International Multicenter Cohort Study Research Articles

Association between obesity and likelihood of remission or low disease activity status in psoriatic arthritis applying index-based and patient-based definitions of remission: a cross-sectional study

ObjectivesWe aimed to evaluate whether obese patients with psoriatic arthritis (PsA) were less likely to be in remission/low disease activity (LDA).MethodsWe used data from the ReFlaP, an international multi-centre cohort...

BJS 2 Pancreatoduodenectomy for malignancy: which patients are high-risk? Results from an international multicentre cohort study

Abstract Aims Pancreatoduodenectomy (PD) is indicated in fit patients with a resectable cancer affecting the pancreatic head but morbidity rates remain high. This study aimed to identify risk factors for postoperative complications and perioperative mortality. Methods Data were extracted from the Recurrence After Whipple's (RAW) study, a retrospective cohort study of PD patients with confirmed malignancy (29 centres, eight countries). Patients who experienced any complication, clinically relevant postoperative pancreatic fistula (CR-POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were compared to those who did not experience these outcomes. Results 1348 patients were included. Any complication, major morbidity, CR-POPF, PPH and 90-day mortality affected 53.4%, 16.9%, 10.5%, 6.2% and 3.8% of patients, respectively. Following a multivariable analysis, high body mass index (BMI, OR: 1.1, p=0.007), American Society of Anesthesiologists (ASA) grade >II (OR: 2.2, p<0.0001) and a pylorus-resecting approach (OR: 1.6, p=0.005) correlated with overall morbidity. ASA >II patients were at increased risk of major morbidity (OR: 2.2, p<0.0001) and a raised BMI was a risk factor for CR-POPF (OR: 1.1, p=0.001). ASA >II (OR: 2.5, p=0.002) and positive lymph nodes on preoperative imaging (OR: 2.1, p=0.01) were risk factors for PPH, and both preoperative diabetes (OR: 0.4, p<0.05) and a pancreato-jejunostomy anastomosis (OR: 0.5, p=0.03) were protective. No risk factors for 90-day mortality were identified. Conclusion In our study, a high BMI and ASA grade >II were associated with adverse perioperative outcomes. Patients in these groups should be made aware of their increased risk prior to surgery.

FTP7.4 Variations in the type of nutritional support provided after pancreatoduodenectomy: results from an international multicentre retrospective cohort study

Abstract Aims An early oral diet is recommended after pancreatoduodenectomy (PD), however, the nutritional management of PD patients is known to be highly variable, and some centres still provide postoperative parenteral nutrition (PN) routinely. A proportion of patients who receive PN experience clinically significant complications underscoring its judicious use. Using a multicentre cohort, this study aimed to determine the proportion of PD patients that received postoperative nutritional support (NS), describe the variations in this support, and investigate whether receiving PN correlated with morbidity. Methods Data was extracted from the Recurrence After Whipple’s (RAW) study database, a retrospective study of patients undergoing PD for histologically confirmed pancreatic, ampullary or distal bile duct malignancy. Results 1323 patients (89.2%) had data on their postoperative NS status available. Of these, 45.4% received postoperative NS. This was “enteral only”, “parenteral only”, and “enteral and parenteral” in 44.3%, 35.2% and 20.5% of cases, respectively. Body mass index <18.5 kg/m2 (p=0.03), an absence of preoperative biliary stenting (p=0.009) and preoperative serum albumin <36 g/L (p=0.009) all correlated with receiving postoperative NS. Among those who did not develop a serious postoperative complication (Clavien-Dindo grade ≥IIIa), one-fifth received PN. Conclusions Being underweight, not undergoing preoperative biliary stenting and having a low preoperative serum albumin all correlated with receiving postoperative NS. A considerable number of patients who had an uneventful recovery received PN; this should be reserved for those who are unable to take an oral diet or those in whom an oral diet is contraindicated.

The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study.

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.

Coronary Atherosclerotic Plaque Activity and Future Coronary Events

Recurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk. To assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction. This prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years' follow-up. Coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography. Total coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates. Among 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09). In this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

The five periampullary cancers: Not just different siblings but different families—An international multicenter cohort study.

