Influence of dental status on postoperative complications in major visceral surgical and organ transplantation procedures-the bellydent retrospective observational study.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 REGISTRATION: Trial registered under the ethics-number S-082/2022 (Ethic Committee of the University Heidelberg).

Total versus Partial Pancreatectomy in Patients with Pancreatic Cancer Arising from Multifocal or Diffuse Intraductal Papillary Mucinous Neoplasia - A Multicenter Observational Study.

AIM: To investigate the impact of total pancreatectomy (TP) on oncological outcomes for patients at high-risk of local recurrence or secondary progression in the remnant gland after partial pancreatectomy (PP) for IPMN-associated cancer. SUMMARY BACKGROUND DATA: Major risk factors for invasive progression in the remnant gland include multifocality, diffuse main duct dilation, and the presence of invasive cancer. In these high-risk patients, a TP may be oncologically beneficial. However, current guidelines discourage TP, especially in elderly patients. METHODS: This international multicenter study compares TP versus PP in patients with adenocarcinoma arising from multifocal or diffuse IPMN (2002-2022). Log-rank test and multivariable Cox-analysis with interaction analysis was performed to assess overall survival (OS), disease-free survival (DFS), and local-DFS. RESULTS: Of 359 included patients, 162 (45%) were treated with TP, whereas 197 (55%) underwent PP. Despite TP and PP having similar R0-rates (59% vs. 58%, P=0.866), patients undergoing a TP had significantly longer local-DFS compared to PP (P=0.039). However, no difference in OS was observed between the two surgical approaches (P=0.487). In a multivariable analysis, young age (optimal cut-off ≤63.6 yrs) was associated with an OS benefit derived from TP (HR:0.44, 95%CI:0.22-0.89), whereas no significant difference was observed in elderly patients (HR:1.24, 95%CI:0.92-1.67, Pinteraction=0.007). CONCLUSION: Since overall, patients with diffuse or multifocal IPMN with an invasive component do not benefit from TP in terms of OS, the indication for TP may be individualized to young patients who have sufficient life expectancy to benefit from the prevention of secondary progression or local recurrence.

A Comparative Analysis of the Impact of Two Different Cognitive Aid Bundle Designs on Adherence to Best Clinical Practice in Simulated Perioperative Emergencies.

Background: Stress and human error during perioperative emergency situations can significantly impact patient morbidity and mortality. Previous research has shown that cognitive aid bundles (CABs) minimize critical misses by 75%. This study aimed to compare the effectiveness of two different CAB designs with the same content in reducing missed critical management steps for simulated perioperative emergencies. Methods: A multicenter randomized controlled simulation-based study was conducted including 27 teams, each consisting of three participants; each team performed four simulation scenarios. In the first scenario for each team (Scenario 1), no CAB was used. Scenarios 2 and 3 were randomly allocated to the groups, with either a branched, clustered design (CAB-1) or a linear, step-by-step design (CAB-2) of the cognitive aid. In Scenario 4, the groups used one of the previously mentioned CABs according to their own preference. The primary outcome was the difference in the percentage of missed critical management steps between the two different CABs. Secondary outcomes included user preference for one CAB design and the reduction in percentage of missed critical management steps using any CAB versus no CAB. Results: Twenty-seven teams simulated 108 perioperative emergency situations. The percentage of missed critical management steps was similar between CAB-1 and CAB-2 (27% [interquartile range (IQR) 20-29] versus 29% [IQR 20-35], p = 0.23). However, most participants favored the branched, clustered design CAB-1 (77.8%). Additionally, employing any CAB reduced the percentage of missed critical management steps by 36% (33% missed steps vs. 21% missed steps, p = 0.003). Conclusions: While the two CAB designs did not differ significantly in reducing missed critical management steps, the branched, clustered design was perceived as more user-friendly. Importantly, using any CAB significantly reduced the percentage of missed critical management steps compared to not using a cognitive aid, emphasizing the need for CAB use in the operating room.

Impact of Adjuvant Chemotherapy on Resected Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Cancer: Results From an International Multicenter Study.

