University Medical Center Mannheim Research Articles

Analysis of cell free DNA to predict outcome to bevacizumab therapy in colorectal cancer patients

To predict outcome to combination bevacizumab (BVZ) therapy, we employed cell-free DNA (cfDNA) to determine chromosomal instability (CIN), nucleosome footprints (NF) and methylation profiles in metastatic colorectal cancer (mCRC) patients. Low-coverage whole-genome sequencing (LC-WGS) was performed on matched tumor and plasma samples, collected from 74 mCRC patients from the AC-ANGIOPREDICT Phase II trial (NCT01822444), and analysed for CIN and NFs. A validation cohort of plasma samples from the University Medical Center Mannheim (UMM) was similarly profiled. 61 AC-ANGIOPREDICT plasma samples collected before and following BVZ treatment were selected for targeted methylation sequencing. Using cfDNA CIN profiles, AC-ANGIOPREDICT samples were subtyped with 92.3% accuracy into low and high CIN clusters, with good concordance observed between matched plasma and tumor. Improved survival was observed in CIN-high patients. Plasma-based CIN clustering was validated in the UMM cohort. Methylation profiling identified differences in CIN-low vs. CIN high (AUC = 0.87). Moreover, significant methylation score decreases following BVZ was associated with improved outcome (p = 0.013). Analysis of CIN, NFs and methylation profiles from cfDNA in plasma samples facilitates stratification into CIN clusters which inform patient response to treatment.

Erratum: Immunofluorescence Imaging of Neutrophil Extracellular Traps in Human and Mouse Tissues.

An erratum was issued for:Immunofluorescence Imaging of Neutrophil Extracellular Traps in Human and Mouse Tissues. The Authors section was updated from: Lavinia Schöenfeld1 Birgit Appl1 Laia Pagerols-Raluy1 Annika Heuer3 Konrad Reinshagen1 Michael Boettcher1,2 1Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg 2Department of Pediatric Surgery, University Medical Center Mannheim, University of Heidelberg 3Division of Spine Surgery, Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf (UKE) to: Lavinia Schoenfeld1 Birgit Appl1 Laia Pagerols-Raluy1 Annika Heuer3 Konrad Reinshagen1 Michael Boettcher1,2 1Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg 2Department of Pediatric Surgery, University Medical Center Mannheim, University of Heidelberg 3Division of Spine Surgery, Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf (UKE).

Dissecting contributions of individual systemic inflammatory response syndrome criteria from a prospective algorithm to the prediction and diagnosis of sepsis in a polytrauma cohort.

Sepsis is the leading cause of death in intensive care units (ICUs), and its timely detection and treatment improve clinical outcome and survival. Systemic inflammatory response syndrome (SIRS) refers to the concurrent fulfillment of at least two out of the following four clinical criteria: tachycardia, tachypnea, abnormal body temperature, and abnormal leukocyte count. While SIRS was controversially abandoned from the current sepsis definition, a dynamic SIRS representation still has potential for sepsis prediction and diagnosis. We retrospectively elucidate the individual contributions of the SIRS criteria in a polytrauma cohort from the post-surgical ICU of University Medical Center Mannheim (Germany). We used a dynamic and prospective SIRS algorithm tailored to the ICU setting by accounting for catecholamine therapy and mechanical ventilation. Two clinically relevant tasks are considered: (i) sepsis prediction using the first 24 h after admission to our ICU, and (ii) sepsis diagnosis using the last 24 h before sepsis onset and a time point of comparable ICU treatment duration for controls, respectively. We determine the importance of individual SIRS criteria by systematically varying criteria weights when summarizing the SIRS algorithm output with SIRS descriptors and assessing the classification performance of the resulting logistic regression models using a specifically developed ranking score. Our models perform better for the diagnosis than the prediction task (maximum AUROC 0.816 vs. 0.693). Risk models containing only the SIRS level average mostly show reasonable performance across criteria weights, with prediction and diagnosis AUROCs ranging from 0.455 (weight on leukocyte criterion only) to 0.693 and 0.619 to 0.800, respectively. For sepsis prediction, temperature and tachypnea are the most important SIRS criteria, whereas the leukocytes criterion is least important and potentially even counterproductive. For sepsis diagnosis, all SIRS criteria are relevant, with the temperature criterion being most influential. SIRS is relevant for sepsis prediction and diagnosis in polytrauma, and no criterion should a priori be omitted. Hence, the original expert-defined SIRS criteria are valid, capturing important sepsis risk determinants. Our prospective SIRS algorithm provides dynamic determination of SIRS criteria and descriptors, allowing their integration in sepsis risk models also in other settings.

