Prospective Multicenter Study Research Articles

EGS SO26 - Back Under the Knife: Unveiling the Fate of non-trauma Patients Returning to the Emergency Theatre

Abstract Background Offering a planned or unplanned second operation in emergency general surgery is not uncommon. However, there is a scarcity of data in this context. This study aims to evaluate the outcomes of patients who were offered two emergency operations to those who required one operation, focusing on complications, increased level of care at discharge and mortality rates. Method We identified those patients who underwent planned and unplanned revisits to the emergency theatre between July 2020 and July 2023. Inclusion criteria were consistent with the established UK National Emergency Laparotomy Audit (NELA at our centre over three years.. We examined demographics, ASA (American Society of Anesthesiologists) classification, indications and outcomes in terms of complications, increased post-operative care levels and mortality rates. Results 390 patients (89.3%) required one operation (1OP) and 47 (10.7%)patients underwent two operations (2OP) . The median age was 70 years for 1OP and 71 years for 2OP, with a male-to-female ratio of 192:198 in 1OPG and 22:25 in 2OP. The median ASA score (2 vs. 3), median frailty score (3 vs. 4) and the median Clavien-Dindo classification (2 vs. 4), and length of stay in days (12 vs. 21) were significantly higher for the 2OP. The increase in the level of care at discharge (30.6% vs. 59%) and the mortality (7.4% vs. 32%) were higher in the 2OP. Conclusion Our study shows that non-trauma patients requiring a second emergency operation face significantly worse outcomes compared to those undergoing only one surgery. Specifically, the group needing two operations experienced higher rates of complications, increased levels of post-operative care, and significantly higher mortality rates. These findings underscore the critical need for close monitoring and a multidisciplinary approach perioperatively. Moreover, these insights can help provide patients and their families with informed decision-making regarding the potential risks and benefits of additional surgical interventions. A prospective multicentre study would be valuable in providing further insights into this subgroup of patients.

EGS SO13 - Evaluation of Different Surgical Risk Prediction Models in Predicting Morbidity and Mortality in Giant Hiatus and Diaphragmatic Hernia Repairs

Abstract Background Emergency giant hiatus hernia and diaphragmatic hernia repairs are associated with high rates of mortality and morbidity; different studies reported variable outcomes. Accurate risk assessment empowers patients to provide informed consent and also serves as a valuable tool for identifying individuals who may require enhanced postoperative care, such as respiratory support and critical care admission. Various risk prediction tools have been developed to assist clinicians in making decisions to aid in stratifying the risk of surgical management. We aimed to assess the effectiveness of different risk prediction models in predicting mortality and morbidity in this patient cohort. Method Retrospective analysis performed on cases between May, 2010 and January, 2021 in a tertiary adult upper gastro-intestinal centre. The outcomes from the operations were assessed and compared with the predicted morbidity and mortality for different risk prediction models. Including the Surgical Outcome Risk Tool (SORT), the National Emergency Laparotomy Audit (NELA), parsimonious NELA and the American College of Surgeons National Surgical Quality Improvement Programme (ACS-NSQIP). The models were compared using the area under the curve (AUC). Morbidity models included Portsmouth Physiological and Operative Severity Score (P-POSSUM) and the ACS-NSQIP. Morbidity was evaluated by calculating the comprehensive complication index (CCI). Results A total of 108 patients met the criteria and were included in the analysis. Among these 50.9% were females. The median age was 69 (IQR 59-78). The 30-day mortality rate was 6.93% (7 patients), six patients died during the same admission, and one patient died during a re-admission. ACS-NQSIP had the highest predictive power for mortality (AUC = 0.6344), in comparison to NELA (AUC=0.5665), parsimonious NELA (AUC=0.4866) and SORT (AUC = 0.4342). Both ACS-NSQIP and P-POSSUM showed moderate correlation to CCI (rho = 0.489, p<0.001 and 0.446, p<0.001 respectively). Conclusion ACS-NSQIP is a better predictor of both mortality and morbidity in emergency giant hiatus and diaphragmatic hernia repairs when compared to NELA, parsimonious NELA, P-POSSUM and SORT. Interestingly, parsimonious NELA had a lower prediction rate when compared with the older NELA model. ACS-NSQIP may have a role in pre-assessment and consenting of emergency hiatus and diaphragmatic hernia repairs. Multi-centre prospective studies could be used to validate these findings.

HPB SO41 - Does Adjuvant Chemotherapy Provide a Survival Benefit in Elderly Patients (≥70 years) with Pancreatic Cancer? A Retrospective Cohort-study

