Inflammation Disrupts the Brain Network of Executive Function after Cardiac Surgery.

OBJECTIVE: To investigate postoperative functional connectivity (FC) alterations across impaired cognitive domains and their causal relationships with systemic inflammation. BACKGROUND: Postoperative cognitive dysfunction commonly occurs after cardiac surgery, and both systemic and neuroinflammation may trigger its development. Whether FC alterations underlying deficits in specific cognitive domains after cardiac surgery are affected by inflammation remains unclear. METHODS: Seventeen patients, who underwent cardiac valve replacement, completed a neuropsychological test battery and brain MRI scan before surgery and on days 7 and 30 after surgery compared to age-matched healthy controls. Blood samples were taken for tumor necrosis factor-a and interleukin-6 measurements. Seed-to-voxel FC of the left dorsolateral prefrontal cortex (DLPFC) was examined. Bivariate correlation and linear regression models were used to determine the relationships among cognitive function, FC alterations, and cytokines. RESULTS: Executive function was significantly impaired after cardiac surgery. At day 7 follow-up, the surgical patients, compared to the controls, demonstrated significantly decreased DLPFC FC with the superior parietal lobe and attenuated negative connectivity in the default mode network, including the angular gyrus and posterior cingulate cortex. The left DLPFC enhanced the connectivity in the right DLPFC and posterior cingulate cortex, all of which were related to the increased tumor necrosis factor-a and decreased executive function up to day 7 after cardiac surgery. CONCLUSIONS: The decreased FC of executive control network and its anticorrelation with the default mode network may contribute to executive function deficits after cardiac surgery. Systemic inflammation may trigger these transient FC changes and executive function impairments.

High daily caffeine intake is associated with lower propofol requirements for anesthetic induction.

Background and Aims: There is significant interindividual variation in the dose of propofol required for anesthetic induction. Factors dictating this are poorly described, but understanding them would be useful for anesthetic drug dosing. It has been shown in rats and recently in humans that caffeine administration accelerates recovery from anesthesia, but no study has assessed the effect on anesthetic induction. Material and Methods: Forty American Society of Anesthesiologists (ASA)-I, 18-65-year-old patients, undergoing day case general anesthesia with propofol and fentanyl took part in this observational study. Total daily caffeine intake (mg) was estimated using the caffeine assessment tool and caffeine content values from the US Department of Agriculture National Nutrient Database. Pharmacokinetic-pharmacodynamic modeling was used to estimate the effect site concentration of propofol at loss of consciousness (Ce(p) LOC). Results: Median (interquartile range [IQR]) daily caffeine intake was 106 (51-193) mg. Ce(p) LOC was lower in those with caffeine intake greater than or equal to the median of 106 mg (median (IQR) = 0.64 µg/ml (0.51-0.72) vs. 0.70 µg/ml (0.57-1.10), P = 0.04). The effect was robust when controlling for weight-adjusted fentanyl dose, age, smoking status, and alcohol intake (F (1,34) = 4.66, P = 0.04). Conclusion: High daily caffeine intake is associated with lower propofol requirements for day case anesthetic induction. We propose that high daily caffeine intake may cause lower arousal levels prior to surgery due to a relative caffeine deficit caused by being nil by mouth. As such, assessment of daily caffeine intake preoperatively may aid anesthetic drug dosing.

Prognosis and antibody profiles in survivors of critical illness from COVID-19: a prospective multicentre cohort study.

