Outcome-Orientated Organ Allocation-A Composite Risk Model for Pancreas Graft Evaluation and Acceptance.

Background: Pancreas transplantation (PTX) remains the most effective treatment to prevent long-term complications and provide consistent euglycemia in patients with endocrine pancreatic insufficiency, mainly in type I diabetic patients. Considering early graft loss (EGL) and the perioperative complication rate, an optimal risk stratification based on donor risk factors is paramount. Methods: In our single-center study, we retrospectively assessed the risk factors for EGL and reduced graft survival in 97 PTXs (82 simultaneous pancreas and kidney [SPK], 11 pancreases transplanted after kidney [PAK] and 4 pancreases transplanted alone [PTA]) between 2010 and 2021. By statistically analyzing the incorporation of different donor risk factors using the Kaplan-Meier method and a log-rank test, we introduced a composite risk model for the evaluation of offered pancreas grafts. Results: The overall EGL rate was 6.5%. In the univariate analysis of donor characteristics, age > 45 years, BMI > 25 kg/m2, lipase > 60 U/L, cerebrovascular accident (CVA) as the cause of death, mechanical cardiopulmonary resuscitation (mCPR), cold ischemia time (CIT) > 600 min and retrieval by another center were identified as potential risk factors; however, they lacked statistical significance. In a multivariate model, age > 45 years (HR 2.05, p = 0.355), BMI > 25 kg/m2 (HR 3.18, p = 0.051), lipase > 60 U/L (HR 2.32, p = 0.148), mCPR (HR 8.62, p < 0.0001) and CIT > 600 min (HR 1.89, p = 0.142) had the greatest impact on pancreas graft survival. We subsumed these factors in a composite risk model. The combination of three risk factors increased the rate of EGL significantly (p = 0.003). Comparing the pancreas graft survival curves for ≥3 risk factors to <3 risk factors in a Kaplan-Meier model revealed significant inferiority in the pancreas graft survival rate (p = 0.029). Conclusions: When evaluating a potential donor organ, grafts with a combination of three or more risk factors should only be accepted after careful consideration to reduce the risk of EGL and to significantly improve outcomes after PTX.

Morbidity and Mortality after Cytoreductive Surgery and HIPEC in a National Reference Center: A Six-Year Experience under Independent Evaluation.

Introduction: Cytoreductive surgery (CRS) coupled with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative approach to peritoneal disease (PD) and corresponds to the needs of patients with dire survival rates. However, the oncological community remains cautious toward this procedure because of its significant morbidity and mortality rates. This evolving evidence around CRS and HIPEC and its impact suggests a need for more standardized procedures in existing centers. Because of its complexity and potential for high morbidity and mortality, critical observation of our center's complication rates using complication management documentation tools were crucial to further develop our standard operating procedures (SOP) and maximize patient safety. Methods: Our prospectively maintained institutional database was queried to identify all patients who underwent CRS and HIPEC and had a filled-out quality management (QM) and complication management documentation tool at discharge at the surgical department of the Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany, between January 2018 and December 2023. Results: A total of 155 patients had a surgical and/or medical complication recorded. In total, 305 surgeries were surveyed. Some patients had more than one postoperative complication; hence, 344 events in 50 categories were recorded, of which 267 were graded 3a or higher in 92 patients. The most common medical complications were of pulmonary and renal origin. On the surgical side, surgical site infections (SSI) were most common. The incidence of anastomotic leakage (AL) was 5% (n = 8), with no events between 2021 and the present. Patients with longer surgery duration times were at higher risk for developing postoperative complications. Conclusions: Major abdominal surgeries like CRS and HIPEC are associated with significant patient morbidity despite achieving optimal oncological outcomes. Postoperative complications are managed through strict surveillance and transparency, particularly in our large reference centers, to minimize patient risk. Quality management programs in our department have successfully maintained high standards of care without compromising patient safety.