Abstract Background There is currently conflicting evidence surrounding the use of adjuvant chemotherapy (AC) for elderly patients (over 70 years) with pancreatic adenocarcinoma. Limited existing studies debate its effect on overall survival (OS) and relapse-free survival (RFS). The aim of this study is to assess whether adjuvant chemotherapy following pancreaticoduodenectomy provides a survival benefit in elderly patients with pancreatic cancer. Method A retrospective review including elderly adult patients, seventy years and older, who underwent a Whipple’s pancreatoduodenectomy for pancreatic adenocarcinoma between 1st January 2015 and 31st December 2020, at a tertiary HPB centre was performed. Information on baseline characteristics, preoperative assessment, histopathology, postoperative complications and course, and adjuvant chemotherapy were collected. Elderly patients who received AC were compared to those who did not undergo AC. Statistical analysis was performed using Jamovi 2.3. Results Sixty-eight patients were included with 44 (65%) receiving AC. There was no difference in age (p=0.72), sex (p=0.19), preoperative characteristics (all p<0.05), and resection margin (p=0.67) between the groups. There was no difference in complication rates (p=0.20), including Clavien-Dindo3+ (p=0.68). The length of hospital stay was shorter in the AC group, without statistical significance (15.7±11.9 vs 23.2±20.3 days, p=0.06). There was no difference in RFS between the groups (22.7±20 vs 15.4±23.6 months, p=0.18). However, patients who received AC had a significantly greater OS compared to those who did not (30.7±18.2 vs 18.6±22.2 months, p=0.02). Conclusion AC improved overall survival in elderly (≥70 years) patients with pancreatic adenocarcinoma. Whilst many elderly patients may not receive adjuvant chemotherapy due to postoperative complications and/or longer hospital stay, our study suggests age alone should not be a deciding factor when considering adjuvant chemotherapy in this cohort. A future large, multicentre prospective study is needed to further examine OS with the use of AC in elderly patients with pancreatic adenocarcinoma.

Abstract A049: Peritoneal tumor DNA as a prognostic biomarker in locally advanced gastroesophageal cancer: A pilot prospective cohort study

Abstract Background: Gastroesophageal cancers commonly spread to the peritoneum. Peritoneal disease significantly alters patient prognosis and treatment-intent. Currently, peritoneal lavage cytology (PLC) is the method of choice for detecting peritoneal micro-metastasis within the peritoneum. Despite its pervasive use, PLC has a variable sensitivity of 10% - 80% in detecting peritoneal micro-metastasis in gastroesophageal cancers. Peritoneal tumor DNA (ptDNA) is tumor-derived DNA detectable in peritoneal lavage fluid. ptDNA-positivity may indicate peritoneal micro- metastasis and may be more sensitive than PLC in staging the peritoneum and predicting disease- free survival (DFS) and overall survival (OS). We aimed to develop and test a tumor-informed platform for ptDNA detection and validate its sensitivity and specificity against PLC. Methods: For this pilot study, peritoneal lavage fluid were collected at staging laparoscopy from 15 patients with gastroesophageal cancer. Cytology and peritoneal metastases (where clinically detectable) were confirmed by histopathology. A tumor-informed ptDNA testing was performed via whole-genome sequencing of tumor tissue and buffy coat to identify somatic variants for each patients, followed by tracking of up to 96 variants in each patient’s peritoneal fluid. Results: 5 out of 15 patients were either cytology positive or had macroscopic peritoneal disease and ptDNA was detectable in all 5 cases. Additionally, out of the 10 cytology-negative patients without macroscopic peritoneal disease, ptDNA positivity was detected in 6 patients prior to commencing neoadjuvant chemotherapy or surgery. Two of these 6 patients demonstrated radiological evidence of recurrence at 15- and 18-months follow-up respectively. Interestingly, one patient with macroscopic peritoneal disease tested negative for cytology. In this case, peritoneal lavage was carried out to the upper two abdominal quadrants only, and the pelvic deposit of disease was detected after the lavage had been completed. Despite a negative cytology result, ptDNA was detected using the same fluid sample, suggesting a higher sensitivity compared to PLC. Conclusions: This pilot study demonstrates that a tumor-informed ptDNA detection platform is feasible and potentially more sensitive than PLC in gastroesophageal cancer. To further validate the clinical utility of ptDNA we are proceeding to a multi-center prospective cohort study. Citation Format: Zexi Allan, Yuxuan Wang, Jeanne Tie, Niall Tebbutt, Nicholas Clemons, Nickolas Papadopoulos, Kenneth Kinzler, Bert Vogelstein, David SH Liu. Peritoneal tumor DNA as a prognostic biomarker in locally advanced gastroesophageal cancer: A pilot prospective cohort study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A049.

Abstract PR009: Application of Liquid Biopsy-RECIST (LB-RECIST) criteria to track metastatic colorectal cancer (mCRC) molecular response in first-line (1L) setting: Findings from the PLATFORM-B study