PURPOSE: The benefit of adjuvant therapy for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) remains unclear because of severely limited evidence. Although biologically distinct entities, adjuvant therapy practices for IPMN-derived PDAC are largely founded on pancreatic intraepithelial neoplasia-derived PDAC. We aimed to evaluate the role of adjuvant chemotherapy in IPMN-derived PDAC. METHODS: This international multicenter retrospective cohort study (2005-2018) was conceived at the Verona Evidence-Based Medicine meeting. Cox regressions were performed to identify risk-adjusted hazard ratios (HR) associated with overall survival (OS). Kaplan-Meier curves and log-rank tests were employed for survival analysis. Logistic regression was performed to identify factors motivating adjuvant chemotherapy administration. A decision tree was proposed and categorized patients into overtreated, undertreated, and optimally treated cohorts. RESULTS: In 1,031 patients from 16 centers, nodal disease (HR, 2.88, P < .001) and elevated (≥37 to <200 µ/mL, HR, 1.44, P = .006) or markedly elevated (≥200 µ/mL, HR, 2.53, P < .001) carbohydrate antigen 19-9 (CA19-9) were associated with worse OS. Node-positive patients with elevated CA19-9 had an associated 34.4-month improvement in median OS (P = .047) after adjuvant chemotherapy while those with positive nodes and markedly elevated CA19-9 had an associated 12.6-month survival benefit (P < .001). Node-negative patients, regardless of CA19-9, did not have an associated benefit from adjuvant chemotherapy (all P > .05). Based on this model, we observed undertreatment in 18.1% and overtreatment in 61.2% of patients. Factors associated with chemotherapy administration included younger age, R1-margin, poorer differentiation, and nodal disease. CONCLUSION: Almost half of patients with resected IPMN-derived PDAC may be overtreated or undertreated. In patients with node-negative disease or normal CA19-9, adjuvant chemotherapy is not associated with a survival benefit, whereas those with node-positive disease and elevated CA19-9 have an associated benefit from adjuvant chemotherapy. A decision tree was proposed. Randomized controlled trials are needed for validation.

Metavert synergises with standard cytotoxics in human PDAC organoids and is associated with transcriptomic signatures of therapeutic response.

BACKGROUND: Despite some recent advances, pancreatic ductal adenocarcinoma (PDAC) remains a growing oncological challenge. New drugs capable of targeting more than one oncogenic pathway may be one way to improve patient outcomes. This study characterizes the effectiveness of Metavert a first-in-class dual inhibitor of GSK3-ß and histone deacetylase in treating PDAC as a single agent or in combination with standard cytotoxics. METHODS: Thirty-six Patient-Derived Organoids (hPDOs) characterised by RNASeq and whole exome sequencing were treated with Metavert alone or in combination with standard cytotoxics. Transcriptomic signatures (TS) representing sensitivity to Metavert alone or sensitivity to Metavert + irinotecan (IR) were evaluated in 47 patient samples, chemo-naïve in 26 and post-chemotherapy in 21 (gemcitabine=5; FOLFIRINOX=14, both=2) with companion multiplexed immunofluorescence and RNASeq data. RESULTS: Metavert combined with gemcitabine, irinotecan, 5FU, oxaliplatin, and paclitaxel was synergistic in the hPDOs. Basal-subtype hPDOs were more sensitive to Metavert alone whereas the Metavert+IR combination exhibited synergy in Classical-subtype hPDOs with increased apoptosis and autophagy. hPDO-derived TS evaluated in PDAC tissues demonstrated that Metavert-TSHi samples were enriched for mRNA splicing and DNA repair processes; they were associated with Basal-like tissues but also with GATA6+ve-chemo-naïve samples and were higher following gemcitabine but not FOLFIRINOX treatment. In contrast, Metavert+IR-TSHI samples were enriched for TP53 pathways; they were associated with Classical-like pretreatment samples and with GATA6+ve/KRT17+ve hybrid cell types following FOLFIRINOX, but not gemcitabine treatment, and were unrelated to transcriptional subtypes. CONCLUSIONS: Metavert as a single agent and in combination with irinotecan offers novel strategies for treating pancreatic cancer.

Informing Decision-making for Transected Margin Reresection in Intraductal Papillary Mucinous Neoplasm-derived PDAC: An International Multicenter Study.

