A Global Perspective with Systematic Review and Meta-Analysis of Observational Studies

Acute cardiovascular disease after community-acquired pneumonia is a well-accepted complication for which definitive treatment strategies are lacking. These complications share some common features but have distinct diagnostic and treatment approaches. We therefore undertook an updated systematic review and meta-analysis of observational studies reporting the incidence of overall complications, acute coronary syndromes, new or worsening heart failure, new or worsening arrhythmias and acute stroke, as well as short-term mortality outcomes. To set a framework for future research, we further included a holistic review of the interplay between the two conditions. From 1984 to 2019, thirty-nine studies were accrued, involving 92,188 patients, divided by setting (inpatients versus outpatients) and clinical severity (low risk versus high risk). Overall cardiac complications occurred in 13.9% (95% confidence interval (CI) 9.6-18.9), acute coronary syndromes in 4.5% (95% CI 2.9-6.5), heart failure in 9.2% (95% CI 6.7-12.2), arrhythmias in 7.2% (95% CI 5.6-9.0) and stroke in 0.71% (95% CI 0.1-3.9) of pooled inpatients. During this period, meta-regression analysis suggests that the incidence of overall and individual cardiac complications is decreasing. After adjusting for confounders, cardiovascular events taking place after community-acquired pneumonia independently increase the risk for short-term mortality (range of odds-ratio: 1.39-5.49). These findings highlight the need for effective, large trial based, preventive and therapeutic interventions in this important patient population.publishersversionpublishe

How strong is this 'strong' evidence?

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one of the forgotten diseases

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The Role of Biomarkers, Pharmacokinetics, and Pharmacodynamics

The high prevalence of infectious diseases in the intensive care unit (ICU) and consequently elevated pressure for immediate and effective treatment have led to increased antimicrobial therapy consumption and misuse. Moreover, the emerging global threat of antimicrobial resistance and lack of novel antimicrobials justify the implementation of judicious antimicrobial stewardship programs (ASP) in the ICU. However, even though the importance of ASP is generally accepted, its implementation in the ICU is far from optimal and current evidence regarding strategies such as de-escalation remains controversial. The limitations of clinical guidance for antimicrobial therapy initiation and discontinuation have led to multiple studies for the evaluation of more objective tools, such as biomarkers as adjuncts for ASP. C-reactive protein and procalcitonin can be adequate for clinical use in acute infectious diseases, the latter being the most studied for ASP purposes. Although promising, current evidence highlights challenges in biomarker application and interpretation. Furthermore, the physiological alterations in the critically ill render pharmacokinetics and pharmacodynamics crucial parameters for adequate antimicrobial therapy use. Individual pharmacokinetic and pharmacodynamic targets can reduce antimicrobial therapy misuse and risk of antimicrobial resistance.publishersversionpublishe

A critical review

Biomarkers of infection, namely C-reactive protein and procalcitonin (PCT), are potentially useful in the diagnosis of infection as well as in the assessment of its response to antibiotic therapy. C-reactive protein variations overtime appears to have a good performance for the diagnosis of infection. Procalcitonin shows a better correlation with clinical severity. In addition, to overcome the worldwide problem of antibiotic overuse as well as misuse, biomarker guidance of antibiotic stewardship represents a promising new approach. In several randomized, controlled trials, including adult critically ill patients, PCT guidance was repeatedly associated with a decrease in the duration of antibiotic therapy. However, these trials present several limitations, namely high rate of patients' exclusion, high rate of algorithm overruling, long duration of antibiotic therapy in the control group, disregard the effect of renal failure on PCT level, and above all a possible higher mortality and higher late organ failure in the PCT arm. In addition, some infections (e.g., endocarditis) as well as frequent nosocomial bacteria (e.g., Pseudomonas aeruginosa) are not suitable to be assessed by PCT algorithms. Therefore, the true value of PCT-guided algorithm of antibiotic stewardship in assisting the clinical decision-making process at the bedside remains uncertain. Future studies should take into account the issues identified in the present review.publishersversionpublishe

SARS-CoV-2 and cytomegalovirus co-infections—a case series of critically ill patients

The SARS-CoV-2 pandemic has placed great strain on the most developed of health care systems, especially in the context of critical care. Although co-infections with cytomegalovirus (CMV) are frequent in the critically ill due to underlying immune suppression of multiple causes, the impact on COVID-19 patients remains unclear. Furthermore, severe COVID-19 has recently been associated with significant immune suppression, and this may in turn impact CMV reactivation, possibly contributing to clinical course. Nevertheless, multiple confounding factors in these patients will certainly challenge upcoming research. The authors present a case series of five patients admitted to the intensive care unit (ICU) in the context of respiratory failure due to severe COVID-19. All patients evolved with CMV reactivation during ICU stay.publishersversionpublishe

beyond reasonable doubt?

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Corticosteroids in severe community-acquired pneumonia: the path we choose depends on where we want to get

Severe community-acquired pneumonia is a major cause of admission to intensive care units and its mortality rates remain exceedingly high. In the search for adjunctive therapies, clinicians who were encouraged by available, though limited, evidence prescribed steroids in most patients with severe sepsis or septic shock, including those with community-acquired pneumonia. Current evidence demonstrates that, whereas corticosteroids should not be routinely employed as adjuvant therapy for severe community-acquired pneumonia, there is sufficient equipoise to continue studying the use of corticosteroids