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BACKGROUND: Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS: We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS: A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P=0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS: This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. [ABSTRACT FROM AUTHOR]

Background: Postoperative infections remain a crucial challenge in health care, resulting in high morbidity, mortality, and costs. Accurate identification and labeling of patients with postoperative bacterial infections is crucial for developing prediction models, validating biomarkers, and implementing surveillance systems in clinical practice., Objective: This scoping review aimed to explore methods for identifying patients with postoperative infections using electronic health record (EHR) data to go beyond the reference standard of manual chart review., Methods: We performed a systematic search strategy across PubMed, Embase, Web of Science (Core Collection), the Cochrane Library, and Emcare (Ovid), targeting studies addressing the prediction and fully automated surveillance (ie, without manual check) of diverse bacterial infections in the postoperative setting. For prediction modeling studies, we assessed the labeling methods used, categorizing them as either manual or automated. We evaluated the different types of EHR data needed for the surveillance and labeling of postoperative infections, as well as the performance of fully automated surveillance systems compared with manual chart review., Results: We identified 75 different methods and definitions used to identify patients with postoperative infections in studies published between 2003 and 2023. Manual labeling was the predominant method in prediction modeling research, 65% (49/75) of the identified methods use structured data, and 45% (34/75) use free text and clinical notes as one of their data sources. Fully automated surveillance systems should be used with caution because the reported positive predictive values are between 0.31 and 0.76., Conclusions: There is currently no evidence to support fully automated labeling and identification of patients with infections based solely on structured EHR data. Future research should focus on defining uniform definitions, as well as prioritizing the development of more scalable, automated methods for infection detection using structured EHR data., (©Siri Lise van der Meijden, Anna M van Boekel, Harry van Goor, Rob GHH Nelissen, Jan W Schoones, Ewout W Steyerberg, Bart F Geerts, Mark GJ de Boer, M Sesmu Arbous. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 10.09.2024.)

Novel interventions for seroma prevention are urgently needed in clinical practice. Animal models are pivotal tools for testing these interventions; however, a significant translational gap persists between clinical and animal model outcomes. This systematic review aims to assess the methodological characteristics and quality of animal models utilized for seroma prevention. A meta-analysis was performed to estimate the expected seroma incidence rate for control groups and determine the effect size of typical interventions. We systematically retrieved all studies describing animal models in which seroma formation was induced. Methodological characteristics, risks of bias, and study quality were assessed. Seroma volume and -incidence data were used for the meta-analysis. In total, 55 studies were included, with 42 eligible for meta-analysis. Rats (69%) were the most frequently used species, with mastectomy (50%) being the predominant surgical procedure in these models. Despite significant risks of bias across all studies, an improving trend in reporting quality per decade was observed. The meta-analysis revealed an average seroma incidence of 90% in typical control groups. The average intervention halved the seroma incidence (RR = 0.49; CI 0.35, 0.70) and significantly reduced seroma volume (SMD = -3.31; CI -4.21, -2.41), although notable heterogeneity was present. In conclusion, animal models for seroma prevention exhibit methodological flaws and multiple risks of bias. Implementing sufficiently powered positive and negative control groups could improve the internal validity of these models. More research is needed for further development of animal seroma models., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Steven E.M. Poos is an employee of GATT Technologies. Harry van Goor was a scientific advisor for GATT Technologies until 31 December 2021, but not in relation to this research.

Objective: Systemic sclerosis-interstitial lung disease (SSc-ILD) is the leading cause of death in SSc, affecting around 50 % of the patients. Lung tissue of patients with early-stage SSc-ILD is characterized by a predominant inflammatory response with inconspicuous fibrosis, which may progress to honeycombing fibrosis. Hence, a better understanding of the molecular mechanisms underpinning SSc-ILD pathogenesis is needed to improve treatment options and progression prediction. This transcriptomic study aims to reveal the differential gene expression between control (ctrl) lung tissue and inflammatory, prefibrotic and fibrotic lung tissue to capture progression of early to late phase SSc-ILD., Methods: Twelve explanted lungs from patients with SSc-ILD were used to analyze gene expression from formalin-fixed paraffin-embedded lung tissues with varying stages of ILD (n = 18) and control lung tissue (n = 6). The SSc-ILD tissues were stratified into three ROIs: inflammatory, prefibrotic, and fibrotic using histological assessments to define a longitudinal simulation of early to late phases of SSc-ILD. The nanoString (nS) nCounter Human Fibrosis Panel was used to profile the transcriptome in the regions of interest. Validation of potential targetswas performed with immunohistochemistry in the same tissues that were used for transcriptome analysis., Results: To validate our simulation model, we performed subgroup analysis that showed an incremental increase in pathway scores related to the severity of fibrosis. Ctrl vs SSc-ILD comparison demonstrated 24 differentially expressed genes, two of which had the most pronounced p-values. Cyclin-dependent kinase inhibitor (cdkn2c) was overexpressed (P = 0.00052) in SSc-ILD compared to ctrl, while expression of Pellino E3 ubiquitin-protein ligase 1 (peli1) showed lower expression (P = 0.0012). Additionally, in all four groups, cdkn2c and peli1 gene expression showed an incremental increase and decrease, respectively. Immunohistochemistry of cdkn2c showed consistent results with the nS analysis., Conclusion: More cdkn2c and less peli1 expression were associated with more advanced stages of SSc-ILD on histologic assessment. We report the potential of the cell cycle inhibitor and senescence marker, cdkn2c (p18) to be associated with fibrosis progression., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Virtual reality (VR) is a promising tool in a multimodal analgesic approach; however, evidence regarding virtual reality for postsurgical pain is limited. This study investigates the initial effectiveness and feasibility of self-administered virtual reality in postsurgical pain management., Methods: Patients reporting a postsurgical pain score ≥4 were randomized for control or VR, stratified for 3 interventions with varying levels of immersion and interaction. Subjects were instructed to use virtual reality as add-on treatment at least 3 times a day for 10 minutes on days 2 till 4 postoperatively. Primary outcome was the mean daily pain intensity. Results of pain scores were related to patient and intervention characteristics, to explore which characteristics interact with virtual reality effects. Secondary outcomes were analgesic use, anxiety, stress, and feasibility., Results: One hundred patients were included in the analyses: 37 in the control group and 63 for VR. VR did not demonstrate a significant effect on self-reported pain scores (P = .43), nor were specific patient or intervention characteristics associated with greater VR effects. Analgesic usage did not differ between groups. However, there was a trend toward greater cumulative percentages of patients achieving a 30% pain reduction, and significantly lower daily experienced stress (P = .01) and anxiety (P = .03) levels in VR intervention groups. VR was used less than prescribed, mainly because of illness and pain. Adverse events included disorientation, nausea, and fatigue., Conclusions: This explorative study did not demonstrate initial effectiveness of VR as add-on pain treatment regarding pain and analgesic use; however, VR positively affected stress and anxiety. VR is safe and suitable for a wide target audience, and feasibility differed between interventions. Personalizing and improving VR technology may enhance its effectiveness., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Post-COVID-19 syndrome (PCS) remains a major health issue worldwide, while its pathophysiology is still poorly understood. Systemic oxidative stress (OS) may be involved in PCS, which is reflected by lower circulating free thiols (R-SH, sulfhydryl groups), as they are receptive to rapid oxidation by reactive species. This study aimed to investigate the longitudinal dynamics of serum R-SH after SARS-CoV-2 infection and its association with the development of PCS in individuals with mild COVID-19., Methods: Baseline serum R-SH concentrations were measured and compared between 135 non-hospitalized COVID-19 subjects and 82 healthy controls (HC). In COVID-19 subjects, serum R-SH concentrations were longitudinally measured during the acute disease phase (up to 3 weeks) and at 3, 6, and 12 months of follow-up, and their associations with relevant clinical parameters were investigated, including the