Abstract Introduction: Circulating tumor DNA (ctDNA) analysis is a minimally invasive and reproducible method to explore tumor molecular biology. Recently, Gouda et al. proposed the LB-RECIST criteria to monitor molecular response, validating them on a heterogeneous metastatic population. However, data on mCRC are lacking. Here, we report the first attempt to apply LB-RECIST in the multicenter prospective PLATFORM-B study, which enrolled 130 mCRC patients (pts) receiving 1L standard therapy, with ctDNA analysis performed at different time points. Materials and Methods: Baseline (BL) and week 8 (W8) plasma samples were analyzed using a targeted NGS-based approach (Ion S5 system). Changes in ctDNA detectability were assessed to determine molecular response as per qualitative LB-RECIST criteria: Group1 (G1, detectable ctDNA at BL and W8); Group2 (G2, detectable BL and undetectable W8); Group3 (G3, undetectable BL and detectable W8); Group4 (G4, undetectable at BL and W8). Changes in aggregate variant allele frequency (VAF) - the sum of all VAFs of the studied genes in a sample - were used to assess quantitative LB-RECIST responses: ctDNA Complete Response (CCR, clearance after initial detectability), Partial Response (CPR, decrease >10%), Stable Disease (CSD, no change or decrease <10%), Progressive Disease (CPD, increase >10% or new mutations), and Non-measurable Disease (CND, undetectable at BL and W8). Molecular results were correlated with clinical outcomes. Statistically significant differences were assessed across different groups using 2-sided P values with an α ≤ .05 level of significance. Results: Overall, 79 pts had paired BL and W8 samples. Quantitative LB-RECIST identified 32 CCR, 18 CND, 20 CPR, 8 CPD, and 1 CSD cases. Qualitative LB-RECIST found 22 G1, 32 G2, 7 G3, and 18 G4 cases. Radiological RECIST identified 6 CR, 47 PR, 21 SD, and 5 PD. CCR showed the highest survival rates: with a median follow-up of 25 months (mo) (range: 1–49), median progression-free survival (mPFS) was not reached (NR) and median overall survival (mOS) was 41.8 mo. The CND group had similar rates (mPFS NR; mOS 41.1 mo). CPR and CPD had the poorest outcomes: for CPR, mPFS was 12.7 and mOS 16.4 mo; for CPD, mPFS and mOS were 11.9 and 25.5 mo, respectively. In the G1, G2, G3, and G4 groups, mPFS was 11.9, NR, 14.2, and NR, respectively, while mOS was 16.4, 41.8, 33.4, and 41.1 mo. Kaplan-Meier analysis of the quantitative groups showed statistically significant differences (P < .0001) for both PFS and OS curves. The same level of significance was found in the qualitative groups. Conclusion: LB- RECIST can be a rapid and reproducible method to assess molecular response in mCRC. However, concerns remain. The CND group (23% of cases) showed survival rates similar to the CCR group, as observed also between G4 and G2. These data suggest that absence of ctDNA at W8 is the best surrogate for OS. Moreover, CPD had higher OS rates than CPR, but similar PFS. Further investigations in larger populations are needed to refine these criteria and improve molecular response stratification Citation Format: Valentino Martelli, Joana Vidal, Maria Concepción Fernández-Rodríguez, Pilar García-Alfonso, David Páez, Joan Gibert, Jennifer Linares, Annarita Sibilio, Vicente Alonso, Maria Teresa Cano, Cristina Santos, Gema Duran, Elena Élez, José Luis Manzano, Rocio Garcia-Carbonero, Reyes Ferreiro, Ferran Losa, Estela Pineda, Javier Sastre, Auxiliadora Gomez-España, Rodrigo Toledo, Fernando Rivera, Beatriz Bellosillo, Josep Tabernero, Ramon Ramon Salazar, Enrique Aranda, Clara Montagut. Application of Liquid Biopsy-RECIST (LB-RECIST) criteria to track metastatic colorectal cancer (mCRC) molecular response in first-line (1L) setting: Findings from the PLATFORM-B study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR009.

Healthcare costs in relation to kidney function among older people: the SCOPE study.

In this study, a comprehensive analysis of costs of chronic kidney disease (CKD) was performed, to understand factors associated with the economic burden of the disease in a multicentre international framework. The impact on costs of demographics, socio-economics, clinical, and functional variables was tested in 2204 subjects aged 75years or more attending outpatient clinics in Europe using a multicentre 2-year prospective cohort study. By means of collected resources consumption and unit cost data a comprehensive cost database was built and then investigated using multilevel regression modeling. Overall, hospitalization, medications and specialist visits were the main cost items, with a notable variability among countries. Estimated yearly costs were 4478€ ± 9804€, rising up to 6683€ ± 10,953€ for subjects with estimated Glomerular Filtration Rate (eGFR) < 30. Costs increased significantly according to the severity of the disease, gender and age. Clinical and functional covariates were also significantly associated with CKD-related total costs, even after correcting for the inter-country variability. Findings corroborate the importance of multidimensional assessment of participants with CKD, as multimorbidity and functional disability produce a detrimental impact on participant's prognosis and cost of care. Preservation of functional impairment and adequate management of comorbidities may thus help decreasing the overall consumption on health care resources in CKD patients, especially in older people.

LeAf Trauma- an intersectoral prospective multicenter study assessing quality of life and return to work after majortrauma-study protocol.

With increasing survival rates, the functional outcome and quality of life of trauma patients are gaining more importance. Survivors suffer from chronic pain, psychosomatic disorders, and unemployment as well as increased post-traumatic morbidity, which can lead to an impaired quality of life. So far, the TraumaRegister DGU® records patient data during in-hospital treatment. In this study severely injured patients after major trauma are assessed when discharged from hospital, as well as 6, 12 and 18 months after trauma. The aim is to document cross-sector patient pathways and to identify and quantify the factors influencing the health-related quality of life (hrQoL) and the return to work (RTW), using patient-reported experience measures (PREM) and patient reported outcome measures (PROM). Patients are recruited in certified trauma centers of the German Society for Trauma Surgery (DGU). This study protocol describes the methodology of the prospective multicentre study of LeAf Trauma. Translation of the results will be implemented by using the network structures of the German Society for Trauma Surgery (DGU) for the treatment of patients with major trauma.