BACKGROUND: There is a need to assess the long-term outcomes of survivors of critical illness from COVID-19. METHODS: Ninety-two survivors of critical illness from COVID-19 from four hospitals in Hubei Province, China participated in this prospective cohort study. Multiple characteristics, including lung function (lung volumes, diffusing capacity for carbon monoxide, chest computed tomography scores, and walking capacity); immune status (SARS-CoV-2-neutralising antibody and all subtypes of immunoglobulin (Ig) G against SARS-CoV-2, immune cells in response to ex vivo antigen peptide stimuli, and lymphocyte count and its subtypes); liver, coagulation, and kidney functions; quality of life; cognitive function; and mental status, were assessed after 3, 6, and 12 months of follow-up. RESULTS: Amongst the 92 enrolled survivors, 72 (78%) patients required mechanical ventilation. At 12 months, the predicted percentage diffusing capacity of lung for carbon monoxide was 82% (inter-quartile range [IQR]: 76-97%) with a residual volume of 77 (64-88)%. Other lung function parameters and the 6-min walk test improved gradually over time and were almost back to normal by 12 months. The titres of IgG and neutralising antibody to COVID-19 remained high at 12 months compared with those of controls who were not infected with COVID-19, although IgG titres decreased significantly from 34.0 (IQR: 23.8-74.3) to 15.0 (5.8-24.3) AU ml-1 (P<0.001), whereas neutralising antibodies decreased from 29.99 (IQR: 19.43-53.93) AU ml-1 at 6 months to 19.75 (13.1-29.8) AU ml-1 (P<0.001) at 12 months. In general, liver, kidney, physical, and mental functions also improved over time. CONCLUSIONS: Survivors of critical illness from COVID-19 show some persistent long-term impairments in lung function. However, a majority of these tests were normal by 12 months. These patients still had detectable levels of neutralising antibodies against SARS-CoV-2 and all types of IgG at 12 months, but the levels had declined over this time period. CLINICAL TRIAL REGISTRATION: None.

Development and implementation of a COVID-19 near real-time traffic light system in an acute hospital setting.

Common causes of death in COVID-19 due to SARS-CoV-2 include thromboembolic disease, cytokine storm and adult respiratory distress syndrome (ARDS). Our aim was to develop a system for early detection of disease pattern in the emergency department (ED) that would enhance opportunities for personalised accelerated care to prevent disease progression. A single Trust's COVID-19 response control command was established, and a reporting team with bioinformaticians was deployed to develop a real-time traffic light system to support clinical and operational teams. An attempt was made to identify predictive elements for thromboembolism, cytokine storm and ARDS based on physiological measurements and blood tests, and to communicate to clinicians managing the patient, initially via single consultants. The input variables were age, sex, and first recorded blood pressure, respiratory rate, temperature, heart rate, indices of oxygenation and C-reactive protein. Early admissions were used to refine the predictors used in the traffic lights. Of 923 consecutive patients who tested COVID-19 positive, 592 (64%) flagged at risk for thromboembolism, 241/923 (26%) for cytokine storm and 361/923 (39%) for ARDS. Thromboembolism and cytokine storm flags were met in the ED for 342 (37.1%) patients. Of the 318 (34.5%) patients receiving thromboembolism flags, 49 (5.3% of all patients) were for suspected thromboembolism, 103 (11.1%) were high-risk and 166 (18.0%) were medium-risk. Of the 89 (9.6%) who received a cytokine storm flag from the ED, 18 (2.0% of all patients) were for suspected cytokine storm, 13 (1.4%) were high-risk and 58 (6.3%) were medium-risk. Males were more likely to receive a specific traffic light flag. In conclusion, ED predictors were used to identify high proportions of COVID-19 admissions at risk of clinical deterioration due to severity of disease, enabling accelerated care targeted to those more likely to benefit. Larger prospective studies are encouraged.

Xenon Treatment Protects against Remote Lung Injury after Kidney Transplantation in Rats.

