Exploring the impact of durvalumab on biliary tract cancer: insights from real-world clinical data.

INTRODUCTION: This study assesses the effectiveness of durvalumab with platinum and gemcitabine for biliary tract cancers (BTC). It aims to confirm the TOPAZ-1 trial results in a real-world context and explore the link between BTC molecular profiles and patient outcomes. METHODS: A retrospective analysis was conducted on 102 BTC patients treated with durvalumab, platinum, and gemcitabine at five cancer centers in Austria and one in Germany from 2022 to 2024. Molecular profiling used targeted DNA and RNA assays. Clinical endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed using log-rank tests and Cox regression, with correlations to second-line molecular-targeted therapies. RESULTS: Among 102 patients, 60.8% had intrahepatic cholangiocarcinoma. The treatment achieved a disease control rate of 71.57% and an overall response rate of 35.11%. Median PFS was 6.51 months, and OS was 13.61 months. Patients under 65 had significantly better OS. Alterations in chromatin remodeling or homologous recombination repair genes were not predictive of survival benefit (HR: 0.45; p = 0.851 and HR: 1.63; p = 0.26, respectively). Patients with molecular-informed second-line therapy showed a trend toward survival benefit (HR: 0.23; p = 0.052). CONCLUSION: This study confirms the phase 3 trial results of durvalumab with platinum and gemcitabine, providing a substantial real-world dataset with detailed molecular characterization. No specific patient subgroup showed a markedly better response to durvalumab based on conventional NGS panels. Further research is needed to explore the link between immunotherapy responses and molecular subgroups.

Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies.

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.

Prognostic value of anti-SARS-CoV-2 antibodies: a systematic review.

OBJECTIVES: Globally, over 772 million cases of COVID-19 have been reported. New variants of interest with corresponding spikes in case numbers continue to be identified. Vulnerable patients, including older adults or patients with severe comorbidities, continue to be at risk. A large body of evidence has been accumulated regarding anti-SARS-CoV-2-antibodies and COVID-19 but the usefulness of antibody measurements remains unclear. This systematic review aims to assess the prognostic value of anti-SARS-CoV-2-antibodies and their usefulness for guiding booster vaccinations. METHODS: Studies in English and published between January 2020 and October 2023 were included. Studies that relied on multiparameter-models or comprised fewer than 100 participants were excluded. PubMed and via the WHO COVID-19 research database, Embase and Medline databases were searched. Study selection and quality assessment was conducted independently by two researchers. RESULTS: After screening 1,160 studies, 33 studies comprising >30 million individuals were included. Anti-SARS-CoV-2-antibodies were strongly associated with reduced risk of SARS-CoV-2-infection and better outcomes, including mortality. Risk of infection and COVID-19 severity decreased with increasing antibody levels. CONCLUSIONS: Anti-SARS-CoV-2-antibodies are useful for early identification of high-risk patients and timely adjustment of therapy. Protective thresholds may be applied to advise booster vaccinations but verification in separate cohorts is required.

Enhanced recovery and reduced conversion rates in robotic rectal cancer surgery: a single-center retrospective cohort study.

PURPOSE: This study aimed to compare the outcomes of robotic-assisted rectal resection with conventional laparoscopic and open approaches, focusing on complication rates, conversion rates, length of hospital stay, and oncologic outcomes. METHODS: A retrospective single-center cohort study included 106 patients with non-metastatic rectal cancer (UICC stages I-III) who underwent rectal resection from January 2013 to December 2023. Patients were assigned to open surgery (n = 23), conventional laparoscopic surgery (n = 55), or robotic-assisted surgery (n = 28). RESULTS: Robotic surgery demonstrated significantly lower conversion rates compared to minimal-invasive surgeries (p = 0.047) and shorter hospital stays (11.5 ± 8 days) compared to open (17.91 ± 12 days) and laparoscopic (17.2 ± 14 days) surgeries (p = 0.001). The quality of the specimen was significantly better (Score 1) in robotic (85.71%) and open (89.09%) cases compared to laparoscopic approaches (47.83%) (p < 0.001). Laparoscopic surgery was identified as a risk factor for worse specimen quality (p < 0.001). Older patients (> 63 years) had a higher risk for conversion in univariate analysis (p = 0.049). Morbidity was comparable between the groups (p = 0.131), and the anastomotic leakage rate did not differ significantly (laparoscopic: 18.18%, open: 13.04%, robotic: 17.86%). Kaplan-Meier survival curves showed no significant differences in overall survival probabilities among the groups. CONCLUSION: Robotic-assisted rectal resection provides significant advantages in terms of lower conversion rates, better specimen quality, and shorter hospital stays while maintaining comparable complication rates and oncologic outcomes to conventional laparoscopic and open approaches. These findings support robotic surgery as a standard treatment option for rectal cancer.