4167 Background: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC) and ampullary adenocarcinoma (AAC). Based on histopathology, the AAC is currently subdivided in the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype. Despite close anatomical resemblance, it is unclear how the ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. Methods: This is an international multicenter cohort study, including patients after curative intent resection for periampullary cancer retrieved from 45 centers (from Europe, USA, Asia and Canada) between 2010 and 2021. Pre-operative CA19-9, differences in pathology and postoperative pancreatic fistula (POPF, grade B/C), 8-year overall survival (OS) and disease-free interval (DFI) were compared between DAC, AmpIT, AmpPB, dCCA and PDAC. Results: Overall, 3809 patients were included of which 348 DAC, 774 AmpIT, 848 AmpPB, 1036 dCCA and 803 PDAC. The best 8-years overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, p<0.001), dCCA (26.4%, p=0.020) and last, PDAC (12.9%, P<0.001). The best 8-years DFI was measured for AmpIT (62.7%) and the worst for both dCCA and PDAC (24.9% and 21.8%). This pattern correlated with the height of the pre-operative CA19-9 but not with the pathology, in which the largest and most progressed tumors were found in DAC. The incidence of POPF was lower in the pancreas-related tumor types (AmpPB 18.5%, PDAC 8.3%) compared to the non-pancreas related types (DAC 27.3%, AmpIT 25.5%, dCCA 27.6%). Conclusions: Despite the close anatomic relation of the five periampullary cancers, this study shows that there are prognostic and clinically relevant differences in terms of preoperative blood markers, pathology, complications, long-term survival, and recurrence. More characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for “periampullary cancers”, this study emphasizes the need for individual evaluation of each histopathological periampullary subtype with the ampullary subtypes as individual entities in future studies.

Clinical characteristics and long-term outcomes following pancreatic injury – An international multicenter cohort study

BackgroundTrauma to the pancreas is rare but associated with significant morbidity. Currently available management guidelines are based on low-quality evidence and data on long-term outcomes is lacking. This study aimed to evaluate clinical characteristics and patient-reported long-term outcomes for pancreatic injury. MethodsA retrospective cohort study evaluating treatment for pancreatic injury in 11 centers across 5 European nations over >10 years was performed. Data relating to pancreatic injury and treatment were collected from hospital records. Patients reported quality of life (QoL), changes to employment and new or ongoing therapy due to index injury. ResultsIn all, 165 patients were included. The majority were male (70.9%), median age was 27 years (range: 6–93) and mechanism of injury predominantly blunt (87.9%). A quarter of cases were treated conservatively; higher injury severity score (ISS) and American Association for the Surgery of Trauma (AAST) pancreatic injury scores increased the likelihood for surgical, endoscopic and/or radiologic intervention. Isolated, blunt pancreatic injury was associated with younger age and pancreatic duct involvement; this cohort appeared to benefit from non-operative management. In the long term (median follow-up 93; range 8–214 months), exocrine and endocrine pancreatic insufficiency were reported by 9.3% of respondents. Long-term analgesic use also affected 9.3% of respondents, with many reported quality of life problems (QoL) potentially attributable to side-effects of opiate therapy. Overall, impaired QoL correlated with higher ISS scores, surgical therapy and opioid analgesia on discharge. ConclusionsPancreatic trauma is rare but can lead to substantial short- and long-term morbidity. Near complete recovery of QoL indicators and pancreatic function can occur despite significant injury, especially in isolated, blunt pancreatic injury managed conservatively and when early weaning off opiate analgesia is achieved.

Survival outcomes of young patients under 40 with breast cancer in Asian countries according to subtype: An international multicenter cohort study.

