International Prospective Cohort Research Articles

Determinants of bleeding before and during immune tolerance in 222 boys with severe hemophilia A and inhibitors >5 BU

AbstractPrevention of bleeding and its consequences is the main goal of hemophilia treatment and determines treatment choices for patients who develop inhibitors. To assess bleeding before and during immune tolerance induction (ITI) and its association with ITI regimen and inhibitor titer, we selected and analyzed data on patients receiving high-titer inhibitors from the international prospective PedNet cohort study. In total, 222 patients with severe hemophilia A and inhibitor titers of >5 Bethesda units (BU) were followed from the first positive to the first negative inhibitor result (median overall follow-up, 1.7 years). Mean annual (joint) bleeding rates (AJBR) and 95% confidence intervals (CIs) were compared according to treatment and inhibitor titer using multivariable negative binomial regression. Before ITI, 115 patients showed an ABR of 6.1 (5.0-7.4) and an AJBR 2.6 (2.1-3.2). Bleeding was independent of inhibitor titer. During ITI, 202 patients had an ABR of 4.4 (3.9-5.1) and an AJBR of 1.7 (1.5-2.0). AJBR during ITI increased with inhibitor titer (hazard ratio [HR] for ≥200 BU vs 5 to 39 BU [4.9; CI, 3.2-7.4]) and decreased with daily ITI infusions (HR, 0.4; CI, 0.3-0.6) or activated prothrombin complex concentrate prophylaxis (HR, 0.4; CI, 0.2-0.8), whereas ITI dose and recombinant activated factor VII prophylaxis did not independently affect bleeding. These data provide evidence for a protective effect of repeated FVIII infusions (ITI) on bleeding in patients who have developed inhibitors; these data should be used to plan ITI and/or serve as a comparator for prophylaxis with nonreplacement therapy.

Derivation and external validation of machine-learning- models for risk stratification in chest pain with normal troponin

Abstract Importance Risk stratification of patients with chest pain and a high-sensitivity cardiac troponin T (hs-cTnT) concentration 180 minutes). Probability thresholds for safe discharge were derived in the derivation cohort. Methods This prognosis study used a single centre cohort (July 2016-Decembre 2019) to develop and internally validate the models and a international prospective APACE cohort to perform the external validation. All Patients presenting to the ED with a complaint of chest pain and a first hs-cTnT concentration <99th percentile (14 ng/L).Candidate predictors included demographics, tradicional cardiovascular risks factors, electrocardiogram and blood tests (haemoglobin, creatinine and hs-cTnT). The endpoint was90-days death or myocardial infarction Four machine learning-based models and one logistic regression (LR) model were trained on 4075 patients and externally validated on 3609 patients. Models were compared with GRACE and HEART scores and a single undetectable hs-cTnT-based strategy (u-cTn; hs-cTnT<5ng/L and time from symptoms onset>180 minutes). Probability thresholds for safe discharge were derived in the derivation cohort. Results A 99.1% (4074) of the patients completed the follow-up in the derivation cohort and a 99.4% (3609) in the validation cohort.The endpoint occurred in 105 (2.6%) patients in the training set and 98 (2.7%) in the external validation set. Gradient boosting full (GBf) showed the best discrimination (AUC=0.808). Calibration was good for the reduced NNET and LR models. GBf identified the highest proportion of patients for safe discharge (36.7% vs 23.4% vs 27.2%; GBf vs LR vs u-cTn, respectively) with similar safety (missed endpoint per 1000 patients: 2.2 vs. 3.5 vs. 3.1, respectively). All derived models were superior to the HEART and GRACE scores (p<0.001). Conclusions and relevance Machine learning and logistic regression prediction models were superior to the HEART, GRACE and u-cTn for risk stratification of patients with chest pain and a baseline hs-cTnT.

Nonoperative treatment of multiple rib fractures, the results to beat: International multicenter prospective cohort study among 845 patients.

