International Cohort Research Articles

SP8.8 - Inspiring Overseas Surgeons for a Life in the NHS: Results from an International Cohort

Abstract Aims Entry into the NHS can be fraught with difficulty, especially when entering from outside of the UK. Numerous socioeconomic and cultural barriers exist, which can be prohibitory. Currently only extremely limited methods of motivating international medical graduates (IMG) exist. Surgical specialist training recruitment has decreased over the past few years. We instigated an innovative introduction to the NHS with the aim of inspiring overseas doctors to pursue a career within surgery in the NHS. Methods An agenda was created targeted at medical students and IMG. Speakers were recruited based upon these including students and doctors who had visited the NHS or are current workers. Collaboration was sought with international students who aided with distribution. Individuals were invited to sign up via an electronic link. The session was delivered with free online video conferencing software. Participants answered a series of 5-point Likert scale questions. Results 102 registrations were received. Participants attended from Brazil (64.3%), USA (14.3%), India (7.1%) and the UK (7.1%). The event attracted a wide range of seniority from medical students (35.7%) to residents (7.1%). 100% of participants stated they had a better understanding of the NHS and 100% were more likely to attempt to enter the NHS after attending the event. Conclusions Chronic staffing shortages are a ubiquitous problem in the NHS. Application rates for surgical posts have been declining. Our innovative method of inspiring surgeons of the future has been shown to be effective in our international cohort.

Recurrent pericarditis in older adults: Clinical and laboratory features and outcome.

Current guidelines for the diagnosis and treatment of pericarditis refer to the general adult population. Few and fragmentary data regarding recurrent pericarditis in older adults exist. Given the absence of specific data in scientific literature, we hypothesized that there might be clinical, laboratory and outcome differences between young adults and older adults affected by idiopathic recurrent pericarditis. We performed an international multicentric retrospective cohort study analyzing data from patients affected by recurrent pericarditis (idiopathic or post-cardiac injury) and referring to tertiary referral centers. Clinical, laboratory, and outcome data were compared between patients younger than 65 years (controls) and patients aged 65 or older. One hundred and thirty-three older adults and 142 young adult controls were enrolled. Comorbidities, including chronic kidney diseases, atrial fibrillation, and diabetes, were more present in older adults. The presenting symptom was dyspnea in 54.1% of the older adults versus 10.6% in controls (p < 0.001); pain in 32.3% of the older adults versus 80.3% of the controls (p < 0.001). Fever higher than 38°C was present in 33.8% versus 53.5% (p = 0.001). Pleural effusion was more prevalent in the older adults (55.6% vs 34.5%, p < 0.001), as well as severe pericardial effusion (>20 mm) (24.1% vs 12.7%, p = 0.016) and pericardiocentesis (16.5% vs 8.5%, p = 0.042). Blood leukocyte counts were significantly lower in the older adults (mean + SE: 10,227 + 289/mm3 vs 11,208 + 285/mm3, p = 0.016). Concerning therapies, NSAIDS were used in 63.9% of the older adults versus 80.3% in the younger (p = 0.003), colchicine in 76.7% versus 87.3% (p = 0.023), corticosteroids in 49.6% versus 26.8% (p < 0.001), and anakinra in 14.3% versus 23.9% (p = 0.044). Older adults affected by recurrent pericarditis show a different clinical pattern, with more frequent dyspnea, pleural effusion, severe pericardial effusion, and lower fever and lower leukocyte count, making the diagnosis sometimes challenging. They received significantly less NSAIDs and colchicine, likely due to comorbidities; they were also treated less commonly with anti-IL1 agents, and more frequently with corticosteroids.