OBJECTIVE: To assess the prognostic impact of margin status in patients with resected intraductal papillary mucinous neoplasms (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and to inform future intraoperative decision-making on handling differing degrees of dysplasia on frozen section. SUMMARY BACKGROUND DATA: The ideal oncologic surgical outcome is a negative transection margin with normal pancreatic epithelium left behind. However, the prognostic significance of reresecting certain degrees of dysplasia or invasive cancer at the pancreatic neck margin during pancreatectomy for IPMN-derived PDAC is debatable. METHODS: Consecutive patients with resected and histologically confirmed IPMN-derived PDAC (2002-2022) from six international high-volume centers were included. The prognostic relevance of a positive resection margin (R1) and degrees of dysplasia at the pancreatic neck margin were assessed by log-rank test and multivariable Cox-regression for overall survival (OS) and recurrence-free survival (RFS). RESULTS: Overall, 832 patients with IPMN-derived PDAC were included with 322 patients (39%) having an R1-resection on final pathology. Median OS (mOS) was significantly longer in patients with an R0 status compared to those with an R1 status (65.8 vs. 26.3 mo P<0.001). Patients without dysplasia at the pancreatic neck margin had similar OS compared to those with low-grade dysplasia (mOS: 78.8 vs. 66.8 months, P=0.344). However, high-grade dysplasia (mOS: 26.1 mo, P=0.001) and invasive cancer (mOS: 25.0 mo, P<0.001) were associated with significantly worse OS compared to no or low-grade dysplasia. Patients who underwent conversion of high-risk margins (high-grade or invasive cancer) to a low-risk margin (low-grade or no dysplasia) after intraoperative frozen section had significantly superior OS compared to those with a high-risk neck margin on final pathology (mOS: 76.9 vs. 26.1 mo P<0.001). CONCLUSIONS: In IPMN-derived PDAC, normal epithelium or low-grade dysplasia at the neck have similar outcomes while pancreatic neck margins with high-grade dysplasia or invasive cancer are associated with poorer outcomes. Conversion of a high-risk to low-risk margin after intraoperative frozen section is associated with survival benefit and should be performed when feasible.

Arming AAV9 with a Single-Chain Fragment Variable Antibody Against PD-1 for Systemic Glioblastoma Therapy.

Glioblastoma (GBM) is a highly aggressive brain cancer with a low survival rate, prompting the exploration of novel therapeutic strategies. Immune checkpoint inhibitors have shown promise in cancer treatment but are associated with immune-related toxicities and brain penetration. Here, we present a targeted approach using an adeno-associated virus serotype 9 (AAV9) to systemically deliver a single-chain fragment variable antibody against PD-1 (scFv-PD-1) into the tumor microenvironment (TME). Single-cell RNA sequencing analysis revealed robust PD-1 expression in GBM TME, predominantly on T cells. AAV9-scFv-PD-1 expressed and secreted scFv-PD-1, which effectively binds to PD-1. Systemic administration of AAV9-scFv-PD-1 in an immunocompetent GBM mouse model resulted in a robust cytolytic T-cell activation at the tumor site, marked by accumulation of IFN-γ and Granzyme B, leading to a significant reduction in tumor growth. Importantly, AAV9-scFv-PD-1 treatment conferred a survival benefit, highlighting its therapeutic potential. This study demonstrates the feasibility of systemically delivered AAV9-mediated local expression of scFv-PD-1 for targeted immunotherapy in GBM and warrants further investigation for clinical translation.

Effect of biochar amendment on bacterial community and their role in nutrient acquisition in spinach (Spinacia oleracea L.) grown under elevated CO2.

Global climate change is anticipated to shift the soil bacterial community structure and plant nutrient utilization. The use of biochar amendment can positively influence soil bacterial community structure, soil properties, and nutrient use efficiency of crops. However, little is known about the underlying mechanism and response of bacterial community structure to biochar amendment, and its role in nutrient enhancement in soil and plants under elevated CO2. Herein, the effect of biochar amendment (0, 0.5, 1.5%) on soil bacterial community structure, spinach growth, physiology, and soil and plant nutrient status were investigated under two CO2 concentrations (400 and 600 µmol mol-1). Findings showed that biochar application 1.5% (B.2.E) significantly increased the abundance of the bacterial community responsible for growth and nutrient uptake i.e. Firmicutes (42.25%) Bacteroidetes (10.46%), and Gemmatimonadetes (125.75%) as compared to respective control (CK.E) but interestingly abundance of proteobacteria decreased (9.18%) under elevated CO2. Furthermore, the soil available N, P, and K showed a significant increase in higher biochar-amended treatments under elevated CO2. Spinach plants exhibited a notable enhancement in growth and photosynthetic pigments when exposed to elevated CO2 levels and biochar, as compared to ambient CO2 conditions. However, there was variability observed in the leaf gas exchange attributes. Elevated CO2 reduced spinach roots and leaves nutrient concentration. In contrast, the biochar amendment (B2.E) enhanced root and shoot Zinc (494.99%-155.33%), magnesium (261.15%-183.37%), manganese (80.04%-152.86%), potassium (576.24%-355.17%), calcium (261.88%-165.65%), copper (325.42%-282.53%) and iron (717.63%-177.90%) concentration by influencing plant physiology and bacterial community. These findings provide insights into the interaction between plant and bacterial community under future agroecosystems in response to the addition of biochar contributing to a deeper understanding of ecological dynamics.