BACKGROUND: Ischemia-reperfusion injury (IRI) of renal grafts may cause remote organ injury including lungs. The authors aimed to evaluate the protective effect of xenon exposure against remote lung injury due to renal graft IRI in a rat renal transplantation model. METHODS: For in vitro studies, human lung epithelial cell A549 was challenged with H2O2, tumor necrosis factor-α, or conditioned medium from human kidney proximal tubular cells (HK-2) after hypothermia-hypoxia insults. For in vivo studies, the Lewis renal graft was stored in 4°C Soltran preserving solution for 24 h and transplanted into the Lewis recipient, and the lungs were harvested 24 h after grafting. Cultured lung cells or the recipient after engraftment was exposed to 70% Xe or N2. Phospho (p)-mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1α (HIF-1α), Bcl-2, high-mobility group protein-1 (HMGB-1), TLR-4, and nuclear factor κB (NF-κB) expression, lung inflammation, and cell injuries were assessed. RESULTS: Recipients receiving ischemic renal grafts developed pulmonary injury. Xenon treatment enhanced HIF-1α, which attenuated HMGB-1 translocation and NF-κB activation in A549 cells with oxidative and inflammatory stress. Xenon treatment enhanced p-mTOR, HIF-1α, and Bcl-2 expression and, in turn, promoted cell proliferation in the lung. Upon grafting, HMGB-1 translocation from lung epithelial nuclei was reduced; the TLR-4/NF-κB pathway was suppressed by xenon treatment; and subsequent tissue injury score (nitrogen vs. xenon: 26 ± 1.8 vs. 10.7 ± 2.6; n = 6) was significantly reduced. CONCLUSION: Xenon treatment confers protection against distant lung injury triggered by renal graft IRI, which is likely through the activation of mTOR-HIF-1α pathway and suppression of the HMGB-1 translocation from nuclei to cytoplasm.

The therapeutic potential of atorvastatin in a mouse model of postoperative cognitive decline.

OBJECTIVE: Postoperative cognitive decline is emerging as a significant complication of surgery among older adults. Animal models indicate a central role of hippocampal inflammatory responses in the pathophysiology of postoperative cognitive decline. We hypothesized that atorvastatin, shown to exert neuroprotective potential in central nervous system (CNS) disorders, would attenuate neuroinflammation and improve cognitive function in mice after surgery and anesthesia. METHODS: C57BL6 adult mice were pretreated with atorvastatin (250 µg) or vehicle, orally, for 5 days before undergoing unilateral nephrectomy under isoflurane anesthesia. We evaluated behavioral parameters related to cognitive function (fear conditioning and Morris Water Maze) and determined systemic and hippocampal interleukin-1ß levels, postoperatively. Endothelial COX-2 expression, gross NF-κB and microglial (IBA1, CD68) activation, synaptic function (synapsin-1, PSD95, COX-2), heme oxygenase-1, and GSK3ß were also examined. RESULTS: Surgery induced a significant reduction in hippocampal-dependent fear response that was attenuated by treatment with atorvastatin, which also preserved spatial memory on day 7 after surgery. Atorvastatin evoked significant protection from hippocampal interleukin-1ß production, but not systemic interleukin-1ß production, accompanied by a marked reduction in hippocampal endothelial COX-2, NF-κB activation and decreased microglial reactivity. Surgery triggered an acute decline in synapsin-1, paralleled by an increase in postsynaptic COX-2 that was partially attenuated by atorvastatin. Furthermore, phosphorylation and inactivation of neuronal GSK3ß was significantly enhanced after atorvastatin treatment. CONCLUSIONS: These findings indicate that cognitive decline is very likely associated with synaptic pathology after systemic and central inflammation induced by peripheral surgery/isoflurane anesthesia and suggest that the anti-inflammatory and neuroprotective properties of atorvastatin provide a rationale for its use as a therapeutic strategy for postoperative cognitive decline.

Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release.

BACKGROUND: The nuclear protein high-mobility group box 1 (HMGB1) is a key trigger for the inflammatory reaction during liver ischemia reperfusion injury (IRI). Hydrogen treatment was recently associated with down-regulation of the expression of HMGB1 and pro-inflammatory cytokines during sepsis and myocardial IRI, but it is not known whether hydrogen has an effect on HMGB1 in liver IRI. METHODS: A rat model of 60 minutes 70% partial liver ischemia reperfusion injury was used. Hydrogen enriched saline (2.5, 5 or 10 ml/kg) was injected intraperitoneally 10 minutes before hepatic reperfusion. Liver injury was assessed by serum alanine aminotransferase (ALT) enzyme levels and histological changes. We also measured malondialdehyde (MDA), hydroxynonenal (HNE) and 8-hydroxy-guanosine (8-OH-G) levels as markers of the peroxidation injury induced by reactive oxygen species (ROS). In addition, pro-inflammatory cytokines including TNF-α and IL-6, and high mobility group box B1 protein (HMGB1) were measured as markers of post ischemia-reperfusion inflammation. RESULTS: Hydrogen enriched saline treatment significantly attenuated the severity of liver injury induced by ischemia-reperfusion. The treatment group showed reduced serum ALT activity and markers of lipid peroxidation and post ischemia reperfusion histological changes were reduced. Hydrogen enriched saline treatment inhibited HMGB1 expression and release, reflecting a reduced local and systemic inflammatory response to hepatic ischemia reperfusion. CONCLUSION: These results suggest that, in our model, hydrogen enriched saline treatment is protective against liver ischemia-reperfusion injury. This effect may be mediated by both the anti-oxidative and anti-inflammatory effects of the solution.