MOY 3 - Development and external validation of the “Global Surgical-Site Infection” (GloSSI) predictive model in adult patients undergoing abdominal surgery

Abstract Aims Identification of patients at high-risk of surgical-site infections (SSI) may allow surgeons to minimise associated morbidity. However, there are significant concerns with the methodological quality and transportability of models previously developed. We aimed to develop a novel score to predict 30-day SSI risk following gastrointestinal surgery across a global context, and externally validate against existing models. Methods This was a secondary analysis of 2 prospective international cohort studies: GlobalSurg-1 (July-November 2014) and GlobalSurg-2 (January-July 2016). Consecutive adults undergoing gastrointestinal surgery were eligible. Model development was performed in GlobalSurg-2 data, with novel and previous scores externally validated in GlobalSurg-1. The primary outcome was 30-day SSI, with two predictive techniques explored: penalised regression (LASSO) and machine learning (XGBOOST). Final model selection based on prognostic accuracy and clinical utility. Results There were 14,019 patients (SSI=12.3%) for derivation, and 8,464 (SSI=11.4%) for external validation. The LASSO model was selected due to similar discrimination to XGBoost (AUC: 0.738, 0.725-0.750 versus 0.737, 0.709-0.765), but greater explainability. The final score included six variables: country income, ASA grade, diabetes, and operative contamination, approach, and duration. Model performance remained good on external validation (AUC: 0.730, 0.715-0.744; calibration-in-the-large: -0.098, slope: 1.008), and demonstrated superior performance to external validation of all previous models. Conclusion The GloSSI score allowed accurate prediction of the risk of SSI with 6 simple variables which are routinely available at the time of surgery across global settings. This can inform use of intraoperative and postoperative interventions to modify the risk of SSI and minimise associated harm.

Endovascular treatment in patients with acute ischemic stroke presenting beyond 6 h after symptom onset: An international multicenter cohort study of the EVA-TRISP collaboration.

After positive findings in clinical trials the time window for endovascular thrombectomy (EVT) for patients with an acute ischemic stroke has been expanded up to 24 h from symptom onset or last seen well (LSW). We aimed to compare EVT patients' characteristics and outcomes in the early versus extended time window and to compare outcomes with the DAWN and DEFUSE 3 trial results. Consecutive EVT patients from 16 mostly European comprehensive stroke centers from the EVA-TRISP cohort were included. We compared rates of 90-day good functional outcomes (Modified Rankin Scale 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality between patients treated in the early (<6 h after onset or LSW) versus extended (6-24 h after onset or LSW) time windows. We included 9313 patients, of which 6876 were treated in the early and 2437 in the extended time window. National Institutes of Health Stroke Scale (NIHSS) score at presentation was lower in patients treated in the extended time window (median 13 [IQR 7-18] vs 15 [IQR 9-19], p < 0.001). The percentage of patients with good functional outcome was slightly lower in the extended time window (37.4% vs 42.2%, p < 0.001). However, rates of successful recanalization, sICH, and mortality were similar. Good functional outcome rates after EVT were slightly lower for patients in the extended window in the EVA-TRISP cohort as compared to DAWN and DEFUSE 3. According to this large multicenter cohort study reflecting daily clinical practice, EVT use in the extended time window appears safe and effective.

Compassionate inquiry: digital storytelling and the ethics of care

ABSTRACT In this paper, we identify the use of Digital Storytelling (DS) as a mode of pedagogy aligned with an ethics of care. We consider how DS, as summative assessment, may foreground care ethics such as attentiveness, responsiveness, and trust. Our interest in this topic stems from our concern over the impact on staff and students of the massification of higher education, which includes low attendance, social isolation, and educator burnout. This paper presents an empirical study of students’ summative work and educators’ views on the use of DS in the classroom in the context of a large, international cohort of first year undergraduates on an Education Studies programme. We conclude that DS may help students overcome some of the negative issues of massification and the legacy of Covid-19 identified in this paper, and that educators may also derive benefits from its use.

