2 Minute Medicine Rewind April 10, 2023
Efficacy and Safety of Anakinra Plus Standard of Care for Patients With Severe COVID-19
1. In this randomized trial, in patients with severe COVID-19 pneumonia and biochemical evidence of hyperinflammation, there was no significant difference in the proportion of patients requiring mechanical ventilation at day 15 following treatment initiation between patients who received anakinra plus standard of care (SoC) versus only SoC.
Evidence Rating Level: 1 (Excellent)
COVID-19 has resulted in millions of cases worldwide, and multiple variants of SARS-CoV-2 have emerged. Most people experience mild symptoms, but a substantial portion can be critically ill; a subgroup of patients with severe COVID-19 show hyperinflammatory features, with increased circulating levels of cytokines, which are associated with poor outcomes. Anakinra is a recombinant IL-1 receptor antagonist, and evidence from retrospective and prospective studies has found improvement in mortality and mechanical ventilation in patients with COVID-19. This multicenter, randomized, open-label, phase 2/3 clinical trial was designed to assess the clinical outcomes of Anakinra with standard of care (SoC) versus SoC alone in patients with severe COVID-19 pneumonia. Adult patients with confirmed severe COVID-19 pneumonia and evidence of hyperinflammation were recruited from 12 hospitals in Spain between May 2020 and March 2021. Participants were randomly assigned to receive SoC plus anakinra or SoC alone in a 1:1 ratio, and the primary outcome studied was the proportion of patients not requiring mechanical ventilation 15 days after treatment initiation. In total, 161 patients were included in the final analysis, with 83 (52%) patients in the anakinra group and 78 patients in the SoC group (48%). With respect to the primary outcome, the proportion of patients not requiring mechanical ventilation up to day 15 in the anakinra group was not different from that in the SoC group (77.1% vs 85.9%; RR, 0.90; 95% CI 0.77-1.04; P=.16). In addition, there was no significant difference between groups in the proportion of patients requiring invasive mechanical ventilation up to day 15 (P>.99), nor any difference between the groups in the time to mechanical ventilation (P=.14). There was also no difference in the proportion of patients requiring ICU admission up to day 15, and no difference in the length of ICU stay between the two groups. Overall, the findings from this study suggest that the use of anakinra together with SoC does not prevent the need for mechanical ventilation or reduce mortality risk compared with SoC alone in hospitalized patients with severe COVID-19 pneumonia and evidence of hyperinflammation. A major limitation of this study was its open-label design, allowing for confounding factors such as the differential use of cointerventions. This study is an important step in studying medications that may be beneficial in patients with hyperinflammation, specifically due to severe COVID-19 pneumonia.
1. In this retrospective cohort study, patients with obesity and non-alcohol-related fatty liver disease (NAFLD) who received a bariatric surgery (BS) had a significantly lower risk of major adverse cardiovascular outcomes than patients who did not receive BS.
2. Patients with obesity and NAFLD who received bariatric surgery had a significantly lower all-cause mortality than patients with obesity and NAFLD who did not receive bariatric surgery.
Evidence Rating Level: 2 (Good)
Non-alcohol-related fatty liver disease (NAFLD) is a common cause of liver disorders, considered to be a hepatic manifestation of metabolic disorders including obesity, insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Previous research suggests that NAFLD is associated with a significantly higher risk of all-cause mortality, with the leading cause of death being cardiovascular diseases (CVDs). Bariatric surgery (BS) is an efficient weight-loss intervention in patients with obesity and may be indicated in patients with obesity and NAFLD to maintain weight loss. However, there is a paucity of data surrounding the impact of BS specifically on cardiovascular outcomes in patients with NAFLD. Thus, this retrospective cohort study aimed to study the association of BS with major adverse cardiovascular events and all-cause mortality in patients with NAFLD. Eligible patients were identified from January 2005 to December 2021 and divided into two groups – those who underwent BS and those who did not undergo BS – and were matched to each other using 1:1 propensity score matching (PSM). The primary outcome studied was the incidence of major adverse cardiovascular events, including new onset heart failure (HF), composite cardiovascular events, composite cerebrovascular events, and composite coronary artery interventions. In total, 4,687 patients were included in each group after PSM. The BS group was found to have a significantly lower risk of new onset of HF (HR, 0.60; 95% CI, 0.51-0.70), composite cardiovascular events (HR, 0.53; 95% CI, 0.44-0.65), composite cerebrovascular events (HR, 0.59; 95% CI, 0.51-0.69), and composite coronary artery interventions (HR, 0.47; 95% CI, 0.35-0.63) compared with the non-BS group. Furthermore, all-cause mortality was significantly lower in the BS group than in the non-BS group (HR, 0.56; 95% CI, 0.42-0.74). When further stratified, risks of 1-, 3-, 5-, and 7-year all-cause mortality were significantly lower in the BS group than the matched non-BS controls. Overall, the findings from this study suggest that BS is associated with improved long-term adverse cardiovascular outcomes in patients with obesity and NAFLD. A major limitation of this study was the nature of the data collected from electronic health records, which are susceptible to errors in coding or data entry. This study is an important step toward further research in mitigating adverse cardiovascular outcomes in patients with NAFLD.