Perioperative research into memory (PRiMe), part 2: Adult burns intensive care patients show altered structure and function of the default mode network.

BACKGROUND: Long-term cognitive impairment (LTCI) is experienced by up to two thirds of patients discharged from burns intensive care units (BICUs), however little is known about its neurobiological basis. This study investigated if patients previously admitted to BICU showed structural and functional MRI changes of the Default Mode Network (DMN). METHODS: Fifteen patients previously admitted to BICU with a significant burns injury, and 15 matched volunteers, underwent structural and functional MRI scans. Functional connectivity, fractional anisotropy and cortical thickness of the main DMN subdivisions (anterior DMN (aDMN), posterior DMN (pDMN) and right (rTPJ) and left (lTPJ) temporo-parietal junctions) were compared between patients and volunteers, with differences correlated against cognitive performance. RESULTS: Functional connectivity between rTPJ and pDMN (t = 2.91, p = 0.011) and between rTPJ and lTPJ (t = 3.18, p = 0.008) was lower in patients compared to volunteers. Functional connectivity between rTPJ and pDMN correlated with cognitive performance (r2 =0.33, p < 0.001). Mean fractional anisotropy of rTPJ (t = 2.70, p = 0.008) and lTPJ (T = 2.39, p = 0.015) was lower in patients but there was no difference in cortical thickness. CONCLUSIONS: Patients previously admitted to BICU show structural and functional disruption of the DMN. Since functional changes correlate with cognitive performance, this should direct further research into intensive-care-related cognitive impairment.

A protocol for a pilot study to assess the feasibility of a randomised clinical trial of perioperative intravenous lidocaine on colorectal cancer outcome after surgery (FLICOR trial).

Background: Cancer recurrence after curative cancer surgery significantly impacts patients and healthcare services. Before surgery, a small number of clinically undetectable circulating tumour cells are often present. The surgical stress response promotes the distribution and proliferation of circulating tumour cells leading to cancer recurrence and metastasis. Preclinical evidence suggests that lidocaine may exert 'anti-cancer' effects and alleviate pro-metastatic environments. The Feasibility Study of Lidocaine Infusion During Bowel Cancer Surgery for Cancer Outcome (FLICOR) will assess the feasibility of conducting a clinical trial on perioperative intravenous lidocaine infusion for postoperative colorectal cancer outcomes. Methods: The study is a double-blinded, randomised, controlled pilot study for a full trial comparing intravenous lidocaine administration at 1.5 mg kg-1 bolus followed by 1.5 mg kg-1 h-1 infusion for 24 h with placebo in patients undergoing minimally invasive (laparoscopy or robotic) colorectal cancer surgery. The feasibility of data collection instruments will be measured, including those for future economic evaluation and clinical and patient-reported outcomes. For the exploratory outcomes, blood samples will be collected before and after surgery on days 0, 1, and 3. Recruitment is planned for two NHS Trusts over 6 months with a 12-month follow-up. Patients and clinicians will be asked for their feedback on the study process. Dissemination plan: Study data will be disseminated to trial participants, the public, and academic communities. The work will be presented at national and international conferences to stimulate interest and enthusiasm for centres to participate in the future definitive trial. This research will also be published in peer-reviewed open-access journals. Clinical trial registration: ISRCTN29594895 (ISRCTN), NCT05250791 (ClinicalTrials.gov). Protocol version number and date: 3.0, February 8, 2023.