Abstract A074: Early detection of breast implant associated anaplastic large cell lymphoma by multiplex lateral flow assay of CD30 and IL-10

Abstract Introduction: More than 1300 women have developed a unique breast implant associated anaplastic large cell lymphoma (BIA-ALCL) around breast implants. BIA-ALCL presents as an accumulation of fluid (seroma) a median of 9 years after implant placement. When detected early, survival with surgery alone is nearly 100%. Remaining patients present with masses and/or lymph node metastases requiring radiation, chemotherapy and/or immunotherapy and fatalities have occurred. Methods: Preliminary studies identified CD30 and IL-10 as the most sensitive and specific biomarkers for BIA-ALCL in seroma fluids. Therefore, we constructed a multiplex LFA to detect both CD30 and IL-10 in 30 mL seroma fluid within 20 minutes. LFA is a point of care immunoassay using capture and detection antibodies that detect separate epitopes of the target molecule. The detection antibody is linked to a colored particle; in this multiplex assay CD30 antibody was linked to blue and IL-10 to red particles. Separate positive test lines (blue and red) indicate presence of CD30 or IL-10. A control line confirms migration of the seroma fluid past the test lines. To determine the dynamic range of sensitivity we spiked recombinant CD30 and IL-10 into benign seromas. Test and control lines were quantitated with NIH Image J software and ratios of test line to control line calculate for each sample. Forty-eight hour supernatants of supernatants of BIA-ALCL lines TLBR1 and TLBR2 were tested for IL-10 and CD30. Fifteen patients, 8 with BIA-ALCL and 7 with benign seromas provided consent for testing of their seroma fluids. Results: Multiplex CD30/IL10 LFA produced positive test lines for neat and 1:10 dilutions of 48 hour supernatnats of BIA-ALCL lines TLBR1 and TLBR2. Both IL-10 and CD-30 could be detected on the multiplex LFA strip using a 1:3 dilution of seroma fluids. The multiplex LFA shows both IL-10 and CD30 are significantly higher in malignant samples (IL-10 TL/CL: malignant, 0.2±0.16 n=8 vs benign, 0.004±0.007 n=7, p&amp;lt;0.05; CD30 TL/CL: malignant, 0.38±0.2 vs benign, 0.02±0.02, p&amp;lt;0.001, two-way ANOVA). Importantly, when either IL-10 or CD30 yields a faint positive test line, the other is not detected reducing the possibility of false positives. Conclusions: The CD30/IL-10 multiplex LFA had 100% positive and negative predictive value in this pilot study. The assay was able to distinguish lymphoma from recurrent breast cancer and more common benign seromas. The use of this multiplex assay mitigates positive false positive results from more sensitive CD30 LFA which has been detected in some benign seromas. This LFA will potentially allow early pre-operative detection of ALCL allowing surgeons to plan their surgical approach. The LFA can replace more costly time-consuming flow cytometry, immunohistochemistry, cyto- and histopathologic studies which require at least 10 ml of fluid. The LFA can be performed outside of medical centers in rural and underserved areas. A larger prospective multicenter study including intra-operative sampling is planned to validate these results. Citation Format: Peng Xu, Katerina Kourentzi, Richard Willson, Marshall Kadin. Early detection of breast implant associated anaplastic large cell lymphoma by multiplex lateral flow assay of CD30 and IL-10 [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A074.

Abstract Sa1101: Association Between Changes in Hypoxic-Ischemic Brain Injury and Neurological Outcomes in Cardiac Arrest Survivors.

Aim: Quantitative analysis of hypoxic-ischemic brain injury (HIBI) using apparent diffusion coefficient (ADC) values from brain magnetic resonance imaging (MRI) is used to predict poor neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors. Our study aimed to determine the association between changes in HIBI and neurological outcomes in OHCA survivors using two types of MRI. Methods: This observational study used data collected prospectively from a tertiary academic hospital. The study included adult comatose OHCA survivors who underwent targeted temperature management (TTM) and brain MRI within 6 hours (first) and 72–96 hours (second) using the same MR scanner. We analyzed the neurological outcomes based on brain volumes below a specific ADC value using 10-step intervals within the range of 200–1200 × 10 -6 mm 2 /s for the first and second MRIs. ADC-R(x) represents the proportion of total brain volume occupied by voxels, with ADC values ranging from 200 × 10 -6 mm 2 /s to each threshold. Additionally, ADC(x) represents the proportion of total brain volume occupied by voxels that are “threshold - 10” at each threshold. Poor neurological outcomes were categorized as cerebral performance levels 3–5, observed 6 months after OHCA. Results: Overall, 122 patients (25% female) were included in the analysis, of whom 61 (50%) showed poor neurological outcomes. Higher ADC-R(x) were observed in the poor neurological outcome group on both the first and second MRI scans at all ADC intervals (all P &lt; 0.05) (Figure 1). In the Good Neurological Outcome group, the ADC-R values ranged between 370 and 940, with the second MRI value being smaller than that of the first (right shift, P &lt; 0.05). In contrast, the Poor Neurological Outcome group showed ADC-R values ranging between 340 and 1190, with the second MRI value being higher than that of the first (left shift, P &lt; 0.05) (Figure 2). The difference in ADC(x) between the second and first MRI based on neurological outcome showed a positive change in ADC below 620 for a poor neurological outcome and a positive change in ADC above 740 for a good neurological outcome (Figure 3). Conclusions: In this cohort study, we observed that the initial HIBI that occurred during OHCA worsened or returned to normal depending on the neurological outcome after TTM. Prospective multicenter studies are required to generalize our findings.

Possible rapid reduction of anti-RBD antibody titre after SARS-CoV-2 mRNA vaccination in pregnant women: Multicentre prospective study.

