Fuera de equilibrio. moralidad y racionalidad indirecta.

Madrid: Ed. Complutense, 2008. 201 pp

Myofascial Pain Syndrome:A Nociceptive Condition Comorbid with Neuropathic or Nociplastic Pain

Myofascial pain syndrome is featured by the presence of myofascial trigger points (TrPs). Whether TrPs are primary or secondary phenomena or if they relate to central or peripheral nervous system disorders is controversial. Referred pain, a cardinal sign of TrPs, is a central phenomenon driven by peripheral input. In 2021, the InternationalAssociation for the Study of Pain (IASP) proposed a clinical criteria and grading system for classifying patients with pain on nociceptive, neuropathic, or nociplastic phenotypes. Myofascial TrP pain has been traditionally categorized as a nociceptive phenotype; however, increasing evidence supports that this condition could be present in patients with predominantly nociplastic pain, particularly when it is associated with an underlying medical condition. The clinical response of some therapeutic approaches for managing TrPs remains unclear. Accordingly, the ability to classify myofascial TrP pain into one of these phenotypes would likely be critical for producing more successful clinical treatment outcomes by a precision medicine approach. This consensus paper presents evidence supporting the possibility of subgrouping individuals with myofascial TrP pain into nociceptive, nociplastic, or mixed-type phenotype. It is concluded that myofascial pain caused by TrPs is primarily a nociceptive pain condition, is unlikely to be classified as neuropathic or nociplastic, but can be present in patients with predominantly neuropathic or nociplastic pain. In the latter cases, management of the predominant central pain problem should be a major treatment goal, but the peripheral drive from TrPs should not be ignored, since TrP treatment has been shown to reduce sensitization-associated symptomatology in nociplastic pain conditions, e.g., fibromyalgia

Distortion of the QRS in elderly patients with myocardial infarction

Background: Distortion of the terminal portion of the QRS in the initial electrocardiogram (ECG) is a strong predictor of adverse outcome in myocardial infarction. Our purpose is to assess the relationship of distortion of QRS and other ECG characteristics with older age. Methods and results: We analysed 634 consecutive patients (age 62.6 &#177; 13.7, 77% male) admitted in the first 12 hours of ST-elevation myocardial infarction. Two groups of age were defined: < 75 years-old and &#8805; 75 years-old. Additionally, we defined two ECG groups according to the presence of ST segment elevation with distortion of the terminal portion of the QRS in two or more adjacent leads (QRS+) or the absence of this pattern (QRS&#8211;). Older people had more often QRS+ (30% vs. 20%, p = 0.023). The older group with QRS+ had an in-hospital mortality of 18%, vs. 7% with QRS&#8211; (p = 0.04), and an incidence of major adverse events of 40% vs. 14% (p = 0.002). In the multivariate analysis, age &#8805; 75 years was an independent predictor of distortion of the QRS (odds ratio 2.1, 1.2&#8211;4.9, p = 0.016). Conclusions: The distortion of the terminal portion of the QRS in myocardial infarction is more frequent in elderly people, and is significantly related to adverse prognosis. This ECG finding can be helpful to promptly stratify the risk in elderly patient

Prognostic Factors for Postoperative Chronic Pain after Knee or Hip Replacement in Patients with Knee or Hip Osteoarthritis: An Umbrella Review

Knee and hip osteoarthritis are highly prevalent in the older population. Management of osteoarthritis-related pain includes conservative or surgical treatment. Although knee or hip joint replacement is associated with positive outcomes, up to 30% of patients report postoperative pain in the first two years. This study aimed to synthesize current evidence on prognostic factors for predicting postoperative pain after knee or hip replacement. An umbrella review of systematic reviews was conducted to summarize the magnitude and quality of the evidence for prognostic preoperative factors predictive of postoperative chronic pain (&gt;6 months after surgery) in patients who had received knee or hip replacement. Searches were conducted in MEDLINE, CINAHL, PubMed, PEDro, SCOPUS, Cochrane Library, and Web of Science databases from inception up to 5 August 2022 for reviews published in the English language. A narrative synthesis, a risk of bias assessment, and an evaluation of the evidence confidence were performed. Eighteen reviews (nine on knee surgery, four on hip replacement, and seven on both hip/knee replacement) were included. From 44 potential preoperative prognostic factors, just 20 were judged as having high or moderate confidence for robust findings. Race, opioid use, preoperative function, neuropathic pain symptoms, pain catastrophizing, anxiety, other pain sites, fear of movement, social support, preoperative pain, mental health, coping strategies, central sensitization-associated symptoms, and depression had high/moderate confidence for an association with postoperative chronic pain. Some comorbidities such as heart disease, stroke, lung disease, nervous system disorders, and poor circulation had high/moderate confidence for no association with postoperative chronic pain. This review has identified multiple preoperative factors (i.e., sociodemographic, clinical, psychological, cognitive) associated with postoperative chronic pain after knee or hip replacement. These factors may be used for identifying individuals at a risk of developing postoperative chronic pain. Further research can investigate the impact of using such prognostic data on treatment decisions and patient outcomes.</p

