Prognostic factors for chronic post-surgical pain after lung or pleural surgery: A protocol for a systematic review and meta-analysis

INTRODUCTION: Chronic post-surgical pain (CPSP) after lung or pleural surgery is a common complication and associated with a decrease in quality of life, long-term use of pain medication and substantial economic costs. An abundant number of primary prognostic factor studies are published each year, but findings are often inconsistent, methods heterogeneous and the methodological quality questionable. Systematic reviews and meta-analyses are therefore needed to summarise the evidence. METHODS AND ANALYSIS: The reporting of this protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. We will include retrospective and prospective studies with a follow-up of at least 3 months reporting patient-related factors and surgery-related factors for any adult population. Randomised controlled trials will be included if they report on prognostic factors for CPSP after lung or pleural surgery. We will exclude case series, case reports, literature reviews, studies that do not report results for lung or pleural surgery separately and studies that modified the treatment or prognostic factor based on pain during the observation period. MEDLINE, Scopus, Web of Science, Embase, Cochrane, CINAHL, Google Scholar and relevant literature reviews will be searched. Independent pairs of two reviewers will assess studies in two stages based on the PICOTS criteria. We will use the Quality in Prognostic Studies tool for the quality assessment and the CHARMS-PF checklist for the data extraction of the included studies. The analyses will all be conducted separately for each identified prognostic factor. We will analyse adjusted and unadjusted estimated measures separately. When possible, evidence will be summarised with a meta-analysis and otherwise narratively. We will quantify heterogeneity by calculating the Q and I ETHICS AND DISSEMINATION: Ethical approval will not be necessary, as all data are already in the public domain. Results will be published in a peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER: CRD42021227888

Lost in transition? Immune regulatory mechanisms in early life

Fetal life and early infancy are recognized as a critical period to shape the immune system for life. Slowly the neonatal immune system changes its regulatory responses into effector responses. Genes, environmental factors and the interaction between both, the epigenome, will influence this maturation process and different developmental trajectories might be initiated leading to disease pathways. This concept has been recognized in the 1000 days campaign and the WHO’s Every Newborn Action Plan but pathophysiological mechanisms supporting this theory are mostly unidentified. In this thesis, it is pitched that immune homeostasis in early life is (partly) achieved by the unique increased ability of neonatal immunity to induce adaptive immune tolerance and that innate cells play an important role in driving this mechanism. Indeed, the predilection of neonatal naive CD4+ T cells to differentiate into FOXP3+ Tregs, in which PD-1/PD-L1 interactions play a role through a mechanism involving PKB signaling (chapter 2), and the inability to differentiate into TH17 cells, which is blocked at the level of RORC2 (chapter 3), confirmed a profound programmed development of na.ve T cells upon activation and their role in the development of immune tolerance in early life. Neonatal T cells develop the capacity to differentiate into TH17 cells during the first 3 months and retained a propensity to become Treg cells until the age of at least 12 months (chapter 4). However, IL-17, as well as high levels of IL-6 and TNFα are produced in vivo during severe neonatal infections, when strong pro-inflammatory stimuli are present. Thus, deficient innate and effector responses in neonates are partial and can be overcome once innate stimuli are strong enough (chapter 5). System immunology, provided that it is standardized in use (chapter 6), enables identification of divergent patterns in immune maturation related to long term health outcomes. It is crucial for long term health outcomes to protect and secure this programmed, age-dependent and stereotypic immune development. Therefore, unnecessary (longtime) antibiotic treatment should be avoided since this will disturb proper immune development by means of destruction of the composition of the microbiome and subsequently affects proper immune maturation. Development and clinical implementation of better diagnostic tools to identify or exclude neonatal sepsis are mandatory to secure future health outcomes

Prognostic models for outcome prediction following in-hospital cardiac arrest using pre-arrest factors: a systematic review, meta-analysis and critical appraisal

Abstract Background Several prediction models of survival after in-hospital cardiac arrest (IHCA) have been published, but no overview of model performance and external validation exists. We performed a systematic review of the available prognostic models for outcome prediction of attempted resuscitation for IHCA using pre-arrest factors to enhance clinical decision-making through improved outcome prediction. Methods This systematic review followed the CHARMS and PRISMA guidelines. Medline, Embase, Web of Science were searched up to October 2021. Studies developing, updating or validating a prediction model with pre-arrest factors for any potential clinical outcome of attempted resuscitation for IHCA were included. Studies were appraised critically according to the PROBAST checklist. A random-effects meta-analysis was performed to pool AUROC values of externally validated models. Results Out of 2678 initial articles screened, 33 studies were included in this systematic review: 16 model development studies, 5 model updating studies and 12 model validation studies. The most frequently included pre-arrest factors included age, functional status, (metastatic) malignancy, heart disease, cerebrovascular events, respiratory, renal or hepatic insufficiency, hypotension and sepsis. Only six of the developed models have been independently validated in external populations. The GO-FAR score showed the best performance with a pooled AUROC of 0.78 (95% CI 0.69–0.85), versus 0.59 (95%CI 0.50–0.68) for the PAM and 0.62 (95% CI 0.49–0.74) for the PAR. Conclusions Several prognostic models for clinical outcome after attempted resuscitation for IHCA have been published. Most have a moderate risk of bias and have not been validated externally. The GO-FAR score showed the most acceptable performance. Future research should focus on updating existing models for use in clinical settings, specifically pre-arrest counselling. Systematic review registration PROSPERO CRD42021269235. Registered 21 July 2021