562 Background: The incidence of young Asian women with breast cancer has been increasing but these patients are underrepresented in global data. We analyzed the epidemiology and outcomes of the young Asian patients with breast cancer in different subtypes with clinically unmet need. Methods: Female patients of age 20 years or older diagnosed with early breast cancer of stage I, II, or III from the prospective cohort of the Asian Breast Cancer Cooperative Group (ABCCG) were analyzed. For comparison, data of patients with early breast cancer from Surveillance, Epidemiology, and End Results Program (SEER) cancer registry was used. The patients were divided into three age groups: young (below 40 years), alleged premenopausal mid-age (40-49 years), and alleged postmenopausal elderly (50 years and older). Multivariable Cox proportional-hazard models for survivals were adjusted with age, subtypes consisting of hormone receptor (HR) and human epithelial growth factor receptor 2 (HER2) status, histologic grade, T stage, nodal status, and countries. Patients diagnosed in 2000–2010 were censored at 6 years for comparability with SEER database. Results: Total 45,021 patients with breast cancer from Asian countries, 496,332 of SEER Whites and 18,279 from SEER non-Whites were included. The median age at diagnosis was younger in Asians compared to SEER Whites and non-Whites (51, 62, 58 years, respectively). Among subtypes, HR-positive and HER2-negative breast cancer was more frequent among SEER Whites and SEER non-Whites, compared to Asians (75.89%, 73.38% vs. 65.75%, respectively). In the young group, HR-positive and HER2-negative breast cancer was prevalent in Asians and SEER non-Whites, compared to SEER Whites (61.2% and 59.8% vs. 54.7%, respectively). In the elderly group, the proportion of HR-positive breast cancer increased in SEER Whites, while that of triple-negative breast cancer (TNBC) increased in Asians. Elderly group showed the worst survival in all subtypes and in all populations. In Asian population, the mid-age group of the patients with HR-positive and HER2-negative breast cancer showed significantly superior overall survival (OS) than the young group (6 year OS 96.6% vs. 94.4%; hazard ratio 0.62, 95% confidence interval 0.50-0.76; p<0.001). Similarly, young patients in SEER Whites also showed early decline of survival curve compared those in mid-age group (89.1% vs. 94.0%, p<0.001), while young patients of SEER non-Whites showed equivalent prognosis to those in mid-age group (92.4% vs. 95.0%, p=0.118). Conclusions: Young Asian breast cancer patients diagnosed with HR-positive and HER2-negative subtypes, but not HER2-positive or TNBC subtypes, are more likely to have worse survival outcomes than those in mid-age. Further studies on young patients with breast cancer are needed for tailored treatments among different subtypes and ethnic groups.

Why treatment of proximal humeral fractures remains unresolved despite randomized trials

Most proximal humeral fractures can be treated nonoperatively, but there are specific indications to perform surgery for some of these fractures. Optimal treatment remains subject to debate, since no consensus has been reached for the best therapy for these fractures. This review provides an overview of randomized controlled trials (RCTs) comparing treatment for proximal humeral fractures. Fourteen RCTs comparing different operative and nonoperative types of treatment for PHF are included. Different RCTs comparing the same interventions for PHF have drawn different conclusions. It also highlights reasons why consensus has not been reached based on these data, and how this could be addressed in future research. Previous RCTs have included different patient groups and fracture patterns, may have been prone to selection bias, often were underpowered for subgroup analysis, and showed inconsistency in the outcome measures used. Based on this, and appreciating that treatment may be tailored to specific fracture types and patient characteristic like age, a better way to move forward could be to use a (international) multicenter prospective cohort study. Such a registry-type study should use accurate patient selection and enrollment, well-defined fracture patterns, standardized surgical techniques performed according to the preferences of the surgeon, and with a standardized follow-up.

Presentation, care and outcomes of patients with NSTEMI according to World Bank country income classification: Prospective international multicentre cohort study of the ESC EORP NSTEMI registry