WHY STOP? A prospective observational vignette-based study to determine the cognitive-behavioural effects of rapid diagnostic PCR-based point-of-care test results on antibiotic cessation in ICU infections.

OBJECTIVES: Point-of-care tests (POCTs) for infection offer accurate rapid diagnostics but do not consistently improve antibiotic stewardship (ASP) of suspected ventilator-associated pneumonia. We aimed to measure the effect of a negative PCR-POCT result on intensive care unit (ICU) clinicians' antibiotic decisions and the additional effects of patient trajectory and cognitive-behavioural factors (clinician intuition, dis/interest in POCT, risk averseness). DESIGN: Observational cohort simulation study. SETTING: ICU. PARTICIPANTS: 70 ICU consultants/trainees working in UK-based teaching hospitals. METHODS: Clinicians saw four case vignettes describing patients who had completed a course of antibiotics for respiratory infection. Vignettes comprised clinical and biological data (ie, white cell count, C reactive protein), varied to create four trajectories: clinico-biological improvement (the 'improvement' case), clinico-biological worsening ('worsening'), clinical improvement/biological worsening ('discordant clin better'), clinical worsening/biological improvement ('discordant clin worse'). Based on this, clinicians made an initial antibiotics decision (stop/continue) and rated confidence (6-point Likert scale). A PCR-based POCT was then offered, which clinicians could accept or decline. All clinicians (including those who declined) were shown the result, which was negative. Clinicians updated their antibiotics decision and confidence. MEASURES: Antibiotics decisions and confidence were compared pre-POCT versus post-POCT, per vignette. RESULTS: A negative POCT result increased the proportion of stop decisions (54% pre-POCT vs 70% post-POCT, χ2(1)=25.82, p<0.001, w=0.32) in all vignettes except improvement (already high), most notably in discordant clin worse (49% pre-POCT vs 74% post-POCT). In a linear regression, factors that significantly reduced clinicians' inclination to stop antibiotics were a worsening trajectory (b=-0.73 (-1.33, -0.14), p=0.015), initial confidence in continuing (b=0.66 (0.56, 0.76), p<0.001) and involuntary receipt of POCT results (clinicians who accepted the POCT were more inclined to stop than clinicians who declined it, b=1.30 (0.58, 2.02), p<0.001). Clinician risk averseness was not found to influence antibiotic decisions (b=-0.01 (-0.12, 0.10), p=0.872). CONCLUSIONS: A negative PCR-POCT result can encourage antibiotic cessation in ICU, notably in cases of clinical worsening (where the inclination might otherwise be to continue). This effect may be reduced by high clinician confidence to continue and/or disinterest in POCT, perhaps due to low trust/perceived utility. Such cognitive-behavioural and trajectorial factors warrant greater consideration in future ASP study design.

The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats.

OBJECTIVE: Xenon provides neuroprotection in multiple animal models; however, little is known about the other noble gases. The aim of the current study was to compare xenon, argon, and helium neuroprotection in a neonatal asphyxia model in rats. DESIGN: Randomized controlled trial. SETTING: Laboratory. SUBJECTS: Seven-day-old postnatal Sprague-Dawley rats. INTERVENTIONS: Seventy percent argon, helium, xenon, or nitrogen balanced with oxygen after hypoxic-ischemic brain injury. MEASUREMENTS AND MAIN RESULTS: Control animals undergoing moderate hypoxic-ischemia endured reduced neuronal survival at 7 days with impaired neurologic function at the juvenile age compared with naïve animals. Severe hypoxic-ischemic damage produced a large cerebral infarction in controls. After moderate hypoxic-ischemia, all three noble gases improved cell survival, brain structural integrity, and neurologic function on postnatal day 40 compared with nitrogen. Interestingly, argon improved cell survival to naïve levels, whereas xenon and helium did not. When tested against more severe hypoxic-ischemic injury only, argon and xenon reduced infarct volume. Furthermore, postinjury body weight in moderate insult was lower in the helium-treated group compared with the naïve, control, and other noble gas treatment groups, whereas in the severe injurious setting, it is lower in both control and helium-treated groups than other groups. In the nondirectly injured hemisphere, argon, helium, and xenon increased the expression of Bcl-2, whereas helium and xenon increased Bcl-xL. In addition, Bax expression was enhanced in the control and helium groups. CONCLUSIONS: These studies indicate that argon and xenon provide neuroprotection against both moderate and severe hypoxia-ischemic brain injury likely through prosurvival proteins synthesis.