Prognostic models for outcome prediction following in-hospital cardiac arrest using pre-arrest factors: a systematic review, meta-analysis and critical appraisal

Background: Several prediction models of survival after in-hospital cardiac arrest (IHCA) have been published, but no overview of model performance and external validation exists. We performed a systematic review of the available prognostic models for outcome prediction of attempted resuscitation for IHCA using pre-arrest factors to enhance clinical decision-making through improved outcome prediction. Methods: This systematic review followed the CHARMS and PRISMA guidelines. Medline, Embase, Web of Science were searched up to October 2021. Studies developing, updating or validating a prediction model with pre-arrest factors for any potential clinical outcome of attempted resuscitation for IHCA were included. Studies were appraised critically according to the PROBAST checklist. A random-effects meta-analysis was performed to pool AUROC values of externally validated models. Results: Out of 2678 initial articles screened, 33 studies were included in this systematic review: 16 model development studies, 5 model updating studies and 12 model validation studies. The most frequently included pre-arrest factors included age, functional status, (metastatic) malignancy, heart disease, cerebrovascular events, respiratory, renal or hepatic insufficiency, hypotension and sepsis. Only six of the developed models have been independently validated in external populations. The GO-FAR score showed the best performance with a pooled AUROC of 0.78 (95% CI 0.69–0.85), versus 0.59 (95%CI 0.50–0.68) for the PAM and 0.62 (95% CI 0.49–0.74) for the PAR. Conclusions: Several prognostic models for clinical outcome after attempted resuscitation for IHCA have been published. Most have a moderate risk of bias and have not been validated externally. The GO-FAR score showed the most acceptable performance. Future research should focus on updating existing models for use in clinical settings, specifically pre-arrest counselling. Systematic review registration PROSPERO CRD42021269235. Registered 21 July 2021

Implementation of barcode medication administration (BMCA) technology on infusion pumps in the operating rooms

Background Medication administration errors (MAEs) are a major cause of morbidity and mortality. An updated barcode medication administration (BCMA) technology on infusion pumps is implemented in the operating rooms to automate double check at a syringe exchange.Objective The aim of this mixed-methods before-and-after study is to understand the medication administrating process and assess the compliance with double check before and after implementation.Methods Reported MAEs from 2019 to October 2021 were analysed and categorised to the three moments of medication administration: (1) bolus induction, (2) infusion pump start-up and (3) changing an empty syringe. Interviews were conducted to understand the medication administration process with functional resonance analysis method (FRAM). Double check was observed in the operating rooms before and after implementation. MAEs up to December 2022 were used for a run chart.Results Analysis of MAEs showed that 70.9% occurred when changing an empty syringe. 90.0% of MAEs were deemed to be preventable with the use of the new BCMA technology. The FRAM model showed the extent of variation to double check by coworker or BCMA.Observations showed that the double check for pump start-up changed from 70.2% to 78.7% postimplementation (p=0.41). The BCMA double check contribution for pump start-up increased from 15.3% to 45.8% (p=0.0013). The double check for changing an empty syringe increased from 14.3% to 85.0% (p<0.0001) postimplementation. BCMA technology was new for changing an empty syringe and was used in 63.5% of administrations. MAEs for moments 2 and 3 were significantly reduced (p=0.0075) after implementation in the operating rooms and ICU.Conclusion An updated BCMA technology contributes to a higher double check compliance and MAE reduction, especially when changing an empty syringe. BCMA technology has the potential to decrease MAEs if adherence is high enough