Incidence of atrial and ventricular arrhythmias in obese patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan.

To compare clinical outcomes among patients with heart failure and reduced ejection fraction (HFrEF) according to body mass index (BMI) after initiating treatment with an angiotensin-receptor neprilysin inhibitor (ARNI). We gathered data from 2016 to 2020 at the University Medical Center Mannheim; 208 consecutive patients were divided into two groups according to BMI (< 30 kg/m2 ; n = 116, ≥ 30 kg/m2 ; n = 92). Clinical outcomes, including mortality rate, all-cause hospitalizations and congestion, were systematically analysed. At the 12-month follow-up, the mortality rate was similar in both groups (7.9% in BMI < 30 kg/m2 vs. 5.6% in BMI ≥ 30 kg/m2 ; P = .76). All-cause hospitalization before ARNI treatment was comparable in both groups (63.8% in BMI < 30 kg/m2 vs. 57.6% in BMI ≥ 30 kg/m2 ; P = .69). After ARNI treatment, the hospitalization rate was also comparable in both groups at the 12-month follow-up (52.2% in BMI < 30 kg/m2 vs. 53.7% in BMI ≥ 30 kg/m2 ; P = .73). Obese patients experienced more congestion compared with non-obese patients at follow-up, without statistical significance (6.8% in BMI < 30 kg/m2 vs. 15.5% in BMI ≥ 30 kg/m2 ; P = .11). Median left ventricular ejection fraction (LVEF) improved in both groups, but significantly more in non-obese compared with obese patients at the 12-month follow-up (from 26% [3%-45%] [min.-max.] vs. 29% [10%-45%] [min.-max.] [P = .56] to 35.5% [15%-59%] [min.-max.] vs. 30% [13%-50%] [min.-max.] [P = .03], respectively). The incidence of atrial fibrillation (AF), non-sustained (ns) and sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) was less in non-obese than in obese patients after initiation of sacubitril/valsartan at the 12-month follow-up (AF: 43.5% vs. 53.7%; P = .20; nsVT: 9.8% vs. 28.4%; P = .01; VT: 14.1% vs. 17.9%; P = .52; VF: 7.6% vs. 13.4%; P = .23). The incidence of congestion in obese patients was higher compared with non-obese patients. LVEF improved significantly more in non-obese compared with obese HFrEF patients. Furthermore, AF and the ventricular tachyarrhythmia rate were revealed more in obesity compared with those without obesity at the 12-month follow-up.

Clinical ground truth in machine learning for early sepsis diagnosis

Clinical ground truth in machine learning for early sepsis diagnosis

Treatment satisfaction of patients with psoriasis with topical therapy in a real-world setting: unmet need for higher effectiveness

BackgroundTopical medication is the mainstay for treatment of mild psoriasis. However, dissatisfaction with topicals is common and rates of non-adherence are high. Assessing patients’ perspectives can help to identify unmet needs.ObjectiveOur aim was to investigate satisfaction of patients with psoriasis with topical therapy and to determine influencing factors.MethodsPatients were recruited from the Department of Dermatology, University Medical Center Mannheim, Germany. Satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication version 1.4 with the domains effectiveness, side effects, convenience, and global satisfaction (scale 0–100 each). The impact of sociodemographic and disease characteristics was determined by multivariate regression.ResultsAveraged across the cohort (n = 122, mean age 52.5 years, 58.2% male), the side effects domain had the highest mean satisfaction score (89.7), followed by convenience (72.5), global satisfaction (60.8), and effectiveness (55.0). Comparing specific medications, combinations of corticosteroids and vitamin D analogues were rated best in effectiveness. Treatment satisfaction was influenced by age, partnership, ability to apply topicals independently, disease-related quality-of-life impairment, sole or adjunctive use of topicals and pruritus.ConclusionsParticipants were particularly satisfied with safety but rather dissatisfied with effectiveness of topicals. Topical therapy should be adapted to individual needs with special attention to effectiveness.