Robots in Healthcare: a Scoping Review.

Purpose of Review: Robots are increasingly being adopted in healthcare to carry out various tasks that enhance patient care. This scoping review aims to establish the types of robots being used in healthcare and identify where they are deployed. Recent Findings: Technological advancements have enabled robots to conduct increasingly varied and complex roles in healthcare. For instance, precision tasks such as improving dexterity following stroke or assisting with percutaneous coronary intervention. Summary: This review found that robots have played 10 main roles across a variety of clinical environments. The two predominant roles were surgical and rehabilitation and mobility. Although robots were mainly studied in the surgical theatre and rehabilitation unit, other settings ranged from the hospital ward to inpatient pharmacy. Healthcare needs are constantly evolving, as demonstrated by COVID-19, and robots may assist in adapting to these changes. The future will involve increased telepresence and infrastructure systems will have to improve to allow for this. Supplementary Information: The online version contains supplementary material available at 10.1007/s43154-022-00095-4.

Heat shock protein 72 overexpression prevents early postoperative memory decline after orthopedic surgery under general anesthesia in mice.

BACKGROUND: Problems with learning and memory are common after surgery in the elderly and are associated with high morbidity. Heat shock protein 72 (Hsp72) confers neuroprotection against acute neurologic injury. We hypothesized that overexpression of Hsp72 would prevent the development of postoperative memory loss. METHODS: C57BL/6 wild-type and Hsp72 overexpressing transgenic mice were randomly allocated to the following: control, isoflurane anesthesia alone, or tibial fracture during isoflurane anesthesia. Animals were trained 24 h before surgery using a fear conditioning protocol and assessed in their training environment and in a novel context on posttreatment days 1, 3, and 7. Microglial activation was assessed by immunostaining. RESULTS: Adult male C57BL/6 wild-type mice exhibited reduced memory evidenced by a decreased percentage freezing time on days 1 and 3 after anesthesia alone (58.8 ± 5, 46.5 ± 5 mean ± SEM) and after surgery (53.4 ± 6, 44.1 ± 7), compared with controls (78.8 ± 5, 63.4 ± 6; P < 0.05 and P < 0.001, respectively). Hsp72 mice showed no difference by treatment on any day. Similarly, nonhippocampal-dependent memory was significantly impaired on days 1 and 3 after surgery and day 3 after anesthesia. The genotype effect was significant on days 1 and 7. CD68-immunopositive activated microglia in the hippocampus varied modestly with subregion and time; on day 7, there was a significant treatment effect with no genotype effect, with more activated microglia after surgery in all regions. CONCLUSION: Hsp72 overexpression is associated with prevention of postoperative hippocampal-dependent and -independent memory deficit induced by anesthesia and/or surgery. Memory deficit is not correlated with numbers of activated hippocampal microglia.

Continuous Non-Invasive Eye Tracking In Intensive Care.

Delirium, an acute confusional state, is a common occurrence in Intensive Care Units (ICUs). Patients who develop delirium have globally worse outcomes than those who do not and thus the diagnosis of delirium is of importance. Current diagnostic methods have several limitations leading to the suggestion of eye-tracking for its diagnosis through in-attention. To ascertain the requirements for an eye-tracking system in an adult ICU, measurements were carried out at Chelsea & Westminster Hospital NHS Foundation Trust. Clinical criteria guided empirical requirements of invasiveness and calibration methods while accuracy and precision were measured. A non-invasive system was then developed utilising a patient-facing RGB camera and a scene-facing RGBD camera. The system's performance was measured in a replicated laboratory environment with healthy volunteers revealing an accuracy and precision that outperforms what is required while simultaneously being non-invasive and calibration-free The system was then deployed as part of CONfuSED, a clinical feasibility study where we report aggregated data from 5 patients as well as the acceptability of the system to bedside nursing staff. To the best of our knowledge, the system is the first eye-tracking systems to be deployed in an ICU for delirium monitoring.