Intravenous lidocaine for refractory pain in patients with pancreatic ductal adenocarcinoma and chronic pancreatitis (LIDOPAN): a multicenter prospective non-randomized pilot study.

INTRODUCTION: Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively. METHODS: Multicentre prospective non-randomized pilot study including patients with moderate or severe pain (NRS ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5mg/kg, was followed by continuous infusion at 1.5 mg/kg/hour. The dose was raised every 15 minutes until treatment response (up to a maximum 2mg/kg/hour) and consecutively administered for two hours. Primary outcome was the mean difference in pain severity, pre-infusion and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥ 1.3 points was considered clinically relevant. RESULTS: Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day one was 1.1 (SD±1.3) points for patients with PDAC and 0.5 (SD±1.7) for CP patients. A clinically relevant decrease in BPI on day one was reported in 9/29 patients (31%), this response lasted up to one month. No serious complications were reported, and only three minor complications (vertigo, nausea, tingling of mouth). Treatment with lidocaine did not impact quality of life. CONCLUSION: Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group, and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.

Outcomes in intraductal papillary mucinous neoplasm-derived pancreatic cancer differ from PanIN-derived pancreatic cancer.

BACKGROUND AND AIM: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) management is generally extrapolated from pancreatic intraepithelial neoplasia (PanIN)-derived PDAC guidelines. However, these are biologically divergent, and heterogeneity further exists between tubular and colloid subtypes. METHODS: Consecutive upfront surgery patients with PanIN-derived and IPMN-derived PDAC were retrospectively identified from international centers (2000-2019). One-to-one propensity score matching for clinicopathologic factors generated three cohorts: IPMN-derived versus PanIN-derived PDAC, tubular IPMN-derived versus PanIN-derived PDAC, and tubular versus colloid IPMN-derived PDAC. Overall survival (OS) was compared using Kaplan-Meier and log-rank tests. Multivariable Cox regression determined corresponding hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: The median OS (mOS) in 2350 PanIN-derived and 700 IPMN-derived PDAC patients was 23.0 and 43.1 months (P < 0.001), respectively. PanIN-derived PDAC had worse T-stage, CA19-9, grade, and nodal status. Tubular subtype had worse T-stage, CA19-9, grade, nodal status, and R1 margins, with a mOS of 33.7 versus 94.1 months (P < 0.001) in colloid. Matched (n = 495), PanIN-derived and IPMN-derived PDAC had mOSs of 30.6 and 42.8 months (P < 0.001), respectively. In matched (n = 341) PanIN-derived and tubular IPMN-derived PDAC, mOS remained poorer (27.7 vs 37.4, P < 0.001). Matched tubular and colloid cancers (n = 112) had similar OS (P = 0.55). On multivariable Cox regression, PanIN-derived PDAC was associated with worse OS than IPMN-derived (HR: 1.66, 95% CI: 1.44-1.90) and tubular IPMN-derived (HR: 1.53, 95% CI: 1.32-1.77) PDAC. Colloid and tubular subtype was not associated with OS (P = 0.16). CONCLUSIONS: PanIN-derived PDAC has worse survival than IPMN-derived PDAC supporting distinct outcomes. Although more indolent, colloid IPMN-derived PDAC has similar survival to tubular after risk adjustment.

Omitting the Escalating Dosage of Alpha-adrenergic Blockade before Pheochromocytoma Resection: Implementation of a Treatment Strategy in Discordance with Current Guidelines.