1. This retrospective study found that in patients presenting to the emergency department with acute dyspnea, elevated high-sensitivity cardiac troponin T (hs-cTnT) was associated with a higher 3-month all-cause mortality than those without an elevated hs-cTnT level.
2. Patients presenting with acute dyspnea along with an elevated hs-cTnT were older, more frequently male, more often hospitalized, had more deranged vital signs at admittance, were admitted with more severe symptoms, had fewer normal ECGs, and had a higher proportion of ECGs with ST-depression than patients without an elevated hs-cTnT.
Evidence Rating Level: 2 (Good)
Acute dyspnea is a common and challenging presentation in the emergency department, and a quick and safe identification of patients at risk for worse prognosis is important. High-sensitivity cardiac troponin T (hs-cTnT) has been found to safely rule out myocardial infarction (MI), though elevated levels can also mirror myocardial injury in other types of diseases other than MI. This retrospective study aimed to examine the association between myocardial injury and mortality in the absence of acute myocardial infarction, specifically noting the association between myocardial injury and patient characteristics. Data were obtained from the Acute Dyspnea Study (ADYS) cohort which was collected from December 2013 to January 2019. In total, 1001 adult patients presenting with acute dyspnea were included in the final analysis and these patients were interviewed by a research nurse using a standard questionnaire. Patients were also subdivided by levels of hs-cTnT and categorized into three groups based on their hs-cTnT level, no elevation (hs-cTnT < 15 ng/L), mild elevation (hs-cTnT 15 – 100 ng/L), and moderate elevation (hs-cTnT >100 ng/L). Compared to patients with normal hs-cTnT, patients with an elevated hs-cTnT were older, more frequently male, more often hospitalized, had more deranged vital signs at admittance, were admitted with more severe symptoms, had fewer normal ECGs, and had a higher proportion of ECGs with ST-depression. In addition, patients with increased hs-cTnT levels had a significantly higher proportion of comorbidities and higher mortality after 3-month follow-up. Regarding sex, men were found to have higher hs-cTnT levels than women (p<.003). When comparing the two groups with an increase in hs-cTnT above the clinical cut-off, the moderate increase group had a significantly higher hospitalization rate, a higher proportion of ‘high medical urgency cases’, a higher proportion of patients with renal disease, and higher 3 months mortality compared with the mild increase group. Furthermore, cox regression analysis for 3-month mortality in the three groups revealed five that were found to be significantly associated with mortality: respiratory frequency, saturation, CHF, renal disease, and BMI. Overall, a higher hs-cTnT level was associated with significantly higher 3-month mortality, and those with higher hs-cTnT levels tended to have more comorbidities and presented with more severe characteristics. A limitation of this study is the lack of previous interventions for cardiac disease, including medication, that could affect the results of this study. This study is important to further explore strategies and risk factors for negative outcomes in patients who present with acute dyspnea in the emergency department.
1. In this retrospective cohort study, patients with sepsis and high-mean arterial pressure (MAP) management had a significantly lower 30-, 60-, and 100-day mortality than patients with low-MAP management.
