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Christoffer Valdorff Madsen,1,2 Lars Nannestad Jørgensen,3 Bonna Leerhøy,3 Ismail Gögenur,4 Sarah Ekeloef,4 Ahmad Sajadieh,1 Helena Domínguez1,2 1Department of Cardiology, Bispebjerg-Frederiksberg Hospital, Frederiksberg, Denmark; 2Department of Biomedical Science, Copenhagen University, Copenhagen, Denmark; 3Digestive Disease Center, Bispebjerg Hospital, Copenhagen, Denmark; 4Department of Surgery, Zealand University Hospital, Køge, DenmarkCorrespondence: Helena DomínguezDepartment of Cardiology, Bispebjerg-Frederiksberg Hospital, Nordre Fasanvej 57, Frederiksberg 2000, DenmarkTel +45 38166068Fax +45 22989343Email mdom0002@regionh.dkAbstract: Postoperative atrial fibrillation (POAF) in relation to abdominal surgery can cause clinical deterioration, prolonged hospitalization, admittance to intensive care units, stroke and increased mortality. The current review focus on patients developing POAF in relation to abdominal surgery and aims to present the current knowledge on predictors of this condition. Furthermore, predictors identified in other surgical populations that may be transferable and guide future research within the field of abdominal surgery will be presented. A systematic literature search of patients undergoing abdominal surgery and developing POAF was performed on PubMed and Embase. All types of study interventions, comparators and designs were included. All studies included reported POAF as primary or secondary outcome. All peer-reviewed English full-text manuscripts regardless of publication date were included. We included five studies out of the 149 unique records identified. Age, congestive heart failure, hypertension, vascular disease and surgical approach are risk factors associated with the development of POAF. Furthermore, inflammation biomarkers, dobutamine stress echocardiography and cardiac single-photon emission computed tomography can predict POAF. Insights from other surgical cohorts reveal that other biomarkers (ie, brain natriuretic peptide (BNP) and N-terminal pro-BNP), electrocardiography and echocardiography can be used to predict POAF and may be applied in future research projects within the field of abdominal surgery. In conclusion, very scarce evidence is currently available in predicting POAF after abdominal surgery. However, predicting POAF seems possible and feasible, why the authors encourage readers to initiate new research to close the current knowledge gap and improve clinical management.Keywords: postoperative atrial fibrillation, surgery, biomarkers, electrocardiogram, echocardiography, complications

Frederik Berrevoet,1 Carl Doerhoff,2 Filip Muysoms,3 Steven Hopson,4 Marco Gallinella Muzi,5 Simon Nienhuijs,6 Eric Kullman,7 Tim Tollens,8 Mark R Schwartz,9 Karl LeBlanc,10 Vic Velanovich,11 Lars Nannestad Jørgensen12 1Department of General and Hepatopancreaticobiliary Surgery, Ghent University Hospital, Ghent, Belgium; 2General Surgery, Surgicare of Missouri, Jefferson City, MO, USA; 3Department of Surgery, AZ Maria Middelares Ghent, Ghent, Belgium; 4Bon Secours Hernia Center, Mary Immaculate Hospital, Newport News, VA, USA; 5University Hospital Tor Vergata, Rome, Italy; 6Catharina Hospital, Eindhoven, the Netherlands; 7Medicinskt Centrum Linköping, Linköping, Sweden; 8Imelda Hospital-General Surgery Imelda Hospital, Bonheiden, Belgium; 9Monmouth Medical Center, Long Branch, NJ, 10Our Lady of Lakes Regional Medical Center, Baton Rouge, LA, 11Tampa General Hospital, University of South Florida, Tampa, FL, USA; 12Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark Purpose: This study assessed the recurrence rate and other safety and efficacy parameters following ventral hernia repair with a polyester composite prosthesis (Parietex™ Composite Ventral Patch [PCO-VP]).Patients and methods: A single-arm, multicenter prospective study of 126 patients undergoing open ventral hernia repair with the PCO-VP was performed. Patient outcomes were assessed at discharge and at 10 days, 1, 6, 12, and 24 months postoperative.Results: All patients had hernioplasty for umbilical (n = 110, 87.3%) or epigastric hernia (n = 16, 12.7%). Mean hernia diameter was 1.8 ± 0.8 cm. Mean operative time was 36.2 ±15.6 minutes, with a mean mesh positioning time of 8.1 ± 3.4 minutes. Surgeons reported satisfaction with mesh ease of use in 95% of surgeries. The cumulative hernia recurrence rate at 1 year was 2.8% (3/106). Numeric Rating Scale (NRS) pain scores showed improvement from 2.1 ± 2.0 at preoperative baseline to 0.5 ± 0.7 at 1 month postoperative (P < 0.001), and this low pain level was maintained at 12 months postsurgery (P < 0.001). The mean global Carolina’s Comfort Scale® (CCS) score improved postoperatively from 3.8 ± 6.2 at 1 month to 1.6 ± 3.5 at 6 months (P < 0.001). One patient was unsatisfied with the procedure.Conclusion: This 1-year interim analysis using PCO-VP for primary umbilical and epigastric defects shows promising results in terms of mesh ease of use, postoperative pain, and patient satisfaction. Recurrence rate is low, but, as laparoscopic evaluation shows a need for patch repositioning in some cases, an accurate surgical technique remains of utmost importance. Keywords: intraperitoneal mesh, epigastric hernia, umbilical hernia, pain

Frederik Helgstrand,1 Lars Nannestad Jorgensen2 1Department of Surgery, Køge Hospital, University of Copenhagen, Køge, Denmark; 2Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen NV, Denmark Aim: The Danish Ventral Hernia Database (DVHD) provides national surveillance of current surgical practice and clinical postoperative outcomes. The intention is to reduce postoperative morbidity and hernia recurrence, evaluate new treatment strategies, and facilitate nationwide implementation of evidence-based treatment strategies. This paper describes the design and purpose of DVHD. Study population: Adult (≥18 years) patients with a Danish Civil Registration Number and undergoing surgery under elective or emergency conditions for ventral hernia in a Danish surgical department from 2007 and beyond. A total of 80% of all ventral hernia repairs performed in Denmark were reported to the DVHD. Main variables: Demographic data (age, sex, and center), detailed hernia description (eg, type, size, surgical priority), and technical aspects (open/laparoscopic and mesh related factors) related to the surgical repair are recorded. Data registration is mandatory. Data may be merged with other Danish health registries and information from patient questionnaires or clinical examinations. Descriptive data: More than 37,000 operations have been registered. Data have demonstrated high agreement with patient files. The data allow technical proposals for surgical improvement with special emphasis on reduced incidences of postoperative complications, hernia recurrence, and chronic pain. Conclusion: DVHD is a prospective and mandatory registration system for Danish surgeons. It has collected a high number of operations and is an excellent tool for observing changes over time, including adjustment of several confounders. This national database registry has impacted on clinical practice in Denmark and led to a high number of scientific publications in recent years. Keywords: database management system, registries, ventral hernia, outcome, national, morbidity