Optimal treatment (i.e., nonoperative or operative) for patients with multiple rib fractures remains debated. Studies that compare treatments are rationalized by the alleged poor outcomes of nonoperative treatment. The aim of this prospective international multicenter cohort study (between January 2018 and March 2021) with 1-year follow-up, was to report contemporary outcomes of nonoperatively treated patients with multiple rib fractures. Including 845 patients with three or more rib fractures. Primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay (HLOS), (pulmonary) complications, and quality of life. Mean age was 57.7 ± 17.0 years, median Injury Severity Score was 17 (13-22) and the median number of rib fractures was 6 (4-8). In-hospital mortality rate was 1.5% (n = 13), 112 (13.3%) patients had pneumonia and four (0.5%) patients developed a symptomatic nonunion. The median HLOS was 7 days (4-13 days), and median intensive care unit length of stay was 2 days (1-5 days). Mean 5-Level Quality of Life Questionnaire index value was 0.83 ± 0.18 1 year after trauma. Polytrauma patients had a median HLOS of 10 days (6-18 days), a pneumonia rate of 17.6% (n = 77) and mortality rate of 1.7% (n = 7). Elderly patients (≥65 years) had a median HLOS of 9 days (5-15 days), a pneumonia rate of 19.7% (n = 57) and mortality rate of 4.1% (n = 12). Overall, nonoperative treatment of patients with multiple rib fractures shows low mortality and morbidity rate and good quality of life after 1 year. Future studies evaluating the benefit of operative stabilization should use contemporary outcomes to establish the therapeutic margin of rib fixation. Therapeutic/Care Management; Level III.

Patient-reported outcomes before treatment for localized prostate cancer: are there differences among countries? Data from the True North Global Registry

IntroductionSimilar Patient-Reported Outcomes (PROs) at diagnosis for localized prostate cancer among countries may indicate that different treatments are recommended to the same profile of patients, regardless the context characteristics (health systems, medical schools, culture, preferences…). The aim of this study was to assess such comparison.MethodsWe analyzed the EPIC-26 results before the primary treatment of men diagnosed of localized prostate cancer from January 2017 onwards (revised data available up to September 2019), from a multicenter prospective international cohort including seven regions: Australia/New Zealand, Canada, Central Europe (Austria / Czech Republic / Germany), United Kingdom, Italy, Spain, and the United States. The EPIC-26 domain scores and pattern of three selected items were compared across regions (with Central Europe as reference). All comparisons were made stratifying by treatment: radical prostatectomy, external radiotherapy, brachytherapy, and active surveillance.ResultsThe sample included a total of 13,483 men with clinically localized or locally advanced prostate cancer. PROs showed different domain patterns before treatment across countries. The sexual domain was the most impaired, and the one with the highest dispersion within countries and with the greatest medians’ differences across countries. The urinary incontinence domain, together with the bowel and hormonal domains, presented the highest scores (better outcomes) for all treatment groups, and homogeneity across regions.ConclusionsPatients with localized or locally advanced prostate cancer undergoing radical prostatectomy, EBRT, brachytherapy, or active surveillance presented mainly negligible or small differences in the EPIC-26 domains before treatment across countries.The results on urinary incontinence or bowel domains, in which almost all patients presented the best possible score, may downplay the baseline data role for evaluating treatments’ effects. However, the heterogeneity within countries and the magnitude of the differences found across countries in other domains, especially sexual, support the need of implementing the PRO measurement from diagnosis.

Cost-effectiveness analysis of the Geriatric Fracture Center (GFC) concept: a prospective multicentre cohort study

IntroductionGeriatric Fracture Centers (GFCs) are dedicated treatment units where care is tailored towards elderly patients who have suffered fragility fractures. The primary objective of this economic analysis was to determine...

Comparison of lung ultrasound scoring systems for the prognosis of COVID-19 in the emergency department: An international prospective cohort study.