Enhancing Preoperative Outcome Prediction: A Comparative Retrospective Case-Control Study on Machine Learning versus the International Esodata Study Group Risk Model for Predicting 90-Day Mortality in Oncologic Esophagectomy.

Risk prediction prior to oncologic esophagectomy is crucial for assisting surgeons and patients in their joint informed decision making. Recently, a new risk prediction model for 90-day mortality after esophagectomy using the International Esodata Study Group (IESG) database was proposed, allowing for the preoperative assignment of patients into different risk categories. However, given the non-linear dependencies between patient- and tumor-related risk factors contributing to cumulative surgical risk, machine learning (ML) may evolve as a novel and more integrated approach for mortality prediction. We evaluated the IESG risk model and compared its performance to ML models. Multiple classifiers were trained and validated on 552 patients from two independent centers undergoing oncologic esophagectomies. The discrimination performance of each model was assessed utilizing the area under the receiver operating characteristics curve (AUROC), the area under the precision-recall curve (AUPRC), and the Matthews correlation coefficient (MCC). The 90-day mortality rate was 5.8%. We found that IESG categorization allowed for adequate group-based risk prediction. However, ML models provided better discrimination performance, reaching superior AUROCs (0.64 [0.63-0.65] vs. 0.44 [0.32-0.56]), AUPRCs (0.25 [0.24-0.27] vs. 0.11 [0.05-0.21]), and MCCs (0.27 ([0.25-0.28] vs. 0.15 [0.03-0.27]). Conclusively, ML shows promising potential to identify patients at risk prior to surgery, surpassing conventional statistics. Still, larger datasets are needed to achieve higher discrimination performances for large-scale clinical implementation in the future.

The Impact of the COVID-19 Pandemic on Esophageal and Gastric Cancer Surgery in Germany: A Four-Year Retrospective Single-Center Study of 287 Patients.

Background: Disruptions to surgical care for cancer patients during the COVID-19 pandemic remain an ongoing debate. This study assesses the effects of the COVID-19 pandemic on perioperative outcomes in a continuous series of surgically treated esophageal and gastric carcinoma patients at a large university hospital in Europe over 48 months. Methods: We conducted a retrospective single-center cohort study at a tertiary referral center. All patients who underwent oncologic esophageal or gastric resection between March 2018 and February 2022 were included in the analysis. The sample was split into a 24 months COVID-19 and an equivalent pre-COVID-19 control period. Outcome variables included caseload, in-hospital mortality, morbidity, treatment course, and disease stage at presentation. Results: Surgeons performed 287 operations, with around two-thirds (62%) of the cohort undergoing esophagectomy and one-third (38%) gastrectomy. The in-hospital mortality was 1% for the COVID-19 and the control periods. Patients did not present at a later disease stage nor did they wait longer for treatment. There was no decrease in caseload, and patients did not suffer from more perioperative complications during COVID-19. Conclusions: Esophageal and gastric carcinoma patients received safe and timely surgical care during the pandemic. Future pandemic protocols may streamline oncologic care towards tertiary referral centers.

Use and accuracy of decision support systems using artificial intelligence for tumor diseases: a systematic review and meta-analysis.

Background: For therapy planning in cancer patients multidisciplinary team meetings (MDM) are mandatory. Due to the high number of cases being discussed and significant workload of clinicians, Clinical Decision Support System (CDSS) may improve the clinical workflow. Methods: This review and meta-analysis aims to provide an overview of the systems utilized and evaluate the correlation between a CDSS and MDM. Results: A total of 31 studies were identified for final analysis. Analysis of different cancers shows a concordance rate (CR) of 72.7% for stage I-II and 73.4% for III-IV. For breast carcinoma, CR for stage I-II was 72.8% and for III-IV 84.1%, P≤ 0.00001. CR for colorectal carcinoma is 63% for stage I-II and 67% for III-IV, for gastric carcinoma 55% and 45%, and for lung carcinoma 85% and 83% respectively, all P>0.05. Analysis of SCLC and NSCLC yields a CR of 94,3% and 82,7%, P=0.004 and for adenocarcinoma and squamous cell carcinoma in lung cancer a CR of 90% and 86%, P=0.02. Conclusion: CDSS has already been implemented in clinical practice, and while the findings suggest that its use is feasible for some cancers, further research is needed to fully evaluate its effectiveness.