Pregnant women are at increased risk for severe illness associated with coronavirus disease 2019 (COVID-19) compared to nonpregnant women. The aim of this multicenter prospective study was to assess the current COVID-19 vaccination status of pregnant women in the southern Osaka district and to compare their antibody titers with those of nonpregnant women. Serum antibody titers of anti-NCP antibodies (antibodies against the SARS-CoV-2 nucleocapsid) and anti-RBD antibodies (the receptor binding domain of the S1 subunit of the spike protein) were evaluated in 753 pregnant women at 34-35 weeks of gestation from October 2021 to March 2022. Anti-RBD antibody titre was also investigated in 1003 health care workers at Kindai University hospital 3 and 6 months after a second dose of the vaccine from March 2021 to April 2021. 519 (68.9%) pregnant women were vaccinated during pregnancy, of whom 497 (95.8%) received two doses. The COVID-19 infection rate calculated from the number of pregnant women with a positive anti-NCP antibody titre or with confirmed diagnosis was 5.1% (12/234) in the unvaccinated and 3.5% (18/519) in the vaccinated. The estimated half-life calculated from anti-RBD antibody titers and the number of days between vaccination and antibody testing was 39.9 days. The antibody titre and half-life in pregnant women were significantly lower and shorter than in nonpregnant women aged 20-39 years (109.4 days). Our study showed that pregnant women may have lower vaccine-acquired COVID-19 immunity than nonpregnant women.

Biomarkers of response to ocrelizumab in relapsing-remitting multiple sclerosis.

To ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing-remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response. Multicenter prospective study including 115 RRMS patients initiating ocrelizumab treatment between February 2020 and March 2022 followed during a year. Serum samples were collected at baseline and every 3 months to measure sNfL and sGFAP levels using single-molecule array (SIMOA) technology. Based on age and body mass index, sNfL values were standardized using z-score. NEDA (non-evidence of disease activity)-3 status was defined for patients free of disease activity after a year of follow-up. Inflammation (INFL) was considered when new relapses occurred during follow-up or new MRI lesions were found at 1-year exploration. PIRA (progression independent of relapse activity) was defined as disability progression occurring in the absence of relapses or new MRI activity. After a year on ocrelizumab, 85 patients (73.9%) achieved NEDA-3. Thirty patients did not achieve NEDA: 20 (17.4%) because of INFL and 10 (8.7%) because of PIRA. Of INFL patients, 6 (30.0%) had relapses, and 17 (85.0%) had at least one new MRI lesion at the 12-month examination. At baseline, INFL patients had higher sNfL (p = 0.0003) and sGFAP (p = 0.03) than the NEDA-3 group. PIRA patients mostly exhibited low sNfL and heterogeneous sGFAP levels. After a year, NEDA-3 and INFL patients showed similar decreases in sNfL (p < 0.0001) and sGFAP (p < 0.0001 for NEDA-3 and p = 0.001 for INFL ones). However, the decrease occurred earlier in NEDA-3 patients. Accordingly, sNfL > 1.5 z-score 3 months after ocrelizumab initiation indicated a higher risk of inflammation (OR = 13.6; p < 0.0001). Decrease in sGFAP values occurred later in both groups, with significant reductions observed at 12 months for INFL and 6 and 12 months for NEDA-3. No significant changes in sNfL or sGFAP were observed in PIRA patients. Ocrelizumab induced normalization of sNfL and sGFAP in the majority of NEDA-3 and inflammatory patients but did not cause changes in the PIRA group. Our data suggest that normalization of sNfL and sGFAP is associated with the lack of inflammatory-associated disease progression but it may not affect non-inflammatory PIRA.

RADT-50. CLINICAL OUTCOME OF DAILY 5-FRACTIONATED GAMMA KNIFE RADIOSURGERY FOR LARGE BRAIN METASTASES

Abstract INTRODUCTION With the introduction of the Gamma Knife Icon, hypo-fractionated Gamma Knife radiosurgery (GKRS) for large brain metastases (LBMs) is beginning to be performed. This study aimed to assess the clinical outcome and risk of the daily 5-fractionated GKRS for LBMs. METHODS A total of 100 patients who underwent 5-fractionated GKRS for LBMs (&amp;gt; 14cm3) were enrolled. Forty-six were male patients, and the median age was 60 years. Most common primary cancer sites were lung (41 non-small cell cancers), breast (24), and kidney (14). The median tumor volume was 22cm3 (14 – 69cm3) and marginal dose was 35Gy (50% isodose line) in 5 fractions. Median follow-up duration was 18 months (3 – 72 months). RESULTS The last follow-up showed local tumor control in 74 cases. The cumulative 1, 2, and 3-year local tumor control rates were 73, 65, and 60%, respectively. Eighty-six tumors showed best MRI response in a year, and median tumor volume decrease rate was 80% (22 – 100%). Thirty patients experienced dramatically tumor volume decrease (&amp;gt; 95%). Median progression free and overall survival were 7 and 16 months, respectively. Radiation necrosis occurred in 24 patients, of which only 9 had neurological symptoms and treated with steroid and bevacizumab. CONCLUSIONS The daily 5-fractionated GKRS for very LBMs showed favorable local tumor control and acceptable radiation necrosis, but questionable survival benefit. In the future, prospective multi-center study is needed.