Performance of Scheduling Policies in Adversarial Networks with Non-synchronized Clocks

In this paper we generalize the Continuous Adversarial Queuing Theory (CAQT) model (Blesa et al. in MFCS, Lecture Notes in Computer Science, vol. 3618, pp. 144–155, 2005) by considering the possibility that the router clocks in the network are not synchronized. We name the new model Non Synchronized CAQT (NSCAQT). Clearly, this new extension to the model only affects those scheduling policies that use some form of timing. In a first approach we consider the case in which although not synchronized, all clocks run at the same speed, maintaining constant differences. In this case we show that all universally stable policies in CAQT that use the injection time and the remaining path to schedule packets remain universally stable. These policies include, for instance, Shortest in System (SIS) and Longest in System (LIS). Then, we study the case in which clock differences can vary over time, but the maximum difference is bounded. In this model we show the universal stability of two families of policies related to SIS and LIS respectively (the priority of a packet in these policies depends on the arrival time and a function of the path traversed). The bounds we obtain in this case depend on the maximum difference between clocks. This is a necessary requirement, since we also show that LIS is not universally stable in systems without bounded clock difference. We then present a new policy that we call Longest in Queues (LIQ), which gives priority to the packet that has been waiting the longest in edge queues. This policy is universally stable and, if clocks maintain constant differences, the bounds we prove do not depend on them. To finish, we provide with simulation results that compare the behavior of some of these policies in a network with stochastic injection of packets

Adjuvant dabrafenib and trametinib for patients with resected BRAF-mutated melanoma: DESCRIBE-AD real-world retrospective observational study

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF-V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF-mutated melanoma patients aged & GE;18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations

Study of CD27 and CCR4 Markers on Specific CD4+ T-Cells as Immune Tools for Active and Latent Tuberculosis Management

The immunological characterization of different cell markers has opened the possibility of considering them as immune tools for tuberculosis (TB) management, as they could correlate with TB latency/disease status and outcome. CD4+ T-cells producing IFN-γ+ with a low expression of CD27 have been described as an active TB marker. In addition, there are unknown homing receptors related to TB, such as CCR4, which might be useful for understanding TB pathogenesis. The aim of our study is focused on the assessment of several T-cell subsets to understand immune-mechanisms in TB. This phenotypic immune characterization is based on the study of the specific immune responses of T-cells expressing CD27 and/or CCR4 homing markers. Subjects enrolled in the study were: (i) 22 adult patients with active TB, and (ii) 26 individuals with latent TB infection (LTBI). Blood samples were drawn from each patient. The expression of CD27 and/or CCR4 markers were analyzed within CD4+ T-cells producing: (i) IFN-γ+, (ii) TNF-α+, (iii) TNF-α+IFN-γ+, and (iv) IFN-γ+ and/or TNF-α+. The percentage of CD27− within all CD4+ T-cell populations analyzed was significantly higher on active TB compared to LTBI after PPD or ESAT-6/CFP-10 stimulation. As previously reported, a ratio based on the CD27 median fluorescence intensity (MFI) was also explored (MFI of CD27 in CD4+ T-cells over MFI of CD27 in IFN-γ+CD4+ T-cells), being significantly increased during disease (p &lt; 0.0001 after PPD or ESAT-6/CFP-10 stimulation). This ratio was also assessed on the other CD4+ T-cells functional profiles after specific stimulation, being significantly associated with active TB. Highest diagnostic accuracies for active TB (AUC ≥ 0.91) were achieved for: (i) CD27 within IFN-γ+TNF-α+CD4+ T-cells in response to ESAT-6/CFP-10, (ii) CD27 and CCR4 markers together within IFN-γ+CD4+ T-cells in response to PPD, and (iii) CD27 MFI ratio performed on IFN-γ+TNF-α+CD4+ T-cells after ESAT-6/CFP-10 stimulation. The lowest diagnostic accuracy was observed when CCR4 marker was evaluated alone (AUC ≤ 0.77). CD27 and CCR4 expression detection could serve as a good method for immunodiagnosis. Moreover, the immunological characterization of markers/subset populations could be a promising tool for understanding the biological basis of the disease

Cut-offs and response criteria for the Hospital Universitario la Princesa Index (HUPI) and their comparison to widely-used indices of disease activity in rheumatoid arthritis

Objective To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Methods Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. Results The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if =2, low disease activity if >2 and =5), moderate if >5 and <9 and high if =9. HUPI''s AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28''s AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756) and CDAI (AUCs: 0.789 and 0.728). HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values. Conclusions The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis