In recent years, a threatening rise in carbapenem-resistant Citrobacter spp. (CRC) has been observed in various global regions. Sewage systems have repeatedly been suggested as reservoirs. At our tertiary-care hospital in Germany, CRC have become the most frequently detected species among the carbapenem-resistant Enterobacterales (CRE) over the past six years. This study aimed to analyze CRC's site-specific epidemiological development, assess their clinical significance, and elucidate the potential role of the hospital wastewater system in the observed increase in CRC. A retrospective epidemiological investigation was conducted using Poisson models. Clinical baseline data of affected patients were evaluated. Whole-genome sequencing and a subcluster analysis of 138 CRC patient isolates were performed. The wastewater systems of three clinical wards located in two separate hospital buildings were examined. The annual proportion of CRC in CRE increased from 9.2% in 2019 to 37.8% in 2024 (P < 0.001). 27.5% of isolates were detected in clinical specimens, most frequently in urine samples (52.6%). There were no cases of bacteremia. We identified 26 MLST types and 22 subclusters. Ninety-three percent of isolates had one (77.5%), two (14.7%), or three (0.8%) carbapenemases. Wastewater analysis identified 27 of 37 (73.0%) environmental CRC isolates as genetically consistent with patient-derived strains. Our findings reveal a newly emerging complexity, characterized by the spread of various genetically distinct CRC across several departments of our hospital. While CRC colonization increased, the frequency and severity of infections remained moderate. The hospital wastewater system represents a key factor in CRC's dissemination. IMPORTANCE:In this study, we analyzed the significant increase in CRC strains at our tertiary-care hospital over the past six years. Our findings revealed that, unlike classical outbreak scenarios - typically characterized by the clonal expansion of one strain within a single ward or unit - the rising incidence of CRC was driven by the dissemination of numerous genetically diverse strains across multiple departments. The hospital sewage system was identified as a reservoir and plays an important role in the rapid proliferation and dissemination of CRC. The high complexity of the situation presents a new challenge, as transmission pathways are now difficult to trace, hindering effective prevention. Remarkably, the majority of patients affected by CRC were merely colonized, and severe infections were not observed. It remains to be determined whether this pattern reflects a site-specific phenomenon or indicates a broader trend on a European or even global scale.
In the face of growing transplant waitlists and aging donors, sound pre-transplant evaluation of organ offers is paramount. However, many transplant centres lack clear criteria on organ acceptance. Often, previous scores for donor characterisation have not been validated for the Eurotransplant population and are not established to support graft acceptance decisions. Here, we investigated 1353 kidney transplantations at three different German centres to develop and validate novel statistical models for the prediction of early adverse graft outcome (EAO), defined as graft loss or CKD ≥4 within three months. The predictive models use generalised estimating equations (GEE) accounting for potential correlations between paired grafts from the same donor. Discriminative accuracy and calibration were determined via internal and external validation in the development (935 recipients, 309 events) and validation cohort (418 recipients, 162 events) respectively. The expert model is based on predictor ratings by senior transplant nephrologists, while for the data-driven model variables were selected via high-dimensional lasso generalised estimating equations (LassoGee). Both models show moderate discrimination for EAO (C-statistic expert model: 0,699, data-driven model 0,698) with good calibration. In summary, we developed novel statistical models that represent current clinical consensus and are tailored to the older deceased donor population. Compared to KDRI, our described models are sparse with only four and three predictors respectively and account for paired grafts from the same donor, while maintaining a discriminative accuracy equal or better than the established KDRI-score.
Accurate assessment of graft function trajectories after kidney transplantation is essential for optimizing patient management. Slow graft function (SGF) and delayed graft function (DGF) are associated with impaired recovery, yet current diagnostic tools lack granularity for timely risk stratification. Proenkephalin A 119-159 (penKid) may improve graft function assessment, enhancing risk stratification for SGF, DGF, and associated outcomes. This prospective study evaluated 159 kidney transplant recipients at Heidelberg University Hospital to compare plasma penKid levels with current risk-indicators for poor (functional) graft trajectories. Validation was conducted using an independent transplant cohort from Sydney. Clinical relevance of biomarker-indicated changes in graft function was assessed using multivariable regression models and AUROC analyses. From day one post-transplant, penKid outperformed serum creatinine (SCr) in identifying functional trajectories associated with DGF (AUROC penKid: 0.87 vs. SCr: 0.56) and differentiated SGF from DGF (AUROC penKid: 0.79 vs. SCr: 0.33) up to eight days earlier. PenKid further demonstrated superior granularity in assessing DGF severity and 30-day outcomes. After adjustment for common risk factors, penKid remained the strongest risk stratifier for all tested outcomes. PenKid is a superior biomarker for earlier assessment of graft function trajectories, offering potential to enhance personalized care and clinical trial designs in kidney transplantation.
BACKGROUND:Post-hepatectomy bile leakage is a challenging issue that can lead to morbidities and mortality after liver resection. This leakage can occur either from a bilioenteric anastomosis (BEA) or from the transected surface of the liver. This study investigated the incidence, risk factors, and effective management of BEA leakage after major liver resection. METHODS:Bile leakage was diagnosed through drain fluid analysis based on the International Study Group of Liver Surgery definition. Leakage from a BEA was confirmed via fluoroscopy during percutaneous interventions or reoperation. Perioperative data and data on the management of patients with BEA leakage were collected and analysed. Bivariate analysis used Mann-Whitney U and χ2 tests, and binary logistic regression identified risk factors for BEA leakage, with variables having P < 0.200 included in multivariable analysis. RESULTS:Of 2936 patients undergoing hepatectomy between 2008 and 2023, 229 underwent liver resection with BEA. Leakage from the BEA was identified in 44 patients (19.2%). These patients had a higher rate of post-hepatectomy haemorrhage (P = 0.005), major complications (P = 0.001), BEA stenosis (P = 0.006), and mortality (P = 0.043). The success rate of the management of BEA leakage was 70% for reoperation and 58% for percutaneous transhepatic cholangiography and drainage (PTCD). CONCLUSION:BEA leakage after major liver resection is a severe complication associated with higher morbidity and mortality rates. Surgical treatment appeared to be more successful than PTCD in the early postoperative phase. PTCD proved to be a valuable additional therapy option following reoperation. These conclusions should be taken with caution and need to be confirmed through further prospective studies.
Background: Bile leakage remains a significant challenge following major liver resection, with potential for improvement depending on the transection technique used. In this study, we aimed to evaluate the effectiveness of our hybrid resection technique—utilizing both LigaSure and stapler devices—in reducing bile leakage after major liver resection compared to our conventional stapler-only technique. As a secondary aim, we compared overall morbidity, costs, and reimbursements. Method: Patients who underwent major hepatectomy without biliary reconstruction using either the hybrid or stapler technique between August 2014 and December 2021 were included in the study. Propensity score matching was performed using a one-to-two algorithm. Perioperative data, bile leakage rates, and cost and reimbursement information based on the diagnosis-related group (DRG) system were analyzed. Results: In total, data from 492 patients were evaluated (hybrid = 152; stapler = 340). After one-to-two propensity score matching, the operation time was significantly longer in the hybrid group (p = 0.005). A cost analysis showed no significant difference in total operative costs between the two techniques (p = 0.092). However, the hybrid group had a significantly lower rate of bile leakage (p = 0.002), as well as shorter intensive care unit (ICU) and overall hospital stays (p = 0.034 and p = 0.007, respectively). Consequently, ICU and ward costs were significantly lower in the hybrid group (p = 0.024 and p = 0.014, respectively) compared to the stapler group. The financial difference calculated as DRG reimbursement minus costs was two-fold higher in the hybrid group (p = 0.02). Conclusions: Although the hybrid technique resulted in a longer operating time, it proved superior to the stapler technique in reducing postoperative bile leakage and shortening ICU and hospital stays. Furthermore, the use of the hybrid technique was more cost efficient and resulted in a greater positive financial margin.