Regulation of the Lewis Blood Group Antigen Expression: A Literature Review Supplemented with Computational Analysis.

Background: The Lewis (Le) blood group system, unlike most other blood groups, is not defined by antigens produced internally to the erythrocytes and their precursors but rather by glycan antigens adsorbed on to the erythrocyte membrane from the plasma. These oligosaccharides are synthesized by the two fucosyltransferases FUT2 and FUT3 mainly in epithelial cells of the digestive tract and transferred to the plasma. At their place of synthesis, some Lewis blood group carbohydrate antigen variants also seem to be involved in various gastrointestinal malignancies. However, relatively little is known about the transcriptional regulation of FUT2 and FUT3. Summary: To address this question, we screened existing literature and additionally used in silico prediction tools to identify novel candidate regulators for FUT2 and FUT3 and combine these findings with already known data on their regulation. With this approach, we were able to describe a variety of transcription factors, RNA binding proteins and microRNAs, which increase FUT2 and FUT3 transcription and translation upon interaction. Key Messages: Understanding the regulation of FUT2 and FUT3 is crucial to fully understand the blood group system Lewis (ISBT 007 LE) phenotypes, to shed light on the role of the different Lewis antigens in various pathologies, and to identify potential new diagnostic targets for these diseases.

The Lewis (Le) blood group system, in contrast to the majority of blood groups, is not able to synthesize its antigens itself. It depends on the attachment of different oligosaccharides to the erythrocyte membrane, which are adsorbed from the plasma. These glycans are modified by the fucosyltransferases 2 and 3 enzymes (FUT2/3). Beside their role in defining the Lewis blood group, FUT2 and FUT3 are also known to be involved in the susceptibility and progression of various gastrointestinal pathologies, like inflammatory bowel diseases (IBD) or colorectal cancer (CRC). Even though different expression levels of FUT2 and FUT3 have been described in these malignancies, relatively little is known about the mechanisms behind their transcriptional regulation. In this review, we aim to shed light on transcription factors (TFs) responsible for FUT2 and FUT3 expression as well as on post-transcriptional regulators by the means of RNA binding proteins (RBPs) and microRNAs (miRNAs). To achieve our goal, we combined previous knowledge on FUT2 and FUT3 expression regulation with a computational analysis to predict additional novel regulators. On this way, we are able to broaden our knowledge on FUT2 and FUT3 expression regulation and consequently might be able to transfer our findings into diagnostics or therapeutics in the future.

Machine Learning Approach to Metabolomic Data Predicts Type 2 Diabetes Mellitus Incidence.