Background: The hemibiotrophic fungus Zymoseptoria tritici causing Septoria tritici blotch (STB), is a devastating foliar pathogen of wheat worldwide. A common group of fungicides used to control STB are the demethylation inhibitors (DMIs). DMI fungicides restrict fungal growth by inhibiting the sterol 14-α-demethylase, a protein encoded by CYP51 gene and essential for maintaining fungal cell permeability. However, the adaptation of Z. tritici populations in response to intensive and prolonged DMI usage has resulted in a gradual shift towards reduced sensitivity to this group of fungicides. In this study, 311 isolates were collected pre-treatment from nine wheat-growing regions in Europe in 2019. These isolates were analysed by high-throughput amplicon-based sequencing of nine housekeeping genes and the CYP51 gene., Results: Analyses based on housekeeping genes and the CYP51 gene revealed a lack of population structure in Z. tritici samples irrespective of geographical origin. Minimum spanning network (MSN) analysis showed clustering of multilocus genotypes (MLGs) based on CYP51 haplotypes, indicating an effect of selection due to DMI fungicide use. The majority of the haplotypes identified in this study have been reported previously. The diversity and frequencies of mutations varied across regions., Conclusion: Using a high-throughput amplicon-sequencing approach, we found several mutations in the CYP51 gene combined in different haplotypes that are likely to cause fungicide resistance. These mutations occurred irrespective of genetic background or geographical origin. Overall, these results contribute to the development of effective and sustainable risk monitoring for DMI fungicide resistance. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Aim: Although vital signs have a well-described 24-h cyclic variation (circadian rhythm), this variation is often not considered in clinical vital sign monitoring despite being influenced by physiologic stress from complications. This study aimed to evaluate the lowest heart rate at night (night-nadir) (NN-HR) as a novel risk marker for serious adverse events (SAE) in postoperative patients, rather than the average nocturnal heart rate., Methods: This was a propensity-matched nested case-control study of continuously monitored vital sign data (heart rate (HR), respiration rate, oxygen saturation and blood pressure) for up to 5 days after major non-cardiac surgery. The primary outcome was any SAE that occurred up to 24 h after a circadian value calculation. We compared NN-HR between patients who developed SAE and those who did not during similar postoperative periods., Results: Out of 588 patients, 104 (17.8 %) experienced an SAE during the monitored period and were matched with a median of 201 controls. The NN-HR was significantly higher in patients with impending SAE (median 74.0 bpm [IQR 68.2-81.8] vs. 68.3 bpm [IQR 61.5-76.0], p < 0.001). An NN-HR threshold of >67 bpm identified patients at increased risk (risk ratio 2.43, 99 % CI 1.24-5.00) for SAE, however with only moderate predictive performance (F1 score 0.58)., Conclusion: Absence of HR below 67 bpm at night, was significantly associated with increased SAE risk, highlighting the potential value of NN-HR as a monitoring target.The potential clinical utility of monitoring NN-HR to prevent SAE warrants further prospective investigation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CSM, EKA have founded a company, WARD247 ApS, with the aim of pursuing the regulatory and commercial activities of the WARD-project (developing a clinical support system for continuous wireless monitoring of vital signs). WARD247 ApS has obtained a licence agreement for any WARD-project software and patents. One patent has been filed: “Wireless Assessment of Respiratory and circulatory Distress (WARD), EP 21184712.4 and EP 21205557.8”., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Implementation of screening modalities has reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy., Methods: In this prospective multicenter study, 8 blood-based biomarkers (carcinoembryonic antigen, ferritin, high-sensitivity C-reactive protein, human epididymis protein 4, Cyfra21-1, hepsin, interleukin 8, and osteoprotegerin) were investigated in 1977 FIT-positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on Architect i2000, Architect c8000 (both from Abbott, Chicago, Ill, USA), or Luminex xMAP machines (MilliporeSigma, St. Louis, Mo, USA). FIT analyses and blood-based biomarker data were combined with clinical data (ie, age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity., Results: The cohort included individuals with CRC (n = 240), adenomas (n = 938), or no neoplastic lesions (n = 799). The cross-validated algorithm combining the 8 biomarkers, quantitative FIT result, and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (area under the receiver operating characteristic curve, 0.77 vs 0.67, respectively; P < .001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the areas under the receiver operating characteristic curve were 0.68 versus 0.64 for the algorithm and FIT model, respectively., Conclusions: The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenoma detection rates or vice versa., Competing Interests: Disclosure The following authors disclosed financial relationships: C. Therkildsen: Research grants from Abbott Diagnostics Division and New Day Diagnostics. J. Liggett: Full-time employee of New Day Diagnostics. C. M. T. Beertsen: Research grant from Abbott Diagnostics Division. S. Gawel: Full-time employee of Abbott Diagnostics Division. E. Mayer: Full-time employee of New Day Diagnostics. G. J. Davis: Full-time employee of Abbott Diagnostics Division. All analyses were made blinded to J. Liggett, S. Gawel, E. Mayer, and G. J. Davis, whereafter molecular data were merged with clinical data by the academic team at Copenhagen University Hospital, Hvidovre, which also performed statistical analyses. Although statistical analyses were discussed with the industrial partners, the academic research team at Hvidovre Hospital decided on and performed the formal analyses independently. All other authors disclosed no financial relationships. Patient inclusion, sample collection and storage, and salary for all of the clinical and academic research team was provided by external funding granted to Hans Jørgen Nielsen and the Colorectal Cancer Research Unit at Hvidovre Hospital. This work was supported by the Andersen Foundation, Augustinus Foundation, Beckett Foundation, Inger Bonnéns Fund, Hans and Nora Buchards Fund, Walter Christensen Fund, P. M. Christiansen Fund, Kong Chr. X’s Fund, Aase and Ejnar Danielsens Fund, Family Erichsens Fund, Knud and Edith Eriksens Fund, Svend Espersens Fund, Elna and Jørgen Fagerholts Cancer Research Foundation, Sofus Carl Emil Friis Scholarship, Torben and Alice Frimodts Fund, Eva and Henry Frænkels Fund, Gangsted Foundation, Thora and Viggo Groves Memorial Scholarship, H-Foundation, Erna Hamiltons Scholarship, Søren and Helene Hempels Scholarship, Sven and Ina Hansens Fund, Henrik Henriksen Fund, Carl and Ellen Hertz Scholarship, Jørgen Holm and Elisa F. Hansen Memorial Scholarship, Jochum Foundation, Kurt and Ingeborg Daell's Foundation, Kornerup Foundation, Linex Foundation, Dagmar Marshalls Fund, Midtjyske Fund, Axel Muusfeldts Fund, Børge Nielsens Fund, Michael Hermann Nielsens Memorial Scholarship, Arvid Nilssons Fund, Obelske Family Fund, Krista and Viggo Petersens Fund, Willy and Ingeborg Reinhards Fund, Kathrine and Vigo Skovgaards Fund, Toyota Foundation, Vissing Foundation, P. Carl Petersen Fund, Danish Cancer Research Foundation, and Hvidovre Hospitals Research Fund. Furthermore, the collaborative companies, Abbott Diagnostics Division and New Day Diagnostics, have sponsored the study by providing the reagents, facilities, and staff required for the molecular analyses as well as a sample fee to Hvidovre Hospital for sample requisition., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. All rights reserved.)

Fusarium head blight (FHB) continues to be a major problem in wheat production and is considered a disease complex caused by several fungal pathogens including Fusarium culmorum, F. graminearum and F. equiseti. With the objective of investigating diversity of mycoviruses in FHB-associated pathogens, we isolated Fusarium spp. from six wheat (Triticum aestivum) cultivars. In total, 56 Fusarium isolates (29 F. culmorum, 24 F. graminearum, one F. equiseti) were screened for mycoviruses by extracting and sequencing double-stranded RNA. We found that a large proportion of Fusarium isolates (46 %) were infected with mycoviruses. F. culmorum, previously described to harbor only one mycovirus, tended to host more viruses than F. graminearum, with a few isolates harboring seven mycoviruses simultaneously. Based on the RNA-dependent RNA polymerase domain analysis, ten were positive-sense single-stranded RNA viruses (related to viruses from families Mitoviridae, Botourmiaviridae, Narnaviridae, Tymoviridae, Gammaflexiviridae, as well as proposed Ambiguiviridae and ormycovirus viral group), one was double-stranded RNA virus (Partitiviridae), and five were negative-sense single-stranded RNA viruses (related to members in the families of Yueviridae, Phenuiviridae, Mymonaviridae, as well as proposed Mycoaspiviridae). Five mycoviruses were shared between F. graminearum and F. culmorum. These results increase our general understanding of mycovirology. To our knowledge, this is the first in-depth report of the mycovirome in F. culmorum and the first report on the diversity of mycoviruses from Danish isolates of FHB-causing fungi in general., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup., Methods: ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722)., Results: After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6)., Conclusions: Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate All participants provided informed consent and the study was approved by the Danish Committees on Health Research Ethics (j. no 1-10-72-223-14, H-4-2013-050, and 1-10-72-3-18) and reported according to STROBE guidelines [36]., (© 2024. The Author(s).)

Azole-resistant Aspergillus fumigatus (ARAf) fungi have been found inconsistently in the environment in Denmark since 2010. During 2018-2020, nationwide surveillance of clinical A. fumigatus fungi reported environmental TR 34 /L98H or TR 46 /Y121F/T289A resistance mutations in 3.6% of isolates, prompting environmental sampling for ARAf and azole fungicides and investigation for selection of ARAf in field and microcosmos experiments. ARAf was ubiquitous (20% of 366 samples; 16% TR 34 /L98H- and 4% TR 46 /Y121F/T289A-related mechanisms), constituting 4.2% of 4,538 A. fumigatus isolates. The highest proportions were in flower- and compost-related samples but were not correlated with azole-fungicide application concentrations. Genotyping showed clustering of tandem repeat-related ARAf and overlaps with clinical isolates in Denmark. A. fumigatus fungi grew poorly in the field experiment with no postapplication change in ARAf proportions. However, in microcosmos experiments, a sustained complete (tebuconazole) or partial (prothioconazole) inhibition against wild-type A. fumigatus but not ARAf indicated that, under some conditions, azole fungicides may favor growth of ARAf in soil.

Purpose: The study objective is to document value created by real-world evidence from the Abdominal Core Health Quality Collaborative (ACHQC) for regulatory decisions. The ACHQC is a national effort that generates data on hernia repair techniques and devices., Methods: Two retrospective cohort evaluations compared cost and time of ACHQC analyses to traditional postmarket studies. The first analysis was based on 25 reports submitted to the European Medicines Agency of 20 mesh products for post-market surveillance. A second analysis supported label expansion submitted to the Food and Drug Administration, Center for Devices and Radiological Health for a robotic-assisted surgery device to include ventral hernia repair. Estimated costs of counterfactual studies, defined as studies that might have been done if the registry had not been available, were derived from a model described in the literature. Return on investment, percentage of cost savings, and time savings were calculated., Results: 45,010 patients contributed to the two analyses. The cost and time differences between individual 25 ACHQC analyses (41,112 patients) and traditional studies ranged from $1.3 to $2.2 million and from 3 to 4.8 years, both favoring use of the ACHQC. In the second label expansion analysis (3,898 patients), the estimated return on investment ranged from 11 to 461% with time savings of 5.1 years favoring use of the ACHQC., Conclusions: Compared to traditional postmarket studies, use of ACHQC data can result in cost and time savings when used for appropriate regulatory decisions in light of key assumptions., (© 2024. The Author(s).)