The purpose of this study was to evaluate whether the lung ultrasound (LUS) scores applied to an international cohort of patients presenting to the emergency department (ED) with suspected COVID-19, and subsequently admitted with proven disease, could prognosticate clinical outcomes. This was an international, multicentre, prospective, observational cohort study of patients who received LUS and were followed for the composite primary outcome of intubation, intensive care unit (ICU) admission or death. LUS scores were later applied including two 12-zone protocols ('de Alencar score' and 'CLUE score'), a 12-zone protocol with lung and pleural findings ('Ji score') and an 11-zone protocol ('Tung-Chen score'). The primary analysis comprised logistic regression modelling of the composite primary outcome, with the LUS scores analysed individually as predictor variables. Between April 2020 to April 2022, 129 patients with COVID-19 had LUS performed according to the protocol and 24 (18.6%) met the composite primary endpoint. No association was seen between the LUS score and the composite primary end point for the de Alencar score [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97-1.11; P = 0.29], the CLUE score (OR = 1.03; 95% CI: 0.96-1.10; P = 0.40), the Ji score (OR = 1.02; 95% CI: 0.97-1.07; P = 0.40) or the Tung-Chen score (OR = 1.02; 95% CI: 0.97-1.08). Compared to these earlier studies performed at the start of the pandemic, the negative outcome of our study could reflect the changing scenario of the COVID-19 pandemic, including patient, disease, and system factors. The analysis suggests that the study may have been underpowered to detect a weaker association between a LUS score and the primary outcome. In an international cohort of adult patients presenting to the ED with suspected COVID-19 disease who had LUS performed and were subsequently admitted to hospital, LUS severity scores did not prognosticate the need for invasive ventilation, ICU admission or death.

Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6–8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks’ gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks’ gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.

Assessing impulse control behaviors in early Parkinson's disease: a longitudinal study.

Impulse control behaviors (ICBs) frequently coexist with Parkinson's disease (PD). However, the predictors of ICBs in PD remain unclear, and there is limited data on the biological correlates of ICBs in PD. In this study, we examined clinical, imaging, and biological variables to identify factors associated with longitudinal changes in ICBs in early-stage PD. The data for this study were obtained from the Parkinson's Progression Markers Initiative, an international prospective cohort study that evaluates markers of disease progression in PD. We examined clinical, imaging, and biological variables to determine their associations with ICBs over a period of up to 5 years. Cox regression models were employed to investigate the predictors of ICBs in early-stage, untreated PD. The study enrolled 401 individuals with PD and 185 healthy controls (HC). At baseline, 83 PD subjects (20.7%) and 36 HC (19.5%) exhibited ICBs. Over the course of 5 years, the prevalence of ICBs increased in PD (from 20.7% to 27.3%, p < 0.001), while it decreased in HC (from 19.5% to 15.2%, p < 0.001). Longitudinally, the presence of ICBs in PD was associated with depression, anxiety, autonomic dysfunction, and excessive daytime sleepiness (EDS). However, there was no significant association observed with cognitive dysfunction or motor severity. Treatment with dopamine agonists was linked to ICBs at years 3 and 4. Conversely, there was no association found between ICBs and presynaptic dopaminergic dysfunction. Additionally, biofluid markers in baseline and the first year did not show a significant association with ICBs. A predictive index for ICBs was generated, incorporating three baseline characteristics: anxiety, rapid eye movement sleep behavior disorder (RBD), and p-tau levels in cerebrospinal fluid (CSF). During the early stages of PD, there is a notable increase in ICBs over time. These ICBs are associated with depression, anxiety, autonomic dysfunction, EDS, and the use of dopaminergic medications, particularly dopamine agonists. Anxiety, RBD, and p-tau levels in CSF are identified as predictors for the incident development of ICBs in early PD. Further longitudinal analyses will provide a more comprehensive understanding of the associations between ICBs and imaging findings, as well as biomarkers. These analyses will help to better characterize the relationships and implications of these factors in the context of ICBs in early PD.

International Variations in Surgical Morbidity and Mortality Post Gynaecological Oncology Surgery: A Global Gynaecological Oncology Surgical Outcomes Collaborative Led Study (GO SOAR1).