Metabolomics, with its wealth of data, offers a valuable avenue for enhancing predictions and decision-making in diabetes. This observational study aimed to leverage machine learning (ML) algorithms to predict the 4-year risk of developing type 2 diabetes mellitus (T2DM) using targeted quantitative metabolomics data. A cohort of 279 cardiovascular risk patients who underwent coronary angiography and who were initially free of T2DM according to American Diabetes Association (ADA) criteria was analyzed at baseline, including anthropometric data and targeted metabolomics, using liquid chromatography (LC)-mass spectroscopy (MS) and flow injection analysis (FIA)-MS, respectively. All patients were followed for four years. During this time, 11.5% of the patients developed T2DM. After data preprocessing, 362 variables were used for ML, employing the Caret package in R. The dataset was divided into training and test sets (75:25 ratio) and we used an oversampling approach to address the classifier imbalance of T2DM incidence. After an additional recursive feature elimination step, identifying a set of 77 variables that were the most valuable for model generation, a Support Vector Machine (SVM) model with a linear kernel demonstrated the most promising predictive capabilities, exhibiting an F1 score of 50%, a specificity of 93%, and balanced and unbalanced accuracies of 72% and 88%, respectively. The top-ranked features were bile acids, ceramides, amino acids, and hexoses, whereas anthropometric features such as age, sex, waist circumference, or body mass index had no contribution. In conclusion, ML analysis of metabolomics data is a promising tool for identifying individuals at risk of developing T2DM and opens avenues for personalized and early intervention strategies.

Evaluation of SARS-CoV-2 antibody levels on hospital admission as a correlate of protection against mortality.

BACKGROUND: Millions of people have now been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is still unclear which antibody levels provide protection against mortality. It is further unknown whether measuring antibody concentrations on hospital admission allows for identifying patients with a high risk of mortality. OBJECTIVES: To evaluate whether anti-SARS-CoV2-spike antibodies on hospital admission predict in-hospital mortality in patients with coronavirus disease 2019. METHODS: We conducted a prospective, multicentre cohort study on 1152 hospitalized patients who tested positive for SARS-CoV-2 with a polymerase chain reaction-based assay. Patients were classified by vaccination status. Anti-SARS-CoV-2 spike antibodies were determined on hospital admission. The investigated end point was in-hospital mortality for any cause. RESULTS: Spike antibodies on hospital admission were significantly lower in non-survivors in both non-vaccinated (73 U/ml, 95%CI 0-164 vs. 175 U/ml, 95%CI 124-235, p = 0.002) and vaccinated patients (1056 U/ml, 95%CI 701-1411 vs. 1668 U/ml, 95%CI 1580-1757, p < 0.001). Further, spike antibodies were significantly lower in fully vaccinated and boostered patients who died compared to those who survived (mean 883 U/ml, 95%CI 406-1359 vs. 1292 U/ml, 95%CI 1152-1431, p = 0.017 and 1485 U/ml, 95%CI 836-2133 vs. 2050 U/ml, 95%CI 1952-2149, p = 0.036). Patients infected with the currently prevailing Omicron variant were three times more likely to die if spike antibodies were <1200 U/ml (OR 3.458, 95%CI 1.562-7.656, p = 0.001). After adjusting for potential confounders, this value increased to an aOR of 4.079 (95%CI 1.809-9.198, p < 0.001). CONCLUSION: Anti-SARS-CoV2 spike-antibody levels on hospital admission are inversely associated with in-hospital mortality. Hospitalized patients with lower antibody levels have a higher risk of mortality.

Efficacy and safety of heterologous booster vaccination with Ad26.COV2.S after BNT162b2 mRNA COVID-19 vaccine in haemato-oncological patients with no antibody response.

Patients with haemato-oncological malignancies are one of the high-risk groups for a severe course in case of COVID-19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato-oncological patients without antibody response after double-dose BNT162b2 messenger (m-)RNA COVID-19 vaccine. A total of 32 haemato-oncological non-responders to double-dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double-dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato-oncological patients.

Interplay of inflammatory markers and anti-SARS-CoV-2 antibodies in COVID-19 mortality: A prospective cohort study.