Objective: To describe the management of T1 colon cancer in a retrospective study of a national cancer registry., Background: There is increasing interest in the potential of local excision (LE) as an organ-preserving treatment for early colon cancer. However, accurate identification of patients who may have lymph node metastases (LNM) and require further surgery is a major challenge., Methods: Patients diagnosed with T1 colon cancer in Denmark from 2016 to 2020 were included and divided according to treatment: polypectomy (referred to as LE), upfront colectomy and completion colectomy. Primary outcome was the proportion of patients diagnosed by LE. Secondary outcomes included the rate of LNM, the association of histopathological risk factors with LNM, and overall survival., Results: 1,749 patients were included, and 1,022 patients (58.4%) underwent initial LE. The rate of R1 margins after initial LE was 31.0%. Colectomy was performed in 1,160 patients (upfront in 727, completion in 433), of whom 58.3% had pT1 cancer. The rate of LNM was 11.5%. Rates of LNM were similar in patients undergoing upfront or completion colectomy (10.2% vs 12.4%, P=0.392), and in patients with any single histopathological risk factor compared to those with none (8.9% vs 10.6%, P=0.565). Although overall survival was significantly shorter in patients undergoing LE alone, no association between survival and treatment strategy was found on multivariable analysis., Conclusions: LE is the most common mode of diagnosis in patients with T1 colon cancer and does not negatively impact survival and postoperative outcomes. Current strategies to stratify patients to completion surgery appear insufficient, and more robust predictors are needed., Competing Interests: Conflicts of Interest and Sources of Funding: Dr. Krarup has received personal fees and served as proctor and speaker for Intuitive Surgical, and received a research grant from Pharmacosmos A/S. The remaining authors declare no conflicts of interest. The current study was supported by the Arvid Nilsson’s Foundation, Bispebjerg and Frederiksberg Hospitals’ Internal Research Grants, the Else and Mogens Wedell-Wedellsborg’s Foundation, the Inge and Jørgen Larsen’s Memorial Foundation, and the NEYE Foundation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aim: Scarce data exist on the true incidence of postoperative atrial fibrillation (POAF) after acute abdominal surgery and associated outcomes. The current study aimed to identify the frequencies of clinically recognized POAF and associated complications, along with their risk factors., Methods: This study was a prospective, single-center cohort study of unselected adult patients referred for acute abdominal surgery during a 3-month period. Through careful review, demographics, comorbidity, and surgical characteristics were prospectively drawn from medical charts. The primary outcome was clinically recognized POAF occurring in-hospital. Logistic regression was used to determine the risk factors of POAF and associated complications. A subgroup was enrolled in a feasibility study of peri- and postoperative continuous cardiac rhythm monitoring., Results: In total, 450 patients were enrolled. Clinically recognized in-hospital POAF was observed in 22 patients (4.9%). All cases were observed in patients aged ≥60 years, corresponding to 22 of 164 patients (13.4%). Multiple risk factors were observed, such as age, prior atrial fibrillation, heart failure, hypertension, diabetes mellitus, chronic renal disease, and major (vs. minor) surgery. POAF was associated with severe in-hospital complications (POAF group 45.5% vs. non-POAF group 8.6%, p < .001) and in-hospital mortality (POAF group 13.6% vs. non-POAF group 3.0%, p = .043). In total, 295 patients were monitored by continuous cardiac rhythm monitoring for 12,148 h, yielding five patients with asymptomatic AF., Conclusions: In conclusion, this prospective study of POAF in patients undergoing acute abdominal surgery showed that one in 20 patients developed clinically recognized in-hospital POAF. Multiple risk factors of POAF were identified. POAF was associated with severe complications up to 30 days after surgery., (© 2023 Acta Anaesthesiologica Scandinavica Foundation.)

Background: National colorectal cancer screening commenced in Denmark in 2014. Little is known about the effects of organized colorectal cancer screening on intraoperative and postoperative events. The aim of this nationwide cohort study was to evaluate the difference in intraoperative and postoperative outcomes between patients with screen-detected colorectal cancer and non-screen-detected colorectal cancer within the first 90 days after surgery., Methods: National register data were collected for Danish residents diagnosed with colorectal cancer between January 2014 and March 2018. Outcomes for the two cohorts were reported as relative risk or weighted mean difference. Intraoperative outcomes were blood loss, blood transfusion, tumour perforation, and organ lesion. Postoperative outcomes were complications (surgical and non-surgical) and 90-day mortality. Discrete data estimates were calculated from a general linear model. Analyses were adjusted for potential healthy user bias with respect to sex, age, location of the cancer (colon/rectum), and Charlson co-morbidity index., Results: In total, 10 606 patients were included. Compared with patients in the non-screen-detected colorectal cancer group (4497 patients), patients in the screen-detected colorectal cancer group (6109 patients) had reduced intraoperative blood loss (-52 mL, 95% c.i. -67 to -37, P < 0.001), a shorter duration of hospitalization (-2.3 days, 95% c.i. -2.8 to -1.8, P < 0.001), and reduced rates of intraoperative organ lesion (0.76, 95% c.i. 0.59 to 0.99, P = 0.042), surgical complications (0.79, 95% c.i. 0.73 to 0.87, P < 0.001), non-surgical complications (0.68, 95% c.i. 0.60 to 0.78, P < 0.001), and 90-day mortality (0.29, 95% c.i. 0.21 to 0.39, P < 0.001)., Conclusion: In comparison with non-screen-detected colorectal cancer, surgery for screen-detected colorectal cancer remains associated with improvement in several intraoperative and early postoperative outcomes after considering healthy user bias., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Objective: During the last two decades, organised colorectal cancer (CRC) screening has been widely implemented. It remains to be established if screen-detected CRC (SD-CRC) is associated with reduced long-term requirements for treatment as compared with patients with non-screen-detected CRC (NSD-CRC)., Study Design and Methods: This nationwide cohort study evaluated differences in treatment and healthcare contacts from the date of diagnosis to two years after comparing patients with SD-CRC and NSD-CRC. Data were collected from national healthcare registers, including patients aged 50-75 years and diagnosed with CRC between January 1st 2014 and March 31st 2018. Analyses were stratified into UICC stages and adjusted for sex, 5-year age groups, type of cancer (colonic/rectal), and Charlson comorbidity index score to address healthy user bias., Results: In total, 12,040 patients were included, 4708 with SD-CRC and 7332 with NSD-CRC. In patients with SD-CRC, the duration of hospitalisation and rate of emergency surgery were reduced by 38 % (relative risk [RR] = 0.62) and 66 % (RR = 0.34), respectively. Moreover, this group was characterised by a 75 % reduction in oncological outpatient visits (RR = 0.35) and a reduced number of treatments with chemotherapy (RR = 0.57) and radiotherapy (RR = 0.50). There were no significant differences between the two populations in the rates of metastasectomy and the number of contacts with primary healthcare providers., Conclusion: Compared to patients with NSD-CRC, patients with SD-CRC experience less hospitalisation and treatment within the first two years after diagnosis., (Copyright © 2023 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess the 5-year recurrence rate of incisional hernia repair in Ventral Hernia Working Group (VHWG) 3 hernia with a slowly resorbable mesh., Summary Background Data: Incisional hernia recurs frequently after initial repair. In potentially contaminated hernia, recurrences rise to 40%. Recently, the biosynthetic Phasix mesh has been developed that is resorbed in 12-18 months. Resorbable meshes might be a solution for incisional hernia repair to decrease short- and long-term (mesh) complications. However, long-term outcomes after resorption are scarce., Methods: Patients with VHWG grade 3 incisional midline hernia, who participated in the Phasix trial (Clinilcaltrials.gov: NCT02720042) were included by means of physical examination and computed tomography (CT). Primary outcome was hernia recurrence; secondary outcomes comprised of long-term mesh complications, reoperations, and abdominal wall pain [visual analogue score (VAS): 0-10]., Results: In total, 61/84 (72.6%) patients were seen. Median follow-up time was 60.0 [interquartile range (IQR): 55-64] months. CT scan was made in 39 patients (68.4%). A recurrence rate of 15.9% (95% confidence interval: 6.9-24.8) was calculated after 5 years. Four new recurrences (6.6%) were found between 2 and 5 years. Two were asymptomatic. In total, 13/84 recurrences were found. No long-term mesh complications and/or interventions occurred. VAS scores were 0 (IQR: 0-2)., Conclusions: Hernia repair with Phasix mesh in high-risk patients (VHWG 3, body mass index >28) demonstrated a recurrence rate of 15.9%, low pain scores, no mesh-related complications or reoperations for chronic pain between the 2- and 5-year follow-up. Four new recurrences occurred, 2 were asymptomatic. The poly-4-hydroxybutyrate mesh is a safe mesh for hernia repair in VHWG 3 patients, which avoids long-term mesh complications like pain and mesh infection., Competing Interests: Disclosure: The authors state that they have no proprietary interest in the products named in this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Major abdominal surgery is associated with considerable mortality in the elderly. Anemia has been linked to increased mortality in other types of surgery, such as hip and cardiac surgery. This study aimed to assess the impact of preoperative anemia on mortality in the elderly undergoing major abdominal surgery, and how allogeneic red cell blood transfusion influences mortality in these patients., Materials and Methods: We conducted a single-center, register-based retrospective study on patients, who were aged beyond 60 years and underwent one of 81 open abdominal surgical procedures. Patients operated on during the period from January 1, 2000, to May 31, 2013, were consecutively identified in the Danish National Patient Registry. Plasma hemoglobin was measured within 30 days prior to surgery and the primary endpoint was 30-day postoperative mortality. Information about patient transfusions from the hospital blood bank was available from 1998 to 2010., Results: A total of 3199 patients were included of whom 85% underwent emergency surgery. The total mortality after 30 days was 20%. The median preoperative hemoglobin value of survivors was 7.7 mmol/L vs 6.9 mmol/L in those who died. The difference in hemoglobin values, between those who survived or died, decreased from the pre- to the post-operative phase. The 30-day postoperative mortality was 28%, 20%, and 12% in patients with a preoperative hemoglobin level in the lower, median, and upper quartile respectively. Transfusion therapy was associated with higher postoperative mortality, except in patients with very low hemoglobin values., Conclusion: Preoperative anemia has a clear association with surgically related mortality. The distribution of hemoglobin values in patients with a fatal outcome differs significantly from that of survivors. Red cell transfusion is associated with increased mortality, except in patients with very low hemoglobin values which supports recent guidelines suggesting a restrictive transfusion strategy., (© 2023. The Author(s).)