Vitamin C Intervention for Critical COVID-19: A Pragmatic Review of the Current Level of Evidence.

Severe respiratory infections are characterized by elevated inflammation and generation of reactive oxygen species (ROS) which may lead to a decrease in antioxidants such as vitamin C and a higher requirement for the vitamin. Administration of intravenous vitamin C to patients with pneumonia and sepsis appears to decrease the severity of the disease and potentially improve survival rate. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes pneumonia, sepsis and acute respiratory distress syndrome (ARDS) in severe cases, and is referred to as coronavirus disease 2019 (COVID-19). Patients with COVID-19 infection also appear to have depleted vitamin C status and require additional supplementation of vitamin C during the acute phase of the disease. To date there have been 12 vitamin C and COVID-19 trials published, including five randomised controlled trials (RCTs) and seven retrospective cohort studies. The current level of evidence from the RCTs suggests that intravenous vitamin C intervention may improve oxygenation parameters, reduce inflammatory markers, decrease days in hospital and reduce mortality, particularly in the more severely ill patients. High doses of oral vitamin C supplementation may also improve the rate of recovery in less severe cases. No adverse events have been reported in published vitamin C clinical trials in COVID-19 patients. Upcoming findings from larger RCTs will provide additional evidence on vitamin supplementation in COVID-19 patients.

Surgical Tracheostomy Outcomes in COVID-19-Positive Patients.

OBJECTIVE: The aim of this case series was to demonstrate that surgical tracheostomy can be undertaken safely in critically ill mechanically ventilated patients with coronavirus disease 2019 (COVID-19) and that it is an effective weaning tool. STUDY DESIGN: Retrospective case series. SETTING: Single academic teaching hospital in London. METHODS: All adult patients admitted to the adult intensive care unit (AICU), diagnosed with severe COVID-19 infection and requiring surgical tracheostomy between the March 10, 2020, and May 1, 2020, were included. Data collection focused upon patient demographics, AICU admission data, tracheostomy-specific data, and clinical outcomes. RESULTS: Twenty patients with COVID-19 underwent surgical tracheostomy. The main indication for tracheostomy was to assist in respiratory weaning. Patients had undergone mechanical ventilation for a median of 16.5 days prior to surgical tracheostomy. Tracheostomy remained in situ for a median of 12.5 days. Sixty percent of patients were decannulated at the end of the data collection period. There were no serious immediate or short-term complications. Surgical tracheostomy facilitated significant reduction in intravenous sedation at 48 hours after tracheostomy formation. There was no confirmed COVID-19 infection or reported sickness in the operating surgical or anesthetic teams. CONCLUSION: Surgical tracheostomy has been demonstrated to be an effective weaning tool in patients with severe COVID-19 infection.

Early risk assessment for COVID-19 patients from emergency department data using machine learning.

Since its emergence in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with more than 55 million reported cases and 1.3 million estimated deaths worldwide. While epidemiological and clinical characteristics of COVID-19 have been reported, risk factors underlying the transition from mild to severe disease among patients remain poorly understood. In this retrospective study, we analysed data of 879 confirmed SARS-CoV-2 positive patients admitted to a two-site NHS Trust hospital in London, England, between January 1st and May 26th, 2020, with a majority of cases occurring in March and April. We extracted anonymised demographic data, physiological clinical variables and laboratory results from electronic healthcare records (EHR) and applied multivariate logistic regression, random forest and extreme gradient boosted trees. To evaluate the potential for early risk assessment, we used data available during patients' initial presentation at the emergency department (ED) to predict deterioration to one of three clinical endpoints in the remainder of the hospital stay: admission to intensive care, need for invasive mechanical ventilation and in-hospital mortality. Based on the trained models, we extracted the most informative clinical features in determining these patient trajectories. Considering our inclusion criteria, we have identified 129 of 879 (15%) patients that required intensive care, 62 of 878 (7%) patients needing mechanical ventilation, and 193 of 619 (31%) cases of in-hospital mortality. Our models learned successfully from early clinical data and predicted clinical endpoints with high accuracy, the best model achieving area under the receiver operating characteristic (AUC-ROC) scores of 0.76 to 0.87 (F1 scores of 0.42-0.60). Younger patient age was associated with an increased risk of receiving intensive care and ventilation, but lower risk of mortality. Clinical indicators of a patient's oxygen supply and selected laboratory results, such as blood lactate and creatinine levels, were most predictive of COVID-19 patient trajectories. Among COVID-19 patients machine learning can aid in the early identification of those with a poor prognosis, using EHR data collected during a patient's first presentation at ED. Patient age and measures of oxygenation status during ED stay are primary indicators of poor patient outcomes.