OBJECTIVES: Despite high global vaccination coverage, it remains unclear how vaccination and anti-SARS-CoV-2 antibodies affect immune responses and inflammation levels in patients with COVID-19. It is further unclear whether the inflammatory response differs depending on antibody levels and whether the combination of antibody and inflammation levels in COVID-19 patients affects mortality rates. METHODS: We conducted a prospective multicenter cohort study that included 1031 hospitalized COVID-19 patients from five hospitals. Anti-SARS-CoV-2-spike antibodies, interleukin-6 (IL6), and CRP were measured on hospital admission. The prespecified endpoint was all-cause in-hospital mortality. RESULTS: We observed significantly lower levels of CRP (P<0.001) and IL6 (P<0.001) in patients with antibody levels above 1200 BAU/ml. After adjusting for potential confounders, patients with high levels of inflammatory markers (CRP>6 mg/dl or IL6>100 pg/ml) combined with low levels of anti-SARS-CoV-2-spike antibodies (<1200 BAU/ml) were approximately 8 times more likely to die than patients with low inflammatory responses and high antibody levels (CRP: aHR 7.973, 95% CI 2.744-23.169, P<0.001; IL6: aHR 8.973, 95% CI 3.549-22.688, P<0.001). CONCLUSION: Hospitalized COVID-19 patients presenting with high inflammatory markers and low antibody levels exhibited the highest mortality risks. Higher antibody levels are associated with lower levels of inflammation in hospitalized COVID-19 patients.

Anti-SARS-CoV-2 Antibodies versus Vaccination Status in CAD Patients with COVID-19: A Prospective, Propensity Score-Matched Cohort Study.

OBJECTIVES: Despite the currently prevailing, milder Omicron variant, coronary artery disease (CAD) patients constitute a major risk group in COVID-19, exhibiting 2.6 times the mortality risk of non-CAD patients and representing over 22% of non-survivors. No data are currently available on the efficacy of antibody levels in CAD patients, nor on the relevance of vaccination status versus antibody levels for predicting severe courses and COVID-19 mortality. Nor are there definitive indicators to assess if individual CAD patients are sufficiently protected from adverse outcomes or to determine the necessity of booster vaccinations. METHODS: A prospective, propensity-score-matched, multicenter cohort study comprising 249 CAD patients and 903 controls was conducted. Anti-SARS-CoV-2-spike antibodies were measured on hospital admission. Prespecified endpoints were in-hospital mortality, intensive care, and oxygen administration. RESULTS: After adjustment for potential confounders, CAD patients exhibited 4.6 and 6.1-times higher mortality risks if antibody levels were <1200 BAU/mL and <182 BAU/mL, respectively, compared to CAD patients above these thresholds (aOR 4.598, 95%CI 2.426-8.714, p < 0.001; 6.147, 95%CI 2.529-14.941, p < 0.001). Risk of intensive care was 3.7 and 4.0 (p = 0.003; p < 0.001), and risk of oxygen administration 2.6 and 2.4 times higher below these thresholds (p = 0.004; p = 0.010). Vaccination status was a weaker predictor of all three outcomes than both antibody thresholds. CONCLUSION: Antibody levels are a stronger predictor of outcome in CAD patients with COVID-19 than vaccination status, with 1200 BAU/mL being the more conservative threshold. Measuring anti-SARS-CoV-2 antibodies in CAD patients may ensure enhanced protection by providing timely booster vaccinations and identifying high-risk CAD patients at hospital admission.

Antibody levels versus vaccination status in the outcome of older adults with COVID-19.