Chronic kidney disease–associated pruritus: a comparison of instruments and associations with patient-reported outcomes using an electronic patient-reported outcome survey in Europe

ABSTRACT Background The associations between self-reported chronic kidney disease–associated pruritus (CKD-aP) and patient-reported outcomes (PROs) have been reported using various instruments to assess itch. Data collection via multiple CKD-aP instruments allows the evaluation of different domains and measurements of CKD-aP burden and may help tailor data capture for future research or clinical care. Methods An electronic PRO (ePRO) survey was distributed to European hemodialysis (HD) patients enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in 2021–23. The DOPPS is an international cohort study that aims to investigate practice patterns and outcomes in HD patients. The ePRO survey included multiple CKD-aP instruments: Average Itch and Worst Itching Intensity Numerical Rating Scales (AI-NRS, WI-NRS) and a Kidney Disease Quality of Life (KDQOL)-36 single question. Linear and logistic regression were used to estimate adjusted associations between CKD-aP instruments and various PROs. Results This analysis included 769 patients who completed the WI-NRS from HD facilities in France, Germany, Italy, Spain, Sweden and the UK. The correlation between WI-NRS and the KDQOL-36 itch question was 0.88 overall and 0.46 among patients at least somewhat bothered by itch. Mean WI-NRS scores stratified by response to the KDQOL-36 itch question were 8.1, 6.4, 4.1 and 3.1 for extremely, very much, moderately and somewhat bothered, respectively. Patients with worse WI-NRS scores reported worse sleep quality, greater fatigue, more depressive symptoms, and lower mental and physical quality of life; these associations were similar to those observed for the KDQOL-36 itch question. Conclusion Correlation between CKD-aP instruments was high overall, but moderate among the subgroup of patients bothered by itch; differences can be partially attributed to the recall period for the KDQOL-36 (4 weeks) vs the AI- and WI-NRS (24 h). The consistent associations of these instruments with poor outcomes underscores the importance to identify and effectively treat HD patients suffering from pruritus.

Outcome of Minimally Invasive and Open Pancreatoduodenectomy in Patients with Intestinal- and Pancreatobiliary Subtype Ampullary Cancer: An International Multicenter Cohort Study.

To compare minimally invasive and open pancreatoduodenectomy in different subtypes of ampullary adenocarcinoma. Ampullary adenocarcinoma (AAC) is widely seen as the best indication for minimally invasive pancreatoduodenectomy (MIPD) due to the lack of vascular involvement and dilated bile and pancreatic duct. However, it is unknown whether outcomes of MIPD for AAC differ between the pancreatobiliary (AAC-PB) and intestinal (AAC-IT) subtypes as large studies are lacking. This is an international cohort study, encompassing 27 centers from 12 countries. Outcome of MIPD and open pancreatoduodenectomy (OPD) were compared in patients with AAC-IT and AAC-PB. Primary end points were R1 rate, lymph node yield, and 5-year overall survival (5yOS). Overall, 1187 patients after MIPD for AAC were included, of whom 572 with AAC-IT (62 MIPD, 510 OPD) and 615 with AAC-PB (41 MIPD and 574 OPD). The rate of R1 resection was not significantly different between MIPD and OPD for both AAC-IT (3.4% vs 6.9%, P=0,425) and AAC-PB (9.8% vs 14.9%, P=0,625). AAC-IT, more lymph nodes were resected with MIPD group (19 vs 16, P=0.007), compared to OPD. The 5y-OS did not differ after MIPD and OPD for both AAC-IT (56.8% vs 59.5%, P=0.827 and AAC-PB (52.5% vs 44.4%, P=0.357). The rates of surgical complication between MIPD and OPD did not differ between AmpIT and AmpPB. This international multicenter study found no differences in outcomes between MIPD and OPD for AAC-IT and AAC-PB. MIPD and OPD demonstrated comparable outcomes in oncological resection, survival and surgical outcomes for both subtypes of AAC.

Mechanical circulatory support early after pediatric heart transplantation—an analysis from the Pediatric Heart Transplant Society

BackgroundThe use of early Mechanical Circulatory Support (MCS) following pediatric heart transplantation is not well-published. This paper attempts to uncover the incidence, predisposing factors and outcomes of MCS in a large, international cohort. MethodsThe Pediatric Heart Transplant Society Database (an international, prospective, event-driven database) was retrospectively analyzed for all cases of primary heart transplant over an 11-year period (2010-2020), dividing the cohort based on need for MCS within 30 days of transplantation. ResultsOf 4321 primary transplants, 249 (5.8%) required MCS (230 ECMO, 19 VAD). In a Cox proportional hazard model, congenital heart disease (p = 0.0002), older donor age (p < 0.0001), and longer ischemic time (p = 0.018) were each related to an increased need for MCS; increasing recipient body surface area (p < 0.0001) and increasing donor left ventricular ejection fraction (p = 0.016) were both correlated with less MCS use. 1-year survival in those requiring MCS was 54.2%, compared with 94.8% in those who did not need MCS (p < 0.0001). Later survival in patients surviving to one year was similar between the groups. ConclusionsMCS is used infrequently following pediatric heart transplant, and is related to donor, recipient and transplant factors. Although mortality is high, those surviving the first year post-transplant have excellent outcomes. Judicious use in those patients who would otherwise perish is therefore justified.