Background: The effect of organized colorectal cancer (CRC) screening on type of primary treatment remains sparsely investigated. This study evaluated the difference in primary treatment strategy between patients diagnosed with screen-detected (SD-CRC) and non-screen-detected colorectal cancer (NSD-CRC) in a national CRC screening program., Methods: This was a retrospective national register-based cohort study. Data on patients aged between 50 and 75 years and diagnosed with SD-CRC or NSD-CRC were retrieved from the national colorectal cancer screening database and the Danish Colorectal Cancer Group database. Outcomes related to surgical invasiveness were compared between the two cohorts. Differences were expressed as relative risks using log-binomial generalized linear regression models. UICC stage IV specific outcomes were analyzed using the same method. All analyses were adjusted for sex, age, type of cancer (colonic/rectal), and Charlson comorbidity index., Results: The study included 4707 patients with SD-CRC and 7328 with NSD-CRC. Therapeutic flexible endoscopy (SD-CRC: n = 636 vs. NSD-CRC: n = 334, RR: 2.50, P < 0.001), (robotic-assisted) laparoscopic resection ((n = 616 vs. n = 773, RR: 1.27, P < 0.001), n = 2759 vs. n = 3471, RR: 1.11, P < 0.001), and radical resection (n = 3890 vs. n = 4834, RR: 1.02, P = 0.002) were significantly more frequent in the SD-CRC group. The rates of emergency priority (n = 32 vs. n = 562, RR: 0.09, P < 0.001), open surgery (n = 391 vs. n = 1410, RR: 0.53, P < 0.001), supplementary organ resection (n = 259 vs. n = 860, RR: 0.56, P < 0.001), and stoma formation (n = 526 vs. n = 1040, RR: 0.89, P = 0.007) were significantly lower in the SD-CRC group. The rate of patients undergoing surgery with UICC stage IV disease was significantly higher in the SD-CRC group (SD-CRC: n = 262, NSD-CRC: n = 994, RR: 1.43, P < 0.001)., Conclusion: SD-CRC remained associated with less invasive primary surgical treatment following adjustment for potential healthy user bias. UICC stage IV disease may be less advanced in patients with SD-CRC., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT + ) screening population and thereby reduce the colonoscopy burden., Materials and Methods: From the Danish National Colorectal Cancer Screening Program, 4048 FIT + (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling., Results: The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs., Conclusion: A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin., Competing Interests: Disclosure Gerard Davis, Susan Gawel and Frans Martens are all employees of Abbott Laboratories Inc. All other authors declare that they have no competing interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the frequency and duration of hypo- and hyperglycemia, assessed by continuous glucose monitoring (CGM) during and after major surgery, in departments with implemented diabetes care protocols., Summary Background Data: Inadequate glycemic control in the perioperative period is associated with serious adverse events, but monitoring currently relies on point blood glucose measurements, which may underreport glucose excursions., Methods: Adult patients without (A) or with diabetes [non-insulin-treated type 2 (B), insulin-treated type 2 (C) or type 1 (D)] undergoing major surgery were monitored using CGM (Dexcom G6), with an electrochemical sensor in the interstitial fluid, during surgery and for up to 10 days postoperatively. Patients and health care staff were blinded to CGM values, and glucose management adhered to the standard diabetes care protocol. Thirty-day postoperative serious adverse events were recorded. The primary outcome was duration of hypoglycemia (glucose <70 mg/dL). Clinicaltrials.gov: NCT04473001., Results: Seventy patients were included, with a median observation time of 4.0 days. CGM was recorded in median 96% of the observation time. The median daily duration of hypoglycemia was 2.5 minutes without significant difference between the 4 groups (A-D). Hypoglycemic events lasting ≥15 minutes occurred in 43% of all patients and 70% of patients with type 1 diabetes. Patients with type 1 diabetes spent a median of 40% of the monitoring time in the normoglycemic range 70 to 180 mg/dL and 27% in the hyperglycemic range >250 mg/dL. Duration of preceding hypo- and hyperglycemia tended to be longer in patients with serious adverse events, compared with patients without events, but these were exploratory analyses., Conclusions: Significant duration of both hypo- and hyperglycemia was detected in high proportions of patients, particularly in patients with diabetes, despite protocolized perioperative diabetes management., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a pronounced fibrotic tumor microenvironment, which impairs treatment response. Type I and V collagens are responsible for the densely packed fibrils in the tumor fibrosis environment. While the role of the major type I collagen in cancer is well described, less is known about the minor type V collagen. Quantifying collagen propeptides in serum has been shown to have prognostic and predictive value. In this study, we evaluated the clinical utility of measuring the propeptide of type V collagen (PRO-C5) in serum from a discovery cohort and a validation cohort of patients with PDAC as well as in non-pancreatic solid tumor types to explore the relevance of the PRO-C5 biomarker in cancer. Methods: Serum PRO-C5 was measured in three cohorts: a discovery cohort (19 healthy controls, 12 patients with chronic pancreatitis and 33 patients with PDAC (stage I-IV)), a validation cohort (800 patients with PDAC (stage I-IV)), and a non-pancreatic solid tumor type cohort of 33 healthy controls and 200 patients with 10 different non-pancreatic solid tumor types. The levels of serum PRO-C5 in patients with cancer were compared to levels in healthy controls. The association between PRO-C5 levels and overall survival (OS) was evaluated in patients with PDAC after adjusting for established prognostic factors. Results: PRO-C5 was significantly increased in serum from patients with PDAC compared to healthy controls ( p < 0.001). High PRO-C5 levels were significantly associated with short OS in both the discovery- and the validation cohort, especially in early stages of PDAC (validation cohort stage II, HR = 2.0, 95%CI1.2-3.4). The association was independent of other prognostic parameters including stage, performance status and CA19-9. Furthermore, serum levels of PRO-C5 were significantly increased in serum from patients with other non-pancreatic solid tumor types compared to healthy controls. Conclusion: High levels of serum PRO-C5 is prognostic for short OS in patients with PDAC and may provide clinical value in many other tumor types beyond PDAC. This underlines the importance of type V collagen in tumor fibrosis. PRO-C5 could have the potential to be used in several aspects within drug discovery, patient stratification and drug efficacy., Competing Interests: NN, CJ, EM, JT-U, MK, and NW are all employed by Nordic Bioscience A/S. 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 © 2023 Nissen, Johansen, Chen, Jensen, Madsen, Hansen, Thorlacius-Ussing, Karsdal, Johansen, Diab, Jørgensen and Willumsen.)