BACKGROUNDDespite the currently prevailing, milder Omicron variant of COVID-19, older adults remain at elevated risk of hospital admission, critical illness, and death. Loss of efficacy of the immune system, including reduced strength, quality, and durability of antibody responses, may render generalized recommendations on booster vaccinations inadequate. There is a lack of data on the efficacy of antibody levels in older adults and on the utility of vaccination status versus antibody levels as a correlate of protection. It is further unclear whether antibody levels may be used to guide the timing of booster vaccinations in older adults.METHODSWe conducted a prospective multicenter cohort study comprising hospitalized patients with COVID-19. Anti-SARS-CoV-2 spike antibodies were measured on hospital admission. The primary endpoint was in-hospital mortality. Patients were stratified by age, antibody levels, and vaccination status. Multiple logistic regression and Cox regression analyses were conducted.RESULTSIn total, 785 older patients (≥60 years of age [a]) and 367 controls (<60a) were included. After adjusting for confounders, risk of mortality, ICU admission, endotracheal intubation, and oxygen administration was 4.9, 2.6, 6.5, and 2.3 times higher, respectively, if antibody levels were < 1,200 BAU/mL (aOR, 4.92 [95%CI, 2.59-9.34], P < 0.0001; aOR, 2.64 [95%CI, 1.52-4.62], P = 0.0006; aOR, 6.50 [95%CI, 1.48-28.47], P = 0.013; aOR, 2.34 [95%CI, 1.60-3.343], P < 0.0001). Older adults infected with the Omicron variant were approximately 6 times more likely to die if antibody levels were < 1,200 BAU/mL (aOR, 6.3 [95% CI, 2.43-16.40], P = 0.0002).CONCLUSIONAntibody levels were a stronger predictor of in-hospital mortality than vaccination status. Monitoring antibody levels may constitute a better and more direct approach for safeguarding older adults from adverse COVID-19 outcomes.

Anti-SARS-CoV-2 Antibody Testing: Role and Indications.

Since the onset of the COVID-19 pandemic in March 2020, over 769 million confirmed COVID-19 cases, including close to 7 million COVID-19-related deaths, have been reported. Although mortality rates have dropped notably compared to the first months of the pandemic, spikes in reported cases and mortality rates continue to be registered. Both recent spikes in case numbers and the continued emergence of new variants suggest that vulnerable patient groups, including older adults, immunocompromised patients, and patients with severe comorbidities, are going to continue to be affected by COVID-19. In order to curb the pandemic, relieve the pressure on primary care facilities, and reduce mortality rates, global vaccination programs have been established by the WHO, with over 13.5 billion vaccine doses having been administered globally. In most immunocompetent individuals, vaccination against COVID-19 results in the production of anti-SARS-CoV-2 spike antibodies. However, certain patient subsets have inadequate or reduced immune responses, and immune responses are known to decrease with age. General recommendations on the timing of booster vaccinations may therefore be insufficient to protect vulnerable patients. This review aims to evaluate the clinical role of anti-SARS-CoV-2 antibodies, focusing on measurement indications, prognostic value, and potential as a correlate of protection to guide future booster vaccination strategies.

Association between Lipid Levels, Anti-SARS-CoV-2 Spike Antibodies and COVID-19 Mortality: A Prospective Cohort Study.

BACKGROUND: Recent studies suggest that both lipid levels and anti-severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) antibody levels are associated with outcome in coronavirus disease 2019 (COVID-19). While both parameters have separately been implicated in the neutralization and clearance of pathogens during severe infections, it is currently unclear whether the interplay of these parameters affects outcome in COVID-19. We therefore aimed to determine whether there was a relationship between lipoproteins, anti-SARS-CoV-2 antibodies, and COVID-19 mortality. METHODS: In this prospective, multicenter cohort study, we recruited 1152 hospitalized patients with COVID-19 from five hospitals. Total cholesterol (TC), LDL-C, HDL-C, triglycerides, and anti-SARS-CoV-2 spike antibodies were measured on hospital admission. The investigated endpoint was in-hospital mortality. RESULTS: LDL-C, HDL-C, and TC were significantly lower in non-survivors than in survivors (mg/dL, 95%CI; 56.1, 50.4-61.8 vs. 72.6, 70.2-75.0, p < 0.001; 34.2, 31.7-36.8 vs. 38.1, 37.2-39.1, p = 0.025; 139.3, 130.9-147.7 vs. 157.4, 54.1-160.6, p = 0.002). Mortality risk increased progressively with lower levels of LDL-C, HDL-C, and TC (aOR 1.73, 1.30-2.31, p < 0.001; 1.44, 1.10-1.88, p = 0.008; 1.49, 1.14-1.94, p < 0.001). Mortality rates varied between 2.1% for high levels of both LDL-C and anti-SARS-CoV-2 antibodies and 16.3% for low levels of LDL-C and anti-SARS-CoV-2 antibodies (aOR 9.14, 95%CI 3.17-26.34, p < 0.001). Accordingly, for total cholesterol and anti-SARS-CoV-2 antibodies, mortality rates varied between 2.1% and 15.0% (aOR 8.01, 95%CI 2.77-23.18, p < 0.001). CONCLUSION: The combination of serum lipid levels and anti-SARS-CoV-2 antibodies is strongly associated with in-hospital mortality of patients with COVID-19. Patients with low levels of LDL-C and total cholesterol combined with low levels of anti-SARS-CoV-2 antibodies exhibited the highest mortality rates.