Abstract Funding Acknowledgements Type of funding sources: None. Background The majority of NSTEMI burden resides outside high income countries (HICs). Care that conforms to the European Society of Cardiology (ESC) guidelines has been demonstrated to improve outcomes,2-6 but places a financial burden on healthcare systems.7 Whether care quality and outcomes vary by country economic prosperity is unknown. The EURObservational Research Programme (EORP) NSTEMI registry was designed and implemented to identify patterns in NSTEMI care and outcomes across the heterogeneous context of ESC country members and affiliated countries. Purpose We describe presentation, care and outcomes of NSTEMI by World Bank country income classification. Methods Prospective cohort study (11 March 2019 to 6 March 2021) including 2947 adult patients with NSTEMI from 287 centres in 59 countries. For each patient demographic features, therapeutic methods, treatment delays, risk stratification and medication prescription during admission and on discharge were recorded. Quality of care was evaluated based on 12 guideline-recommended care interventions. The all-or-none scoring composite performance measure was used to define receipt of optimal care. Outcomes included in-hospital repeat myocardial infarction, acute heart failure and death, and 30-day mortality. Results Patients admitted with NSTEMI in low-lower middle income countries (LLMICs), compared to patients in HICs, were younger (median age 58 years [IQR 51-65] vs 68 [59-77]), more commonly diabetic (48.6% vs 34.2%) but with a lower burden of other comorbidities (Table 1). Of patients with NSTEMI in LLMICs, 76.7% met very high risk criteria for an immediate invasive strategy. Compared to patients in HICs, the proportion of patients in LLMICs presenting in Killip Class III or IV was three-fold higher; and ongoing chest pain, life-threatening arrhythmias, and hemodynamic instability were at least twice as common. Invasive coronary angiography use increased with ascending income classification (LLMICs, 79.2%; upper middle income countries [UMICs], 83.7%; HICs, 91.0%), but overall care quality did not (≥80% of eligible interventions achieved: LLMICS, 64.8%; UMICs 69.6%; HICs 55.1%) (Figure 1). Rates of acute heart failure (LLMICS, 21.3%; UMICs, 12.1%; 3.2%; HICs, 6.8%; p<0.001), repeat myocardial infarction (LLMICS: 2.5%; UMICs: 1.5%; HICs: 0.9%; p=0.04), in-hospital mortality (LLMICS, 3.6%; UMICs: 2.8%; HICs: 1.0%; p<0.001) and 30 day mortality (LLMICs, 4.9 %; UMICs, 3.9%; HICs, 1.5%; p<0.001) exhibited an inverse economic gradient. Conclusions Patients with NSTEMI in LLMICs present at a younger age, with fewer comorbidities, at a more advanced stage of acute disease, and have worse outcomes compared with HICs. Overall care did not vary by income classification, but there was a shortfall in provision of interventional procedures in LLMICs. A cardiovascular health narrative is needed to address this inequity across economic boundaries.

High-Definition Videobronchoscopy for the Diagnosis of Airway Involvement in Sarcoidosis: The Enhance Sarcoidosis Multicenter Study

The ability of high-definition (HD) videobronchoscopy to detect airway involvement in sarcoidosis has not been evaluated previously. What is the role of HD videobronchoscopy in the identification of sarcoidosis-associated airway abnormalities (AAs)? What are the patterns of AAs more commonly observed and more frequently associated with the detection of granulomas in endobronchial biopsy (EBB)? In this prospective international multicenter cohort study, consecutive patients with suspected sarcoidosis underwent airway inspection with an HD videobronchoscope and EBB using a standardized workflow. AAs were classified according to six patterns defined a priori: nodularity, cobblestoning, thickening, plaque, increased vascularity, and miscellaneous. We assessed diagnostic yield of EBB, prevalence of AAs, and interobserver agreement for different patterns of AAs. AAs were identified in 64 of 134 patients with sarcoidosis (47.8%), with nodularity (n= 23 [17.2%]), plaque (n= 19 [14.2%]), and increased vascularity (n= 19 [14.2%]) being the most prevalent. The diagnostic yield of EBB was 36.6%. AAs were significantly more prevalent in patients with than in those without nonnecrotizing granulomas on EBB (67.4%vs36.5%; P= .001). Likewise, parenchymal disease on CT scan imaging was significantly more common in patients with than in those without nonnecrotizing granulomas on EBB (79.6%vs54.1%; P= .003). On a per-lesion analysis, nonnecrotizing granulomas were seen especially in EBB samples obtained from areas of cobblestoning (9/10 [90%]) and nodularity (17/29 [58.6%]). The overall diagnostic yield of random EBB was low (31/134 [23.1%]). The interobserver agreement for the different patterns of AA was fair (Fleiss κ = 0.34). In a population with a large prevalence of White Europeans, HD videobronchoscopy detected AAs in approximately one-half of patients with sarcoidosis. The diagnostic yield of EBB was higher in patients with parenchymal involvement on CT scan imaging and in those with AAs, especially if manifesting as cobblestoning and nodularity. ClinicalTrials.gov; No.: NCT4743596; URL: www. gov.

Robotic versus laparoscopic liver resection for huge (≥10 cm) liver tumors: an international multicenter propensity-score matched cohort study of 799 cases.