Argon does not affect cerebral circulation or metabolism in male humans

<div><p>Objective</p><p>Accumulating data have recently underlined argon´s neuroprotective potential. However, to the best of our knowledge, no data are available on the cerebrovascular effects of argon (Ar) in humans. We hypothesized that argon inhalation does not affect mean blood flow velocity of the middle cerebral artery (Vmca), cerebral flow index (FI), zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe), resistance area product (RAP) and the arterio-jugular venous content differences of oxygen (AJVDO₂), glucose (AJVDG), and lactate (AJVDL) in anesthetized patients.</p><p>Materials and methods</p><p>In a secondary analysis of an earlier controlled cross-over trial we compared parameters of the cerebral circulation under 15 minutes exposure to 70%Ar/30%O₂ versus 70%N₂/30%O₂ in 29 male patients under fentanyl-midazolam anaesthesia before coronary surgery. Vmca was measured by transcranial Doppler sonography. ZFP and RAP were estimated by linear regression analysis of pressure-flow velocity relationships of the middle cerebral artery. CPPe was calculated as the difference between mean arterial pressure and ZFP. AJVDO₂, AJVDG and AJVDL were calculated as the differences in contents between arterial and jugular-venous blood of oxygen, glucose, and lactate. Statistical analysis was done by t-tests and ANOVA.</p><p>Results</p><p>Mechanical ventilation with 70% Ar did not cause any significant changes in mean arterial pressure, Vmca, FI, ZFP, CPPe, RAP, AJVDO₂, AJVDG, and AJVDL.</p><p>Discussion</p><p>Short-term inhalation of 70% Ar does not affect global cerebral circulation or metabolism in male humans under general anaesthesia.</p></div

Haemodynamic and metabolic data.

<p>Haemodynamic and metabolic data.</p

Effect of argon inhalation on cerebral circulation and metabolism.

<p>Values of mean blood flow velocity of the middle cerebral artery (Vmca), effective cerebral perfusion pressure (CPPe), resistance area product (RAP), arterio-jugular venous differences in oxygen (AJVDO₂) glucose (AJVDG), and lactate (AJVDL) during baseline (70%N₂/30%O₂) compared with argon inhalation (70%Ar/30%O₂). <i>Straight lines</i> link individual values for each subject. Data are mean (SD) for each measurement. The P values, which refer to the difference between two measurement points, were calculated using two-sided t-test for paired data. Due to artefacts during TCD recording, data of patient 1 and 5 have been excluded from respective analysis § n = 28, * n = 27.</p

Heparin-resistance in AL amyloidosis: a case report

Abstract Background Non-AT-III mediated heparin-resistance during CPB occurs by complex-forming with heparin-binding proteins. Currently, there are no specific recommendations for non-AT-III mediated heparin-resistance. Case presentation We present a fatal case of a 70-yr-old male-patient undergoing cardiac-surgery in which refractory heparin-resistance was observed. The massive AL amyloidosis found at autopsy is thought to be responsible and illustrates that awareness and knowledge of the etiology and perioperative strategies of non-AT-III mediated heparin-resistance is important. Conclusion For anticoagulation during cardiopulmonary bypass surgery in case of a non-AT-III medicated heparin resistance, we refer to the decision tree added to this manuscript and if necessary to consider direct thrombin inhibitors, such as bivalirudin or argatroban, as it bypasses the complexing pathway

Cross-sectional relation of long-term glucocorticoids in hair with anthropometric measurements and their possible determinants: A systematic review and meta-analysis

Background: Long-term glucocorticoids (HairGC) measured in scalp hair have been associated with body mass index (BMI), waist circumference (WC), and waist-hip-ratio (WHR) in several cross-sectional studies. We aimed to investigate the magnitude, strength, and clinical relevance of these relations across all ages. Methods: We performed a systematic review and meta-analysis (PROSPERO registration CRD42020205187) searching for articles relating HairGC to measures of obesity. Main outcomes were bivariate correlation coefficients and unadjusted simple linear regression coefficients relating hair cortisol (HairF) and hair cortisone (HairE) to BMI, WC, and WHR. Results: We included k = 146 cohorts (n = 34,342 individuals). HairGC were positively related to all anthropometric measurements. The strongest correlation and largest effect size were seen for HairE-WC: pooled correlation 0.18 (95%CI 0.11–0.24; k = 7; n = 3,158; I2 = 45.7%) and pooled regression coefficient 11.0 cm increase in WC per point increase in 10-log-transformed HairE (pg/mg) on liquid-chromatography-(tandem) mass spectrometry (LC–MS) (95%CI 10.1–11.9 cm; k = 6; n = 3,102). Pooled correlation for HairF-BMI was 0.10 (95%CI 0.08–0.13; k = 122; n = 26,527; I2 = 51.2%) and pooled regression coefficient 0.049 kg/m2 per point increase in 10-log-transformed HairF (pg/mg) on LC–MS (95%CI 0.045–0.054 kg/m2; k = 26; n = 11,635). Discussion: There is a consistent positive association between HairGC and BMI, WC, and WHR, most prominently and clinically relevant for HairE-WC. These findings overall suggest an altered setpoint of the hypothalamic–pituitary–adrenal axis with increasing central adiposity