development of PCS., Results: Baseline albumin-adjusted serum R-SH were significantly reduced in non-hospitalized COVID-19 subjects as compared to HC (p = 0.041), reflecting systemic OS. In mild COVID-19 subjects, trajectories of albumin-adjusted serum R-SH levels over a course of 12 months were longitudinally associated with the future presence of PCS 18 months after initial infection (b = -9.48, p = 0.023)., Conclusion: Non-hospitalized individuals with COVID-19 show evidence of systemic oxidative stress, which is longitudinally associated with the development of PCS. Our results provide a rationale for future studies to further investigate the value of R-SH as a monitoring biomarker and a potential therapeutic target in the development of PCS., Competing Interests: Declaration of competing interest A.R.B. has received a research grant from Janssen Pharmaceuticals and received speaker's fees from AbbVie, outside the submitted work. All other authors have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Vascular calcification is associated with increased mortality in patients with cardiovascular disease. Secondary calciprotein particles are believed to play a causal role in the pathophysiology of vascular calcification. The maturation time (T 50 ) of calciprotein particles provides a measure of serum calcification propensity. We compared T 50 between patients with ST-segment-elevated myocardial infarction and control subjects and studied the association of T 50 with cardiovascular risk factors and outcome., Methods: T 50 was measured by nephelometry in 347 patients from the GIPS-III trial (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction: a Randomized Controlled Trial) and in 254 matched general population controls from PREVEND (Prevention of Renal and Vascular End-Stage Disease). We also assessed the association between T 50 and left ventricular ejection fraction, as well as infarct size, the incidence of ischemia-driven reintervention during 5 years of follow-up, and serum nitrite as a marker of endothelial dysfunction., Results: Patients with ST-segment-elevated myocardial infarction had a significantly lower T 50 (ie, higher serum calcification propensity) compared with controls (T 50 : 289±63 versus 338±56 minutes; P <0.001). In patients with ST-segment-elevated myocardial infarction, lower T 50 was associated with female sex, lower systolic blood pressure, lower total cholesterol, lower LDL (low-density lipoprotein) cholesterol, lower triglycerides, and higher HDL (high-density lipoprotein) cholesterol but not with circulating nitrite or nitrate. Ischemia-driven reintervention was associated with higher LDL ( P =0.03) and had a significant interaction term for T 50 and sex ( P =0.005), indicating a correlation between ischemia-driven reintervention and T 50 above the median in men and below the median in women, between 150 days and 5 years of follow-up., Conclusions: Serum calcification propensity is increased in patients with ST-segment-elevated myocardial infarction compared with the general population, and its contribution is more pronounced in women than in men. Its lack of/inverse association with nitrite and blood pressure confirms T 50 to be orthogonal to traditional cardiovascular disease risk factors. Lower T 50 was associated with a more favorable serum lipid profile, suggesting the involvement of divergent pathways of calcification stress and lipid stress in the pathophysiology of myocardial infarction., Competing Interests: A. Pasch is a founder and employee of Calciscon AG, Switzerland, which commercializes the T50 test. The other authors report no conflicts.

Prolonged air leakage (AL) following pulmonary resections leads to prolonged hospital stay and post-operative complications. Intra- and postoperative quantification of AL might be useful for improving treatment decisions, but these measurements have not been characterised. AL calculations based on inspiratory and expiratory tidal volumes were investigated in an Intensive Care Unit mechanical ventilator circuit (Servo-I). AL was also measured by a digital chest drainage system. This study shows that AL measurements increase in accuracy when corrected for baseline deviations (R: 0.904 > 0.997, p  < 0.001). Bland-Altman analysis revealed a funnel-shape, indicative of a detection threshhold. Corrected measurements were most accurate when averaged over five breaths and AL was >500 mL/min, with an estimated mean systemic bias of 7.4% (95%-limits of agreement [LoA]: 1.1%-13.7%) at 500 mL/min air leak. Breath-by-breath analysis showed most accurate results at AL >20 mL/breath (R: 0.989-0.991, p  < 0.001) at tidal volumes between 350-600 mL. The digital drain had a mean systemic bias of -11.1% (95%-LoA: -18.9% to -3.3%) with homogenous scatter in Bland-Altman analysis and a strong correlation to the control measurement over a large range (0-2000mL/min, R: 0.999, p  < 0.001). This study indicates that the Servo-I can be used for air leak quantification in clinically relevant ranges (>500 mL/min), but is unsuited for small leak detection due to a detection threshold. Researchers and clinicians should be aware of varying accuracy and interoperability characteristics between AL measurement devices.