Concordance of a decision algorithm and multidisciplinary team meetings for patients with liver cancer-a study protocol for a randomized controlled trial.

INTRODUCTION: Multidisciplinary team meetings (MDMs), also known as tumor conferences, are a cornerstone of cancer treatments. However, barriers such as incomplete patient information or logistical challenges can postpone tumor board decisions and delay patient treatment, potentially affecting clinical outcomes. Therapeutic Assistance and Decision algorithms for hepatobiliary tumor Boards (ADBoard) aims to reduce this delay by providing automated data extraction and high-quality, evidence-based treatment recommendations. METHODS AND ANALYSIS: With the help of natural language processing, relevant patient information will be automatically extracted from electronic medical records and used to complete a classic tumor conference protocol. A machine learning model is trained on retrospective MDM data and clinical guidelines to recommend treatment options for patients in our inclusion criteria. Study participants will be randomized to either MDM with ADBoard (Arm A: MDM-AB) or conventional MDM (Arm B: MDM-C). The concordance of recommendations of both groups will be compared using interrater reliability. We hypothesize that the therapy recommendations of ADBoard would be in high agreement with those of the MDM-C, with a Cohen's kappa value of ≥ 0.75. Furthermore, our secondary hypotheses state that the completeness of patient information presented in MDM is higher when using ADBoard than without, and the explainability of tumor board protocols in MDM-AB is higher compared to MDM-C as measured by the System Causability Scale. DISCUSSION: The implementation of ADBoard aims to improve the quality and completeness of the data required for MDM decision-making and to propose therapeutic recommendations that consider current medical evidence and guidelines in a transparent and reproducible manner. ETHICS AND DISSEMINATION: The project was approved by the Ethics Committee of the Charité - Universitätsmedizin Berlin. REGISTRATION DETAILS: The study was registered on ClinicalTrials.gov (trial identifying number: NCT05681949; https://clinicaltrials.gov/study/NCT05681949 ) on 12 January 2023.

Validation of the Enhanced Recovery after Surgery (ERAS) society recommendations for liver surgery: a prospective, observational study.

Background: Twenty-three recommendations were summarized by the Enhanced Recovery After Surgery (ERAS) society for liver surgery. The aim was to validate the protocol especially with regard to adherence and the impact on morbidity. Methods: Using the ERAS Interactive Audit System (EIAS), ERAS items were evaluated in patients undergoing liver resection. Over a period of 26 months, 304 patients were prospectively enrolled in an observational study (DRKS00017229). Of those, 51 patients (non-ERAS) were enrolled before and 253 patients (ERAS) after the implementation of the ERAS protocol. Perioperative adherence and complications were compared between the two groups. Results: Overall adherence increased from 45.2% in the non-ERAS group to 62.7% in the ERAS group (P<0.001). This was associated with significant improvements in the preoperative and postoperative phase (P<0.001), rather than in the outpatient and intraoperative phase (both P>0.05). Overall complications decreased from 41.2% (n=21) in the non-ERAS group to 26.5% (n=67) in the ERAS group (P=0.0423), which was mainly due to the reduction of grade 1-2 complications from 17.6% (n=9) to 7.6% (n=19) (P=0.0322). As for patients undergoing open surgery, implementation of ERAS lead to a reduction of overall complications in patients scheduled for minimally invasive liver surgery (MILS) (P=0.036). Conclusions: Implementation of the ERAS protocol for liver surgery according to the ERAS guidelines of the ERAS Society reduced Clavien-Dindo grade 1-2 complications particularly in patients who underwent MILS. The ERAS guidelines are beneficial for the outcome, while adherence to the various items has not yet been satisfactorily defined.

