Artificial intelligence in surgery.

Artificial intelligence (AI) is rapidly emerging in healthcare, yet applications in surgery remain relatively nascent. Here we review the integration of AI in the field of surgery, centering our discussion on multifaceted improvements in surgical care in the preoperative, intraoperative and postoperative space. The emergence of foundation model architectures, wearable technologies and improving surgical data infrastructures is enabling rapid advances in AI interventions and utility. We discuss how maturing AI methods hold the potential to improve patient outcomes, facilitate surgical education and optimize surgical care. We review the current applications of deep learning approaches and outline a vision for future advances through multimodal foundation models.

Effect of recipient age on prioritisation for liver transplantation in the UK: a population-based modelling study.

BACKGROUND: Following the introduction of an algorithm aiming to maximise life-years gained from liver transplantation in the UK (the transplant benefit score [TBS]), donor livers were redirected from younger to older patients, mortality rate equalised across the age range and short-term waiting list mortality reduced. Understanding age-related prioritisation has been challenging, especially for younger patients and clinicians allocating non-TBS-directed livers. We aimed to assess age-related prioritisation within the TBS algorithm by modelling liver transplantation prioritisation based on data from a UK transplant unit and comparing these data with other regions. METHODS: In this population-based modelling study, serum parameters and age at liver transplantation assessment of patients attending the Scottish Liver Transplant Unit, Edinburgh, UK, between December, 2002, and November, 2023, were combined with representative synthetic data to model TBS survival predictions, which were compared according to age group (25-49 years vs ≥60 years), chronic liver disease severity, and disease cause. Models for end-stage liver disease (UKELD [UK], MELD [Eurotransplant region], and MELD 3.0 [USA]) were used as validated comparators of liver disease severity. FINDINGS: Of 2093 patients with chronic liver disease, 1808 (86%) had complete datasets and liver disease parameters consistent with eligibility for the liver transplant waiting list in the UK (UKELD ≥49). Disease severity as assessed by UKELD, MELD, and MELD 3.0 did not differ by age (median UKELD scores of 56 for patients aged ≥60 years vs 56 for patients aged 25-49 years; MELD scores of 16 vs 16; and MELD 3.0 scores of 18 vs 18). TBS increased with advancing age (R=0·45, p<0·0001). TBS predicted that transplantation in patients aged 60 years or older would provide a two-fold greater net benefit at 5 years than in patients aged 25-49 years (median TBS 1317 [IQR 1116-1436] in older patients vs 706 [411-1095] in younger patients; p<0·0001). Older patients were predicted to have shorter survival without transplantation than younger patients (263 days [IQR 144-473] in older patients vs 861 days [448-1164] in younger patients; p<0·0001) but similar survival after transplantation (1599 days [1563-1628] vs 1573 days [1525-1614]; p<0·0001). Older patients could reach a TBS for which a liver offer was likely below minimum criteria for transplantation (UKELD <49), whereas many younger patients were required to have high-urgent disease (UKELD >60). US and Eurotransplant programmes did not prioritise according to age. INTERPRETATION: The UK liver allocation algorithm prioritises older patients for transplantation by predicting that advancing age increases the benefit from liver transplantation. Restricted follow-up and biases in waiting list data might limit the accuracy of these benefit predictions. Measures beyond overall waiting list mortality are required to fully capture the benefits of liver transplantation. FUNDING: None.

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

Changes in hospital mortality in patients with cancer during the COVID-19 pandemic (ISARIC-CCP-UK): a prospective, multicentre cohort study.