Ex situ heart perfusion (ESHP) has emerged as an important strategy to preserve donation after brain death (DBD) and donation after circulatory death (DCD) donor hearts. Clinically, both DBD and DCD hearts are successfully preserved using ESHP. Viability assessment is currently based on biochemical values, while a reliable method for graft function assessment in a physiologic working mode is unavailable. As functional assessment during ESHP has demonstrated the highest predictive value of outcome post-transplantation, this is an important area for improvement. In this study, a novel method for ex situ assessment of left ventricular function with pressure-volume loop analyses is evaluated. Ovine hearts were functionally evaluated during normothermic ESHP with the novel pressure-volume loop system. This system provides an afterload and adjustable preload to the left ventricle. By increasing the preload and measuring end-systolic elastance, the system could successfully assess the left ventricular function. End-systolic elastance at 60 min and 120 min was 2.8 ± 1.8 mmHg/mL and 2.7 ± 0.7 mmHg/mL, respectively. In this study we show a novel method for functional graft assessment with ex situ pressure-loop analyses during ESHP. When further validated, this method for pressure-volume assessments, could be used for better graft selection in both DBD and DCD donor hearts., Competing Interests: Authors BW, AvP, and FN were employed by XVIVO. ME holds a patent with XVIVO. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ertugrul, Puspitarani, Wijntjes, Vervoorn, Ballan, van der Kaaij, van Goor, Westenbrink, van der Plaats, Nijhuis, van Suylen and Erasmus.)

Placental macrophages, which include maternal decidual macrophages and fetal Hofbauer cells, display a high degree of phenotypical and functional plasticity. This provides these macrophages with a key role in immunologically driven events in pregnancy like host defense, establishing and maintaining maternal-fetal tolerance. Moreover, placental macrophages have an important role in placental development, including implantation of the conceptus and remodeling of the intrauterine vasculature. To facilitate these processes, it is crucial that placental macrophages adapt accordingly to the needs of each phase of pregnancy. Dysregulated functionalities of placental macrophages are related to placental malfunctioning and have been associated with several adverse pregnancy outcomes. Although fetal growth restriction is specifically associated with placental insufficiency, knowledge on the role of macrophages in fetal growth restriction remains limited. This review provides an overview of the distinct functionalities of decidual macrophages and Hofbauer cells in each trimester of a healthy pregnancy and aims to elucidate the mechanisms by which placental macrophages could be involved in the pathogenesis of fetal growth restriction. Additionally, potential immune targeted therapies for fetal growth restriction are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bezemer, Faas, van Goor, Gordijn and Prins.)

