumoniae en el pericardio. La pericarditis purulenta polimicrobiana es poco frecuente y la co-infección por los gérmenes mencionados es anecdótica. A pesar del tratamiento antimicrobiano, el aseo quirúrgico, los esteroides y la fibrinolisis intrapericárdica, esta patología tiene un pronóstico ominoso, en parte, debido a la condición basal de los enfermos que la padecen.

Purulent pericarditis is a rare disease with a high mortality rate. In the pre-antibiotic era it was observed as a complication in patients with pneumonia. Gram-positive coccaceae were the most commonly implicated bacteria. Tuberculous pericarditis represents 1% of all tuberculosis (TBC) cases, although it is common in endemic areas, associated with human immunodeficiency virus (HIV) infection. We present the case of a 19-year-old homeless, admitted with HIV and malnutrition, diagnosed with purulent pericarditis. Mycobacterium tuberculosis and Streptococcus pneumoniae were found as a cause of purulent pericarditis. Polymicrobial purulent pericarditis is a rare condition and co-infection with the bacteria previously mentioned is merely anecdotal. Despite antimicrobial treatment, surgical management, steroids, and intrapericardial fibrinolysis, this pathology has an ominous prognosis, due in part to the pre-existing condition of these patients.

Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: 12 months results.

BACKGROUND: Biological agents, such as infliximab, have transformed the outcomes of patients with immune-mediated inflammatory diseases. The advent of biosimilar treatment options such as CT-P13 promises to improve the availability of biological therapy, yet real-world switching data are currently limited. Here, we assess the effectiveness and safety of switching to CT-P13 from infliximab reference product (RP) in patients with inflammatory bowel disease. MATERIALS AND METHODS: This was a prospective single-center observational study in patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). All patients were switched from infliximab RP (Remicade) to CT-P13 treatment and followed up for up to 12 months. The efficacy endpoint was the change in clinical response assessed at 3-monthly intervals, according to the Harvey-Bradshaw score and partial Mayo score for patients with CD and UC, respectively. C-reactive protein (CRP) was also measured. Adverse events were monitored and recorded throughout the study. RESULTS: A total of 98 patients with inflammatory bowel disease (67 CD/31 UC) were included. A total of 83.6% (56/67) of patients with CD were in remission at the time of the switch and 62.7% were in remission at 12 months. The Harvey-Bradshaw score showed a significant change at 12 months (P=0.007) but no significant change was observed in median CRP at this timepoint (P=0.364). A total of 80.6% (25/31) of patients with UC were in remission at the time of the switch and 65.3% (18/28) were in remission at 12 months. No significant changes in the median partial Mayo score (P=0.058) or CRP (P=0.329) were observed at 12 months. Serious adverse events related to medication were reported in 11 (11.2%) patients. CONCLUSION: Switching from infliximab RP to CT-P13 is efficacious and well tolerated in patients with CD or UC for up to 12 months.

Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum ß-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial.

INTRODUCTION: Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future. METHODS AND ANALYSIS: The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals. DISCUSSION: This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy. TRIAL REGISTRATION NUMBER: NCT02142751. EudraCT no: 2013-002922-21. Protocol V.1.1 dated 14 March 2014.

[Seasonal variations in admissions for acute myocardial infarction. The PRIMVAC study]. / Variaciones estacionales en los ingresos por infarto agudo de micardio. El estudio PRIMVAC.

INTRODUCTION AND OBJECTIVES: Some authors have described seasonal variations in the incidence of acute myocardial infarction. The aim of this study was to determine the existence of seasonal rhythms in admissions for acute myocardial infarction to coronary care units, and in mortality, and to analyze the influence of age on environmental factors. PATIENTS AND METHOD: The study included a total of 8400 consecutive patients with acute myocardial infarction admitted to 12 coronary care units in the PRIMVAC registry from January 1995 to December 1999. Seasonal rhythms were analyzed with the time series method and the Cosinor regression equation. The influence of age was analyzed with the chi 2 test. RESULTS: The total number of admissions increased in winter and decreased in summer. The highest peak (acrophase) occurred in winter, with 2183 cases (r2=0.91), specifically in February, with 742 cases (r2=0.66). The age of the patients conditioned seasonal variations (P=.006), and the influence was statistically significant for patients over 65 years of age. Changes in mortality with time did not reach statistical significance. CONCLUSIONS: A seasonal rhythm in admissions for acute myocardial infarction was found, with an increase in winter and a decrease in summer. Age conditioned the effect of environmental factors on acute myocardial infarction, and patients aged 65 years or older were more sensitive to mechanisms that led to increases in admissions in winter.