BACKGROUND: Patients with cancer are at greater risk of dying from COVID-19 than many other patient groups. However, how this risk evolved during the pandemic remains unclear. We aimed to determine, on the basis of the UK national pandemic protocol, how factors influencing hospital mortality from COVID-19 could differentially affect patients undergoing cancer treatment. We also examined changes in hospital mortality and escalation of care in patients on cancer treatment during the first 2 years of the COVID-19 pandemic in the UK. METHODS: We conducted a prospective cohort study of patients aged older than 19 years and admitted to 306 health-care facilities in the UK with confirmed SARS-CoV-2 infection, who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol (CCP) across the UK from April 23, 2020, to Feb 28, 2022; this analysis included all patients in the complete dataset when the study closed. The primary outcome was 30-day in-hospital mortality, comparing patients on cancer treatment and those without cancer. The study was approved by the South Central-Oxford C Research Ethics Committee in England (Ref: 13/SC/0149) and the Scotland A Research Ethics Committee (Ref 20/SS/0028), and is registered on the ISRCTN Registry (ISRCTN66726260). FINDINGS: 177 871 eligible adult patients either with no history of cancer (n=171 303) or on cancer treatment (n=6568) were enrolled; 93 205 (52·4%) were male, 84 418 (47·5%) were female, and in 248 (13·9%) sex or gender details were not specified or data were missing. Patients were followed up for a median of 13 (IQR 6-21) days. Of the 6568 patients receiving cancer treatment, 2080 (31·7%) died at 30 days, compared with 30 901 (18·0%) of 171 303 patients without cancer. Patients aged younger than 50 years on cancer treatment had the highest age-adjusted relative risk (hazard ratio [HR] 5·2 [95% CI 4·0-6·6], p<0·0001; vs 50-69 years 2·4 [2·2-2·6], p<0·0001; 70-79 years 1·8 [1·6-2·0], p<0·0001; and >80 years 1·5 [1·3-1·6], p<0·0001) but a lower absolute risk (51 [6·7%] of 763 patients <50 years died compared with 459 [30·2%] of 1522 patients aged >80 years). In-hospital mortality decreased for all patients during the pandemic but was higher for patients on cancer treatment than for those without cancer throughout the study period. INTERPRETATION: People with cancer have a higher risk of mortality from COVID-19 than those without cancer. Patients younger than 50 years with cancer treatment have the highest relative risk of death. Continued action is needed to mitigate the poor outcomes in patients with cancer, such as through optimising vaccination, long-acting passive immunisation, and early access to therapeutics. These findings underscore the importance of the ISARIC-WHO pandemic preparedness initiative. FUNDING: National Institute for Health Research and the Medical Research Council.

Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

A comprehensive benchmark for COVID-19 predictive modeling using electronic health records in intensive care.

The COVID-19 pandemic highlighted the need for predictive deep-learning models in health care. However, practical prediction task design, fair comparison, and model selection for clinical applications remain a challenge. To address this, we introduce and evaluate two new prediction tasks-outcome-specific length-of-stay and early-mortality prediction for COVID-19 patients in intensive care-which better reflect clinical realities. We developed evaluation metrics, model adaptation designs, and open-source data preprocessing pipelines for these tasks while also evaluating 18 predictive models, including clinical scoring methods and traditional machine-learning, basic deep-learning, and advanced deep-learning models, tailored for electronic health record (EHR) data. Benchmarking results from two real-world COVID-19 EHR datasets are provided, and all results and trained models have been released on an online platform for use by clinicians and researchers. Our efforts contribute to the advancement of deep-learning and machine-learning research in pandemic predictive modeling.

Preoperative nutrition therapy in people undergoing gastrointestinal surgery.