Perioperative Antibiotic Prophylaxis in Radical Prostatectomy: “Single-Shot” versus Multiday Regimen

Introduction: Perioperative antibiotic prophylaxis (AP) is common in radical prostatectomy (RP). Yet there is no standard recommendation in international guidelines due to poor evidence. It is of great importance that these perioperative AP are sufficiently checked and systemically validated. The objective of this study was to determine whether a “single-shot” (single-use) perioperative AP yields equivalent results compared to a multiday prophylaxis in RP regarding postoperative wound infections and urinary tract infections. Methods: 376 patients treated by RP at the University Medical Centre Mannheim, from 2014 to 2016, were included in this retrospective study. RP was performed either in a robotic-assisted or open manner. One group received an intravenous dose of perioperative AP with either ciprofloxacin or levofloxacin, continued by an oral dose of AP with ciprofloxacin or levofloxacin until catheter removal, while the other group received a single-shot intravenous perioperative AP with either ciprofloxacin or cefuroxime. Results: There was no significant difference regarding the occurrence of postoperative infections between both AP regimes (p = 0.5). Age, body mass index, and ASA classification did not differ significantly between both groups (p > 0.25). Except for surgery time (p < 0.05), perioperative parameters, such as the preoperative presence of germ-free urine culture, length of hospital stay, catheter time, drain lay time, Gleason score, and TNM stadium, did not differ significantly. Conclusion: The present study shows that perioperative single-shot AP does not entail any disadvantage compared to the multiday AP in terms of postoperative infections after RP.

Impact of age on the prognosis of patients with ventricular tachyarrhythmias and aborted cardiac arrest.

This study evaluated the prognostic impact of age on patients presenting with ventricular tachyarrhythmias (VTA) and aborted cardiac arrest. The present registry-based, monocentric cohort study included all consecutive patients presenting at the University Medical Center Mannheim (UMM) between 2002 and 2016 with ventricular tachycardia (VT), ventricular fibrillation (VF) and aborted cardiac arrest. Middle-aged (40-60years old) were compared to older patients (> 60years old). Furthermore, age was analyzed as a continuous variable. The primary endpoint was all-cause mortality at 2.5years. The secondary endpoints were cardiac death at 24 h, all-cause mortality at index hospitalization, all-cause mortality after index hospitalization and the composite endpoint at 2.5years of cardiac death at 24 h, recurrent VTA, and appropriate implantable cardioverter defibrillator (ICD) treatment. Atotal of 2259 consecutive patients were included (28% middle-aged, 72% older). Older patients were more often associated with all-cause mortality at 2.5years (27% vs. 50%; hazard ratio, HR = 2.137; 95% confidence interval, CI 1.809-2.523, p = 0.001) and the secondary endpoints. Even patient age as acontinuous variable was independently associated with mortality at 2.5years in all types of VTA. Adverse prognosis in older patients was demonstrated by multivariate Cox regression analyses and propensity score matching. Chronic kidney disease (CKD), systolic left ventricular dysfunction (LVEF) < 35%, cardiopulmonary resuscitation (CPR) and cardiogenic shock worsened the prognosis for both age groups, whereas acute myocardial infarction (STEMI/NSTEMI) and the presence of an ICD improved prognosis. The results of this study suggest that increasing age is associated with increased mortality in VTA patients. Compared to the middle-aged, older patients were associated with higher all-cause mortality at 2.5years and the secondary endpoints.

Deep Learning Analysis of the Adipose Tissue and the Prediction of Prognosis in Colorectal Cancer.

Research has shown that the lipid microenvironment surrounding colorectal cancer (CRC) is closely associated with the occurrence, development, and metastasis of CRC. According to pathological images from the National Center for Tumor diseases (NCT), the University Medical Center Mannheim (UMM) database and the ImageNet data set, a model called VGG19 was pre-trained. A deep convolutional neural network (CNN), VGG19CRC, was trained by the migration learning method. According to the VGG19CRC model, adipose tissue scores were calculated for TCGA-CRC hematoxylin and eosin (H&E) images and images from patients at Zhujiang Hospital of Southern Medical University and First People's Hospital of Chenzhou. Kaplan-Meier (KM) analysis was used to compare the overall survival (OS) of patients. The XCell and MCP-Counter algorithms were used to evaluate the immune cell scores of the patients. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were used to analyze upregulated and downregulated pathways. In TCGA-CRC, patients with high-adipocytes (high-ADI) CRC had significantly shorter OS times than those with low-ADI CRC. In a validation queue from Zhujiang Hospital of Southern Medical University (Local-CRC1), patients with high-ADI had worse OS than CRC patients with low-ADI. In another validation queue from First People's Hospital of Chenzhou (Local-CRC2), patients with low-ADI CRC had significantly longer OS than patients with high-ADI CRC. We developed a deep convolution network to segment various tissues from pathological H&E images of CRC and automatically quantify ADI. This allowed us to further analyze and predict the survival of CRC patients according to information from their segmented pathological tissue images, such as tissue components and the tumor microenvironment.

