Global mean diffusivity: A radiomarker discriminating good outcome long term after traumatic brain injury

BackgroundTraumatic brain injury (TBI) is a chronic pathology responsible for cognitive disorders impacting outcome. Global clinical outcome several years after TBI may be associated with anatomical sequelae. Anatomical lesions are not well described because characterizing diffuse axonal injury and brain atrophy require using specific MRI sequences with quantitative measures. The best radiologic parameter to describe the lesions long term after TBI is not known.ObjectiveWe aimed to first, assess the global volumetric and diffusion parameters related to long-term outcome after TBI and second, define the most discriminating parameter.MethodsIn this observational study, we included 96 patients with severe TBI and 22 healthy volunteers. The mean delay after TBI was 63.2 months [range 31–119]. The Glasgow Outcome Scale Extended (GOS-E) was used to assess the global long-term clinical outcome. All patients underwent multimodal MRI with measures of brain volume, ventricle volume, global fractional anisotropy (FA) and global mean diffusivity (MD).ResultsAll 96 participants had significant impairment in global FA, global MD, brain volume and ventricle volume as compared with the 22 controls (P < 0.01). Only global MD significantly differed between the “good recovery” group (GOS-E score 7-8) and the other two groups: GOS-E scores 3-4 and 5-6. Brain volume significantly differed between the GOS-E 7-8 and 3-4 groups. Global MD was the most discriminating radiological parameter for the “good recovery” group versus other patients, long term after TBI. FA appeared less relevant at this time. Global atrophy was higher in patients than controls but lacked reliability to discriminate groups of patients.ConclusionGlobal mean diffusivity seems a more promising radiomarker than global FA for discriminating good outcome long term after TBI. Further work is needed to understand the evolution of these long-term radiological parameters after TBI.     

Educational Inequalities in Post‐Hip Fracture Mortality: A NOREPOS Studys

Hip fractures are associated with high excess mortality. Education is an important determinant of health, but little is known about educational inequalities in post‐hip fracture mortality. Our objective was to investigate educational inequalities in post‐hip fracture mortality and to examine whether comorbidity or family composition could explain any association. We conducted a register‐based population study of Norwegians aged 50 years and older from 2002 to 2010. We measured total mortality according to educational attainment in 56,269 hip fracture patients (NORHip) and in the general Norwegian population. Both absolute and relative educational inequalities in mortality in people with and without hip fracture were compared. There was an educational gradient in post‐hip fracture mortality in both sexes. Compared with those with primary education only, the age‐adjusted relative risk (RR) of mortality in hip fracture patients with tertiary education was 0.82 (95% confidence interval [CI] 0.77–0.87) in men and 0.79 (95% CI 0.75–0.84) in women. Additional adjustments for Charlson comorbidity index, marital status, and number of children did not materially change the estimates. Regardless of educational attainment, the 1‐year age‐adjusted mortality was three‐ to fivefold higher in hip fracture patients compared with peers in the general population without fracture. The absolute differences in 1‐year mortality according to educational attainment were considerably larger in hip fracture patients than in the population without hip fracture. Absolute educational inequalities in mortality were higher after hip fracture compared with the general population without hip fracture and were not mediated by comorbidity or family composition. Investigation of other possible mediating factors might help to identify new targets for interventions, based on lower educational attainment, to reduce post‐hip fracture mortality. © 2015 American Society for Bone and Mineral Research.     

Insulin resistance is a poor predictor of type 2 diabetes in individuals with no family history of disease

In normoglycemic offspring of two type 2 diabetic parents, low insulin sensitivity (S(I)) and low insulin-independent glucose effectiveness (S(G)) predict the development of diabetes one to two decades later. To determine whether low S(I), low S(G,) or low acute insulin response to glucose are predictive of diabetes in a population at low genetic risk for disease, 181 normoglycemic individuals with no family history of diabetes (FH-) and 150 normoglycemic offspring of two type 2 diabetic parents (FH+) underwent i.v. glucose tolerance testing (IVGTT) between the years 1964-82. During 25 +/- 6 years follow-up, comprising 2,758 person years, the FH- cohort (54 +/- 9 years) had an age-adjusted incidence rate of type 2 diabetes of 1.8 per 1,000 person years, similar to that in other population-based studies, but significantly lower than 16.7 for the FH+ cohort. Even when the two study populations were subdivided by initial values of S(I) and S(G) derived from IVGTT's performed at study entry, there was a 10- to 20-fold difference in age-adjusted incidence rates for diabetes in the FH- vs. FH+ individuals with low S(I) and low S(G). The acute insulin response to glucose was not predictive of the development of diabetes when considered independently or when assessed as a function of S(I), i.e., the glucose disposition index. These data demonstrate that low glucose disposal rates are robustly associated with the development of diabetes in the FH+ individuals, but insulin resistance per se is not sufficient for the development of diabetes in individuals without family history of disease and strongly suggest a familial factor, not detectable in our current measures of the dynamic responses of glucose or insulin to an IVGTT is an important risk factor for type 2 diabetes. Low S(I) and low S(G), both measures of glucose disposal, interact with this putative familial factor to result in a high risk of type 2 diabetes in the FH+ individuals, but not in the FH- individuals.     

Marcadores de daño miocárdico en la predicción del pronóstico a corto plazo de los pacientes con COVID-19

Introduction and objectivesCOVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19.MethodsWe included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT > 14 ng/L, the upper 99th percentile. Levels of NT-proBNP > 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV).ResultsCardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87).ConclusionsMyocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT.     

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO _x (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO _x was measured by chemiluminescence. Serum NO _x levels in SSc (n = 43) were significantly higher (72.4 ± 47.8 μM) than age- and sex-matched controls (n = 41; 37.1 ± 13.5 μM; p < 0.001). Serum NO _x were not found to be associated with lung fibrosis defined by lung function parameters or inflammation and fibrosis scores on HRCT. Twenty-two patients were found to have elevated serum NO _x level defined as mean ± 2 SD of normal controls. Logistic regression analysis revealed that age (OR 1.12, p = 0.02) and elevated pulmonary arterial pressure (PAP) (n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO _x . Prednisolone use was associated with lower serum NO _x level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO _x (p = 0.004 by trend). Serum NO _x in SSc patients were elevated compared to healthy controls. Serum NO _x level was determined by multiple factors including age, prednisolone use, and elevated PAP.     

Experience with Levosimendan in 32 Paediatric Patients

The aim of this study was to describe the off-label conditions of use for levosimendan in the paediatric population of a tertiary referral hospital. This is a retrospective observational study conducted between January 2007 and January 2014. Inclusion criteria were as follows: 100 % of paediatric patients who received intravenous perfusions of levosimendan during the study period. The following data were gathered: age, sex, diagnosis, dose administered, duration and date of the perfusion, number of perfusions per patient, previous inotropic and concomitant treatment, side effects and survival. A total of 32 patients were included in the study (56 % male). The mean age at the moment of administration was 4 months (range 2 days–15 years). During the study period, a total of 70 infusions were recorded. Fifteen of the 32 patients (46.9 %) received repeat doses, with a mean interval between doses of 8 days (range 3–37 days). The doses used were between 0.05 and 0.2 mcg/kg/min. Loading doses were not used in any cases. At the moment of receiving the infusion, all of the patients were receiving conventional treatment without any response, including inotropic support in 88 % of the cases. The administration of levosimendan was only suspended in one case due to the appearance of severe hypotension. In the rest of the administrations, it was well tolerated, without registering any severe side effect during the infusion process. Levosimendan proved to be a safe, effective strategy in our paediatric population. The good tolerance observed may be related to the absence of an initial bolus or loading dose.