Validation of risk scores for allograft failure after liver transplantation in Germany: a retrospective cohort analysis.

A growing number of clinical risk scores have been proposed to predict allograft failure after liver transplantation. However, validation of currently available scores in the Eurotransplant region is still lacking. We aimed to analyze all clinically relevant donor and recipient risk scores on a large German liver transplantation data set and performed a retrospective cohort analysis of liver transplantations performed at the Charité-Universitätsmedizin Berlin from January 2007 until December 2021 with organs from donation after brain death. We analyzed 9 previously published scores in 906 liver transplantations [Eurotransplant donor risk index (ET-DRI/DRI), donor age and model for end-stage liver disease (D-MELD), balance of risk (BAR), early allograft dysfunction (EAD), model for early allograft function (MEAF), liver graft assessment following transplantation (L-GrAFT7), early allograft failure simplified estimation (EASE), and a score by Rhu and colleagues). The EASE score had the best predictive value for 3-month, 6-month, and 12-month graft survival with a c-statistic of 0.8, 0.77, and 0.78, respectively. In subgroup analyses, the EASE score was suited best for male recipients with a high-MELD (>25) and an EAD organ. Scores only based on pretransplant data performed worse compared to scores including postoperative data (eg, ET-DRI vs. EAD, p<0.001 at 3-month graft survival). Out of these, the BAR score performed best with a c-statistic of 0.6. This a comprehensive comparison of the clinical utility of risk scores after liver transplantation. The EASE score sufficiently predicted 12-month graft and patient survival. Despite a relatively complex calculation, the EASE score provides significant prognostic value for patients and health care professionals in the Eurotransplant region.

Robotic-Assisted Ivor Lewis Esophagectomy Is Safe and Cost Equivalent Compared to Minimally Invasive Esophagectomy in a Tertiary Referral Center.

In recent decades, robotic-assisted minimally invasive esophagectomy (RAMIE) has been increasingly adopted for patients with esophageal cancer (EC) or cancer of the gastroesophageal junction (GEJ). However, concerns regarding its costs compared to conventional minimally invasive esophagectomy (MIE) have emerged. This study examined outcomes and costs of RAMIE versus total MIE in 128 patients who underwent Ivor Lewis esophagectomy for EC/GEJ at our department between 2017 and 2021. Surgical costs were higher for RAMIE (EUR 12,370 vs. EUR 10,059, p < 0.001). Yet, median daily (EUR 2023 vs. EUR 1818, p = 0.246) and total costs (EUR 30,510 vs. EUR 29,180, p = 0.460) were comparable. RAMIE showed a lower incidence of postoperative pneumonia (8% vs. 25%, p = 0.029) and a trend towards shorter hospital stays (15 vs. 17 days, p = 0.205), which may have equalized total costs. Factors independently associated with higher costs included readmission to the intensive care unit (hazard ratio [HR] = 7.0), length of stay (HR = 13.5), anastomotic leak (HR = 17.0), and postoperative pneumonia (HR = 5.4). In conclusion, RAMIE does not impose an additional financial burden. This suggests that RAMIE may be considered as a valid alternative approach for esophagectomy. Attention to typical cost factors can enhance postoperative care across surgical methods.

The influence of patient characteristics on the alarm rate in intensive care units: a retrospective cohort study.