Consuming spicy food and type 2 diabetes incidence in Southwestern Chinese aged 30–79: a prospective cohort study

BackgroundCapsaicin is the main component of chili peppers and is believed to have antidiabetic effects. However, the association between spicy food consumption and the incidence of diabetes remains unclear.MethodsA cohort of 20,490 Han residents aged 30–79 without diabetes at baseline were followed from enrollment to June 2, 2023. The consumption of spicy food was obtained through face-to-face surveys conducted during the baseline survey from October 2018 to February 2019. The definition of type 2 diabetes onset was based on the ICD-10 code of E11 in the diabetes case reporting system and death system; Additionally, self-reported diagnosis of diabetes by a physician in active follow-ups, or a fasting blood glucose level of ≥ 7 mmol/L or a glycated hemoglobin percentage of ≥ 6.5% found on-site during the resurvey. Both Cox proportional hazard regression and competing risk regression were used to calculate hazard ratios (HRs) and confidence intervals (CIs).ResultsDuring the follow-up period (53.5 ± 3.0 months), 182 individuals (1.1%) were newly diagnosed with T2D with an incidence rate of 246.2 per 100,000 person-years. Cox regression analyses revealed that spicy food consumers had a 34% reduced risk of developing type 2 diabetes (HR: 0.66, 95% CI: 0.48, 0.91) compared to non-consumers. The HRs (95% CIs) for participants consuming spicy food 3–5 days/week, 6–7 days/week, and with weak pungency were 0.45 (95% CI: 0.25, 0.81), 0.69 (0.49, 0.98), and 0.64 (0.46, 0.90), respectively. However, little significant protective effect was observed among those who consumed spicy food for 1–2 days/week, with moderate pungency, or with strong pungency (all P > 0.05).ConclusionsConsuming spicy food may lower the risk of developing type 2 diabetes, particularly at a frequency of 3–5 days/week, and with weak pungency. Further multicenter prospective studies or interventional studies are needed to confirm these findings.

Effect of methimazole withdrawl period on the I-131 uptake estimation using Tc-99m thyroid scanning in Graves' disease.

The effect of methimazole withdrawl period (MWP) on the estimation of 24 hour-radioiodine thyroid uptake (131IU24h) from 99mTc-pertechnetate thyroid uptake (99mTcTU) remains unclear for patients with Graves disease (GD) . This study aims to investigate the feasibility and reliability of 99mTcTU-based 131IU24h estimation with different MWPs. We enrolled 116 GD patients scheduled for 131I therapy at our hospital between April 2022 and April 2023. Based on MWP, the patients were categorized: standard (no methimazole or MWP>1 month), MWP1 (MWP≤1 week), MWP2 (MWP>1 week to ≤2 weeks) and MWP3 groups (MWP>2 weeks to <1 month). Fisher's exact test, one-way ANOVA or Kruskal-Wallis test were used to compare variables. Fitted curves of 99mTcTU20min versus 131IU24h were plotted for the standard group. Linear relationships and Bland-Altman plots were used to illustrate the relationship and consistency between estimated and measured 131IU24h. 131IU24h was higher in MWP1 group compared to MWP2 (70.22±7.95% vs 61.92±9.84%, P = 0.001), and thyroid masswas greater in MWP1 group (36.15±22.38g) versus MWP3 (21.25±11.90g, P = 0.005). The relationship between131IU24h and 99mTcTU20min in the standard group is described by the algorithm: estimated 131IU24h=11.3ln (99mTcTU20min)+39.4 (R2=0.62). Based on it, the correlation between estimated and measured 131IU24h was weak in MWP1 and MWP2 groups (both P>0.05) but strong in MWP3 (r=0.66, P=0.002). Additionally, the agreement between estimated and measured 131IU24h was highest in the MWP3 group (95% CI, -15.86 to 15.52%), compared to the MWP1and MWP2 groups. Estimated 131IU24h based on 99mTcTU is not suitable for GD patients with MWP less than 2 weeks at our institution, necessitating further prospective multi-center studies for validation.

Machine learning and deep learning models for preoperative detection of lymph node metastasis in colorectal cancer: a systematic review and meta-analysis.

To evaluate the diagnostic performance of Machine Learning (ML) and Deep Learning (DL) models for predicting preoperative Lymph Node Metastasis (LNM) in Colorectal Cancer (CRC) patients. A systematic review and meta-analysis were conducted following PRISMA-DTA and AMSTAR-2 guidelines. We searched PubMed, Web of Science, Embase, and Cochrane Library databases until February 16, 2024. Study quality and risk of bias were assessed using the QUADAS-2 tool. Data were analyzed using STATA v18, applying random-effects models to all analyses. Twelve studies involving 8321 patients were included, with most published in 2021-2024 (9/12). The pooled AUC of ML models for predicting LNM in CRC patients was 0.87 (95% CI: 0.82-0.91, I2:86.17) with a sensitivity of 78% (95% CI: 69-87%) and a specificity of 77% (95% CI: 64%-90%). In addition, when assessing the AUC reported by radiologists, both junior and senior radiologists had similar performance, significantly lower than the ML models. (P < 0.001). Subgroup analysis revealed higher AUCs in prospective studies (0.95, 95% CI: 0.87-1) compared to retrospective studies (0.85, 95% CI: 0.81-0.89) (P = 0.03). Studies without external validation exhibited significantly higher AUCs than those with external validation (P < 0.01). While there was no significant difference in AUC and sensitivity between the T1-T2 and T2-T4 stages, specificity was significantly higher in the T2-T4 stages than the low stages of T1 and T2 (95%, 95% CI: 92-98% vs. 61%, 95% CI: 44-78%; P < 0.01). ML models demonstrate strong potential for preoperative LNM staging and treatment planning in CRC, potentially reducing the need for additional surgeries and related health and financial burdens. Further prospective multicenter studies, with standardized reporting of algorithms, modality parameters, and LNM staging, are needed to validate these findings.