Chronic kidney disease (CKD) affects over 10% of the global population, amounting to more than 800 million individuals worldwide. The advances in the treatment of CKD have had a significant impact on patient outcomes. While in the past, CKD was often considered a death sentence, with many patients succumbing to the complications of end-stage renal disease, it is now increasingly being managed as a chronic condition with the availability of dialysis and kidney transplantation, as well as new pharmaceutical developments such as SGLT2 inhibitors or nonsteroidal mineralocorticoid receptor antagonists. Yet, there continues to be a growing demand for further exploration into the pathophysiological processes and potential therapeutic interventions. Reliable biological models play a crucial role in facilitating this research. Given the multifaceted nature of renal disease, which encompasses not only cell biology but also vascular microanatomy and endocrine signaling, an appropriate model must possess a level of biological complexity that only an animal model can offer, rendering rodents an obvious choice. This manuscript, therefore, provides an intricate, systematic protocol for surgically reducing renal parenchyma through midline laparotomy and combined total and partial nephrectomy in rats for survival as well as non-survival applications. It emphasizes the critical role of precise surgical techniques in ensuring consistent and reliable outcomes. Prime examples of potential applications for this model include biomolecular and pharmaceutical studies as well as the development of innovative intraoperative imaging modalities, such as hyperspectral imaging, to objectively visualize and differentiate renal malperfusion.
As transplant programmes have evolved to allow a wider donor pool, organ acceptance decisions have become increasingly complex and lack transparency and equality. Clinical scoring tools exist but there is limited consensus on their use. From a prospective observation of consecutive deceased-donor kidney offers in a large urban transplant centre, a simple score was developed based on donor age and other risk characteristics, excluding ischemia time and graft histology. The score was validated in subsequent cohorts of consecutive offers in the United Kingdom and Germany. In the development cohort of 389 kidney offers, 110 (28%) were transplanted and 175 (45%) declined. Nine risk factors were incorporated into a score based on age, but adjusted for the number of risk factors present, making an "adjusted donor age," with offers separated into equal quintiles by decade. The score was validated in a UK cohort of 380 subsequent offers, and a German cohort of 431 offers. In both cohorts adjusted donor age discriminated between favourable and poor post-transplant outcomes (C-statistic 0.77 in the United Kingdom, 95% CI 0.65-0.88, and 0.71 in Germany, 95% CI 0.64-0.77). Adjusted donor age is a simple score quantifying deceased donor kidney quality, which is consistent with current practice and predicts post-transplant outcome.
IntroductionThe impact of deceased donor characteristics on kidney transplant outcomes is controversial. Correspondingly, the predictive performance of deceased donor scores remains moderate, and many transplant centers lack validated criteria for graft acceptance decisions. To better dissect donor-related risk from recipient and periprocedural variables, we analyzed outcomes of kidney donor pairs transplanted in different individuals.MethodsThis study explored (a)symmetry of early outcomes of 328 cadaveric kidney transplant recipients from 164 donor pairs transplanted at three Eurotransplant centers. The primary discriminatory factor was (a)symmetry of partner graft function, defined as early graft loss or impaired graft function [estimated glomerular filtration rate (eGFR) <30 mL/min] 3 months after transplantation. We reasoned that a relevant impact of donor factors would result in a high concordance rate of limited graft function or failure.ResultsThe observed number of symmetric graft failure after transplantation was less than statistically expected (3 months: 1 versus 2, p = 0.89; and 12 months: 3 versus 5, p = 0.26). However, we found a trend toward an impaired 5-year graft survival of grafts with good function 3 months after transplantation but a failed or impaired partner graft compared to symmetrically well-functioning grafts (p = 0.09). Subsequently, we explored the impact of individual donor and recipient variables on early transplant outcomes. Generalized estimating equations after feature selection with LassoGEE bootstrap selected donor age, donor body mass index, and donor eGFR as the relevant risk factors.DiscussionOur findings indicate that donor factors impact early outcomes in kidney transplantation but may have a limited role in long-term graft survival, once a graft has been accepted for transplantation. Utilizing donor-based clinical scores has the potential to aid clinicians in acceptance decisions, giving them an estimate of individual posttransplant outcomes. However, the ultimate decision for acceptance should rest with clinicians, who must consider the complex interplay of donor factors, as well as recipient and periprocedural characteristics.
BackgroundGlycogen storage disorder (GSD) type IIIa is a rare inherited genetic disorder affecting liver and muscle tissue. Liver transplantation (LT) improves metabolic control, but muscle involvement persists.CaseWe report the case of a 31-year-old man who underwent orthotopic LT for end-stage liver disease caused by GSD type IIIa. After LT, he developed worsening clinical signs of myopathy, along with exponentially increasing levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and creatine kinase. Liver-related elevations of AST and ALT were excluded through liver biopsy and endoscopic cholangiography; consequently, AST and ALT elevations were attributed to the underlying muscle involvement. Exacerbation of muscle disease after LT could be attributed to restoration of liver glycogen metabolism after LT, leading to increased glucose accumulation in muscle cells, where the gene defect persists. A dietary intervention with a high-protein, ketogenic diet was initiated but did not lead to significant improvement of myalgia.ConclusionLT exacerbated muscle disease in a patient with GSD type IIIa. Patients should be counseled about this possible side effect of LT in GSD type IIIa.
Background: We aimed to assess the safety of a modified peritoneal fenestration technique with clipping of the window edges during kidney transplantation (KTx) and to determine its impact on reducing lymphocele following KTx. We compared the outcomes of this modified method with those of peritoneal fenestration without clipping. Methods: Among 430 consecutive KTxs performed between 2015 and 2019, preventive peritoneal fenestration and clipping of the margins were performed in 25 patients. These patients were compared with 75 matched patients in whom the margins were not clipped. Postoperative lymphocele formation and other patient data were compared between these two groups. Results: The rate of clinically relevant lymphocele decreased by 2.7% after peritoneal fenestration with clipping, although this decrease was not statistically significant (p = 0.829). There was no significant increase in the rate of other complications in the modified fenestration group (p = 0.067). The incidence of clinically significant lymphocele formation was notably higher in patients with a body mass index greater than 25 kg/m2 (p = 0.028). Univariate analysis indicated that older recipients, individuals with a history of previous abdominal surgery, those receiving the kidney from deceased and older donors were at increased risk of developing a clinically relevant lymphocele. Conclusions: Our preliminary results suggest that peritoneal fenestration with clipping may be as effective as the conventional fenestration technique in preventing lymphocele formation. Further clinical trials with larger sample sizes are required to determine the exact role of preventive peritoneal fenestration with clipping in preventing clinically relevant lymphocele after KTx.
Besides sepsis and malignancy, malperfusion is the third leading cause of tissue degradation and a major pathomechanism for various medical and surgical conditions. Despite significant developments such as bypass surgery, endovascular procedures, extracorporeal membrane oxygenation, and artificial blood substitutes, tissue malperfusion, especially of visceral organs, remains a pressing issue in patient care. The demand for further research on biomedical processes and possible interventions is high. Valid biological models are of utmost importance in enabling this kind of research. Due to the multifactorial aspects of tissue perfusion research, which include not only cell biology but also vascular microanatomy and rheology, an appropriate model requires a degree of biological complexity that only an animal model can provide, rendering rodents the obvious model of choice. Tissue malperfusion can be differentiated into three distinct conditions: (1) isolated arterial ischemia, (2) isolated venous congestion, and (3) combined malperfusion. This article presents a detailed step-by-step protocol for the controlled and reversible induction of these three types of visceral malperfusion via midline laparotomy and clamping of the abdominal aorta and caval vein in rats, underscoring the significance of precise surgical methodology to guarantee uniform and dependable results. Prime examples of possible applications of this model include the development and validation of innovative intraoperative imaging modalities, such as Hyperspectral Imaging (HSI), to objectively visualize and differentiate malperfusion of gastrointestinal, gynecological, and urological organs.
BACKGROUND:There are multiple methods for preventing lymphocele formation after kidney transplantation (KTx). However, lymphoceles still develop in up to one third of patients and the effectiveness of these different methods in preventing lymphocele is not well described. Here, we summarize the current strategies for preventing lymphocele after KTx. METHODS:We conducted searches across several literature databases, including Medline (via PubMed), Web of Science, EMBASE, and Cochrane Central. Lymphocele formation after KTx was the outcome of interest. A random-effects model was applied to evaluate pooled estimates, which were presented as hazard ratios (HRs) and odds ratios (ORs), along with the random pooled estimate (ES), 95% confidence interval (95% CI), and P value. We calculated the pooled rate of lymphocele formation after KTx with the following preventive methods: LigaSure, haemostatic materials, prophylactic drainage, ligation, peritoneal fenestration, and bipolar cautery techniques. RESULTS:The literature search retrieved 87 unique studies after excluding duplicates. Twenty papers reporting on 5445 patients were incorporated in the qualitative analysis. The pooled lymphocele rate was 3.0% (95% CI = 0.6-13.7) for the LigaSure method, 8.3% (95% CI = 6.4-10.7) for drainage, 9.2% (95% CI = 5.9-14.1) for haemostatic materials, 12.2% (95% CI = 9.2-16.1) for ligation, 14.4% (95% CI = 12.0-17.3) for peritoneal fenestration, and 20.5% (95% CI = 10.2-36.8) for bipolar sealing. CONCLUSION:Despite preventive methods, the incidence of lymphocele following KTx remains high. The use of LigaSure appears to be the most effective method for preventing lymphocele. However, given the broad range of reported lymphocele rates and lack of control groups, further validation of these findings is necessary.
Background. Groundbreaking biomedical research has transformed renal transplantation (RT) into a widespread clinical procedure that represents the mainstay of treatment for end-stage kidney failure today. Here, we aimed to provide a comprehensive bibliometric perspective on the last half-century of innovation in clinical RT.Methods. The Web of Science Core Collection was used for a comprehensive screening yielding 123 303 research items during a 50-y period (January 1973-October 2022). The final data set of the 200 most-cited articles was selected on the basis of a citation-based strategy aiming to minimize bias.Results. Studies on clinical and immunological outcomes (n = 63 and 48), registry-based epi research (n = 38), and randomized controlled trials (n = 35) dominated the data set. Lead US authors have signed 110 of 200 articles. The overall level of evidence was high, with 84% of level1 and -2 reports. Highest numbers of these articles were published in New England Journal of Medicine, Transplantation, and American Journal of Transplantation. Increasing trend was observed in the number of female authors in the postmillennial era (26% versus 7%).Conclusions. This study highlights important trends in RT research of the past half-century. This bibliometric perspective identifies the most intensively researched areas and shift of research interests over time; however, it also describes important imbalances in distribution of academic prolificacy based on topic, geographical aspects, and gender.
Journal Article Portal vein arterialization as a salvage method in advanced hepatopancreatobiliary surgery Get access Ali Majlesara, Ali Majlesara Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, GermanyLiver Cancer Center Heidelberg (LCCH), University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Mohammad Golriz, Mohammad Golriz Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, GermanyLiver Cancer Center Heidelberg (LCCH), University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Ali Ramouz, Ali Ramouz Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Elias Khajeh, Elias Khajeh Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Thilo Hackert, Thilo Hackert Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Oliver Strobel, Oliver Strobel Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Ali Adeliansedehi, Ali Adeliansedehi Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Ehsan Aminizadeh, Ehsan Aminizadeh Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar De-Hua Chang, De-Hua Chang Liver Cancer Center Heidelberg (LCCH), University of Heidelberg, Heidelberg, GermanyDepartment of Interventional Radiology, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Mark O Wielpütz, Mark O Wielpütz Department of Interventional Radiology, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar ... Show more Benjamin Goeppert, Benjamin Goeppert Liver Cancer Center Heidelberg (LCCH), University of Heidelberg, Heidelberg, GermanyInstitute of Pathology, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Uta Merle, Uta Merle Liver Cancer Center Heidelberg (LCCH), University of Heidelberg, Heidelberg, GermanyDepartment of Internal Medicine IV, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Markus Mieth, Markus Mieth Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, GermanyLiver Cancer Center Heidelberg (LCCH), University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Markus W Büchler, Markus W Büchler Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar Arianeb Mehrabi Arianeb Mehrabi Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, GermanyLiver Cancer Center Heidelberg (LCCH), University of Heidelberg, Heidelberg, Germany Correspondence to: Arianeb Mehrabi, Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany (e-mail: Arianeb.Mehrabi@med.uni-heidelberg.de) https://orcid.org/0000-0001-6163-1525 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 111, Issue 3, March 2024, znae053, https://doi.org/10.1093/bjs/znae053 Published: 13 March 2024 Article history Received: 17 December 2022 Revision received: 17 July 2023 Accepted: 05 February 2024 Published: 13 March 2024
The significance of dental status and oral hygiene on a range of medical conditions is well-recognised. However, the correlation between periodontitis, oral bacterial dysbiosis and visceral surgical outcomes is less well established. To this end, we study sought to determine the influence of dental health and oral hygiene on the rates of postoperative complications following major visceral and transplant surgery in an exploratory, single-center, retrospective, non-interventional study. Our retrospective non-interventional study was conducted at the Department of General, Visceral, and Transplant Surgery, University Hospital Heidelberg, Germany. Patients operated on between January 2018 and December 2019 were retrospectively enrolled in the study based on inclusion (minimum age of 18 years, surgery at our Department, intensive care / IMC treatment after major surgery, availability of patient-specific preoperative dental status assessment, documentation of postoperative complications) and exclusion criteria (minor patients or legally incapacitated patients, lack of intensive care or intermediate care (IMC) monitoring, incomplete documentation of preoperative dental status, intestinal surgery with potential intraoperative contamination of the site by intestinal microbes, pre-existing preoperative infection, absence of data regarding the primary endpoints of the study). The primary study endpoint was the incidence of postoperative complications. Secondary study endpoints were: 30-day mortality, length of hospital stay, duration of intensive care stay, Incidence of infectious complications, the microbial spectrum of infectious complication. A bacteriology examination was added whenever possible (if and only if the examination was safe for the patient)for infectious complications. The final patient cohort consisted of 417 patients. While dental status did not show an influence (p = 0.73) on postoperative complications, BMI (p = 0.035), age (p = 0.049) and quick (p = 0.033) were shown to be significant prognostic factors. There was significant association between oral health and the rate of infectious complications for all surgical procedures (p = 0.034), excluding transplant surgery. However, this did not result in increased 30-day mortality rates, prolonged intensive care unit treatment or an increase in the length of hospital stay (LOS) for the cohort as a whole. In contrast there was a significant correlation between the presence of oral pathogens and postoperative complications for a group as a whole (p < 0.001) and the visceral surgery subgroup (p < 0.001). Whilst this was not the case in the cohort who underwent transplant surgery, there was a correlation between oral health and LOS in this subgroup (p = 0.040). Bacterial swabs supports the link between poor oral health and infectious morbidity. Dental status was a significant predictor of postoperative infectious complications in this visceral surgery cohort. This study highlights the importance preoperative dental assessment and treatment prior to major surgery, particularly in the case of elective surgical procedures. Further research is required to determine the effect of oral health on surgical outcomes in order to inform future practice. Trial registered under the ethics-number S-082/2022 (Ethic Committee of the University Heidelberg).
Abstract Background and Aims Delayed graft function (DGF) frequently occurs following kidney transplantation, and prolonged duration of DGF adversely affects 1-year graft function and long-term graft survival. Recently, Proenkephalin A 119-159 (penKid) was shown to reflect kidney function and predict acute kidney injury (AKI) in critically ill patients. Given the similarities between DGF in transplanted and AKI in native kidneys, we hypothesized that penKid may aid in identifying and risk-stratifying DGF post-transplantation. Method In a prospective study of 159 consecutive kidney transplant recipients at Heidelberg University Hospital from November 2021 to July 2023, penKid was quantified using an immunoluminometric assay until patient discharge. DGF was primarily defined as the necessity for dialysis within 7 days post-transplant. Additionally, penKid was examined in the context of DGF severity, discriminating the different durations of post-transplant dialysis treatment. Similarly, penKid was assessed to differentiate uptake of graft function, defined as slow or immediate by a serum creatinine reduction ratio of pre-transplant and 7 days post-transplant levels of <0.7 and ≥0.7, respectively. Results DGF, defined as the need for dialysis within the first week post-transplant, occurred in 53/159 (33.3%) patients. penKid enabled the differentiation of patients with and without DGF from the first day post-transplant onward (P < 0.001, Fig. 1), and consistently outperformed SCr in discriminating DGF from no DGF at all time points studied (P < 0.001). Additionally, penKid allowed identification of DGF severity from the first day post-transplant (P < 0.001) and early differentiation between slow and delayed graft function (AUC 0.79 [95% CI 0.68-0.90]). In a multivariate model, delta penKid from pre-transplant to the first day post-transplant emerged as the strongest predictor for DGF (C index = 0.88). On the first day post-transplant, penKid, with a cut-off at 300 pmol/L, discriminated DGF from no DGF with a sensitivity of 95.1% (95% CI 83.9–98.7) and a specificity of 56.5% (95% CI 46.3–66.2). Conclusion penKid is a promising biomarker shown to accurately differentiate DGF from no DGF as early as the first day post-transplant and to predict DGF severity, allowing for earlier intervention in these at-risk patients. Due to its high discriminatory power to identify and predict DGF post-transplantation, penKid shows great potential to accompany future studies examining the occurrence of DGF in transplant programs, where DCD is introduced into practice, machine perfusion techniques are assessed, or in trials that assess potential therapeutic interventions in patients with DGF.