OBJECTIVE: This study describes the effects of introducing a protocol omitting preoperative α-blockade dose-escalation (de-escalation) in a prospective patient group. SUMMARY BACKGROUND DATA: The decline of mortality and morbidity associated with pheochromocytoma resection is frequently attributed to the introduction of preoperative α-blockade. Current protocols require preoperative α-blockade dose-escalation and multiple-day hospital admissions. However, correlating evidence is lacking. Moreover, recent data suggest equal perioperative safety regardless of preoperative α-blockade escalation. METHODS: Single-institution evaluation of protocol implementation, including patients who underwent adrenalectomy for pheochromocytoma between 2015 and 2023. Intraoperative hemodynamic control was regulated by active adjustment of blood pressure using vasoactive agents. The primary outcome was intraoperative hypertension, defined as time-weighted average of systolic blood pressure (TWA-SBP) above 200 mm Hg. Secondary outcomes included perioperative hypotension, postoperative blood pressure support requirement, hospital stay duration and complications. RESULTS: Of 102 pheochromocytoma patients, 82 were included; 44 in the de-escalated preoperative α-adrenergic protocol and 38 following the previous dose-escalation protocol. Median [IQR] TWA-SBP above 200 mm Hg was 0.01 [0.0-0.4] mm Hg in the de-escalated group versus 0.0 [0.0-0.1] mm Hg in the dose-escalated group (P=0.073). Median duration of postoperative continuous norepinephrine administration was 0.3 hrs [0.0-5.5] versus 5.1 hrs [0.0-14.3], respectively (P=0.003). Postoperative symptomatic hypotension occurred in 34.2% versus 9.1% of patients (P=0.005). Median hospital stay was 2.5 days [1.9-3.6] versus 7.1 days [6.0-11.9] (P<0.001). No significant differences in complication rates were observed. CONCLUSION: Our data suggest that adrenalectomy for pheochromocytoma employing a de-escalated preoperative α-blockade protocol is safe and results in a shorter hospital stay.

Feasibility of a new endoscopic suturing device: a first Western experience.

BACKGROUND AND AIMS: Endoscopic hand suturing (EHS) is a new technique for the closure of mucosal defects in the gastrointestinal tract. While this method was tested for wound closure after endoscopic submucosal dissection (ESD) in Japan, a feasibility test in a Western setting is lacking. In this study we present our first experience with EHS for different indications and in different anatomical locations. METHODS: Technical success of EHS as well as suturing speed were retrospectively determined for all available EHS cases in our center. Technical success was defined as complete closure of the mucosal defect or visually tight fixation of the target. RESULTS: 19 EHS procedures were performed in 17 patients (mean age 54.9 years, standard error of the mean [SEM] 4.2 years, male 53% [n=9]). Technical success was achieved in 78.9% (n=15). Total EHS operation time was 40.0 min (SEM 3.1 min) with 3.3 min (SEM 0.2 min) per single stitch. In a constant team of endoscopist and assistant mean stitch times declined significantly from the first four to the second four of eight cases (4.0 min [SEM 0.6] vs. 2.3 min [SEM 0.2], p=0.02). CONCLUSIONS: EHS was technically feasible and applicable in different anatomical locations. Further studies may elucidate a possible effect on complication rates of endoscopic resections.

A jsPsych touchscreen extension for behavioral research on touch-enabled interfaces.

Online experiments are increasingly gaining traction in the behavioral sciences. Despite this, behavioral researchers have largely continued to use keyboards as the primary input devices for such online studies, overlooking the ubiquity of touchscreens in everyday use. This paper presents an open-source touchscreen extension for jsPsych, a JavaScript framework designed for conducting online experiments. We additionally evaluated the touchscreen extension assessing whether typical behavioral findings from two distinct perceptual decision-making tasks - the random-dot kinematogram and the Stroop task - can similarly be observed when administered via touchscreen devices compared to keyboard devices. Our findings indicate similar performance metrics for each paradigm between the touchscreen and keyboard versions of the experiments. Specifically, we observe similar psychometric curves in the random-dot kinematogram across the touchscreen and keyboard versions. Similarly, in the Stroop task, we detect significant task, congruency, and sequential congruency effects in both experiment versions. We conclude that our open-source touchscreen extension serves as a promising tool for data collection in online behavioral experiments on forced-choice tasks.

High PEEP/low FiO2 ventilation is associated with lower mortality in COVID-19.