Objectives: More effective lung sealants are needed to prevent prolonged pulmonary air leakage (AL). Polyoxazoline-impregnated gelatin patch (N-hydroxysuccinimide ester functionalized poly(2-oxazoline)s; NHS-POx) was promising for lung sealing ex vivo. The aim of this study is to confirm sealing effectiveness in an in vivo model of lung injury., Methods: An acute aerostasis model was used in healthy adult female sheep, involving bilateral thoracotomy, amputation lesions (bronchioles Ø > 1.5 mm), sealant application, digital chest tube for monitoring AL, spontaneous ventilation, obduction and bursting pressure measurement. Two experiments were performed: (i) 3 sheep with 2 lesions per lung (N = 4 NHS-POx double-layer, N = 4 NHS-POx single-layer, N = 4 untreated) and (ii) 3 with 1 lesion per lung (N = 3 NHS-POx single-layer, N = 3 untreated). In pooled linear regression, AL was analysed per lung (N = 7 NHS-POx, N = 5 untreated) and bursting pressure per lesion (N = 11 NHS-POx, N = 7 untreated)., Results: Baseline AL was similar between groups (mean 1.38-1.47 l/min, P = 0.90). NHS-POx achieved sealing in 1 attempt in 8/11 (72.7%) and in 10/11 (90.9%) in >1 attempt. Application failures were only observed on triangular lesions requiring 3 folds around the lung. No influences of methodological variation between experiments was detected in linear regression (P > 0.9). AL over initial 3 h of drainage was significantly reduced for NHS-POx [median: 7 ml/min, length of interquartile range: 333 ml/min] versus untreated lesions (367 ml/min, length of interquartile range: 680 ml/min, P = 0.036). Bursting pressure was higher for NHS-POx (mean: 33, SD: 16 cmH2O) versus untreated lesions (mean: 19, SD: 15 cmH2O, P = 0.081)., Conclusions: NHS-POx was effective for reducing early AL, and a trend was seen for improvement of bursting strength of the covered defect. Results were affected by application characteristics and lesion geometry., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Introduction: Intraoperative blood loss and postoperative hemorrhage affect outcomes after liver resection. GATT-Patch is a new flexible, pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with N-hydroxy-succinimide polyoxazoline. We evaluated safety and performance of the GATT-Patch for hemostasis at the liver resection plane., Methods: Adult patients undergoing elective open liver surgery were recruited in three centers. GATT-Patch was used for minimal to moderate bleeding at the liver resection plane. The primary endpoint was hemostasis of the first-treated bleeding site at 3 min versus a prespecified performance goal of 65.4%., Results: Two trial stages were performed: I (n = 8) for initial safety and II (n = 39) as the primary outcome cohort. GATT-Patch was applied in 47 patients on 63 bleeding sites. Median age was 60.0 (range 25-80) years and 70% were male. Most (66%) surgeries were for colorectal cancer metastases. The primary endpoint was met in 38 out of 39 patients (97.4%; 95% confidence interval: 84.6%-99.9%) versus 65.4% (P < 0.001). Of all the 63 bleeding sites, hemostasis was 82.7% at 30, 93.7% at 60, and 96.8% at 180 s. No reoperations for rebleeding or device-related issues occurred., Conclusions: When compared to a performance goal derived from state-of-the-art hemostatic agents, GATT-Patch for the treatment of minimal to moderate bleeding during liver surgery successfully and quickly achieved hemostasis with acceptable safety outcomes. (ClinicalTrials.gov Identifier: NCT04819945)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Individuals with type 2 diabetes (T2D) have a higher risk of cardiovascular disease, compared with those without T2D. The serum T50 test captures the transformation time of calciprotein particles in serum. We aimed to assess whether serum T50 predicts cardiovascular mortality in T2D patients, independent of traditional risk factors., Methods: We analyzed 621 individuals with T2D in this prospective cohort study. Cox regression models were performed to test the association between serum T50 and cardiovascular and all-cause mortality. Causes of death were categorized according to ICD-10 codes. Risk prediction improvement was assessed by comparing Harrell's C for models without and with T 50. RESULTS: The mean age was 64.2 ± 9.8 years, and 61% were male. The average serum T50 time was 323 ± 63 min. Higher age, alcohol use, high-sensitive C-reactive protein, and plasma phosphate were associated with lower serum T 50 levels. Higher plasma triglycerides, venous bicarbonate, sodium, magnesium, and alanine aminotransferase were associated with higher serum T50 levels. After a follow-up of 7.5[5.4-10.7] years, each 60 min decrease in serum T50 was associated with an increased risk of cardiovascular (fully adjusted HR 1.32, 95% CI 1.08-1.50, and p = 0.01) and all-cause mortality (HR 1.15, 95%CI 1.00-1.38, and p = 0.04). Results were consistent in sensitivity analyses after exclusion of individuals with estimated glomerular filtration rate <45 or <60 mL/min/1.73 m 2 and higher plasma phosphate levels., Conclusions: Serum T50 improves prediction of cardiovascular and all-cause mortality risk in individuals with T2D. Serum T50 may be useful for risk stratification and to guide therapeutic strategies aiming to reduce cardiovascular mortality in T2D., (© 2024 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)