An accurate multiple sclerosis detection model based on exemplar multiple parameters local phase quantization: ExMPLPQ

Multiple sclerosis (MS) is a chronic demyelinating condition characterized by plaques in the white matter of the central nervous system that can be detected using magnetic resonance imaging (MRI). Many deep learning models for automated MS detection based on MRI have been presented in the literature. We developed a computationally lightweight machine learning model for MS diagnosis using a novel handcrafted feature engineering approach. The study dataset comprised axial and sagittal brain MRI images that were prospectively acquired from 72 MS and 59 healthy subjects who attended the Ozal University Medical Faculty in 2021. The dataset was divided into three study subsets: axial images only (n = 1652), sagittal images only (n = 1775), and combined axial and sagittal images (n = 3427) of both MS and healthy classes. All images were resized to 224 × 224. Subsequently, the features were generated with a fixed-size patch-based (exemplar) feature extraction model based on local phase quantization (LPQ) with three-parameter settings. The resulting exemplar multiple parameters LPQ (ExMPLPQ) features were concatenated to form a large final feature vector. The top discriminative features were selected using iterative neighborhood component analysis (INCA). Finally, a k-nearest neighbor (kNN) algorithm, Fine kNN, was deployed to perform binary classification of the brain images into MS vs. healthy classes. The ExMPLPQ-based model attained 98.37%, 97.75%, and 98.22% binary classification accuracy rates for axial, sagittal, and hybrid datasets, respectively, using Fine kNN with 10-fold cross-validation. Furthermore, our model outperformed 19 established pre-trained deep learning models that were trained and tested with the same data. Unlike deep models, the ExMPLPQ-based model is computationally lightweight yet highly accurate. It has the potential to be implemented as an automated diagnostic tool to screen brain MRIs for white matter lesions in suspected MS patients

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Infections Related To Granulicatella Adiacens: Report Of Two Cases And Review Of Literature

Infections due to nutritionally variant streptococci are diagnosed rarely due to difficulties encountered during identification and isolation. Mortality rate in these infections is high therefore appropriate supplemented media and reliable detection systems should be implemented to isolate these fastidious organisms. Here, we describe two cases of Granulicatella adiacens infections. All microbiologic identifications were made with MALDI-TOF Vitek MS (BioMerieux, France), and the results confirmed by 16S ribotyping.WoSScopu

Estatinas para el síndrome coronario agudo

Antecedentes: El período inmediato después del inicio del síndrome coronario agudo (SCA) representa un estadio crítico de la cardiopatía coronaria con un alto riesgo de eventos recurrentes y muertes. En los pacientes que presentan SCA los efectos a corto plazo del tratamiento precoz con estati-nas sobre resultados relevantes para el paciente son inciertos. Objetivos: Evaluar los efectos beneficiosos y perjudiciales de las estatinas administradas de forma precoz en pacientes con SCA a partir de ensayos controlados aleatorios (ECA). Estrategia de búsqueda: Se hicieron búsquedas en CENTRAL, MEDLINE, EMBASE y CINAHL (hasta el 1 febrero 2010). No se aplicó ninguna restricción en cuanto al idioma. La búsqueda se complementó al establecer contacto con especialistas en el campo, examinar las listas de referencias de las revisiones y los artículos editoriales sobre el tema y al buscar en los registros de ensayos. Criterios de selección: ECA que compararon estatinas con placebo o atención habitual, iniciaron el tratamiento con estatina en el transcurso de los 14 días después del inicio del SCA, tuvieron un seguimiento de al menos 30 días e informaron al menos un resultado clínico. Obtención y análisis de los datos: Dos autores evaluaron de forma independiente la calidad de los estudios y extrajeron los datos. Con un modelo de efectos aleatorios, se agruparon los efectos del tratamiento y se calcularon los cocientes de riesgos (CR) para todos los resultados en los grupos de tratamiento y control. Resultados principales: Dieciocho estudios (14 303 pacientes) compararon el tratamiento precoz con estatina versus placebo o atención habitual en pacientes con SCA. En comparación con el placebo o la atención habitual, el tratamiento precoz con estatina no redujo el resultado primario combinado de muerte, infarto de miocardio (IM) no mortal y accidente cerebrovascular al mes (cociente de riesgos [cR] 0,93; intervalo de confianza [IC] del 95%: 0,80 a 1,08) ni a los cuatro meses (CR 0,93; IC del 95%: 0,81 a 1,06) de seguimiento. No hubo reducciones estadísticamente significativas en el riesgo de las estatinas para muerte total, IM total, accidente cerebrovascular total, muerte cardiovascular, procedimientos de revascularización e insuficiencia cardíaca aguda al mes ni a los cuatro meses, aunque hubo tendencias favorables relacionadas con el uso de las estatinas para cada una de estas variables de evaluación. La incidencia de episodios de angina inestable se redujo significativamente a los cuatro meses después del SCA (CR 0,76; IC del 95%: 0,59 a 0,96). Hubo nueve pacientes con miopatía (niveles elevados de creatinquinasa > 10 veces el límite superior de lo normal) en los pacientes tratados con estatina (0,13%) versus uno (0,015%) en los grupos control. La toxicidad muscular grave estuvo limitada principalmente a los pacientes tratados con simvastatina 80 mg. Conclusiones de los autores: Según las pruebas disponibles, el inicio del tratamiento con estatinas en el transcurso de 14 días después del SCA no reduce la muerte, el infarto de miocardio ni el accidente cerebrovascular hasta los cuatro meses, pero reduce la ocurrencia de angina inestable a los cuatro meses después del SCA