BACKGROUND: Poor preoperative nutritional status has been consistently linked to an increase in postoperative complications and worse surgical outcomes. We updated a review first published in 2012. OBJECTIVES: To assess the effects of preoperative nutritional therapy compared to usual care in people undergoing gastrointestinal surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, three other databases and two trial registries on 28 March 2023. We searched reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people undergoing gastrointestinal surgery and receiving preoperative nutritional therapy, including parenteral nutrition, enteral nutrition or oral nutrition supplements, compared to usual care. We only included nutritional therapy that contained macronutrients (protein, carbohydrate and fat) and micronutrients, and excluded studies that evaluated single nutrients. We included studies regardless of the nutritional status of participants, that is, well-nourished participants, participants at risk of malnutrition, or mixed populations. We excluded studies in people undergoing pancreatic and liver surgery. Our primary outcomes were non-infectious complications, infectious complications and length of hospital stay. Our secondary outcomes were nutritional aspects, quality of life, change in macronutrient intake, biochemical parameters, 30-day perioperative mortality and adverse effects. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. We assessed risk of bias using the RoB 1 tool and applied the GRADE criteria to assess the certainty of evidence. MAIN RESULTS: We included 16 RCTs reporting 19 comparisons (2164 participants). Seven studies were new for this update. Participants' ages ranged from 21 to 79 years, and 62% were men. Three RCTs used parenteral nutrition, two used enteral nutrition, eight used immune-enhancing nutrition and six used standard oral nutrition supplements. All studies included mixed groups of well-nourished and malnourished participants; they used different methods to identify malnutrition and reported this in different ways. Not all the included studies were conducted within an Enhanced Recovery After Surgery (ERAS) programme, which is now current clinical practice in most hospitals undertaking GI surgery. We were concerned about risk of bias in all the studies and 14 studies were at high risk of bias due to lack of blinding. We are uncertain if parenteral nutrition has any effect on the number of participants who had a non-infectious complication (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.36 to 1.02; 3 RCTs, 260 participants; very low-certainty evidence); infectious complication (RR 0.98, 95% CI 0.53 to 1.80; 3 RCTs, 260 participants; very low-certainty evidence) or length of hospital stay (mean difference (MD) 5.49 days, 95% CI 0.02 to 10.96; 2 RCTs, 135 participants; very low-certainty evidence). None of the enteral nutrition studies reported non-infectious complications as an outcome. The evidence is very uncertain about the effect of enteral nutrition on the number of participants with infectious complications after surgery (RR 0.90, 95% CI 0.59 to 1.38; 2 RCTs, 126 participants; very low-certainty evidence) or length of hospital stay (MD 5.10 days, 95% CI -1.03 to 11.23; 2 RCTs, 126 participants; very low-certainty evidence). Immune-enhancing nutrition compared to controls may result in little to no effect on the number of participants experiencing a non-infectious complication (RR 0.79, 95% CI 0.62 to 1.00; 8 RCTs, 1020 participants; low-certainty evidence), infectious complications (RR 0.74, 95% CI 0.53 to 1.04; 7 RCTs, 925 participants; low-certainty evidence) or length of hospital stay (MD -1.22 days, 95% CI -2.80 to 0.35; 6 RCTs, 688 participants; low-certainty evidence). Standard oral nutrition supplements may result in little to no effect on number of participants with a non-infectious complication (RR 0.90, 95% CI 0.67 to 1.20; 5 RCTs, 473 participants; low-certainty evidence) or the length of hospital stay (MD -0.65 days, 95% CI -2.33 to 1.03; 3 RCTs, 299 participants; low-certainty evidence). The evidence is very uncertain about the effect of oral nutrition supplements on the number of participants with an infectious complication (RR 0.88, 95% CI 0.60 to 1.27; 5 RCTs, 473 participants; very low-certainty evidence). Sensitivity analysis based on malnourished and weight-losing participants found oral nutrition supplements may result in a slight reduction in infections (RR 0.58, 95% CI 0.40 to 0.85; 2 RCTs, 184 participants). Studies reported some secondary outcomes, but not consistently. Complications associated with central venous catheters occurred in RCTs involving parenteral nutrition. Adverse events in the enteral nutrition, immune-enhancing nutrition and standard oral nutrition supplements RCTs included nausea, vomiting, diarrhoea and abdominal pain. AUTHORS' CONCLUSIONS: We were unable to determine if parenteral nutrition, enteral nutrition, immune-enhancing nutrition or standard oral nutrition supplements have any effect on the clinical outcomes due to very low-certainty evidence. There is some evidence that standard oral nutrition supplements may have no effect on complications. Sensitivity analysis showed standard oral nutrition supplements probably reduced infections in weight-losing or malnourished participants. Further high-quality multicentre research considering the ERAS programme is required and further research in low- and middle-income countries is needed.

Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury.

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.

Inequities in global cancer surgery: Challenges and solutions.

The disparity in access to and quality of surgical cancer care between high and low resource settings impacts immediate and long-term oncological outcomes. With cancer incidence and mortality set to increase rapidly in the next few decades, we examine the factors leading to inequities in global cancer surgery, and look at potential solutions to overcome these challenges.

Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity.

Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the [Formula: see text] ratio. Because of the ceiling effect in oxyhaemoglobin saturation, [Formula: see text] ratio ceases to reflect pulmonary oxygenation function at high [Formula: see text] values. We found that the correlation of [Formula: see text] with the reference standard ([Formula: see text]/[Formula: see text] ratio) improves substantially when excluding [Formula: see text] and refer to this measure as [Formula: see text]. Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that [Formula: see text] is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. We show that a significant difference in outcome could be detected with the smallest sample size using [Formula: see text]. We demonstrate that [Formula: see text] is an effective intermediate outcome measure in COVID-19. It is a non-invasive measurement, representative of disease severity and provides greater statistical power.

Perioperative optimisation in low- and middle-income countries (LMICs): A systematic review and meta-analysis of enhanced recovery after surgery (ERAS).