Anti-SARS-CoV-2 antibody levels predict outcome in COVID-19 patients with type 2 diabetes: a prospective cohort study.

Patients with type 2 diabetes (T2D) constitute one of the most vulnerable subgroups in COVID-19. Despite high vaccination rates, a correlate of protection to advise vaccination strategies for novel SARS-CoV-2 variants of concern and lower mortality in this high-risk group is still missing. It is further unclear what antibody levels provide protection and whether pre-existing organ damage affects this threshold. To address these gaps, we conducted a prospective multicenter cohort study on 1152 patients with COVID-19 from five hospitals. Patients were classified by diabetes and vaccination status. Anti-SARS-CoV-2-spike-antibodies, creatinine and NTproBNP were measured on hospital admission. Pre-specified endpoints were all-cause in-hospital-mortality, ICU admission, endotracheal intubation, and oxygen administration. Propensity score matching was applied to increase comparability. We observed significantly lower anti-SARS-CoV-2-spike-antibodies in diabetic non-survivors compared to survivors (mean, 95% CI 351BAU/ml, 106-595 vs. 1123, 968-1279, p < 0.001). Mortality risk increased two-fold with each standard deviation-decrease of antibody levels (aHR 1.988, 95% CI 1.229-3.215, p = 0.005). T2D patients requiring oxygen administration, endotracheal intubation and ICU admission had significantly lower antibody levels than those who did not (p < 0.001, p = 0.046, p = 0.011). While T2D patients had significantly worse outcomes than non-diabetic patients, the differences were less pronounced compared to propensity-score-matched non-diabetic patients. Anti-SARS-CoV-2 spike antibodies on hospital admission are inversely associated with oxygen administration, endotracheal intubation, intensive care and in-hospital mortality in diabetic COVID-19 patients. Pre-existing comorbidities may have a greater impact on outcome than diabetes status alone.

Coronary Event Risk Test (CERT) as a Risk Predictor for the 10-Year Clinical Outcome of Patients with Peripheral Artery Disease.

(1) Background: Ceramides are a new kind of lipid biomarker and have already been demonstrated to be valuable risk predictors in coronary patients. Patients with peripheral artery disease (PAD) are a population with a worse prognosis and higher mortality risk compared to coronary artery disease (CAD) patients. However, the value of ceramides for risk prediction in PAD patients is still vague, as addressed in the present study. (2)Methods: This observational study included 379 PAD patients. The primary endpoint was all-cause mortality at 10 years of follow-up. A set of ceramides was measured by LC-MS/MS and combined according to the Coronary Event Risk Test (CERT) score, which categorizes patients into one of four risk groups (low risk, moderate risk, high risk, very high risk). (3) Results: Kaplan-Meier survival curves revealed that the overall survival of patients decreased with the increasing risk predicted by the four CERT categories, advancing from low risk to very high risk. Cox regression analysis demonstrated that each one-category increase resulted in a 35% rise in overall mortality risk (HR = 1.35 [1.16-1.58]). Multivariable adjustment, including, among others, age, LDL-cholesterol, type 2 diabetes, and statin treatment before the baseline, did not abrogate this significant association (HR = 1.22 [1.04-1.43]). Moreover, we found that the beneficial effect of statin treatment is significantly stronger in patients with a higher risk, according to CERT. (4) Conclusions: We conclude that the ceramide-based risk score CERT is a strong predictor of the 10-year mortality risk in patients with PAD.