Improved Risk Prediction in Human Papillomavirus-Associated Endocervical Adenocarcinoma Through Assessment of Binary Silva Pattern-based Classification: An International Multicenter Retrospective Observational Study Led by the International Society of Gynecological Pathologists (ISGyP).

Endocervical adenocarcinomas (EACs) are a group of malignant neoplasms associated with diverse pathogenesis, morphology, and clinical behavior. As a component of the International Society of Gynecological Pathologists International Endocervical Adenocarcinoma Project, a large international retrospective cohort of EACs was generated in an effort to study potential clinicopathological features with prognostic significance that may guide treatment in these patients. In this study, we endeavored to develop a robust human papillomavirus (HPV)-associated EAC prognostic model for surgically treated International Federation of Gynecology and Obstetrics (FIGO) stage IA2 to IB3 adenocarcinomas incorporating patient age, lymphovascular space invasion (LVSI) status, FIGO stage, and pattern of invasion according to the Silva system (traditionally a 3-tier system). Recently, a 2-tier/binary Silva pattern of invasion system has been proposed whereby adenocarcinomas are classified into low-risk (pattern A/pattern B without LVSI) and high-risk (pattern B with LVSI/pattern C) categories. Our cohort comprised 792 patients with HPV-associated EAC. Multivariate analysis showed that a binary Silva pattern of invasion classification was associated with recurrence-free and disease-specific survival (P < 0.05) whereas FIGO 2018 stage I substages were not. Evaluation of the current 3-tiered system showed that disease-specific survival for those patients with pattern B tumors did not significantly differ from that for those patients with pattern C tumors, in contrast to that for those patients with pattern A tumors. These findings underscore the need for prospective studies to further investigate the prognostic significance of stage I HPV-associated EAC substaging and the inclusion of the binary Silva pattern of invasion classification (which includes LVSI status) as a component of treatment recommendations.

Assessment of liver graft quality during hypothermic oxygenated perfusion: the first international validation study

Background and AimWhile it is currently assumed that liver assessment is only possible during normothermic machine perfusion (NMP), there is uncertainty regarding a reliable and quick prediction of graft injury during ex situ hypothermic oxygenated perfusion (HOPE). We therefore intended to test, in an international liver transplant cohort, recently described mitochondrial injury biomarkers measured during HOPE before liver transplantation. Study designPerfusate samples of human livers from 10 centers in 7 countries with HOPE-experience were analyzed for released mitochondrial compounds, i.e. flavin mononucleotide (FMN), NADH, purine derivates and inflammatory markers. Perfusate FMN was correlated with graft loss due to primary non-function or symptomatic non-anastomotic biliary strictures (NAS), and kidney failure, as well as liver injury after transplantation. Livers deemed unsuitable for transplantation served as negative control. ResultsWe collected 473 perfusate samples of human DCD (n=315) and DBD livers (n=158). Fluorometric assessment of FMN in perfusate was validated by mass spectrometry (R=0.7011,p<0.0001). Graft loss due to primary non-function or cholangiopathy was predicted by perfusate FMN values (c-statistic mass spectrometry 0.8418 (95%CI 0.7466-0.9370,p<0.0001), c-statistic fluorometry 0.7733 (95%CI 0.7006-0.8461,p<0.0001). Perfusate FMN values were also significantly correlated with symptomatic NAS and kidney failure, and superior in prediction of graft loss when compared to conventional scores derived from donor and recipient parameters, such as the donor risk index and the balance of risk score. Mitochondrial FMN values in liver tissues of non-utilized livers were low, and inversely correlated to high perfusate FMN values and purine metabolite release. ConclusionsThis first international study validates the predictive value of the mitochondrial co-factor FMN, released from complex I during HOPE, and may therefore contribute to a better risk stratification of injured livers before implantation. Impact and ImplicationsAnalysis of 473 perfusates, collected from 10 international centers during hypothermic oxygenated perfusion (HOPE), revealed that mitochondria derived flavin mononucleotide (FMN) values in perfusate is predictive for graft loss, cholangiopathy, and kidney failure after liver transplantation. This result is of high clinical relevance, as recognition of graft quality is urgently needed to improve the safe utilization of marginal livers. Ex-situ machine perfusion approaches, such as HOPE, are therefore likely to increase the number of useable liver grafts.