Hemodynamic Effects of Sacubitril/Valsartan in Patients with Reduced Left Ventricular Ejection Fraction Over 24 Months: A Retrospective Study.

BackgroundThe effects of sacubitril/valsartan in patients with chronic heart failure with reduced ejection fraction (HFrEF) were recently reported. However, the hemodynamic impact of this well-established treatment in patients with HFrEF has been poorly systematically researched.AimWe aimed to investigate the hemodynamic effects of sacubitril/valsartan among patients with HFrEF.MethodsBetween 2016 and 2020, we retrospectively collected data for patients with HFrEF treated at the University Medical Center Mannheim, Germany. Data for 240 patients with HFrEF were available. We systematically analyzed echocardiographic parameters, all-cause hospitalization, and congestion rate.ResultsThe left ventricular ejection fraction (LVEF) improved from a median (minimum; maximum) of 28% (3; 65) before initiation of sacubitril/valsartan to a median of 34% (13; 64) at 24-month follow-up (p < 0.001). Systolic pulmonary atrial pressure (PAPsys) decreased from a median of 30 mmHg (13; 115) to 25 mmHg (20; 80) at 24-month follow-up (p = 0.005). The median (minimum; maximum) tricuspid annular plane systolic excursion improved from 17 mm (3; 31) at baseline to 20 mm (9; 30) at 12-month follow-up (p = 0.007). The incidence of severe and moderate mitral, tricuspid, and aortic valvular insufficiency improved after treatment. Hospitalization and congestion rates reduced at 24-month follow-up. The mortality rate in echocardiographic and functional nonresponders was higher than in responders (12.1 vs. 5.2%; p = 0.1 and 11.3 vs. 3.1%; p = 0.01, respectively).ConclusionFollow-up 24 months after starting treatment with sacubitril/valsartan revealed sustained improvements in echocardiographic parameters, including LVEF, PAPsys, and cardiac valvular insufficiency. Rates of all-cause hospitalization and congestion had decreased significantly at follow-up. The mortality rate was higher in echocardiographic and functional nonresponders.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-022-00525-w.

Deep learning analysis of the adipose tissue and the prediction of prognosis in colorectal cancer.

139 Background: Colorectal cancer (CRC) is the third most common type of cancer and has a poor prognosis and high recurrence rate. Research has shown that the lipid microenvironment surrounding tumors is closely associated with the occurrence, development, and metastasis of CRC. Recently, advances in artificial intelligence have greatly improved the accuracy of models for CRC prognosis and survival analysis. Methods: According to pathological images from the National Center for Tumor diseases(NCT), the University Medical Center Mannheim(UMM) database and the ImageNet data set, a model called VGG19 was pre-trained. A deep convolutional neural network(CNN), VGG19CRC, was trained by the migration learning method. According to the VGG19CRC model, adipose tissue scores were calculated for TCGA-CRC hematoxylin and eosin(H&amp;E) images and images from patients at Zhujiang Hospital of Southern Medical University and First People’s Hospital of Chenzhou. Kaplan-Meier(KM) analysis was used to compare the overall survival(OS) of patients. The XCell and MCP-Counter algorithms were used to evaluate the immune cell scores of the patients. Gene set enrichment analysis(GSEA) and single-sample GSEA(ssGSEA) were used to analyze upregulated and downregulated pathways. Results: In TCGA-CRC, patients with high-adipocytes(high-ADI) CRC had significantly shorter OS times than those with low-ADI CRC. In a validation queue from Zhujiang Hospital of Southern Medical University(Local-CRC1), patients with high-ADI had worse OS than CRC patients with low-ADI. In another validation queue from First People's Hospital of Chenzhou(Local-CRC2), patients with low-ADI CRC had significantly longer OS than patients with high-ADI CRC. In subgroup analysis, ADI could be used as a prognostic marker for patients with colon adenocarcinoma(COAD) and rectum adenocarcinoma(READ), as well as male and female CRC patients. Among these subgroups, patients with lower ADI also had significantly improved OS. Compared with the low-ADI group, high-ADI patients had significantly decreased CD8+ T cells, T cells,and monocytes in the tumor immune microenvironment(TIME), while M2 macrophages were significantly increased. According to the GSEA and ssGSEA analyses, pathways mediating anti-tumor immunity were significantly downregulated in the high-ADI group, while some oncogenic signaling pathways were significantly upregulated. Conclusions: We developed a deep convolution network to segment various tissues from pathological H&amp;E images of CRC and automatically quantify ADI. This allowed us to further analyze and predict the survival of CRC patients according to information from their segmented pathological tissue images, such as tissue components and the tumor microenvironment. Furthermore, we found that ADI may also predict OS in CRC patients and among the subgroups.

Differential Network Testing Reveals Diverging Dynamics of Organ System Interactions for Survivors and Non-survivors in Intensive Care Medicine.

Statistical network analyses have become popular in many scientific disciplines, where an important task is to test for differences between two networks. We describe an overall framework for differential network testing procedures that vary regarding (1) the network estimation method, typically based on specific concepts of association, and (2) the network characteristic employed to measure the difference. Using permutation-based tests, our approach is general and applicable to various overall, node-specific or edge-specific network difference characteristics. The methods are implemented in our freely available R software package DNT, along with an R Shiny application. In a study in intensive care medicine, we compare networks based on parameters representing main organ systems to evaluate the prognosis of critically ill patients in the intensive care unit (ICU), using data from the surgical ICU of the University Medical Centre Mannheim, Germany. We specifically consider both cross-sectional comparisons between a non-survivor and a survivor group and longitudinal comparisons at two clinically relevant time points during the ICU stay: first, at admission, and second, at an event stage prior to death in non-survivors or a matching time point in survivors. The non-survivor and the survivor networks do not significantly differ at the admission stage. However, the organ system interactions of the survivors then stabilize at the event stage, revealing significantly more network edges, whereas those of the non-survivors do not. In particular, the liver appears to play a central role for the observed increased connectivity in the survivor network at the event stage.

Die prähospitale Therapie eines Spannungspneumothorax bei Kindern – welche Entscheidungen treffen wir?

The preclinical treatment of atraumatic or spontaneous tension pneumothorax remains aparticular challenge in pediatric patients. Currently recommended interventions for decompression are either finger thoracostomy or needle decompression. Due to the tiny intercostal spaces, finger thoracostomy may not be feasible in small children and surgical preparation may be necessary. In needle decompression, the risk of injuring underlying vital structures is increased because of the smaller anatomic structures. As most emergency physicians do not regularly work in pediatric trauma care, decompression of tension pneumothorax is associated with significant uncertainty; however, in this rare emergency situation, consistent and goal-oriented action is mandatory and lifesaving. An assessment of pre-existing experience and commonly used techniques therefore seems necessary to deduce the need for future education and training. In this study an online survey was created to evaluate the experience and the favored prehospital treatment of tension pneumothorax in children among German emergency physicians. An online survey was conducted with 43questions on previous experience with tension pneumothorax in children, favored decompression technique and anatomical structures in different age groups. Surveyed were the emergency physicians of the ground-based emergency medical service of the University Medical Center Mannheim, the German Air Rescue Service (DRF) and the pediatric emergency medical service of the City of Munich. More than half of all respondents stated that there was uncertainty about the procedure of choice. Needle decompression was favored in smaller children and mini-thoracostomy in older children. In comparison with the literature, the thickness of the chest wall was mostly estimated correctly by the emergency medical physicians. The depth of the vital structures was underestimated at most of the possible insertion sites in all age groups. At the lateral insertion sites on the left hemithorax, however, the distance to the left ventricle was overestimated. The caliber of the needle selected for decompression tended to be too large, especially in younger children. Even though having interviewed an experienced group of prehospital emergency physicians, the experience in decompression of tension pneumothorax in children is relatively scant. Knowledge of chest wall thickness and depth to vital structures is sufficient, the choice of needle calibers tends to be too large but still reasonable. For many providers alarge amount of uncertainty about the right choice of technique and equipment arises from the challenge of decompressing atension pneumothorax in children and therefore further theoretical education and regular training are required for safe performance of the procedure.