Intensive care units (ICU) are often overflooded with alarms from monitoring devices which constitutes a hazard to both staff and patients. To date, the suggested solutions to excessive monitoring alarms have remained on a research level. We aimed to identify patient characteristics that affect the ICU alarm rate with the goal of proposing a straightforward solution that can easily be implemented in ICUs. Alarm logs from eight adult ICUs of a tertiary care university-hospital in Berlin, Germany were retrospectively collected between September 2019 and March 2021. Adult patients admitted to the ICU with at least 24 h of continuous alarm logs were included in the study. The sum of alarms per patient per day was calculated. The median was 119. A total of 26,890 observations from 3205 patients were included. 23 variables were extracted from patients' electronic health records (EHR) and a multivariable logistic regression was performed to evaluate the association of patient characteristics and alarm rates. Invasive blood pressure monitoring (adjusted odds ratio (aOR) 4.68, 95%CI 4.15-5.29, p < 0.001), invasive mechanical ventilation (aOR 1.24, 95%CI 1.16-1.32, p < 0.001), heart failure (aOR 1.26, 95%CI 1.19-1.35, p < 0.001), chronic renal failure (aOR 1.18, 95%CI 1.10-1.27, p < 0.001), hypertension (aOR 1.19, 95%CI 1.13-1.26, p < 0.001), high RASS (aOR 1.22, 95%CI 1.18-1.25, p < 0.001) and scheduled surgical admission (aOR 1.22, 95%CI 1.13-1.32, p < 0.001) were significantly associated with a high alarm rate. Our study suggests that patient-specific alarm management should be integrated in the clinical routine of ICUs. To reduce the overall alarm load, particular attention regarding alarm management should be paid to patients with invasive blood pressure monitoring, invasive mechanical ventilation, heart failure, chronic renal failure, hypertension, high RASS or scheduled surgical admission since they are more likely to have a high contribution to noise pollution, alarm fatigue and hence compromised patient safety in ICUs.

The influence of the COVID-19 pandemic on surgical therapy and care: a cross-sectional study.

BACKGROUND: Due to the COVID-19 pandemic, an extensive reorganisation of healthcare resources was necessary-with a particular impact on surgical care across all disciplines. However, the direct and indirect consequences of this redistribution of resources on surgical therapy and care are largely unknown. METHODS: We analysed our prospectively collected standardised digital quality management document for all surgical cases in 2020 and compared them to the years 2018 and 2019. Periods with high COVID-19 burdens were compared with the reference periods in 2018 and 2019. RESULTS: From 2018 to 2020, 10,723 patients underwent surgical treatment at our centres. We observed a decrease in treated patients and a change in the overall patient health status. Patient age and length of hospital stay increased during the COVID-19 pandemic (p = 0.004 and p = 0.002). Furthermore, the distribution of indications for surgical treatment changed in favour of oncological cases and less elective cases such as hernia repairs (p < 0.001). Postoperative thromboembolic and pulmonary complications increased slightly during the COVID-19 pandemic. There were slight differences for postoperative overall complications according to Clavien-Dindo, with a significant increase of postoperative mortality (p = 0.01). CONCLUSION: During the COVID-19 pandemic we did not see an increase in the occurrence, or the severity of postoperative complications. Despite a slightly higher rate of mortality and specific complications being more prevalent, the biggest change was in indication for surgery, resulting in a higher proportion of older and sicker patients with corresponding comorbidities. Further research is warranted to analyse how this changed demographic will influence long-term patient care.

Robotic versus open pancreatic surgery: a propensity score-matched cost-effectiveness analysis.

BACKGROUND: Robotic pancreatic surgery (RPS) is associated with high intraoperative costs compared to open pancreatic surgery (OPS). However, it remains unclear whether several advantages of RPS such as reduced surgical trauma and a shorter postoperative recovery time could lead to a reduction in total costs outweighing the intraoperative costs. The study aimed to compare patients undergoing OPS and RPS with regards to cost-effectiveness in a propensity score-matched (PSM) analysis. METHODS: Patients undergoing OPS and RPS between 2017 and 2019 were included in this monocentric, retrospective analysis. The controlling department provided financial data (costs and revenues, net loss/profit). A propensity score-matched analysis was performed or OPS and RPS (matching criteria: age, American society of anesthesiologists (ASA) score, gender, body mass index (BMI), and type of pancreatic resection) with a caliper 0.2. RESULTS: In total, 272 eligible OPS cases were identified, of which 252 met all inclusion criteria and were thus included in the further analysis. The RPS group contained 92 patients. The matched cohorts contained 41 patients in each group. Length of hospital stay (LOS) was significantly shorter in the RPS group (12 vs. 19 days, p = 0.003). Major postoperative morbidity (Dindo/Clavien ≥ 3a) and 90-day mortality did not differ significantly between OPS and RPS (p > 0.05). Intraoperative costs were significantly higher in the RPS group than in the OPS group (7334€ vs. 5115€, p < 0.001). This was, however, balanced by other financial categories. The overall cost-effectiveness tended to be better when comparing RPS to OPS (net profit-RPS: 57€ vs. OPS: - 2894€, p = 0.328). Binary logistic regression analysis revealed major postoperative complications, longer hospital stay, and ASA scores < 3 were linked to the risk of net loss (i.e., costs > revenue). CONCLUSIONS: Surgical outcomes of RPS were similar to those of OPS. Higher intraoperative costs of RPS are outweighed by advantages in other categories of cost-effectiveness such as decreased lengths of hospital stay.

