Longterm outcomes in patients with acute and chronic myocardial injury

Background: Myocardial injury is defined as any cardiac troponin (cTn) level above the upper reference limit, namely, the 99th percentile value, and is caused by either ischemic or nonischemic events. The presence of acute myocardial injury (i.e., myocardial injury with a dynamic change in cTn levels) with evidence of myocardial ischemia is required for the diagnosis of myocardial infarction (MI). Nonischemic myocardial injury, defined as myocardial injury without evidence of ischemia, and type 2 MI are linked to a substantial risk of death and a poor prognosis. The purpose of this thesis was to study the characteristics, risks of death, and cardiovascular events in patients with type 1 MI, type 2 MI, acute nonischemic myocardial injury and chronic myocardial injury. In addition, this thesis aimed to investigate the impact of common cardiovascular medications within each type of myocardial injury. Methods: Patients with myocardial injury (i.e., high-sensitivity cardiac troponin T (hscTnT)>14 ng/L) identified from a cohort of patients from the emergency department with at least one visit for chest pain at the Karolinska University Hospital 2011 and 2014 were included in the studies. The cohort was obtained from the local administrative database that includes all patients seeking medical attention in the ED, while additional data were obtained from national registers. Study I was performed to investigate the long-term outcome in patients (n=3 853) with hs-cTnT levels>14 ng/L who were categorized as: type 1 MI, type 2 MI, acute nonischemic myocardial injury, and chronic myocardial injury. Study II was performed to investigate the causes of death in patients with myocardial injury compared with those without myocardial injury (hs-cTnT<14ng/L), who died during follow-up (n=2 285). Study III was performed to investigate how the number of commonly prescribed cardiovascular drugs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, statins, and platelet inhibitors) impacts mortality and cardiovascular events in patients with different types of myocardial injury. Study IV was performed to investigate whether prescribed high-, medium-, and low-intensity statin therapy impacts risks and outcomes in patients with different types of myocardial injury. Results: Patients with acute nonischemic myocardial injury and type 2 MI had a high risk of death, similar to patients with chronic myocardial injury, according to the findings of Study I. During a mean 4-year follow-up, nearly half of all patients in groups without type 1 MI died. Patients with nonischemic myocardial injury and patients with type 1 MI had similar high risk of cardiovascular death compared to patients with no myocardial injury. Patients with type 2 MI and chronic myocardial injury treated with 4 common cardiovascular drugs has a lower adjusted risk of death. Patients with nonischemic myocardial injury treated with two or three medications had a lower adjusted mortality risk compared to patients treated with zero or one medication. Patients with nonischemic myocardial injury and type 2 MI treated with high-intensity treatment had lower crude risks compared to patients treated with low-intensity treatment in corresponding groups, but estimates were not significant after adjusting for confounders. Conclusions: Patients with nonischemic myocardial injury and type 2 MI have a high risk of all-cause mortality and share similar risks for cardiovascular death as patients with type 1 MI. Patients with nonischemic myocardial injury and type 2 MI may benefit from common cardiovascular medications. Currently no clinical recommendations are available for how patients with nonischemic myocardial injury or type 2 MI should be managed, and this warrants further attention

Application of the Universal Definition of Myocardial Infarction in Clinical Practice in Scotland and Sweden.