A preliminary study of atorvastatin plasma concentrations in critically ill patients with sepsis

Objective: A lack of published pharmacokinetic data on statins in sepsis has prompted concerns about their safety and toxicity. This study determined single dose pharmacokinetics of Atorvastatin administered orally to acutely ill patients. Design, setting and participants: A prospective open label study conducted in a tertiary referral centre on 5 healthy volunteers, 5 acutely ill patients admitted to the medical ward and a heterogeneous cohort of 25 critically ill patients admitted to an intensive care unit. Intervention: All participants received a single oral dose of 20 mg of atorvastatin. Measurement and results: Plasma pharmacokinetics of atorvastatin as measured by maximal plasma concentration (Cmax) and area under the curve (AUC) (0-24) h. Critically ill patients with sepsis had a significantly higher Cmax and AUC as compared to healthy volunteers [110.5(86.5) vs. 5.9(2.50) ng/ml, p < 0.01 and 1,051(810) vs. 67(48) ng h/ml (p < 0.0001)], respectively. Atorvastatin concentrations in the plasma of critically ill patients with sepsis remained supratherapeutic for up to 20 h after a single dose. The AUC was significantly higher for those patients on concomitant CYP 450 inhibitor therapy as compared to those patients not on inhibitors (1,518 +/- 793 vs. 584 +/- 540 ng h/ml, p = 0.0260). Conclusions: Very high plasma concentrations were achieved in intensive care patients with sepsis. This can only be partly explained by altered metabolism of atorvastatin. Further investigations are essential to better describe the pharmacokinetics of statins in various groups of critically ill patients. Caution should be exercised prior to adopting high dose regimens in patients with severe sepsis

Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE‐MI): design and baseline characteristics

Aims: Patients surviving an acute myocardial infarction (AMI) are at risk of developing symptomatic heart failure (HF) or premature death. We hypothesized that sacubitril/valsartan, effective in the treatment of chronic HF, prevents development of HF and reduces cardiovascular death following high-risk AMI compared to a proven angiotensin-converting enzyme (ACE) inhibitor. This paper describes the study design and baseline characteristics of patients enrolled in the Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial. Methods and results: PARADISE-MI, a multinational (41 countries), double-blind, active-controlled trial, randomized patients within 0.5–7 days of presentation with index AMI to sacubitril/valsartan or ramipril. Transient pulmonary congestion and/or left ventricular ejection fraction (LVEF) ≤40% and at least one additional factor augmenting risk of HF or death (age ≥70 years, estimated glomerular filtration rate &lt;60 mL/min/1.73 m2, diabetes, prior myocardial infarction, atrial fibrillation, LVEF &lt;30%, Killip class ≥III, ST-elevation myocardial infarction without reperfusion) were required for inclusion. PARADISE-MI was event-driven targeting 708 primary endpoints (cardiovascular death, HF hospitalization or outpatient development of HF). Randomization of 5669 patients occurred 4.3 ± 1.8 days from presentation with index AMI. The mean age was 64 ± 12 years, 24% were women. The majority (76%) qualified with ST-segment elevation myocardial infarction; acute percutaneous coronary intervention was performed in 88% and thrombolysis in 6%. LVEF was 37 ± 9% and 58% were in Killip class ≥II. Conclusions: Baseline therapies in PARADISE-MI reflect advances in contemporary evidence-based care. With enrollment complete PARADISE-MI is poised to determine whether sacubitril/valsartan is more effective than a proven ACE inhibitor in preventing development of HF and cardiovascular death following AMI