A novel transfer learning approach for the classification of histological images of colorectal cancer

Colorectal cancer (CRC) is the second most diagnosed cancer in the United States. It is identified by histopathological evaluations of microscopic images of the cancerous region, relying on a subjective interpretation. The Colorectal Histology dataset used in this study contains 5000 images, made available by the University Medical Center Mannheim. This approach proposes the automatic identification of eight types of tissues found in CRC histopathological evaluation. We apply Transfer Learning from architectures of Convolutional Neural Networks (CNNs). We modify the structures of CNNs to extract features from the images and input them to well-known machine learning methods: Naive Bayes, Multilayer Perceptron, k-Nearest Neighbors, Random Forest, and Support Vector Machine (SVM). We evaluated 108 extractor–classifier combinations. The one that achieved the best results is DenseNet169 with SVM (RBF), reaching an Accuracy of 92.083% and F1-Score of 92.117%. Therefore, our approach is capable of distinguishing tissues found in CRC histopathological evaluation.

Deep Convolutional Neural Network-Based Lymph Node Metastasis Prediction for Colon Cancer Using Histopathological Images.

BackgroundHuman evaluation of pathological slides cannot accurately predict lymph node metastasis (LNM), although accurate prediction is essential to determine treatment and follow-up strategies for colon cancer. We aimed to develop accurate histopathological features for LNM in colon cancer.MethodsWe developed a deep convolutional neural network model to distinguish the cancer tissue component of colon cancer using data from the tissue bank of the National Center for Tumor Diseases and the pathology archive at the University Medical Center Mannheim, Germany. This model was applied to whole-slide pathological images of colon cancer patients from The Cancer Genome Atlas (TCGA). The predictive value of the peri-tumoral stroma (PTS) score for LNM was assessed.ResultsA total of 164 patients with stages I, II, and III colon cancer from TCGA were analyzed. The mean PTS score was 0.380 (± SD = 0.285), and significantly higher PTS scores were observed in patients in the LNM-positive group than those in the LNM-negative group (P < 0.001). In the univariate analyses, the PTS scores for the LNM-positive group were significantly higher than those for the LNM-negative group (P < 0.001). Further, the PTS scores in lymphatic invasion and any one of perineural, lymphatic, or venous invasion were significantly increased in the LNM-positive group (P < 0.001 and P < 0.001).ConclusionWe established the PTS score, a simplified reproducible parameter, for predicting LNM in colon cancer using computer-based analysis that could be used to guide treatment decisions. These findings warrant further confirmation through large-scale prospective clinical trials.

Risk factor paradox: No prognostic impact of arterial hypertension and smoking in patients with ventricular tachyarrhythmias.

Data regarding the outcome of patients with ventricular tachyarrhythmias related to arterial hypertension (AHT) and smoking is limited. The study sought to assess the prognostic impact of AHT and smoking on survival in patients presenting with ventricular tachyarrhythmias. All consecutive patients surviving ventricular tachycardia (VT) and ventricular fibrillation (VF) upon admission to the University Medical Center Mannheim (UMM), Germany from 2002 to 2016 were included and stratified according to AHT and smoking by propensity score matching. The primary prognostic endpoint was all-cause mortality at 30 months. A total of 988 AHT-matched patients (494 each, with and without AHT) and a total of 872 smoking-matched patients (436 each, with and without smoking) were included. The rates of VT and VF were similar in both groups (VT: AHT 60% vs. no AHT 60%; smokers 61% vs. non-smokers 62%; VF: AHT 35% vs. no AHT 38%; smokers 39% vs. non-smokers 38%). Neither AHT nor smoking were associated with the primary endpoint of long-term all-cause mortality at 30 months (long-term mortality rates: AHT/no AHT, 26% vs. 28%; log-rank p = 0.525; smoking/non-smoking, 22% vs. 25%; log-rank p = 0.683). Paradoxically, neither AHT nor smoking were associated with differences of long-term all-cause mortality in patients presenting with ventricular tachyarrhythmias.