The use of laparoscopic (LLR) and robotic liver resections (RLR) has been safely performed in many institutions for liver tumours. A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours ≥10 cm. This was a retrospective review of 971 patients who underwent LLR and RLR for huge (≥10 cm) tumors at 42 international centers between 2002-2020. One hundred RLR and 699 LLR which met study criteria were included. The comparison between the 2 approaches for patients with huge tumors were performed using 1:3 propensity-score matching (PSM) (73 vs. 219). Before PSM, LLR was associated with significantly increased frequency of previous abdominal surgery, malignant pathology, liver cirrhosis and increased median blood. After PSM, RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time (242 vs. 290 min, P=0.286), transfusion rate rate (19.2% vs. 16.9%, P=0.652), median blood loss (200 vs. 300 mL, P=0.694), open conversion rate (8.2% vs. 11.0%, P=0.519), morbidity (28.8% vs. 21.9%, P=0.221), major morbidity (4.1% vs. 9.6%, P=0.152), mortality and postoperative length of stay (6 vs. 6 days, P=0.435). RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent outcomes. There was no significant difference in perioperative outcomes after RLR or LLR.

Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study

BackgroundPancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. MethodsData were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012–May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. Results394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. ConclusionsThis multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy.

Prediction of Mortality among Patients with Isolated Traumatic Brain Injury Using Machine Learning Models in Asian Countries: An International Multi-Center Cohort Study.

Traumatic brain injury (TBI) is a significant healthcare concern in several countries, accounting for a major burden of morbidity, mortality, disability, and socioeconomic losses. Although conventional prognostic models for patients with TBI have been validated, their performance has been limited. Therefore, we aimed to construct machine learning (ML) models to predict the clinical outcomes in adult patients with isolated TBI in Asian countries. The Pan-Asian Trauma Outcome Study registry was used in this study, and the data were prospectively collected from January 1, 2015, to December 31, 2020. Among a total of 6540 patients (≥ 15 years) with isolated moderate and severe TBI, 3276 (50.1%) patients were randomly included with stratification by outcomes and subgrouping variables for model evaluation, and 3264 (49.9%) patients were included for model training and validation. Logistic regression was considered as a baseline, and ML models were constructed and evaluated using the area under the precision-recall curve (AUPRC) as the primary outcome metric, area under the receiver operating characteristic curve (AUROC), and precision at fixed levels of recall. The contribution of the variables to the model prediction was measured using the SHapley Additive exPlanations (SHAP) method. The ML models outperformed logistic regression in predicting the in-hospital mortality. Among the tested models, the gradient-boosted decision tree showed the best performance (AUPRC, 0.746 [0.700-0.789]; AUROC, 0.940 [0.929-0.952]). The most powerful contributors to model prediction were the Glasgow Coma Scale, O2 saturation, transfusion, systolic and diastolic blood pressure, body temperature, and age. Our study suggests that ML techniques might perform better than conventional multi-variate models in predicting the outcomes among adult patients with isolated moderate and severe TBI.

Abstract P3-05-36: Prognostic factors in non-metastatic hormone receptor-positive HER2-negative mucinous breast cancer: an international multicentre cohort study