Gynaecological malignancies affect women in low and middle income countries (LMICs) at disproportionately higher rates compared with high income countries (HICs) with little known about variations in access, quality, and outcomes in global cancer care. Our study aims to evaluate international variation in post-operative morbidity and mortality following gynaecological oncology surgery between HIC and LMIC settings. Study design consisted of a multicentre, international prospective cohort study of women undergoing surgery for gynaecological malignancies (NCT04579861). Multilevel logistic regression determined relationships within three-level nested-models of patients within hospitals/countries. We enrolled 1820 patients from 73 hospitals in 27 countries. Minor morbidity (Clavien-Dindo I-II) was 26.5% (178/672) and 26.5% (267/1009), whilst major morbidity (Clavien-Dindo III-V) was 8.2% (55/672) and 7% (71/1009) for LMICs/HICs, respectively. Higher minor morbidity was associated with pre-operative mechanical bowel preparation (OR = 1.474, 95%CI = 1.054-2.061, p = 0.023), longer surgeries (OR = 1.253, 95%CI = 1.066-1.472, p = 0.006), greater blood loss (OR = 1.274, 95%CI = 1.081-1.502, p = 0.004). Higher major morbidity was associated with longer surgeries (OR = 1.37, 95%CI = 1.128-1.664, p = 0.002), greater blood loss (OR = 1.398, 95%CI = 1.175-1.664, p ≤ 0.001), and seniority of lead surgeon, with junior surgeons three times more likely to have a major complication (OR = 2.982, 95%CI = 1.509-5.894, p = 0.002). Of all surgeries, 50% versus 25% were performed by junior surgeons in LMICs/HICs, respectively. We conclude that LMICs and HICs were associated with similar post-operative major morbidity. Capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention.

The degree of obesity has a serious effect on the outcome of acute pancreatitis and the development of other comorbidities: analysis of an international prospective cohort of 2244 cases

The degree of obesity has a serious effect on the outcome of acute pancreatitis and the development of other comorbidities: analysis of an international prospective cohort of 2244 cases

2083P Association between VTE location and risk of recurrent, bleeding and death in the international prospective TESEO SEOM cancer cohort

2083P Association between VTE location and risk of recurrent, bleeding and death in the international prospective TESEO SEOM cancer cohort

Dosimetric Impact of Systematic Mediastinal Staging via Endobronchial Ultrasound for Patients with Locally Advanced Lung Cancer: The SEISMIC Trial

The SEISMIC trial aims to find the best method for mediastinal staging in patients with lung cancer receiving chemoradiotherapy. Currently, CT or PET-CT scans are standard in clinical practice, but histological evaluation of the mediastinum is performed on a case-by-case basis. The study will examine the effect of systematic histological evaluation using Endobronchial Ultrasound (EBUS) on radiotherapy target volumes. The hypothesis of this study is that differences in staging between the diagnostic PET-CT and EBUS would result in reduced tumor coverage and/or increased doses to organs at risk (OAR). SEISMIC is a prospective multicenter international cohort study. Patients were enrolled from Australia, the Netherlands, USA and Canada after regional IRB approvals. Patients were treated with 4DCT simulation. Two iGTV and PTV target volumes were delineated for each patient with discordant staging according to both PET-CT and EBUS, as were OARs. Two VMAT plans were generated for each patient based on either PET-CT or EBUS target volumes using knowledge-based planning methodology. Plans aimed to achieve institutional guidelines for target coverage and OAR dose constraints, with a prescribed dose of 60 Gy in 30 fractions. Target coverage and OAR doses for the PET- and EBUS-defined volumes were compared. In 156 patients, EBUS showed a larger extent of disease than PET in 18 (11.5%) and a smaller extent of lymph node (LN) involvement than PET in 49 (31.4%). Out of 67 patients with PET-EBUS discordant results, 25 underwent upfront radiotherapy and were included in the study. EBUS revealed PET-occult LN involvement in 11/25 patients (44%). In these patients, 10/11 patients received <95% of the prescribed dose to PET-occult LN iGTVs; the median [range] minimum dose to the EBUS iGTV was 9.2 Gy [0.1 - 57.9 Gy]. When planning based on EBUS LN involvement, all patients received ≥95% of the prescribed dose to the iGTV (the median [range] minimum dose to the EBUS iGTV was 58.9 Gy [58.1 - 60.5 Gy]). This resulted in increased median [range] doses to OARs; mean lung dose increased by 1.1 Gy [0.3 - 8.4 Gy], esophagus mean dose increased by 3.6 Gy [0.2 - 24.8 Gy], and mean heart dose increased by 0.5 Gy [-0.6 - 8.5 Gy]. Systematic endoscopic evaluation of the mediastinum had a significant effect on tumor coverage in a clinically meaningful proportion of cases and consequent plan adaptation impacted on organ-at-risk (OAR) doses. Results suggest systematic mediastinal LN staging should be considered in all patients prior to curative-intent radiotherapy. ACTRN12617000333314.