Cognitive decline following major surgery is associated with gliosis, ß-amyloid accumulation, and τ phosphorylation in old mice.

OBJECTIVE: Elderly patients undergoing major surgery often develop cognitive dysfunction and the mechanism of this postoperative complication remains elusive. We sought to determine whether postoperative cognitive dysfunction in old mice is associated with the pathogenesis of Alzheimer's disease. DESIGN: Prospective, randomized study. SETTING: University teaching hospital-based research laboratory. SUBJECTS: One-hundred and twenty C57BL/6 14-mo-old male mice (weighing 30-40 g). INTERVENTIONS: Mice received intraperitoneal injections of either vehicle or Celastrol (a potent anti-inflammatory compound) for 3 days before undergoing sham surgery or partial hepatectomy, on the surgery day, and for a further 4 days after surgery. Cognitive function, hippocampal neuroinflammation, and pathologic markers of Alzheimer's disease were assessed 1 day after surgery day 1, 3, or 7. MEASUREMENTS AND MAIN RESULTS: Cognitive impairment following surgery was associated with the appearance of certain pathologic hallmarks of Alzheimer's disease: microgliosis, astrogliosis, enhanced transcriptional and translational activity of ß-amyloid precursor protein, ß-amyloid production, and τ protein hyperphosphorylation in the hippocampus. Surgery-induced changes in cognitive dysfunction were prevented by the administration of Celastrol as were changes in ß-amyloid and τ processing. CONCLUSIONS: These data suggest that surgery can provoke astrogliosis, ß-amyloid accumulation, and τ phosphorylation in old subjects, which is likely to be associated with the cognitive decline seen in postoperative cognitive dysfunction.

Hemodynamic stability of closed-loop anesthesia systems: a systematic review.

INTRODUCTION: This systematic review investigates the effect of closed-loop anesthesia delivery on the maintenance of cardiovascular parameters. The specific challenges arise from the fact that many physiological variables used for the control of anesthetic delivery and maintenance of hemodynamic stability are regulated by the autonomic nervous system, which is subject to high inter-individual variability. EVIDENCE ACQUISITION: A systematic database search (MEDLINE, EMBASE and Web of Science) was conducted following the PRISMA guidelines and the principles of the Cochrane Handbook for Systematic Reviews of Interventions. Identified articles were screened and studies that fulfilled the eligibility criteria using the PICO approach (Patient, Intervention, Comparison, Outcome) were included in a random effects model to calculate weighted mean and 95% confidence intervals. EVIDENCE SYNTHESIS: Twenty studies (1402 subjects: 706 intervention and 696 control) were included in this review. Meta-analysis showed that closed-loop systems achieved longer duration of heart rate and MAP control, at 90.9% (95% CI: 90.0-91.8%) and 88.2% (95% CI: 87.4-89.0%) respectively, compared to the respective manual control group at 86.6% (95% CI: 85.1-88.0%) and 85.1% (95% CI: 84.3-86.0%). Subgroup analysis demonstrated better performance and faster recovery compared to the control group. CONCLUSIONS: The findings support the use of closed-loop systems for anesthetic delivery. Interpretation should take into account limitations, such as the large variations in the selected studies in the type of parameters used to measure outcomes. In summary, this review provides evidence supporting the importance of considering cardiovascular variables in the design of automated anesthetic delivery systems.