Purpose: Postoperative acute kidney injury is common and associated with increased length of hospital stay, costs and mortality. The impact from postoperative subclinical changes in plasma concentration of creatinine (p-creatinine) on postoperative mortality has received less attention. In this study, the association between the postoperative change of p-creatinine and all-cause mortality was investigated., Methods: A single-centre register-based, retrospective study was conducted including patients ≥60 years undergoing open abdominal surgery from 2000 to 2013. Postoperative p-creatinine change was analysed for association with 30-day mortality following adjustment for age, gender, surgical setting and surgical procedure. Main findings A total of 3,460 patients were included in the study of whom 67.6% underwent emergency surgery. The 30-day mortality rate was 18.3%, and a given 10μmol/L daily postoperative increase in p-creatinine was associated with an increased mortality risk with an odds ratio (OR) of 2.67 (95% CI; 2.28-3.14, P<0.001). In patients undergoing emergency surgery, a daily 10μmol/L increase in p-creatinine increased the risk for a fatal outcome a 2.39 OR (CI 95%; 2.05-2.78), P<0.001). In patients undergoing elective surgery, a similar increase in p-creatinine increased risk of postoperative death with a 28.85 OR (CI 95%; 10.25-81.19)., Conclusion: Even a minor postoperative p-creatinine increase following open abdominal surgery below the criteria for acute kidney injury was associated with increased 30-day mortality in patients aged 60 years or above., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The optimal repair of ventral hernia remains unknown. We aimed to evaluate the results after robotic-assisted laparoscopic transabdominal repair with retrorectus mesh placement (rRetrorectus) compared with laparoscopic intraperitoneal onlay mesh repair (IPOM) for patients with small- or medium-sized ventral hernia., Methods: This was a retrospective cohort study of consecutive patients undergoing elective rRetrorectus or IPOM repair for small or medium-sized primary ventral or incisional hernias. The primary outcome was the postoperative need for transverse abdominis plane (TAP) block or epidural analgesia, secondary outcomes were length of stay and postoperative complications. All patients were followed for 30 days postoperatively., Results: A total of 59 patients were included undergoing rRetrorectus (n = 27) and IPOM (n = 32). Patients in the two groups were comparable in terms of age, sex, comorbidities, smoking status, body mass index (BMI), and type of hernia. The median fascial defect area was slightly larger in the rRetrorectus group (9 cm 2 vs. 6.2 cm 2 , P = 0.031). The duration of surgery was longer for rRetrorectus (median 117.2 min. vs. 84.4, P = 0.003), whereas the postoperative need for TAP block or epidural analgesia was less after rRetrorectus compared with IPOM (3.7% versus 43.7%, P = 0.002). There were no severe complications or reoperations after either procedure. The length of stay was shorter after rRetrorectus (median 0 vs. 1 day, P < 0.001)., Conclusions: rRetrorectus was associated with reduced postoperative analgesic requirement and shorter length of stay compared with laparoscopic IPOM. Registration Clinicaltrial.gov: NCT05320055., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Traditional anterior component separation during incisional hernia repair (IHR) is associated with a high rate of postoperative wound morbidity. Because extensive subcutaneous dissection is avoided by endoscopic anterior component separation (eACS) or open transversus abdominis release (TAR), we hypothesized that these techniques did not increase the incidence of surgical site occurrence (SSO) compared to IHR without component separation (CS)., Material and Method: This was a retrospective single-center cohort study of patients undergoing open retromuscular IHR comparing patients with or without the use of CS. Retromuscular mesh repair was performed in all patients, and CS was obtained by eACS or TAR. The primary outcome was 90-day incidence of postoperative SSO. Secondary outcomes included length of stay (LOS), 90-day readmission, 90-day reoperation rate and 3-year recurrence rate., Results: A total of 321 patients underwent retromuscular repair, 168 (52.3%) of whom received either eACS or TAR. The addition of eACS or TAR was associated neither with development of SSO (odds ratio: 1.80, 95% confidence interval: 0.94-3.46, P = 0.077) nor with hernia recurrence (hazard ratio 0.77, 0.26-2.34, P = 0.648). There was no significant difference between the groups regarding the frequencies of 90-day readmission or 90-day reoperation., Conclusion: eACS or TAR as adjuncts to open retromuscular IHR were not associated with increased wound morbidity or hernia recurrence., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