Can Ileostomy Reversal Be Safely Performed by Surgical Residents?

Background and Objectives: The growing number of colorectal cancer patients has highlighted the importance of surgical education in colorectal surgery. Despite the negative impact of the COVID-19 pandemic on surgical training, recent changes in the Polish surgical training program have increased the number of intestinal procedures required to be completed by residents. This study aims to assess the safety of ileostomy reversal procedures performed by surgical residents. Materials and Methods: A multicenter prospective cohort study, the LILEO study, was conducted from October 2022 until December 2023 across 20 Polish surgical departments. The study included 199 patients who underwent ileostomy reversal and were divided into two groups: 139 patients operated by specialist surgeons and 60 patients operated by surgical residents. The primary outcomes measured were postoperative complications, length of hospital stay (LOS), and 30-day reoperation rate. Secondary outcomes included the severity of perioperative complications assessed using the Clavien-Dindo classification and a focused analysis of loop ileostomy reversal outcomes. Results: The median LOS was significantly shorter in the resident group (5.5 days vs. 6 days, p < 0.05). Although the overall complication rate was lower in the resident group (21.7% vs. 33.1% in the specialist surgeon group), this difference was not statistically significant (p = 0.105). The 30-day reoperation rate was 3.3% in the resident group and 8.6% in the specialist surgeon group (p = 0.179). In terms of severity, minor complications (Clavien-Dindo grades 1 and 2) were more common in the specialist group (p < 0.05). The analysis of loop ileostomy reversals revealed no significant differences in postoperative outcomes between the two groups. Conclusions: Ileostomy reversal procedures performed by surgical residents under supervision are safe and feasible, with outcomes comparable to those performed only by specialist surgeons. These findings support ileostomy reversal as a valuable procedure for developing surgical residents' skills and do not negatively affect postoperative outcomes.

Comparison of strategies based on DTI visualisation for stereotactic minimally invasive surgery in the treatment of moderate-volume thalamo-basal ganglia cerebral haemorrhage: a protocol for a multicenter prospective study

IntroductionHypertensive intracerebral hemorrhage (HICH) is a condition associated with significant morbidity, mortality, and disability, particularly among the elderly population. The management of moderate thalamic-basal ganglia cerebral hemorrhage primarily relies on conservative approaches. Nevertheless, the rate of long-term disability remains high. In recent years, there has been significant advancement in minimally invasive surgery and diffusion tensor imaging techniques. Consequently, the utilization of Diffusion Tensor Imaging (DTI) technology in patients with cerebral haemorrhage allows for the identification of the haematoma’s location in relation to the Corticospinal Tract (CST). This enables the development of precise puncture pathways that can be visualized, thereby avoiding any potential damage to the CST.Methods and analysisDiffusion Tensor Imaging (DTI) is a method used to assess the structural and physiological characteristics of biological tissue by examining the diffusion behavior of water molecules.In the central nervous system, limb paralysis will be inevitable if the corticospinal tract is damaged. By employing DTI imaging techniques on individuals, it becomes possible to visualize the spatial relationship between the hematoma and the CST. This approach allows avoidance of the CST during preoperative planning of the puncture path, thus reducing secondary injuries caused by the procedure. The primary objective of this study was to assess the ability of patients in the minimally invasive surgery group and the conservative group to perform activities of daily living after 6 months of treatment. In addition, secondary outcomes included assessment of hematoma resorption/clearance ratios, cytokine levels, complication rates, and therapeutic indexes at different treatment durations, as well as long-term safety and efficacy at 2–3 years of follow-up. Furthermore, subgroup analysis, and sensitivity analysis were conducted to further analyze the data. Logistic single-variate and multivariate regression analyses were applied to understand the adverse factors affecting prognosis.Ethics and disseminationThe clinical study was reviewed and approved by the Ethics Committee of the First People’s Hospital of Yibin. The ethical number is: 2023 Review (64).Registration numberThis protocol is registered in the Prospective Registry of Chinese Clinical Trial Registries (PROCCTR). The full date of first registration is 28/12/2023. The registration number for PROCCTR is ChiCTR2300079252.

Evaluation of decision support to wean patients from mechanical ventilation in intensive care: a prospective study reporting clinical and physiological outcomes.

This study investigated the clinical and physiological response to use of the BEACON Caresystem, a bedside open-loop decision support system providing advice to guide clinicians when weaning patients from invasive mechanical ventilation. Multicenter prospective study conducted in five adult intensive care units in the UK. Following screening and assent, intubated patients mechanically ventilated for > 24 h were randomized to intervention or usual care. Intervention consisted of application of the BEACON Caresystem's advice on tidal volume/inspiratory pressure, inspired oxygen, respiratory rate and PEEP. Usual care was defined as local clinical practice. The primary outcome was duration of mechanical ventilation. Secondary outcomes quantified prolonged intubation and survival; adverse events; ventilator settings and physiological state; time spent in ventilator modes; links to other therapy; the frequency of advice utilization and time spent outside normal physiological limits. The study was terminated early with a total of 112 patients included. Fifty-four were randomised to the intervention arm and fifty-eight to usual care. The study was underpowered and no significant differences were seen in duration of mechanical ventilation (p = 0.773), prolonged intubation or survival. Intervention arm patients had lower rates of adverse events (p = 0.016), including fewer hypoxaemic events (p = 0.008) and lower values of PEEP (p = 0.030) and tidal volume (p = 0.042). Values of peak inspiratory pressure and pressure support were reduced but at the boarder of statistical significance (p = 0.104, p = 0.093, respectively). No differences were seen for time in ventilator mode or other therapy. Advice presented by the decision support system was applied at the beside an average of 88% of occasions, with a significantly increased number of changes only in inspired oxygen fraction. No significant differences were seen in time spent outside physiological limits. This study investigated the use of the BEACON Caresystem, an open loop clinical decision support system providing advice on ventilator settings. It was terminated early, with no significant difference shown in duration of mechanical ventilation, the primary outcome. Application of advice indicated potential for fewer adverse events and improved physiological status. (Trial registration ClinicalTrials.gov under NCT03249623. Registered 22nd June 2017).