Deep Convolutional Neural Network-Based Lymph Node Metastasis Prediction for Colon Cancer Using Histopathological Images

Background: Human evaluation of pathological slides cannot accurately predict lymph node metastasis (LNM), which is urgently needed to determine treatment and follow-up strategies for colon cancer. We aimed to develop an accurate histopathological feature for LNM in colon cancer. Methods: We developed a deep convolutional neural network model to distinguish the cancer tissue component of colon cancer using data from the tissue bank of the National Center for Tumor Diseases and the pathology archive at the University Medical Center Mannheim in German. This model was applied to whole-slide pathological images of colon cancer patients from The Cancer Genome Atlas (TCGA). The predictive value of the peri-tumoral stroma (PTS) score for LNM was assessed. Findings: A total of 164 patients with stage I, II, and III colon cancer from TCGA were analyzed. The mean PTS score was 0.380 (±SD = 0.285), and significantly higher PTS scores were observed in patients in the LNM-positive group than those in the LNM-negative group (P < 0.001). In the univariate analyses, the PTS scores for the LNM-positive group were significantly higher than the scores for LNM-negative group (P < 0.001). Further, the PTS scores in lymphatic invasion and any one of perineural, lymphatic, or venous invasion were significantly increased in the LNM-positive group (P < 0.001 and P < 0.001). Interpretation: We established the PTS score, a simplified reproducible parameter, for predicting LNM in colon cancer using computer-based analysis that could be used to guide treatment decisions. These findings warrant further confirmation through large prospective clinical trials. Funding Statement: This research was supported by the Basic Science Research Program of National Research Foundation of Korea (NRF), which is funded by the Korean Ministry of Science, ICT and Future Planning (grant number: NRF-2019R1C1C1003524). Declaration of Interests: None of the authors have any conflicts of interest or financial ties to disclose. Ethics Approval Statement: This study was reviewed and approved by the Institutional Review Board of the Kyung Hee University Hospital at Gangdong (KHNMC IRB 2020-09-025). The need for informed consent was waived because all data used in this study were de-identified.

Nephrometry Scores: Can Preoperative Assessment of Sectional Imaging Really Mirror Intraoperative Renal Tumor Anatomy?

Introduction: To compare RENAL, preoperative aspects and dimensions used for an anatomical (PADUA) classification, and Mayo Adhesive Probability (MAP) scores with the respective intraoperative findings and surgeon’s assessment in predicting surgical outcome of patients undergoing partial nephrectomy. Methods: Data of 150 eligible patients treated at the University Medical Center Mannheim between 2016 and 2018 were analyzed. Tumors were radiologically and intraoperatively assessed by PADUA, RENAL, and MAP scores and surgeon’s assessment. Correlations and regression models were created to predict ischemia time (IT), major complications, and Trifecta (negative surgical margin, IT < 25 min, and absence of major complications). Results: There were strong correlations between radiological and intraoperative RENAL (r = 0.68; p < 0.001) and PADUA scores (r = 0.72; p < 0.001). Radiological RENAL, PADUA, and MAP scores and surgeon’s assessment were independent predictors of Trifecta (OR = 0.71, p = 0.015; OR = 0.77, p = 0.035; OR = 0.65, p = 0.012; OR = 0.40, p = 0.005, respectively). IT showed significant associations with radiological RENAL, PADUA, and surgeon’s assessment (OR = 1.41, p = 0.033; OR = 1.34, p = 0.044; OR = 3.04, p = 0.003, respectively). MAP score proved as only independent predictor of major complications (OR = 2.12, p = 0.002). Conclusion: Radiologically and intraoperatively assessed scores correlated well with each other. Intraoperative nephrometry did not outperform radiological scores in predicting outcome confirming the value of the existing systems. MAP score correlates well with surgeon’s assessment of perirenal fat and major complications underlining the importance of perirenal fat characteristics.

Cardiac serum marker alterations after intraoperative radiotherapy with low-energy x-rays in early breast cancer as an indicator of possible cardiac toxicity

PurposeTo assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x‑rays for early breast cancer.MethodsWe prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x‑rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated.ResultsThere were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N‑terminal fragment of B‑type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279).ConclusionTroponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.

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Meet the First Author.