Evidence Rating Level: 2 (Good)
Sepsis is a leading cause of death from infection in the world, with nearly 20 million people suffering from severe sepsis every year. Hemodynamic management is essential in the clinical therapy of sepsis and is critical to stabilize vital signs, delay disease progression, and avoid further tissue and organ failure. However, the range of initial Mean Arterial Pressure (MAP) titration for patients with sepsis remains controversial. An inappropriately low initial MAP results in hypoperfusion of tissues and organs, but if MAP is kept at a high level, the dose of vasoactive drugs needs to be high, and the body may suffer from future re-injury. The 2021 international guidelines for the management of sepsis and septic shock set the initial MAP target as 65 mm Hg, and previous research remains controversial. This retrospective study aimed to study the association between different MAP levels and short-term mortality. Data was obtained from the Medical Information Mart for Intensive Care (MIMIC-III) database, covering detailed information on adult patients admitted to Beth Israel Deaconess Medical Center in Massachusetts from 2001 to 2012. Baseline characteristics and outcome data were collected, and to minimize the potential bias of treatment allocation and confounders, COX regression and Propensity Score Matching (PSM) were utilized to adjust the covariates. Overall, 1,301 patients in the low-MAP group (60 – 65 mm Hg) and the high-MAP group were successfully matched and included in the study. With respect to the primary outcomes, the mortality of the high-MAP group at 30, 60, and 100 was lower than that of the permissive low-MAP group (p<.0001). After adjusting for all covariates by propensity score, the association between the high-MAP group and deceased 30-day mortality was confirmed by COX hazard model multivariate analysis (HR = 0.67; 95% CI, 0.6-0.75, p<.001) in sepsis patients. Overall, the findings from this study suggest that 30-, 60-, and 100-day mortality was significantly higher in the permissive low-MAP group when compared with the high-MAP group. This study is limited by its retrospective nature, which does not allow for the control of all covariates. This study is an important addition to the growing body of evidence regarding sepsis and MAP titration, especially considering the prevalence of sepsis around the world.
Survey on the association between Toxoplasma gondii infection and violent behavior in inmates
1. In this cross-sectional study, T. gondii seropositivity was not associated with increased violent behaviour when compared with T. gondii seronegative participants in a sample of Mexican inmates.
Evidence Rating Level: 2 (Good)
Toxoplasma gondii (T. gondii) is a protozoan parasite that causes infections worldwide; an estimated one-third of humanity has been exposed to this parasite. T. gondii infection is typically associated with cervical lymphadenopathy or ocular disease and can cause blindness and mental retardation in congenitally affected children. In its latent form, T. gondii resides in the central nervous system and drastically alters the behaviour of rodents and is associated with mental disorders such as obsessive-compulsive disorder, schizophrenia, generalized anxiety disorder, bipolar depression, and disorder. Currently, there is a paucity of research regarding the association between T. gondii infection and violent behaviour. This cross-sectional study aimed to investigate the association between T. gondii seropositivity and violent behaviour in a sample of inmates from the Mexican city of Durango. In total, 128 participants were enrolled from a state correctional facility in Durango, including 112 males and 16 females. Participants were tested for anti-T. gondii IgG antibodies and had their risk of violence assessed using multiple scoring tools including the Historical, Clinical, and Risk Management-20 (HCR-20), the assessment of aggression by the Buss-Perry aggression questionnaire (AGQ), and analysis of their crimes. Anti-T. gondii IgG antibodies were found in 6 (4.7%) of the 128 inmates studied. Regarding the risk of violence, 113 (88.3%) of inmates were considered violent in at least one of the evaluations, 50 (39.1%) in at least 2 evaluations, and 4 (3.1%) in all three evaluations. There was no statistically significant difference in anti-T. gondii IgG seroprevalence when comparing violent and non-violent inmates, which was persistent whether the inmates were considered violent in at least one, two, or three evaluations. For example, the mean scores of the AGQ in T. gondii seropositive inmates (73.67 ± 29.09; 95% CI: 50.00–99.31) were similar to those (79.84 ± 25.00; 95% CI: 75.46–84.27) found in T. gondii seronegative inmates (P = 0.55). Further stratification by type of aggression did not reveal any statistically significant differences between the T. gondii seropositive inmates and the T. gondii seronegative inmates. Overall, the findings from this study suggest that T. gondii seropositivity is not associated with violent behaviour in inmates. A major limitation of this study is its small sample size, which may increase the probability of type II error. This study acts as an important step to understanding the effects of T. gondii seropositivity on behaviour, and further research with larger sample sizes is essential to corroborate the findings from this study.
Image: PD
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