Colonoscopy Assisted Laparoscopic Wedge Resection for Colonic Lesions: Impact on Quality of LifE: Results from the LIMERIC Study.

The LIMERIC study has proven that colonoscopy-assisted laparoscopic wedge resection effectively and safely removes benign colonic lesions unsuitable for endoscopic removal, thereby avoiding the need for major surgery. To evaluate the impact of colonoscopy-assisted laparoscopic wedge on health-related quality of life of patients who participated in the LIMERIC study. Prospective multicenter study. The LIMERIC study was performed between 2016 and 2020 in 13 Dutch hospitals. EQ-5D-5L questionnaires were administered at baseline and 3 months after the procedure. Patients with incomplete pre- or postoperative questionnaires or those undergoing combined interventions were excluded from the intention-to-treat analysis. Those for whom CAL-WR was not feasible or who underwent completion surgery were excluded from the per-protocol analysis. Colonoscopy-assisted laparoscopic wedge for either (1) colon polyp unsuitable for endoscopic resection; (2) non-lifting residual or recurrent polyp within scar tissue following previous polypectomy; or (3) Rx/R1 endoscopic removal of a low-risk pT1 colon carcinoma. Three-month health-related quality of life. Colonoscopy-assisted laparoscopic wedge did not affect health-related quality of life in the per-protocol analysis (n = 56), or in the intention-to-treat analysis (n = 67). The majority of patients reported no change in health status (57%). No significant differences were observed in the distribution of responses across all 5 dimensions before and after colonoscopy-assisted laparoscopic wedge. Patients' self-rated EQ-VAS was also unaffected by colonoscopy-assisted laparoscopic wedge, with a median VAS score of 82.5 at baseline and 80 after surgery in the per-protocol analysis (p = 0.63). Solely a patient-reported outcome measure evaluating global health-related quality of life was used, rather than one specifically assessing disease-related quality of life, such as the QLQ-CR29. Colonoscopy-assisted laparoscopic wedge has no significant impact on the health-related quality of life in patients with benign colonic lesions and should therefore be considered before major surgery is performed. See Video Abstract.

Prognostic Implications of Initial Radiological Findings of Pulmonary Fibrosis in Patients with Acute SARS-CoV-2 Infection: A Prospective Multicentric Study.

Pulmonary fibrosis detected during the acute phase of SARS-CoV-2 infection may significantly influence patient prognosis. This study aimed to evaluate the prognostic value of initial high-resolution computed tomography (HRCT) findings of pulmonary fibrosis in hospitalized COVID-19 patients and to examine how these findings relate to disease severity and clinical outcomes, with a particular focus on the development and validation of predictive scoring systems. In this multicentric prospective cohort study from January 2023 to January 2024, 120 adult patients with confirmed SARS-CoV-2 infection requiring hospitalization were enrolled from two Romanian university hospitals. Patients were categorized based on the presence (n = 60) or absence (n = 60) of pulmonary fibrosis signs on admission HRCT scans, identified by reticular opacities, traction bronchiectasis, honeycombing, and architectural distortion. Biochemical analyses, severity scores (SOFA, APACHE II, NEWS 2), and novel compound scores combining clinical and radiological data were assessed. Patients with HRCT evidence of pulmonary fibrosis had significantly higher severity scores and worse clinical outcomes. The HRCT score alone was a strong predictor of severe COVID-19 (area under the ROC curve [AUC] = 0.885), with a best cutoff value of 9.72, yielding 85.7% sensitivity and 79.8% specificity. Compound Score 1, integrating SOFA, APACHE II, and HRCT scores, demonstrated excellent predictive performance with an AUC of 0.947, sensitivity of 92.5%, and specificity of 88.9%. Compound Score 2, combining systemic inflammation markers (SIRI, SII) and NEWS 2, also showed a strong predictive capability (AUC = 0.913), with 89.2% sensitivity and 85.7% specificity at the optimal cutoff. Regression analysis revealed that Compound Score 1 had the highest hazard ratio for severe COVID-19 outcomes (HR = 4.89; 95% CI: 3.40-7.05), indicating its superior prognostic value over individual markers and traditional severity scores. Initial HRCT findings of pulmonary fibrosis are significantly associated with increased disease severity in hospitalized COVID-19 patients. The HRCT score is a valuable prognostic tool, and, when combined with clinical severity scores into Compound Score 1, it enhances the prediction of severe COVID-19 outcomes with high sensitivity and specificity. These compound scores facilitate the early identification of high-risk patients, guiding clinical decision-making and optimizing patient management to improve outcomes.