IMPORTANCE: Whether the diagnostic classifications proposed by the universal definition of myocardial infarction (MI) to identify type 1 MI due to atherothrombosis and type 2 MI due to myocardial oxygen supply-demand imbalance have been applied consistently in clinical practice is unknown. OBJECTIVE: To evaluate the application of the universal definition of MI in consecutive patients with possible MI across 2 health care systems. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2 prospective cohorts enrolling consecutive patients with possible MI in Scotland (2013-2016) and Sweden (2011-2014) to assess accuracy of clinical diagnosis of MI recorded in hospital records for patients with an adjudicated diagnosis of type 1 or type 2 MI. Data were analyzed from August 2022 to February 2023. MAIN OUTCOMES AND MEASURES: The main outcome was the proportion of patients with a clinical diagnosis of MI recorded in the hospital records who had type 1 or type 2 MI, adjudicated by an independent panel according to the universal definition. Characteristics and risk of subsequent MI or cardiovascular death at 1 year were compared. RESULTS: A total of 50 356 patients were assessed. The cohort from Scotland included 28 783 (15 562 men [54%]; mean [SD] age, 60 [17] years), and the cohort from Sweden included 21 573 (11 110 men [51%]; mean [SD] age, 56 [17] years) patients. In Scotland, a clinical diagnosis of MI was recorded in 2506 of 3187 patients with an adjudicated diagnosis of type 1 MI (79%) and 122 of 716 patients with an adjudicated diagnosis of type 2 MI (17%). Similar findings were observed in Sweden, with 970 of 1111 patients with adjudicated diagnosis of type 1 MI (87%) and 57 of 251 patients with adjudicated diagnosis of type 2 MI (23%) receiving a clinical diagnosis of MI. Patients with an adjudicated diagnosis of type 1 MI without a clinical diagnosis were more likely to be women (eg, 336 women [49%] vs 909 women [36%] in Scotland; P < .001) and older (mean [SD] age, 71 [14] v 67 [14] years in Scotland, P < .001) and, when adjusting for competing risk from noncardiovascular death, were at similar or increased risk of subsequent MI or cardiovascular death compared with patients with a clinical diagnosis of MI (eg, 29% vs 18% in Scotland; P < .001). CONCLUSIONS AND RELEVANCE: In this cohort study, the universal definition of MI was not consistently applied in clinical practice, with a minority of patients with type 2 MI identified, and type 1 MI underrecognized in women and older persons, suggesting uncertainty remains regarding the diagnostic criteria or value of the classification

Randomised social-skills training and parental training plus standard treatment versus standard treatment of children with attention deficit hyperactivity disorder - The SOSTRA trial protocol

Abstract Background Children with attention deficit hyperactivity disorder (ADHD) are hyperactive and impulsive, cannot maintain attention, and have difficulties with social interactions. Medical treatment may alleviate symptoms of ADHD, but seldom solves difficulties with social interactions. Social-skills training may benefit ADHD children in their social interactions. We want to examine the effects of social-skills training on difficulties related to the children's ADHD symptoms and social interactions. Methods/Design The design is randomised two-armed, parallel group, assessor-blinded trial. Children aged 8-12 years with a diagnosis of ADHD are randomised to social-skills training and parental training plus standard treatment versus standard treatment alone. A sample size calculation estimated that at least 52 children must be included to show a 4-point difference in the primary outcome on the Conners 3rd Edition subscale for 'hyperactivity-impulsivity' between the intervention group and the control group. The outcomes will be assessed 3 and 6 months after randomisation. The primary outcome measure is ADHD symptoms. The secondary outcome is social skills. Tertiary outcomes include the relationship between social skills and symptoms of ADHD, the ability to form attachment, and parents' ADHD symptoms. Discussion We hope that the results from this trial will show that the social-skills training together with medication may have a greater general effect on ADHD symptoms and social and emotional competencies than medication alone. Trial registration ClinicalTrials (NCT): NCT00937469</p

Interleukin-35 administration counteracts established murine type 1 diabetes - possible involvement of regulatory T cells

The anti-inflammatory cytokine IL-35 is produced by regulatory T (Treg) cells to suppress autoimmune and inflammatory responses. The role of IL-35 in type 1 diabetes (T1D) remains to be answered. To elucidate this, we investigated the kinetics of Treg cell response in the multiple low dose streptozotocin induced (MLDSTZ) T1D model and measured the levels of IL-35 in human T1D patients. We found that Treg cells were increased in MLDSTZ mice. However, the Treg cells showed a decreased production of anti-inflammatory (IL-10, IL-35, TGF-beta) and increased pro-inflammatory (IFN-gamma, IL-2, IL-17) cytokines, indicating a phenotypic shift of Treg cells under T1D condition. IL-35 administration effectively both prevented development of, and counteracted established MLDSTZ T1D, seemingly by induction of Eos expression and IL-35 production in Treg cells, thus reversing the phenotypic shift of the Treg cells. IL-35 administration reversed established hyperglycemia in NOD mouse model of T1D. Moreover, circulating IL-35 levels were decreased in human T1D patients compared to healthy controls. These findings suggest that insufficient IL-35 levels play a pivotal role in the development of T1D and that treatment with IL-35 should be investigated in treatment of T1D and other autoimmune diseases