Influence of ionic and non-ionic radiographic contrast media on leukocyte adhesion molecules.

BACKGROUND: Many papers have focused on the importance of granulocytes in the process of reperfusion and ischemia. Most of the clinical studies measured several parameters of this process during and after coronary angiography, without taking into account the effect of the radiographic contrast media (RCM) used during this procedure. MATERIALS AND METHODS: We performed a randomized patient study (n = 37) to evaluate the effect of ionic and non-ionic RCM on granulocyte adhesion during coronary angiography. We also evaluated the influence of the ionicity and osmolarity of the different substances on granulocyte adhesion molecules in in vitro experiments. RESULTS: The osmolarity of patient serum samples increased from 302 +/- 1 to 309 +/- 1 mOsm/kg (p < 0.05) after infusion of RCM. The CD11b expression in the samples of the non-ionic RCM treated group increased from 221 +/- 21 MFI to 377 +/- 30 MFI (p < 0.05) measured as the absolute mean fluorescence intensity (MFI), yet did not alter significantly in the ionic RCM group. In contrast, the in vitro experiments showed a reduction of the CD11b expression from 360 +/- 70 MFI to 149 +/- 30 MFI (p < 0.05) in the ionic RCM group. CONCLUSIONS: The upregulation of adhesion molecules was significantly reduced in vivo with ionic RCM, while ionic substances caused opposite effects in vitro. This effect should be taken into account when performing leukocyte functional analysis of samples taken during angiography

Systemic Inflammation and Reperfusion Injury in Patients With Acute Myocardial Infarction

Despite early recanalization of an occluded infarct artery, tissue reperfusion remains impaired in more than one-third of the acute myocardial infarction (AMI) patients owing to a process of reperfusion injury. The role of systemic inflammation in triggering this phenomenon is unknown. Proinflammatory factors (hs-CRP, TNF-α) and anti-inflammatory mediators (IL-1 receptor antagonist, IL-10) were measured in 65 patients during the acute phase of a myocardial infarction as well as in 11 healthy control subjects. Myocardial reperfusion injury was defined as the presence of persistent ST-segment elevation despite successful coronary intervention (≥ 50% of the initial value) and was observed in 28 patients. Systemic proinflammatory mediators (particularly hs-CRP and leukocytes) were higher in AMI patients compared to control subjects. Within the group of AMI patients, only serum TNF-α differed significantly between patients with versus without reperfusion injury: a median value of 25 versus 13 pg/mL was observed, respectively. Logistic regression analysis identified a high level of TNF-α as the most important independent determinant of reperfusion injury (P = .001), beyond total ischemic time (P = .01) and extent of jeopardized myocardium (P = .08). There was no correlation between the TNF-α level and the total ischemic time (P = .8) or the extent of jeopardized myocardium (P = .6). Systemic inflammation, in particular high levels of TNF-α, is strongly associated with the occurrence of reperfusion injury after successful recanalization. Our findings suggest that TNF-α is involved in the triggering and/or amplification of local inflammatory responses related to ischemia-reperfusion injury

Childhood traumatic experiences and mental health problems in sexually offending and non-sexually offending juveniles

OBJECTIVE: To examine the relationship between a history of childhood abuse and mental health problems in juveniles who sexually offended (JSOs) over and above general offending behavior. METHODS: A sample of 44 JSOs incarcerated in two juvenile detention centers in the Netherlands between May 2008 and March 2014 were examined for childhood abuse history (Childhood Trauma Questionnaire-Short Form) and mental health problems (Massachusetts Youth Screening Instrument-Version 2). Furthermore, the connection between childhood abuse and mental health problems in JSOs was compared to a sample of 44 propensity score matched juveniles who offended non-sexually (non-JSOs). RESULTS: In JSOs, sexual abuse was related to anger problems, suicidal ideation, and thought disturbance. These associations were significantly stronger in JSOs than in non-JSOs. CONCLUSIONS: Our results suggest that the relationship between childhood abuse and both internalizing and externalizing mental health problems is of more salience for understanding sexual offending than non-sexual offending, and should, therefore, be an important focus in the assessment and treatment of JSOs

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Massachusetts Youth Screening Instrument for mental health needs of youths in residential welfare/justice institutions: identifying gender differences across countries and settings

This study examines the use of the Massachusetts Youth Screening Instrument-Second Version (MAYSI-2) for mental health needs among 1643 youngsters in residential welfare/justice institutions in Europe and the USA, identifying gender differences across countries and settings. Overall, the MAYSI-2 appeared to be a reliable instrument among these youngsters, with only some scales falling (slightly) below the threshold of acceptable internal consistency. Girls (vs. boys) in Belgian/USA justice institutions and Swiss mixed welfare/justice institutions displayed higher scores for the angry–irritable, depressed–anxious, somatic complaints, suicide ideation scales. Also, detained girls from Belgium and Switzerland reported higher scores for traumatic experiences. No gender differences were revealed among adolescents in German welfare institutions. Our findings suggest that the MAYSI-2 may serve as a useful mental health screening instrument among youngsters in welfare/justice institutions and that girls in justice institutions and mixed welfare/justice institutions form a particularly vulnerable population with regard to mental health problems

Nationwide quality assurance of high-throughput diagnostic molecular testing during the SARS-CoV-2 pandemic : role of the Belgian National Reference Centre

Abstract: Since the onset of the coronavirus disease (COVID-19) pandemic in Belgium, UZ/KU Leuven has played a crucial role as the National Reference Centre (NRC) for respiratory pathogens, to be the first Belgian laboratory to develop and implement laboratory developed diagnostic assays for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and later to assess the quality of commercial kits. To meet the growing demand for decentralised testing, both clinical laboratories and government-supported high-throughput platforms were gradually deployed across Belgium. Consequently, the role of the NRC transitioned from a specialised testing laboratory to strengthening capacity and coordinating quality assurance. Here, we outline the measures taken by the NRC, the national public health institute Sciensano and the executing clinical laboratories to ensure effective quality management of molecular testing throughout the initial two years of the pandemic (March 2020 to March 2022)