All plant tissues from leaves, stems, and roots are hosting a wide diversity of fungal species. Our understanding of the assembly of this diversity of fungi during the plant growth cycle is limited. Here, we characterized the mycobiome of three spring barley cultivars grown in Zealand, Denmark, at weekly intervals during a growth season from seedling emergence to senescence and seed maturity. A notable proportion of members of the fungal communities were shared among different plant organs, but community dynamics were tissue-specific. A severe attack of Puccinia hordei occurring during the vegetative stage had profound effects on the mycobiome, and P. hordei biomass displaced that of other taxa. Plant tissue type was the most important factor determining the mycobiome, but also plant age was contributing significantly. Using a random forest model, we found that specific members of the mycobiome were responding differently to plant age, for instance, Olpidium and Articulospora in roots, Dioszegia and Sporobolomyces in leaves, Pyrenophora in stems, and Epicoccum in heads. A co-occurrence network analysis revealed complex interactions among fungal OTUs, and network connectivity was changing as per plant growth stage and plant tissue type. This study contributes to the understanding of assembly of fungal communities in cereals by providing a detailed description of fungal communities associated with barley. This knowledge will be vital for microbiome assisted plant health management and our study will serve as an important baseline for future efforts to harness microbiota in cereal health., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate whether there is a differential impact of histopathological risk factors for lymph node metastases (LNM) in pedunculated and nonpedunculated pT1 colorectal cancers (CRC)., Background: Tumor budding, lymphovascular invasion (LVI), and venous invasion (VI) are recognized risk factors for LNM in pT1 CRC. Whether the importance of these factors varies according to tumor morphology is unknown., Methods: Patients undergoing resection with lymphadenectomy for pT1 CRC in Denmark from January 2016 to January 2019 were identified in the Danish Colorectal Cancer Database and clinicopathological data was reviewed. Prognostic factors for LNM were investigated using multivariable analyses on the cohort as a whole as well as when stratifying according to tumor morphology (pedunculated vs. nonpedunculated)., Results: A total of 1167 eligible patients were identified, of whom 170 had LNM (14.6%). Independent prognostic factors for LNM included LVI [odds ratio (OR)=4.26, P <0.001], VI (OR=3.42, P <0.001), tumor budding (OR=2.12, P =0.002), high tumor grade (OR=2.76, P =0.020), and age per additional year (OR=0.96, P <0.001). On subgroup analyses, LVI and VI remained independently prognostic for LNM regardless of tumor morphology. However, tumor budding was only prognostic for LNM in pedunculated tumors (OR=4.19, P <0.001), whereas age was only prognostic in nonpedunculated tumors (OR=0.61, P =0.003)., Conclusions: While LVI and LI were found to be prognostic of LNM in all pT1 CRC, the prognostic value of tumor budding differs between pedunculated and nonpedunculated tumors. Thus, tumor morphology should be taken into account when considering completion surgery in patients undergoing local excision., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Circulating fragments of type III collagen, measured by PRO-C3, has shown promising results as a tumor fibrosis biomarker. However, the fibrotic tumor microenvironment consists of many other collagens with diverse functions and unexplored biomarker potential. One example hereof is type XXII collagen (COL22). In this study, we investigated the biomarker potential of COL22 by measuring this in serum. An ELISA, named PRO-C22, was developed and measured in two serum cohorts consisting of patients with various solid tumors (n = 220) and healthy subjects (n = 33) (Cohort 1), and patients with pancreatic ductal adenocarcinoma (PDAC) (n = 34), and healthy subjects (n = 20) (Cohort 2). In Cohort 1, PRO-C22 was elevated in the serum from patients with solid tumors, compared to healthy subjects (p < 0.01 to p < 0.0001), and the diagnostic accuracy (AUROC) ranged from 0.87 to 0.98, p < 0.0001. In Cohort 2, the high levels of PRO-C22, in patients with PDAC, were predictive of a worse overall survival (HR = 4.52, 95% CI 1.90−10.7, p = 0.0006) and this remained significant after adjusting for PRO-C3 (HR = 4.27, 95% CI 1.24−10.4, p = 0.0013). In conclusion, PRO-C22 has diagnostic biomarker potential in various solid tumor types and prognostic biomarker potential in PDAC. Furthermore, PRO-C22 complemented PRO-C3 in predicting mortality, suggesting an additive prognostic value when quantifying different collagens.