Abstract Background: Mucinous carcinoma is the third most common histological subtype of breast cancer after ductal and lobular carcinomas, accounting for approximately 3% of invasive breast cancers. Although considered a favourable subtype with de-escalation of treatment recommended in the National Comprehensive Cancer Network guidelines, recurrence can occur and supporting data is limited. We thus examined prognostic factors of pure mucinous breast cancer (PMBC) in an international multicentre cohort study. Methods: Patients diagnosed between January 2000 to December 2015 with hormone receptor-positive HER2-negative stage I to III PMBC, invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) at 6 centers in Singapore, Taiwan, Korea and Japan were evaluated. Cox proportional hazards regression analyses were used to compare relapse-free survival (RFS), distant relapse-free survival (DRFS) and overall survival (OS) by histological subtypes, and to identify prognostic factors for PMBC. Results: Of 23,105 women eligible for analysis, 20,684 had IDC, 1,475 had ILC and 946 had PMBC. The median follow-up was 6.6 years; 5-year RFS, DRFS and OS for PMBC were 94.6%, 96.5% and 98.1% respectively. On multivariable cox regression analyses, PMBC demonstrated superior RFS (hazard ratio [HR] = 0.70, 95% CI: 0.56 - 0.88), DRFS (HR = 0.69, 95% CI: 0.53 - 0.89) and OS (HR = 0.70, 95% CI: 0.52 - 0.93) compared to IDC, while ILC had comparable survival outcomes as IDC. When restricted to only PMBC, significant independent prognostic factors for RFS included ethnicity (vs Chinese, “Others” [non-Chinese/Japanese/Korean, mainly Malay and Indian]: HR = 2.62, 95% CI 1.23 – 5.57), older age (vs < 40 years, >70 years: HR = 3.53, 95% CI 1.67 – 7.46), tumor size (vs T1, T3-4: HR = 2.79, 95% CI 1.45 – 5.37), positive lymph nodes (HR = 2.04, 95% CI: 1.10 – 3.77), use of radiotherapy (HR = 0.54, 95% CI 0.33 – 0.91) and endocrine therapy (HR = 0.31, 95% CI 0.12 – 0.77). On further analysis, the inferior RFS, DRFS and OS in older patients (>70 years) were driven largely by non-breast cancer deaths rather than relapses. Use of endocrine therapy was also associated with superior DRFS (HR = 0.26, 95% CI 0.09 – 0.73) but not OS. In a subgroup analysis, use of chemotherapy was associated with improved DRFS (HR = 0.25, 95% CI 0.08 – 0.82) and OS (HR = 0.07, 95% CI 0.01 – 0.37) with a trend in RFS (HR = 0.41, 95% CI 0.14 – 1.24) for lymph node-positive PMBC; no differences in outcomes were observed for the lymph node-negative subgroup. Conclusions: Larger tumor size, lymph node positivity and ethnicity were significant factors for RFS in PMBC. Use of endocrine therapy was associated with superior RFS and DRFS, while chemotherapy was associated with better DRFS and OS for lymph-node positive PMBC. Citation Format: Ryan Tan, Whee Sze Ong, Kyung-Hun Lee, Seri Park, Jabed Iqbal, Yeon Hee Park, Jeong-Eon Lee, Jong Han Yu, Ching-Hung Lin, Yen-Shen Lu, Makiko Ono, Takayuki Ueno, Yoichi Naito, Tatsuya Onishi, Geok hoon Lim, Su-Ming Tan, Han-Byoel Lee, Jiwon Koh, Han Suk Ryu, Wonshik Han, Veronique Kiak Mien Tan, Fuh-Yong Wong, Seock-Ah Im, Puay Hoon Tan, Yoon-Sim Yap. Prognostic factors in non-metastatic hormone receptor-positive HER2-negative mucinous breast cancer: an international multicentre cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-36.

Abstract OT1-08-01: AXSANA – EUBREAST3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with clinically axillary lymph node involvement metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR23, Lymph-ICF and SOC 13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 2347 patients from 247 study sites and 23 countries were enrolled in the study between June 2020 and June 2022. Among 1804 patients with a defined surgical concept 758 women were scheduled for ALND, 722 for TAD, 232 for SLNB, 16 for TLNB and 19 for other procedures. A target lymph node was marked in 1215 patients, most frequently using clips/coils (982, 82.0%), followed by magnetic seeds (100, 8.4%), carbon ink (99, 8.3%), radar marker (21, 1.8%), radioactive seeds (5, 0.4%), and other techniques (8, 0.7%). Citation Format: Thorsten Kühn. AXSANA – EUBREAST3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-08-01.

Outcomes and survival in patients with advanced intestinal neuroendocrine tumours on home parenteral nutrition, an international multicentre retrospective cohort study

Only limited information is available on the use of home parenteral nutrition (HPN) in patients with advanced neuroendocrine tumours (NETs) causing intestinal failure (IF). This study aims to report the outcomes of the explore the use of HPN in this patient cohort, in the largest case series to date. A retrospective study in the United Kingdom and the Netherlands was performed, using the UK National British Artificial Nutrition Survey (BANS) and local databases in the Netherlands. Data regarding age, sex, NET grading, staging, treatment, HPN characteristics and survival outcomes were collected. Data were collected on 41 patients (n=18 males, 44%) with a median age of 65. Most primary tumours were in the small bowel (n=35, 85%). The NETs were Grade 1 (n=16, 39%), Grade 2 (n=7, 17%), Grade 3 (n=1, 2%). In 28 patients (n=68%) there was stage IV disease with metastases located in the peritoneum, mesentery and or liver. There were two indications for HPN; short bowel syndrome (n=27, 66%) and inoperable malignant bowel obstruction (n=14, 34%). The median period on HPN was 11 months (interquartile range 4-25 months). 11 patients were still alive and receiving HPN treatment after 2 years, and 6 patients after 3 years. Six patients (22%) with short bowel syndrome (SBS) could be weaned from HPN. There was a statistically significant improved survival for patients with short bowel syndrome (median 24 months) compared to inoperable malignant bowel obstruction (median 7 months). The catheter-related bloodstream infection rate was comparable to other HPN patient cohorts at 1.0 per 1000 catheter days. This study shows that HPN can be used safely in patients with NET and IF to increase survival beyond that reasonably expected in the context of either short bowel syndrome or inoperable malignant bowel obstruction. Patients with short bowel syndrome are most likely to benefit. Further prospective studies are necessary to validate survival benefits and to demonstrate the effect of HPN on quality of life.