Increased frequency of CHEK2 germline pathogenic variants among individuals with dermatofibrosarcoma protuberans

PurposeTo identify candidate susceptibility genes for dermatofibrosarcoma protuberans (DFSP). MethodsAll individuals with DFSP from the International Sarcoma Kindred Study (n = 3767 individuals with sarcoma diagnoses from Australia, Europe, New Zealand, and United States) and cohorts that were not ascertained based on sarcoma status or other phenotypes (Geisinger MyCode, n = 170,503 individuals, United States; UK Biobank, n = 469,789 individuals, United Kingdom) were evaluated for germline pathogenic or likely pathogenic (P/LP) variants in 156 cancer genes. ResultsThere were 92 unrelated individuals with DFSP across the 3 cohorts. The mean age at diagnosis (standard deviation) in International Sarcoma Kindred Study, Geisinger, and UK Biobank was 40.8 (14.5), 50.3 (9.4), and 49.4 (13.2) years, respectively. Germline P/LP variants were most common in the CHEK2 gene (4/92 [4.3%]). CHEK2-related cases were often associated with early onset disease (age at diagnosis: 30-39 years) and were observed in all 3 cohorts. Among 640,292 individuals in Geisinger and UK Biobank who were not ascertained based on phenotype, there was a significantly increased frequency of CHEK2 P/LP variants among individuals with DFSP (n = 3/65 [4.6%]) od with those without (n = 6388/640,227 [1.0%]) (Fisher exact, P = .03). Additional genes with P/LP variation (1 case for each gene) included ACD, ERCC5, ERCC1, DOCK8, GBA1, ATM, MUTYH, TP53, RECQL4, and COL7A1. ConclusionThis study of multiple cohorts identifies CHEK2 as a candidate susceptibility gene for DFSP. Additional epidemiologic and functional studies are needed to further characterize this potential gene-tumor relationship.

379P Safety and efficacy of trastuzumab deruxtecan and concomitant radiation therapy in patients with metastatic breast cancer: A multicentre international retrospective cohort study

379P Safety and efficacy of trastuzumab deruxtecan and concomitant radiation therapy in patients with metastatic breast cancer: A multicentre international retrospective cohort study

Impact of Hemoglobin Levels on Composite Cardiac Arrest or Stroke Outcome in Patients With Respiratory Failure Due to COVID-19.

Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. Retrospective analysis of prospectively collected database. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0-11.9 g/dL for women, 10.0-13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). Patients older than 18 years with acute COVID-19 infection in the ICU. None. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05-1.67). In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

1815O Breastfeeding after breast cancer in young BRCA carriers: Results from an international cohort study

1815O Breastfeeding after breast cancer in young BRCA carriers: Results from an international cohort study

737. ETHNIC, GENDER AND TUMOR-SPECIFIC ASSESSMENT OF BODY COMPOSITION IS CRITICAL FOR CLINICAL RELEVANCE IN PATIENTS UNDERGOING THERAPY FOR ESOPHAGEAL

Abstract Background Growing evidence has supported a role for body composition in predicting survival in patients undergoing esophagectomy. A contemporary meta-analysis of published data (n=44 studies) conducted for this study confirmed an association between reduced muscle mass at diagnosis and worse overall survival (HR 1.72, 95%CI 1.49-1.97). Variation in methods of assessing and defining parameters of body composition remain however an important barrier to the wider adoption in routine clinical practice. This is particularly pertinent in esophageal cancer due to known sex, biological and geographical difference in tumor subtypes. This study seeks to define baseline variation in body composition parameters and to report their association with 90-day and overall survival in a large international cohort of patients undergoing esophagectomy for cancer. Methods Patients who underwent esophagectomy in fourteen high-volume centers between January 2007 to December 2019 were eligible for inclusion. Survival data were included up until June 2022. Skeletal muscle, visceral and subcutaneous adipose tissues within CT images, acquired at the time of diagnosis, were analyzed in accordance with a standardized protocol. Results 1716 patients were recruited to this study from three global regions: North America (n=386;22.5%), Europe (n=940;54.8%) and Asia (n=390;22.7%). Patients were predominantly male (79.5%) and adenocarcinoma was the most common histological subtype (66.6%). Wide variation of skeletal muscle (17.1-83.5cm2), visceral adiposity (0.2-170.1cm2) and subcutaneous adiposity (0.2-216.8cm2) was observed at presentation. Characteristics significantly associated with levels of muscle and adiposity were global region, sex, age, and histological subtype (P&amp;lt;0.001) (Figure 1). Compared to adenocarcinoma, squamous cell carcinoma was associated with significantly lower levels of muscle and adiposity, a finding that was independent of global region, sex, and age using a multivariable linear regression model (p&amp;lt;.0001). Median follow-up was 71.3 (95%CI 69.1-73.5) months with a median overall survival of 60.9 (95%CI 53.0-68.9) months. Reduced skeletal muscle and an excess of total adiposity at the time of diagnosis was associated with worse 90-day mortality and long-term survival. An interactive online survival prediction tool was developed to provide personalized survival estimates based on relevant predictors including skeletal muscle, total adiposity at diagnosis and other tumor and patient specific variables. Conclusions This is the first and largest study to adopt standardized methods to define international variation in parameters of body composition in esophageal cancer patients. Findings corroborate the potential role of body composition as a method of prognostication in esophageal cancer and presents a on-line tool for convenient integration into clinical practice.

Climate change and marine cargo insurance - A global survey of insurers' perceptions

The increasing frequency of climate-related hazards poses a significant risk to supply chains and marine insurance companies, which are already grappling with complex and interdependent global operations. Through a survey, this research examines the perceptions of an international cohort of marine insurers regarding their organization's participation in the Supply Chain Risk Management (SCRM) framework for climate change. In addition, the influence of respondents' experience levels and the World Bank's country classifications by income level are investigated. A repeated measures analysis of variance (ANOVA) is conducted to examine the effect of the SCRM framework's steps on perception, revealing significant variations among the steps and identifying gaps for improvement. While experience levels do not significantly affect involvement in the SCRM framework, distinct patterns emerge within each experience group, highlighting nuanced risk management practices. Comparing perceptions across World Bank income level categories reveals that higher country income levels generally correlate with higher average perception scores, indicating a potential association with greater awareness and management of climate change risks. The research also highlights the need for comprehensive involvement in all steps of the SCRM framework. Addressing climate change and building resilient supply chains requires a multi-faceted approach that includes enhanced risk management practices, and to this end, the authors' present areas for future research.

Variability in forgoing life-sustaining treatment practices in critically Ill patients with hospital-acquired bloodstream infections: a secondary analysis of the EUROBACT-2 international cohort

BackgroundThe decision to forgo life-sustaining treatment in intensive care units (ICUs) is influenced by ethical, cultural, and medical factors. This study focuses on a population of patients with hospital-acquired bloodstream infections (HABSI) to investigate the association between patient, pathogen, center and country-level factors and these decisions.MethodsWe analyzed data from the EUROBACT-2 study (June 2019–January 2021) from 265 centers worldwide, focusing on non-COVID-19 patients who died in the hospital or within 28 days after HABSI. We assessed whether death was preceded by a decision to forgo life-sustaining treatment, examining country, center, patient, and pathogen variables. To assess the association of each potentially important variable with the decision to forgo life-sustaining treatment, univariable mixed logistic regression models with a random center effect were performed.ResultsAmong 1589 non-COVID-19 patients, 519 (32.7%) died, with 191 (36.8%) following a decision to forgo life-sustaining treatment. Significant geographical differences were observed, with no reported decisions to forgo life-sustaining treatment in African countries and fewer in the Middle East compared to Western Europe, Australia, and Asia. Once a center effect was considered, only health expenditure (Odds ratio 1.79, 95%CI: 1.45–2.21, p < 0.01) and age (Odds ratio 1.02, 95%CI: 1.002–1.05, p = 0.03) were significantly associated with decisions to forgo life-sustaining treatment, while other patient and pathogen factors were not.ConclusionEconomic and regional disparities significantly impact end-of-life decision-making in ICUs. Global policies should consider these disparities to ensure equitable end-of-life care practices.

Prognostic impact of cytogenetic abnormalities detected by FISH in AL amyloidosis with daratumumab-based frontline therapy

AbstractWe performed an international retrospective study on 283 patients with light chain (AL) amyloidosis to investigate the prognostic impact of cytogenetic abnormalities by fluorescence in situ hybridization, when treated with frontline daratumumab–based therapy. The cytogenetic subgroups of interest were t(11;14), gain/amp(1q) (hereafter, +1q), hyperdiploidy, deletion(13q), del(17p), and myeloma high-risk (HR) translocations (t[4;14], t[14;16], or t[14;20]). The end points of interest were rate of hematologic complete response (heme-CR), very good partial response (VGPR) or better, and hematologic event-free survival (heme-EFS). The incidence of abnormalities was as follows: t(11;14), 53.4%; deletion (13q), 28.9%; +1q, 22.3%; hyperdiploidy, 19.4%; HR translocations, 6.6%; and deletion(17p), 4.5%. The heme-CR rate by cytogenetic subgroups were as follows: t(11;14) vs no t(11;14), 45.2% vs 41.8% (P=0.597); del(13q) vs no del(13q), 46.8% vs 42.8% (P=0.594); +1q vs no +1q, 30.2% vs 47.9% (P=0.022); hyperdiploidy vs no hyperdiploidy, 39.5% vs 44.9% (P=0.541); HR translocations vs none, 45.5% vs 43.1% (P=0.877); and del(17p) vs no del(17p), 50.0% vs 42.9% (P=0.658), respectively. Similarly, +1q was the only subgroup with a significantly lower VGPR or better rate (64.2% vs 79.0%; P=0.033). At a median follow-up of 19.8 months, the median heme-EFS was 49.6 months (95% CI, 24.7-not reached [NR]), and the 2-year overall survival (OS) was 80.98% (95% CI, 75.6-85.4). The presence of +1q was significantly associated with worse heme-EFS on multivariate analysis (HR 2.06, 95% CI, 1.14-3.71; P=0.017). Notably, there was no adverse prognostic impact of t(11;14) on heme-EFS or OS. In conclusion, +1q is associated with worse outcome in the daratumumab-era. Clinical trials testing novel frontline immunotherapies should be enriched in +1q to further improve outcomes in this subgroup.

Benefit of isolated surgical valve repair or replacement for functional tricuspid regurgitation and long-term outcomes stratified by the TRI-SCORE.

Severe tricuspid regurgitation (TR) is associated with increased mortality rates, but benefit of its correction and ideal timing are not clearly determined. This study aimed to identify patient subsets who might benefit from surgery. In TRIGISTRY, an international cohort study of consecutive patients with severe isolated functional TR (33 centers, 10 countries), survival rates up to 10 years were compared between patients who underwent isolated tricuspid valve (TV) surgery (repair or replacement) and those conservatively managed, overall and according to TRI-SCORE category (low: ≤3, intermediate: 4-5, high: ≥6). 1,217 were managed conservatively, and 551 underwent isolated TV surgery (200 repairs, 351 replacements). TRI-SCORE distribution was 33% low, 32% intermediate, and 35% high. At 10 years, survival rates were similar between surgical and conservative management (41% vs. 36%; hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.88-1.08, P=0.57). Surgery improved survival compared to conservative management in the low TRI-SCORE category (72% vs. 44%; HR 0.27; 95% CI 0.20-0.37, P<0.0001), but not in the intermediate (36% vs. 37%, HR 1.17; 95%CI 0.98-1.40, P=0.09) or high categories (20% vs. 24%; HR 1.06; 95% CI 0.91-1.25, P=0.45). Both repair and replacement improved survival in the low TRI-SCORE category (84% and 61% vs. 44%; HR 0.11; 95% CI 0.06-0.19, P<0.0001, and HR 0.65; 95% CI 0.47-0.90, P=0.009). Repair showed benefit in the intermediate category (59% vs. 37%; HR 0.49; 95% CI 0.35-0.68, P<0.0001) while replacement was possibly harmful (25% vs. 37%; HR 1.43; 95% CI 1.18-1.72, P=0.0002). Higher survival rates were observed with repair than replacement and benefit of intervention declined as TRI-SCORE increased with no benefit of any type of surgery in the high TRI-SCORE category. These results emphasize the importance of timely intervention and patient selection to achieve the best outcomes and the need for randomized controlled trials. TRIGISTRY: ClinicalTrials.gov, NCT05825898.

Leukaemia, lymphoma, and multiple myeloma mortality after low-level exposure to ionising radiation in nuclear workers (INWORKS): updated findings from an international cohort study

A major update to the International Nuclear Workers Study (INWORKS) was undertaken to strengthen understanding of associations between low-dose exposure to penetrating forms of ionising radiation and mortality. Here, we report on associations between radiation dose and mortality due to haematological malignancies. We assembled a cohort of 309 932 radiation-monitored workers (269 487 [87%] males and 40 445 [13%] females) employed for at least 1 year by a nuclear facility in France (60 697 workers), the UK (147 872 workers), and the USA (101 363 workers). Workers were individually monitored for external radiation exposure and followed-up from Jan 1, 1944, to Dec 31, 2016, accruing 10·72 million person-years of follow-up. Radiation-mortality associations were quantified in terms of the excess relative rate (ERR) per Gy of radiation dose to red bone marrow for leukaemia excluding chronic lymphocytic leukaemia (CLL), as well as subtypes of leukaemia, myelodysplastic syndromes, non-Hodgkin and Hodgkin lymphomas, and multiple myeloma. Estimates of association were obtained using Poisson regression methods. The association between cumulative dose to red bone marrow, lagged 2 years, and leukaemia (excluding CLL) mortality was well described by a linear model (ERR per Gy 2·68, 90% CI 1·13 to 4·55, n=771) and was not modified by neutron exposure, internal contamination monitoring status, or period of hire. Positive associations were also observed for chronic myeloid leukaemia (9·57, 4·00 to 17·91, n=122) and myelodysplastic syndromes alone (3·19, 0·35 to 7·33, n=163) or combined with acute myeloid leukaemia (1·55, 0·05 to 3·42, n=598). No significant association was observed for acute lymphoblastic leukaemia (4·25, -4·19 to 19·32, n=49) or CLL (0·20, -1·81 to 2·21, n=242). A positive association was observed between radiation dose and multiple myeloma (1·62, 0·06 to 3·64, n=527) whereas minimal evidence of association was observed between radiation dose and non-Hodgkin lymphoma (0·27, -0·61 to 1·39, n=1146) or Hodgkin lymphoma (0·60, -3·64 to 4·83, n=122) mortality. This study reports a positive association between protracted low dose exposure to ionising radiation and mortality due to some haematological malignancies. Given the relatively low doses typically accrued by workers in this study (16 mGy average cumulative red bone marrow dose) the radiation attributable absolute risk of leukaemia mortality in this population is low (one excess death in 10 000 workers over a 35-year period). These results can inform radiation protection standards and will provide input for discussions on the radiation protection system. National Cancer Institute, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Institut de Radioprotection et de Sûreté Nucléaire, Orano, Electricité de France, UK Health Security Agency. For the French translation of the abstract see Supplementary Materials section.