Association between sleep health and rates of self-reported medical errors in intern physicians: an ancillary analysis of the Intern Health Study.

Reduced sleep duration and work hour variability contribute to medical error and physician burnout. This study assesses the relationships between physician performance, burnout, and the dimensions of sleep beyond hours slept. This was an ancillary analysis of 3 years of data from an international prospective cohort study: the Intern Health Study. Actigraphy data from 3,654 intern physicians capturing sleep timing, regularity, efficiency, and duration were used individually and combined as a composite sleep health index to measure the association of multidimensional sleep patterns on self-reported medical errors and burnout. From 2017-2019, interns' work hours decreased by 4 hours per week and total sleep time also decreased (6.7 to 5.99 hours), and sleep efficiency, timing, and regularity all worsened (all P < .05). In the 21.2% of participants who committed an error, there was no difference in sleep duration, timing, or regularity. Lower sleep efficiency was associated with higher odds of committing an error (P = .003) and higher burnout scores (P < .001). Although overall sleep quality was poor in the entire cohort, interns in the lowest quintile of sleep duration, regularity, and efficiency had higher burnout scores than those in the best quintile. Sleep efficiency, not duration, was associated with increased self-reported medical errors and burnout in intern physicians. Overall sleep quality and duration worsened despite fewer hours worked. Future studies on physician burnout should measure all aspects of sleep health. Hassinger AB, Velez C, Wang J, Mador MJ, Wilding GE, Mishra A. Association between sleep health and rates of self-reported medical errors in intern physicians: an ancillary analysis of the Intern Health Study. J Clin Sleep Med. 2024;20(2):221-227.

Improved Symptom Change Enhances Quality of Dying in Patients With Advanced Cancer: An East Asian Cross-Cultural Study.

Symptom burdens tend to increase for patients with cancer and their families over the disease trajectory. There is still a lack of evidence on the associations between symptom changes and the quality of dying and death. In this context, this research investigated how symptom changes influence the quality of dying and death. This international prospective cohort study (the East Asian Collaborative Cross-Cultural Study to Elucidate the Dying Process (EASED), 2017-2019) included 22, 11, and 4 palliative care units across Japan, South Korea, and Taiwan. Eligible participants were adults (Japan and Korea, ≥18 years; Taiwan, ≥20 years) with locally advanced or metastatic cancer. Physical and psychological symptoms were assessed by physicians upon admission and within 3 days before death. Death quality was assessed using the Good Death Scale (GDS), developed in Taiwan. Univariate and multivariate regression analyses were used to identify correlations between symptom severity changes and GDS scores. Among 998 patients (542 [54.3%] men and 456 [45.7%] women; mean [SD] age = 70.1 [± 12.5] years), persistent dyspnea was associated with lower GDS scores when compared to stable dyspnea (β = -0.427, 95% CI = -0.783 to -0.071). Worsened (-1.381, -1.932 to -0.831) and persistent (-1.680, -2.701 to -0.659) delirium were also significantly associated with lower GDS scores. Better quality of dying and death was associated with improved symptom control, especially for dyspnea and delirium. Integrating an outcome measurement for the quality of dying and death is important in the management of symptoms across the disease trajectory in a goal-concordant manner.

One-year outcomes after discharge from noncardiac surgery and association between pre-discharge complications and death after discharge: analysis of the VISION prospective cohort study.

In prior analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. We set out to describe outcomes after discharge from hospital up to one year after inpatient noncardiac surgery and associations between pre-discharge complications and post-discharge death up to one year after surgery. Analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007-2013 of patients aged ≥45 years followed to one year after surgery. We estimated 1) the cumulative post-discharge incidence of death and other outcomes up to a year after surgery and 2) the adjusted time-varying associations between post-discharge death and pre-discharge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. Among 38,898 patients discharged after surgery, the cumulative one-year incidence was 5.8% (95% CI, 5.5-6.0%) for all-cause death and 24.7% (24.2-25.1%) for all-cause hospital readmission. Pre-discharge complications were associated with 33.7% (27.2-40.2%) of deaths up to 30 days after discharge and 15.0% (12.0-17.9%) up to one year. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [9.3-21.9%) of deaths within 30 days, 6.4% [4.1-8.7%] within one year), major bleeding (15.0% [8.3-21.7%] within 30 days, 4.7% [2.2-7.2%] within one year), and sepsis (5.4% [2.2-8.6%] within 30 days, 2.1% [1.0-3.1%] within one year). One in 18 patients ≥45 years old discharged after inpatient noncardiac surgery died within one year and one quarter were readmitted to hospital. The risk of death associated with pre-discharge perioperative complications persists for weeks to months after discharge.