Background: Enhanced recovery after surgery (ERAS) protocols have largely been incorporated into practice in high-income settings due to proven improvement in perioperative outcomes. We aimed to review the implementation of ERAS protocols and other perioperative optimisation strategies in low- and middle-income countries (LMICs) and their impact on length of hospital stay (LOS). Methods: We searched MEDLINE, PubMed, Global Health (CABI), WHO Global Index Medicus, Index Medicus, and Latin American and Caribbean Health Sciences Literature (LILACS) for studies incorporating ERAS or other prehabilitation approaches in LMICs. We conducted a pooled analysis of LOS using a random-effects model to evaluate the impact of such programs. This systematic review was pre-registered on PROSPERO. Results: We screened 1205 studies and included 70 for a full-text review; six were eligible for inclusion and five for quantitative analysis, two of which were randomised controlled trials. ERAS was compared to routine practice in all included studies, while none implemented prehabilitation or other preoperative optimisation strategies. Pooled analysis of 290 patients showed reduced LOS in the ERAS group with a standardised mean difference of -2.18 (95% confidence interval (CI) = -4.13, -.0.05, P < 0.01). The prediction interval was wide (95% CI = -7.85, 3.48) with substantial heterogeneity (I2 = 94%). Conclusions: Perioperative optimisation is feasible in LMICs and appears to reduce LOS, despite high levels of between-study heterogeneity. There is a need for high-quality data on perioperative practice in LMICs and supplementary qualitative analysis to further understand barriers to perioperative optimisation implementation. Registration: PROSPERO: CRD42021279053.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

A multi-country analysis of COVID-19 hospitalizations by vaccination status.

BACKGROUND: Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes. METHODS: Here, we use data from an international consortium to study this question and assess whether differences between these groups are context specific. Data from 83,163 hospitalized COVID-19 patients (34,843 vaccinated, 48,320 unvaccinated) from 38 countries were analyzed. FINDINGS: While typical symptoms were more often reported in unvaccinated patients, comorbidities, including some associated with worse prognosis in previous studies, were more common in vaccinated patients. Considerable between-country variation in both in-hospital fatality risk and vaccinated-versus-unvaccinated difference in this outcome was observed. CONCLUSIONS: These findings will inform allocation of healthcare resources in future surges as well as design of longer-term international studies to characterize changes in clinical profile of hospitalized COVID-19 patients related to vaccination history. FUNDING: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z, and 220757/Z/20/Z); the Bill & Melinda Gates Foundation (OPP1209135); and the philanthropic support of the donors to the University of Oxford's COVID-19 Research Response Fund (0009109). Additional funders are listed in the "acknowledgments" section.

Is socioeconomic deprivation associated with worse quality of life, anxiety and depression in liver transplant recipients? A cross-sectional study in a national transplantation programme.

OBJECTIVE: To identify whether socioeconomic deprivation is associated with worse health-related quality of life (HR-QoL), anxiety and depression following liver transplantation. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Liver transplant recipients within a national transplantation programme. METHODS: Participants completed the condition-specific 'Short Form of Liver Disease Quality of Life' Questionnaire, the Generalised Anxiety Disorder-7 (GAD-7) Questionnaire and the Patient Health Questionnaire-9 (PHQ-9). The aggregate HR-QoL Score (range 0-100) was derived, and multivariable linear regression was performed based on sociodemographic and clinical variables to estimate its independent association with Scottish Index of Multiple Deprivation (SIMD) quintiles. The GAD-7 Questionnaire and PHQ-9 were used to screen respondents for anxiety and depression, and multivariable logistic regression was performed to estimate their independent association with SIMD quintiles. RESULTS: Some 331 patients completed the questionnaires. Quintiles were equally distributed in the cohort, with no significant differences observed in underlying patient characteristics. Following multivariable adjustment, greater socioeconomic deprivation was associated with lower post-transplantation HR-QoL scores, with a difference of 9.7 points (95% CI: 4.6 to 14.9, p<0.001) between the most and least deprived quintiles. Recipients living in areas of least deprivation were less likely to suffer from anxiety (OR 0.05, 95% CI: 0.00 to 0.28, p=0.003) or depression (OR 0.13, 95% CI: 0.02 to 0.56, p=0.009). CONCLUSION: Despite the highly selected nature of liver transplant recipients, those living in the most deprived areas have a significantly lower HR-QoL and are more likely to suffer from anxiety and depression.

Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization.

Post-COVID cognitive deficits, including 'brain fog', are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits.