Timing of endoscopy in patients with elevated lactate levels and acute upper gastrointestinal bleeding; a retrospective comparative study.

BACKGROUND/AIMS: While current guidelines recommend performing endoscopy within 24 h in case of acute upper gastrointestinal bleeding (AUGIB), the precise timing remains an issue of debate. Lactate is an established parameter for risk stratification in a variety of medical emergencies. This study evaluated the predictive ability of elevated lactate levels in identifying patients with UGIB, who may benefit from emergent endoscopy. METHODS: We retrospectively analyzed all patients with elevated lactate levels, who presented to our emergency department between 01 January 2015 and 31 December 2019 due to suspected AUGIB. RESULTS: Of 134 included cases, 81.3% had an Charlson comorbidity index of ≥3 and 50.4% presented with shock. Fifteen (11.2%) patients died and mortality rates rose with increasing lactate levels. Emergent endoscopy within 6 h (EE) and non-EE were performed in 64 (47.8%) and 70 (52.2%) patients, respectively. Patients who underwent EE had lower systolic blood pressure (107.6 mmHg vs. 123.2 mmHg; p = 0.001) and received blood transfusions more frequently (79.7% vs 64.3%; p = 0.048), but interestingly need for endoscopic intervention (26.6% vs 20.0%; p = 0.37), rebleeding (17.2% vs. 15.7%; p = 0.82) and mortality (9.4% vs. 11.4%; p = 0.7) did not differ significantly. CONCLUSION: In conclusion, our findings support the recommendations of current guidelines to perform non-EE after sufficient resuscitation and management of comorbid illnesses.

Learning curve of achieving competency in emergency endoscopy in upper gastrointestinal bleeding: how much experience is necessary?

OBJECTIVES: The management of upper gastrointestinal bleeding (UGIB) has seen rapid advancements with revolutionising innovations. However, insufficient data exist on the necessary number of emergency endoscopies needed to achieve competency in haemostatic interventions. DESIGN: We retrospectively analysed all oesophagogastroduodenoscopies with signs of recent haemorrhage performed between 2015 and 2022 at our university hospital. A learning curve was created by plotting the number of previously performed oesophagogastroduodenoscopies with signs of recent haemorrhage against the treatment failure rate, defined as failed haemostasis, rebleeding and necessary surgical or radiological intervention. RESULTS: The study population included 787 cases with a median age of 66 years. Active bleeding was detected in 576 cases (73.2%). Treatment failure occurred in 225 (28.6%) cases. The learning curve showed a marked decline in treatment failure rates after nine oesophagogastroduodenoscopies had been performed by the respective endoscopists followed by a first plateau between 20 and 50 procedures. A second decline was observed after 51 emergency procedures followed by a second plateau. Endoscopists with experience of <10 emergency procedures had higher treatment failure rates compared with endoscopists with >51 emergency oesophagogastroduodenoscopies performed (p=0.039) or consultants (p=0.041). CONCLUSIONS: Our data suggest that a minimum number of 20 oesophagogastroduodenoscopies with signs of recent haemorrhage is necessary before endoscopists should be considered proficient to perform emergency procedures independently. Endoscopists might be considered as advanced-qualified experts in managing UGIB after a minimum of 50 haemostatic procedure performed. Implementing recommendations on minimum numbers of emergency endoscopies in education programmes of endoscopy trainees could improve their confidence and competency in managing acute UGIB.

DKK3 as a potential novel biomarker in patients with autosomal polycystic kidney disease.

Backgound: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, and leads to a steady loss of kidney function in adulthood. The variable course of the disease makes it necessary to identify the patients with rapid disease progression who will benefit the most from targeted therapies and interventions. Currently, magnetic resonance imaging-based volumetry of the kidney is the most commonly used tool for this purpose. Biomarkers that can be easily and quantitatively determined, which allow a prediction of the loss of kidney function, have not yet been established in clinical practice. The glycoprotein Dickkopf 3 (DKK3) which is secreted in the renal tubular epithelium upon stress and contributes to tubulointerstitial fibrosis via the Wnt signaling pathway, was recently described as a biomarker for estimating risk of kidney function loss, but has not been investigated for ADPKD. This study aimed to obtain a first insight into whether DKK3 may indeed improve outcome prediction in ADPKD in the future. Methods: In 184 ADPKD patients from the AD(H)PKD registry and 47 healthy controls, the urinary DKK3 (uDKK3) levels were determined using ELISA. Multiple linear regression was used to examine the potential of these values in outcome prediction. Results: ADPKD patients showed significantly higher uDKK3 values compared with the controls (mean 1970 ± 5287 vs 112 ± 134.7 pg/mg creatinine). Furthermore, there was a steady increase in uDKK3 with an increase in the Mayo class (A/B 1262 ± 2315 vs class D/E 3104 ± 7627 pg/mg creatinine), the best-established biomarker of progression in ADPKD. uDKK3 also correlated with estimated glomerular filtration rate (eGFR). Patients with PKD1 mutations show higher uDKK3 levels compared with PKD2 patients (PKD1: 2304 ± 5119; PKD2: 506.6 ± 526.8 pg/mg creatinine). Univariate linear regression showed uDKK3 as a significant predictor of future eGFR slope estimation. In multiple linear regression this effect was not significant in models also containing height-adjusted total kidney volume and/or eGFR. However, adding both copeptin levels and the interaction term between copeptin and uDKK3 to the model resulted in a significant predictive value of all these three variables and the highest R2 of all models examined (∼0.5). Conclusion: uDKK3 shows a clear correlation with the Mayo classification in patients with ADPKD. uDKK3 levels correlated with kidney function, which could indicate that uDKK3 also predicts a disproportionate loss of renal function in this collective. Interestingly, we found an interaction between copeptin and uDKK3 in our prediction models and the best model containing both variables and their interaction term resulted in a fairly good explanation of variance in eGFR slope compared with previous models. Considering the limited number of patients in these analyses, future studies will be required to confirm the results. Nonetheless, uDKK3 appears to be an attractive candidate to improve outcome prediction of ADPKD in the future.

Deep Learning Histology for Prediction of Lymph Node Metastases and Tumor Regression after Neoadjuvant FLOT Therapy of Gastroesophageal Adenocarcinoma.

BACKGROUND: The aim of this study was to establish a deep learning prediction model for neoadjuvant FLOT chemotherapy response. The neural network utilized clinical data and visual information from whole-slide images (WSIs) of therapy-naïve gastroesophageal cancer biopsies. METHODS: This study included 78 patients from the University Hospital of Cologne and 59 patients from the University Hospital of Heidelberg used as external validation. RESULTS: After surgical resection, 33 patients from Cologne (42.3%) were ypN0 and 45 patients (57.7%) were ypN+, while 23 patients from Heidelberg (39.0%) were ypN0 and 36 patients (61.0%) were ypN+ (p = 0.695). The neural network had an accuracy of 92.1% to predict lymph node metastasis and the area under the curve (AUC) was 0.726. A total of 43 patients from Cologne (55.1%) had less than 50% residual vital tumor (RVT) compared to 34 patients from Heidelberg (57.6%, p = 0.955). The model was able to predict tumor regression with an error of ±14.1% and an AUC of 0.648. CONCLUSIONS: This study demonstrates that visual features extracted by deep learning from therapy-naïve biopsies of gastroesophageal adenocarcinomas correlate with positive lymph nodes and tumor regression. The results will be confirmed in prospective studies to achieve early allocation of patients to the most promising treatment.