Characteristics and outcomes of patients with acute myeloid leukemia admitted to intensive care unit with acute respiratory failure: a post-hoc analysis of a prospective multicenter study

BackgroundAcute respiratory failure (ARF) is the leading cause of intensive care unit (ICU) admission in patients with Acute Myeloid Leukemia (AML) and data on prognostic factors affecting short-term outcome are needed.MethodsThis is a post-hoc analysis of a multicenter, international prospective cohort study on immunocompromised patients with ARF admitted to ICU. We evaluated hospital mortality and associated risk factors in patients with AML and ARF; secondly, we aimed to define specific subgroups within our study population through a cluster analysis.ResultsOverall, 201 of 1611 immunocompromised patients with ARF had AML and were included in the analysis. Hospital mortality was 46.8%. Variables independently associated with mortality were ECOG performance status ≥ 2 (OR = 2.79, p = 0.04), cough (OR = 2.94, p = 0.034), use of vasopressors (OR = 2.79, p = 0.044), leukemia-specific pulmonary involvement [namely leukostasis, pulmonary infiltration by blasts or acute lysis pneumopathy (OR = 4.76, p = 0.011)] and liver SOFA score (OR = 1.85, p = 0.014). Focal alveolar chest X-ray pattern was associated with survival (OR = 0.13, p = 0.001). We identified 3 clusters, that we named on the basis of the most frequently clinical, biological and radiological features found in each cluster: a “leukemic cluster”, with high-risk AML patients with isolated, milder ARF; a “pulmonary cluster”, consisting of symptomatic, highly oxygen-requiring, severe ARF with diffuse radiological findings in heavily immunocompromised patients; a clinical “inflammatory cluster”, including patients with multi-organ failures in addition to ARF. When included in the multivariate analysis, cluster 2 and 3 were independently associated with hospital mortality.ConclusionsAmong AML patients with ARF, factors associated with a worse outcome are related to patient’s background (performance status, leukemic pulmonary involvement), symptoms, radiological findings, the need for vasopressors and the liver SOFA score.We identified three specific ARF syndromes in AML patients, which showed a prognostic significance and could guide clinicians to optimize management strategies.

751 Incidence and Risk Factors of Postoperative Cardiac Complications: An International Prospective Cohort Study

Abstract Aim Postoperative cardiac complications (PCC) after major surgery remain heterogeneously reported. This international prospective cohort study aimed to define incidence and risk factors for PCC after major abdominal surgery in Europe, Ireland, and UK. Method A prospective, international cohort study was performed between January 23 and May 1, 2022. Data were collected on consecutive patients undergoing major abdominal surgery in 446 hospitals from 28 countries of Europe. The primary outcome was postoperative cardiac complications (PCC) as defined by Standardised Endpoints and COMs for Perioperative and Anaesthetic Care (STeP-COMPAC) to 30-days after surgery. The secondary outcome was 30-day postoperative mortality. Results This study included 24,260 patients, of whom 611 (2.5%) developed PCC and 458 (1.9%) died within 30-days of surgery. Of patients who died, 123 (26.9%) were related to cardiac causes. Mortality rates were higher in patients who developed PCC than those who did not (19.8% vs 1.4%, p&amp;lt;0.001). On adjusted analyses, age &amp;gt;65 years (OR: 2.47, 95% CI: 1.99-3.06), ASA grade III-V (OR: 1.95, 95% CI: 1.58 - 2.40), emergency surgery (OR: 1.62, 95% CI: 1.31 - 2.00), and contaminated/dirty surgery (OR: 1.60, 95% CI: 1.15 - 2.23) were risk factors for PCC. Conclusions PCC are infrequent after major abdominal surgery, yet death from cardiac causes was higher than previously reported in adults undergoing major abdominal surgery. Targeting high-risk groups at risk of PCC and death warrant holistic interventional trials as future research focus.

Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study

Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort). We included 14 726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 [95% CI [0·78-0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61-0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347-641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88-0·91) versus 0.84 (0·82-0·86) for FIB-4. The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care. European Commission under the H20/20 programme; Fondo de Investigación Sanitaria de Salud; Instituto de Salud Carlos III; Spanish Ministry of Economy, Industry, and Competitiveness; the European Regional Development Fund; and the German Ministry of Education and Research (BMBF).

Derivation and external validation of machine-learning models for risk stratification in chest pain with normal troponin.

Risk stratification of patients with chest pain and a high-sensitivity cardiac troponin T (hs-cTnT) concentration <upper reference limit (URL) is challenging. The aim of this study was to develop and externally validate clinical models for risk prediction of 90-day death or myocardial infarction in patients presenting to the emergency department with chest pain and an initial hs-cTnT concentration <URL. Four machine-learning-based models and one logistic regression (LR) model were trained on 4075 patients (single-centre Spanish cohort) and externally validated on 3609 patients (international prospective Advantageous Predictors of Acute Coronary syndromes Evaluation cohort). Models were compared with GRACE and HEART scores and a single undetectable hs-cTnT-based strategy (u-cTn; hs-cTnT < 5 ng/L and time from symptoms onset >180 min). Probability thresholds for safe discharge were derived in the derivation cohort. The endpoint occurred in 105 (2.6%) patients in the training set and 98 (2.7%) in the external validation set. Gradient boosting full (GBf) showed the best discrimination (area under the curve = 0.808). Calibration was good for the reduced neural network and LR models. Gradient boosting full identified the highest proportion of patients for safe discharge (36.7 vs. 23.4 vs. 27.2%; GBf vs. LR vs. u-cTn, respectively) with similar safety (missed endpoint per 1000 patients: 2.2 vs. 3.5 vs. 3.1, respectively). All derived models were superior to the HEART and GRACE scores (P < 0.001). Machine-learning and LR prediction models were superior to the HEART, GRACE, and u-cTn for risk stratification of patients with chest pain and a baseline hs-cTnT <URL. Gradient boosting full models best balanced discrimination, calibration, and efficacy, reducing the need for serial hs-cTnT determination by more than one-third. ClinicalTrials.gov number, NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587.

Impact of the SARS-CoV-2 Pandemic on Treatment Pathways and Outcomes of Esophagogastric Cancer: A Pre- Versus Post-Pandemic Comparison of International Prospective Cohort Data

Introduction: This study aimed to characterize the outcomes of esophagogastric (OG) cancer patients and compare perioperative outcomes with pre-pandemic data. Methods: Three international prospective cohort studies were included in this analysis. First, COVIDSurg-Cancer (n = 1999) included patients with an OG cancer planned for surgery from the start of the pandemic up to 14th April 2020 with follow-up until 31st August 2020. Treatment pathways and outcomes were compared against patients undergoing treatment for OG cancers before the pandemic, Oesophagogastric Anastomosis Audit (OGAA, n = 2246) and GlobalSurg 3 (n = 1256) study. The surgical composite outcome was defined as in patients achieving margin negative resection, resectability and no postoperative mortality. Results: This study included 1999 patients during the COVID-19 pandemic, of which 32.4% had a change from standard pre-pandemic management. Patients with delay to surgery had significantly higher rates of no surgery (24.7%vs 7.5%, P &lt; .001) and less likely to have achieve a composite outcome (57.8%vs 73.4%, P &lt; .001) than those without any delay in surgery. There was no significant difference in 30-day mortality (3.5% vs 3.4%; OR: 0.98, CI95%: 0.69-1.37) or anastomotic leak rate (10.9% vs 10.2%%; OR: 1.11, CI95%: 0.90-1.37) but higher reoperation rates (13.6% vs 10.4%; OR: 1.59, CI95%: 1.30-1.92) in patients between pre-pandemic and pandemic cohorts. Conclusion: The pandemic appears to have led to widespread changes in management pathways affecting one-third of patients. Developing elective surgical pathways resilient to periods of system “stress” are key to minimizing future harm from treatment delay for OG cancer patients.