RATIONALE: The positive end-expiratory pressure (PEEP) strategy in patients with coronavirus 2019 (COVID-19) acute respiratory distress syndrome (ARDS) remains debated. Most studies originate from the initial waves of the pandemic. Here we aimed to assess the impact of high PEEP/low FiO2 ventilation on outcomes during the second wave in the Netherlands. METHODS: Retrospective observational study of invasively ventilated COVID-19 patients during the second wave. Patients were categorized based on whether they received high PEEP or low PEEP ventilation according to the ARDS Network tables. The primary outcome was ICU mortality, and secondary outcomes included hospital and 90-day mortality, duration of ventilation and length of stay, and the occurrence of kidney injury. Propensity matching was performed to correct for factors with a known relationship to ICU mortality. RESULTS: This analysis included 790 COVID-ARDS patients. At ICU discharge, 32 (22.5%) out of 142 high PEEP patients and 254 (39.2%) out of 848 low PEEP patients had died (HR 0.66 [0.46-0.96]; P = 0.03). High PEEP was linked to improved secondary outcomes. Matched analysis did not change findings. CONCLUSIONS: High PEEP ventilation was associated with improved ICU survival in patients with COVID-ARDS.

Who Do We Fail to Rescue after Pancreatoduodenectomy? Outcomes Among >4000 Procedures Expose Windows of Opportunity.

OBJECTIVE: Our investigation on in-hospital mortality after 4474 pancreatoduodenectomies aimed to identify time-dependent risks as well as windows of opportunity to rescue patients from complications. BACKGROUND: Pancreatoduodenectomy is generally considered a safe procedure with a 1-10% perioperative mortality based on complexity and surgical volume. Yet, patients are susceptible for life-threatening complications particularly with extended resections. Recognition of distinct vulnerabilities over time while patients recover is required to permit focused monitoring, sophisticated resource allocation, and greatest surgical safety. METHODS: Patients who deceased in-hospital after pancreatoduodenectomy between 2003-2021 were retrieved from the institutional pancreatectomy registry and analyzed in detail with respect to their postoperative course. RESULTS: Among 4474 pancreatoduodenectomies, 156 patients deceased in-hospital (3.5%). When assessing root causes of mortality, we observed 3 different clusters of complications which were postpancreatectomy-specific (47.4%), visceral vasculature-associated (25.6%), or cardiopulmonary in origin (23.7%). The median times of root cause onset in the 3 categories were postoperative day (POD) 9, POD 4.5 ( P =0.008) and POD 3 ( P <0.001), and medians of in-hospital mortality were POD 31, POD 18 ( P =0.009) and POD 8 ( P <0.001), respectively. Intervals between root cause onset and mortality varied with medians of 23 days, 11 days ( P =0.017), and 1 days ( P <0.001). The 3 categories were similarly distributed between different types of surgical complexity. CONCLUSION: Postpancreatectomy-specific complications prompt almost half of in-hospital mortalities after pancreatoduodenectomy, with rather long intervals for interventions to prevent failure to rescue. In contrast, visceral vasculature-related events and cardiopulmonary complications dominate early in-hospital mortalities with short intervals until mortality, demanding rigorous management of such events or preoperative conditioning. These data externally validate a previous high-volume initiative and highlight distinct windows of opportunity to optimize perioperative safety.

Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review.

Surgical excision of the primary tumor represents the most frequent and curative procedure for solid malignancies. Compelling evidence suggests that, despite its beneficial effects, surgery may impair immunosurveillance by triggering an immunosuppressive inflammatory stress response and favor recurrence by stimulating minimal residual disease. In addition, many factors interfere with the immune effectors before and after cancer procedures, such as malnutrition, anemia, or subsequent transfusion. Thus, the perioperative period plays a key role in determining oncological outcomes and represents a short phase to circumvent anesthetic and surgical deleterious factors by supporting the immune system through the use of synergistic pharmacological and non-pharmacological approaches. In line with this, accumulating studies indicate that anesthetic agents could drive both protumor or antitumor signaling pathways during or after cancer surgery. While preclinical investigations focusing on anesthetics' impact on the behavior of cancer cells are quite convincing, limited clinical trials studying the consequences on survival and recurrences remain inconclusive. Herein, we highlight the main factors occurring during the perioperative period of cancer surgery and their potential impact on immunomodulation and cancer progression. We also discuss patient management prior to and during surgery, taking into consideration the latest advances in the literature.

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.