[Effects of myocardial stretching on excitation frequencies determined by spectral analysis during ventricular fibrillation]. / Efecto del estiramiento micárdico sobre las frecuencias de activación determinadas mediante análisis espectral durante la fibrilación ventricular.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze the effects of myocardial stretching on excitation frequencies, as determined by spectral analysis, during ventricular fibrillation. METHODS: In 12 isolated rabbit heart preparations, ventricular activation during ventricular fibrillation was recorded with multiple electrodes. Recordings were obtained before, during and after ventricular dilatation produced with an intraventricular balloon. The dominant frequency of the signals obtained with each of the electrodes was determined by spectral analysis. RESULTS: During the control phase, the mean, minimum and maximum dominant frequencies were, respectively, 14.3 1.7, 12.5 1.7, and 16.2 1.4 Hz, and the average difference between the maximum and minimum frequencies was 3.6 2.1 Hz. This difference was over 4 Hz in four cases, and in no case did it exceed 8 Hz. During ventricular stretching, the mean dominant frequency increased significantly (21.1 6.1 Hz; p < 0.0001), as did the minimum values (14 2.6 Hz; p < 0.05) and especially the maximum values (26.6 7.7 Hz; p < 0.0001). The difference between the maximum and minimum frequencies (12.6 6.4 Hz; p < 0.001) was over 4 Hz in all cases except one, and over 8 Hz in 9 cases. The maximum values were distributed heterogeneously during ventricular stretching. Upon suppressing ventricular stretching, the dominant frequency did not differ from controls. CONCLUSIONS: Myocardial frequency maps during ventricular fibrillation show limited variations in the dominant frequency of the signals recorded in the lateral wall of the left ventricle. During stretching, the patterns were heterogeneous, due mainly to the marked increase in the maximum dominant frequency. In the experimental model used, the effects of stretching remitted after suppressing ventricular dilatation.

[Animal models of cardiovascular disease]. / Modelos animales de enfermedad cardiovascular.

The use of animal models to study cardiovascular disease has made a substantial contribution to increasing our understanding of disease pathogenesis, has led to the development of diagnostic techniques, and has made it possible to verify the effectiveness of different preventative and therapeutic approaches, whether pharmacological or interventional. The main limitations stem from differences between human and experimentally induced pathology, in terms of both genetic regulatory mechanisms and factors that influence cardiovascular function. The experimental models and preparations used in cardiovascular research include those based on isolated cells or tissues or structures immersed in organ baths. The Langendorff system enables isolated perfused hearts to be studied directly under conditions of either no load or controlled loading. In small mammals, a number of models have been developed of cardiovascular conditions that result from spontaneous genetic mutations or, alternatively, that may be induced by specific genomic modification. One of the techniques employed is gene transfer, which can involve the controlled induction of mutations that result in the expression of abnormalities associated with the development of a broad range of different types of cardiovascular disease. Larger animals are used in experimental models in which it is important that physiological regulatory and homeostatic mechanisms are present.

Significance of the morphological patterns of electrograms recorded during ventricular fibrillation: an experimental study.

Mapping techniques are used to study the significance of the morphological patterns of the electrograms (EGMs) obtained during VF in an experimental model. In 24 isolated rabbit heart preparations recordings were made of activation during VF using a multiple electrode (121 unipolar electrodes) positioned on the lateral wall of the left ventricle. Three types of activation maps were selected: (A) with functional block of an activation front; (B) with epicardial breakthrough; and (C) with a single broad wavefront without block lines. The EGMs were classified as negative (Q), positive-negative with a predominance of the negative (rS) or positive wave (Rs), and positive (R). In 60 type A maps the morphology in the zone limiting the block line corresponded to an R wave in 55 (92%) cases and to Rs in 5 (8%) cases. In 67 type B maps, the EGM in the earliest activation zone most often showed Q wave morphology (48 [72%] cases), followed by rS (18 [27%] cases), and Rs morphology (1 [1%] case); in no case was R wave morphology seen. Finally, in 78 type C maps the morphology corresponded to a Q wave in 15 (19%) cases, rS in 38 (49%), Rs in 24 (31%), and R in a 1 (1%) case. The differences between the three types of maps were significant (P < 0.0001). Q wave EGM sensitivity for indicating the existence of an epicardial breakthrough pattern was 72%, with a specificity of 89%, and positive and negative predictive values of 76% and 87%, respectively. R wave EGM sensitivity for indicating the existence of conduction block was 92%, with a specificity of 99%, and positive and negative predictive values of 98% and 97%, respectively. R wave morphology is highly sensitive and specific for indicating conduction block. EGM recordings with initial positivity predominance are infrequent in the earliest activation zones of epicardial breakthrough during VF. The recording of the EGM with Q wave morphology indicates centrifugal activation from the explored zone.

Effects of acute reduction of temperature on ventricular fibrillation activation patterns.

Because of its electrophysiological effects, hypothermia can influence the mechanisms that intervene in the sustaining of ventricular fibrillation. We hypothesized that a rapid and profound reduction of myocardial temperature impedes the maintenance of ventricular fibrillation, leading to termination of the arrhythmia. High-resolution epicardial mapping (series 1; n = 11) and transmural recordings of ventricular activation (series 2; n = 10) were used to analyze ventricular fibrillation modification during rapid myocardial cooling in Langendorff-perfused rabbit hearts. Myocardial cooling was produced by the injection of cold Tyrode into the left ventricle after induction of ventricular fibrillation. Temperature and ventricular fibrillation dominant frequency decay fit an exponential model to arrhythmia termination in all experiments, and both parameters were significantly correlated (r = 0.70, P < 0.0001). Termination of the arrhythmia occurred preferentially in the left ventricle and was associated with a reduction in conduction velocity (-60% in left ventricle and -54% in right ventricle; P < 0.0001) and with activation maps predominantly exhibiting a single wave front, with evidence of wave front extinction. We conclude that a rapid reduction of temperature to <20 degrees C terminates ventricular fibrillation after producing an important depression in myocardial conduction.