Reducing the Pill Burden: Immunosuppressant Adherence and Safety after Conversion from a Twice-Daily (IR-Tac) to a Novel Once-Daily (LCP-Tac) Tacrolimus Formulation in 161 Liver Transplant Patients.

Non-adherence to immunosuppressant therapy reduces long-term graft and patient survival after solid organ transplantation. The objective of this 24-month prospective study was to determine adherence, efficacy and safety after conversion of stable liver transplant (LT) recipients from a standard twice-daily immediate release Tacrolimus (IR-Tac) to a novel once-daily life cycle pharma Tacrolimus (LCP-Tac) formulation. We converted a total of 161 LT patients at baseline, collecting Tacrolimus trough levels, laboratories, physical examination data and the BAASIS© questionnaire for self-reported adherence to immunosuppression at regular intervals. With 134 participants completing the study period (17% dropouts), the overall adherence to the BAASIS© increased by 57% until month 24 compared to baseline (51% vs. 80%). Patients who required only a morning dose of their concomitant medications reported the largest improvement in adherence after conversion. The intra-patient variability (IPV) of consecutive Tacrolimus trough levels after conversion did not change significantly compared to pre-conversion levels. Despite reducing the daily dose by 30% at baseline as recommended by the manufacturer, Tac-trough levels remained stable, reflected by an increase in the concentration-dose (C/D) ratio. No episodes of graft rejection or loss occurred. Our data suggest that the use of LCP-Tac in liver transplant patients is safe and can increase adherence to immunosuppression compared to conventional IR-Tac.

Perioperative Risk Assessment in Pancreatic Surgery Using Machine Learning.

Pancreatic surgery is associated with a high risk for postoperative complications and death of patients. Complications occur in a variable interval after the procedure. Often, a patient has already left the ICU and is not properly monitored anymore when the complication occurs. Risk stratification models can assist in identifying patients at risk in order to keep these patients in ICU for longer. This, in turn, helps to identify complications earlier and increase survival rates. We trained multiple machine learning models on pre-, intra- and short term postoperative data from patients who underwent pancreatic resection at the Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin. The presented models achieve an area under the precision-recall curve (AUPRC) of up to 0.51 for predicting patient death and 0.53 for predicting a specific major complication. Overall, we found that a classical logistic regression model performs best for the investigated classification tasks. As more patient data becomes available throughout the perioperative stay, the performance of the risk stratification model improves and should therefore repeatedly be computed.

Self-Referenced 200 MHz Octave-Spanning Ti:Sapphire Laser with 50 Attosecond Carrier-Envelope Phase Jitter.

Carrier-envelope phase stabilization of a 200MHz octave-spanning Ti:sapphire laser without external broadening is demonstrated. The individual comb lines spaced by 200MHz can conveniently be resolved using commercial wavemeters. The accumulated in-loop carrier-envelope phase error (integrated from 2.5 mHz to 10 MHz) using a broadband analog mixer as phase detector is 0.117 rad, equivalent to 50 attosecond carrier-envelope phase jitter at 800 nm.