A harmonized protocol for an international multicenter prospective study of nanotechnology workers: the NanoExplore cohort

Nanotechnology applications are fast-growing in many industrial fields. Consequently, health effects of engineered nanomaterials (ENMs) should be investigated. Within the EU-Life project NanoExplore, we developed a harmonized protocol of an international multicenter prospective cohort study of workers in ENM-producing companies. This article describes the development of the protocol, sample size calculation, data collection and management procedures and discusses its relevance with respect to research needs. Within this protocol, workers’ ENM exposure will be assessed over four consecutive working days during the initial recruitment campaign and the subsequent follow-up campaigns. Biomonitoring using noninvasive sampling of exhaled breath condensate (EBC), exhaled air, and urine will be collected before and after 4-day exposure monitoring. Both exposure and effect biomarkers, will be quantified along with pulmonary function tests and diagnosed diseases reported using a standardized epidemiological questionnaire available in four languages. Until now, this protocol was implemented at seven companies in Switzerland, Spain and Italy. The protocol is well standardized, though sufficiently flexible to include company-specific conditions and occupational hygiene measures. The recruitment, to date, of 140 participants and collection of all data and samples, enabled us launching the first international cohort of nanotechnology workers. All companies dealing with ENMs could join the NanoExplore Consortium, apply this harmonized protocol and enter in the cohort, concieved as an open cohort. Its protocol meets all requirements of a hypotheses-driven prospective study, which will assess and reassess effects of ENM exposure on workers’ health by updating the follow-up of the cohort. New hypothesis could be also considered.

Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study.

While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1-365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September2021. Advanced age (HR 2.77, 95%CI 2.53-3.04, p<0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03-4.17, p<0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55-5.00, p<0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14-1.39, p<0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37-0.46, p<0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17-1.54, p<0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20-1.58, p<0.0001), male sex (HR 1.67, 95%CI 1.45-1.93, p<0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80-13.91, p<0.0001), and hypertension (HR 1.22, 95%CI 1.10-1.36, p=0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32-1.67) and 365 days (RR 1.54, 95%CI 1.21-1.96) compared to COVID-19 patients with no AKI. COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery. Authors are supported by various funders, with full details stated in the acknowledgement section.

Investigating paediatric sarcoma management worldwide: a study protocol

AbstractIntroductionCancer is the leading cause of non-accidental death among children worldwide. The most common types of paediatric cancers include sarcomas: a group of cancers that are difficult to manage due to their heterogeneity and lack of defining features. We have designed an international multicentre cohort study to assess the management of paediatric sarcomas at tertiary healthcare centres in Nigeria, Pakistan and the UK.Methods and AnalysisThe centres will screen patient databases to identify eligible patients under the age of 18 with a clinical or histological diagnosis of sarcoma. Data will be extracted from the patient notes through an anonymized form. Patients will be recruited consecutively into the study from January 2015 to January 2021, with a minimum 12-month follow up period. The primary objectives of the study will be to determine all-cause mortality rates at 30 days, 90 days, 12 months and 3 years. Significant differences in mortality rates between countries will be determined using χ2 analysis or Fisher’s exact test. Univariate and multivariable logistic regression will be used to examine the influence of different factors and patient characteristics on outcomes.Ethics and DisseminationAt the host centre, this study was deemed to be exempt from ethical committee approval due to the use of anonymized data. At other centres, participating collaborators have gained local approvals in accordance with institutional ethical regulations. Collaborators will present the data to inform decision makers about how sarcoma management may be improved. The results will be submitted for publication in a peer-reviewed journal.