Risk factors, biomarkers, and mechanisms for persistent inflammation, immunosuppression, and catabolism syndrome (PICS): a systematic review and meta-analysis.

INTRODUCTION: Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic review is to synthesise the available evidence of risk factors, biomarkers, and biological mechanisms underlying PICS. METHODS: MEDLINE, CENTRAL, and EMBASE were searched on June 2, 2023. Our population of interest was adult intensive care unit survivors. The exposure group was patients with PICS and the comparator group was patients with no PICS, CCI, or rapid recovery. Mean differences were pooled for each biomarker using a random effects DerSimonian-Laird method. Risk of bias assessment was done using the Newcastle-Ottawa Scale. RESULTS: Six papers were included. Five were single-centre retrospective cohort studies, and one was a prospective cohort study, with sample sizes ranging from 22 to 391 patients. Two studies showed an increased incidence of PICS with age, and two studies showed an association between PICS and Charlson Comorbidity Index scores. PICS was associated with requiring mechanical ventilation in four studies. Meta-analysis showed a 34.4 mg L-1 higher C-reactive protein (95% confidence interval [CI] 12.7-56.2 mg L-1; P<0.01), a 4.4 g L-1 lower albumin (95% CI 0.5-8.3 g L-1; P<0.01), and a 0.36×109 L-1 lower lymphocyte count (95% CI 0.25-0.47×109 L-1; P=0.01) in the PICS compared with the non-PICS group. There are a large variety of other potential biomarkers but limited validation studies. The overall quality of evidence is limited, and these results should be interpreted accordingly. CONCLUSIONS: While older patients and those with co-morbidities could be at greater risk for PICS, acquired risk factors, such as injury severity, are potentially more predictive of PICS than intrinsic patient characteristics. There are many potential biomarkers for PICS, but limited validation studies have been conducted. Persistent myeloid-derived suppressor cell expansion, the continual release of danger-associated molecular patterns and pathogen-associated molecular patterns propagating inflammation, and bioenergetic failure are all mechanisms underlying PICS that could offer potential for novel biomarkers and therapeutic interventions. CLINICAL TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO; CRD42023427749).

The clinical utility of dysregulated microRNA expression in paediatric solid tumours.

MicroRNAs (miRNAs) are short, non-protein-coding genes that regulate the expression of numerous protein-coding genes. Their expression is dysregulated in cancer, where they may function as oncogenes or tumour suppressor genes. As miRNAs are highly resistant to degradation, they are ideal biomarker candidates to improve the diagnosis and clinical management of cancer, including prognostication. Furthermore, miRNAs dysregulated in malignancy represent potential therapeutic targets. The use of miRNAs for these purposes is a particularly attractive option to explore for paediatric malignancies, where the mutational burden is typically low, in contrast to cancers affecting adult patients. As childhood cancers are rare, it has taken time to accumulate the necessary body of evidence showing the potential for miRNAs to improve clinical management across this group of tumours. Here, we review the current literature regarding the potential clinical utility of miRNAs in paediatric solid tumours, which is now both timely and justified. Exploring such avenues is warranted to improve the management and outcomes of children affected by cancer.

Long COVID-19 and Postural Orthostatic Tachycardia Syndrome- Is Dysautonomia to Be Blamed?

While the increased arrhythmic tendency during acute COVID-19 infection is recognised, the long-term cardiac electrophysiological complications are less well known. There are a high number of patients reporting ongoing symptoms post-infection, termed long COVID. A recent hypothesis is that long COVID symptoms could be attributed to dysautonomia, defined as malfunction of the autonomic nervous system (ANS). The most prevalent cardiovascular dysautonomia amongst young people is postural orthostatic tachycardia syndrome (POTS). Numerous reports have described the development of POTS as part of long COVID. Possible underlying mechanisms, although not mutually exclusive or exhaustive, include hypovolaemia, neurotropism, inflammation and autoimmunity. Treatment options for POTS and other long COVID symptoms are currently limited. Future research studies should aim to elucidate the underlying mechanisms of dysautonomia to enable the development of targeted therapies. Furthermore, it is important to educate healthcare professionals to recognise complications and conditions arising from COVID-19, such as POTS, to allow prompt diagnosis and access to early treatment.