Septoria tritici blotch (STB; Zymoseptoria tritici ) is a severe leaf disease on wheat in Northern Europe. Fungicide resistance in the populations of Z. tritici is increasingly challenging future control options. Twenty-five field trials were carried out in nine countries across Europe from 2019 to 2021 to investigate the efficacy of specific DMI and SDHI fungicides against STB. During the test period, two single DMIs (prothioconazole and mefentrifluconazole) and four different SDHIs (fluxapyroxad, bixafen, benzovindiflupyr and fluopyram) along with different co-formulations of DMIs and SDHIs applied at flag leaf emergence were tested. Across all countries, significant differences in azole performances against STB were seen; prothioconazole was outperformed in all countries by mefentrifluconazole. The effects also varied substantially between the SDHIs, with fluxapyroxad providing the best efficacy overall, while the performance of fluopyram was inferior to other SDHIs. In Ireland and the UK, the efficacy of SDHIs was significantly lower compared with results from continental Europe. This reduction in performances from both DMIs and SDHIs was reflected in yield responses and also linked to decreased sensitivity of Z. tritici isolates measured as EC 50 values. A clear and significant gradient in EC 50 values was seen across Europe. The lower sensitivity to SDHIs in Ireland and the UK was coincident with the prevalence of SDH-C-alterations T79N, N86S, and sporadically of H152R. The isolates' sensitivity to SDHIs showed a clear cross-resistance between fluxapyroxad, bixafen, benzovindiflupyr and fluopyram, although the links with the latter were less apparent. Co-formulations of DMIs + SDHIs performed well in all trials conducted in 2021. Only minor differences were seen between fluxapyroxad + mefentrifluconazole and bixafen + fluopyram + prothioconazole; the combination of benzovindiflupyr + prothioconazole gave an inferior performance at some sites. Fenpicoxamid performed in line with the most effective co-formulations. This investigation shows a clear link between reduced field efficacy by solo SDHIs as a result of increasing problems with sensitivity shifting and the selection of several SDH-C mutations. The presented data stress the need to practice anti-resistance strategies to delay further erosion of fungicide efficacy., Competing Interests: GS was employed by company BASF. JB was employed by company ADAS. 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. Although BASF funded this project, their primary role has been to assist in analysing specific target site alterations and provide the tested chemicals. The products included in the testing represent key fungicide actives and co-formulations belonging to both BASF and their competitors. BASF did not influence the experimental design, selection of locations, or computation and presentation of data., (Copyright © 2022 Jørgensen, Matzen, Heick, O’Driscoll, Clark, Waite, Blake, Glazek, Maumene, Couleaud, Rodemann, Weigand, Bataille, R, Hellin, Kildea and Stammler.)

The adaptive potential of plant fungal pathogens is largely governed by the gene content of a species, consisting of core and accessory genes across the pathogen isolate repertoire. To approximate the complete gene repertoire of a globally significant crop fungal pathogen, a pan genomic analysis was undertaken for Pyrenophora tritici-repentis (Ptr), the causal agent of tan (or yellow) spot disease in wheat. In this study, 15 new Ptr genomes were sequenced, assembled and annotated, including isolates from three races not previously sequenced. Together with 11 previously published Ptr genomes, a pangenome for 26 Ptr isolates from Australia, Europe, North Africa and America, representing nearly all known races, revealed a conserved core-gene content of 57 % and presents a new Ptr resource for searching natural homologues (orthologues not acquired by horizontal transfer from another species) using remote protein structural homology. Here, we identify for the first time a non-synonymous mutation in the Ptr necrotrophic effector gene ToxB , multiple copies of the inactive toxb within an isolate, a distant natural Pyrenophora homologue of a known Parastagonopora nodorum necrotrophic effector (SnTox3), and clear genomic break points for the ToxA effector horizontal transfer region. This comprehensive genomic analysis of Ptr races includes nine isolates sequenced via long read technologies. Accordingly, these resources provide a more complete representation of the species, and serve as a resource to monitor variations potentially involved in pathogenicity.

Background: Blood-based biomarkers used for colorectal cancer screening need to be developed and validated in appropriate screening populations. We aimed to develop a cancer-associated protein biomarker test for the detection of colorectal cancer in a screening population., Methods: Participants from the Danish Colorectal Cancer Screening Program were recruited. Blood samples were collected prior to colonoscopy. The cohort was divided into training and validation sets. We present the results of model development using the training set. Age, sex, and the serological proteins CEA, hsCRP, TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, ferritin and B2M were used to develop a signature test to discriminate between participants with colorectal cancer versus all other findings at colonoscopy., Results: The training set included 4048 FIT-positive participants of whom 242 had a colorectal cancer. The final model for discriminating colorectal cancer versus all other findings at colonoscopy had an AUC of 0.70 (95% CI: 0.66-0.74) and included age, sex, CEA, hsCRP, HE4 and ferritin., Conclusion: The performance of the biomarker signature in this FIT-positive screening population did not reflect the positive performance of biomarker signatures seen in symptomatic populations. Additional biomarkers are needed if the serological biomarkers are to be used as a frontline screening test., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Ventral hernia repair is one of the most commonly performed surgical procedures worldwide. To reduce the risk of complications, patient prehabilitation has received increasing focus in recent years. To assess prehabilitation measures, this European Hernia Society endorsed project was launched. The aim of this systematic review was to evaluate the current literature on patient prehabilitation prior to ventral hernia repair., Methods: The strategies examined were optimization of renal disease, obesity, nutrition, physical exercise, COPD, diabetes and smoking cessation. For each topic, a separate literature search was conducted, allowing for seven different sub-reviews., Results: A limited amount of well-conducted research studies evaluating prehabilitation prior to ventral hernia surgery was found. The primary findings showed that smoking cessation and weight loss for obese patients led to reduced risks of complications after abdominal wall reconstruction., Conclusion: Prehabilitation prior to ventral hernia repair may be widely used; however, the literature supporting its use is limited. Future studies evaluating the impact of prehabilitation before ventral hernia surgery are warranted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Septoria tritici blotch (STB) is among the most devastating diseases in European wheat production. In recent years, there has been increased interest in using cultivar mixtures as part of an integrated control strategy against diseases. This study investigated different cultivar mixtures for their ability to control STB across three years and at seven trial sites in Denmark with a range of fungicide strategies, yielding a total of 194 individual cultivar mixture combinations. The mixtures were composed of two, three, or four cultivars that were either similar or contrasting in their susceptibility to STB. Across all trials, the cultivar mixtures reduced disease severity significantly, by 14% compared with the component cultivars grown in monoculture. The reductions were larger when the disease pressure was high and when the mixtures included more cultivars. Mixtures composed of four cultivars reduced disease severity significantly, by 24%. Across all trials, cultivar mixtures significantly increased yield by 2% compared with the component cultivars grown in monoculture. The yield increase was significant for plots treated with one or two fungicide applications, and cultivar mixtures increased yield significantly, by 4.4% in untreated plots. The yield increase was smaller for mixtures with a high proportion of resistant cultivars. Based on the results from this study, cultivar mixtures can contribute positively to an integrated pest management (IPM) strategy, by reducing disease severity for STB and increasing yield. The most pronounced benefits from cultivar mixtures were found in fields with moderate to low fungicide input, under conditions with high disease pressure, when combining four cultivars with varying susceptibilities.

In the tumor microenvironment, the extracellular matrix (ECM) has been recognized as an important part of cancer development. The dominant ECM proteins are the 28 types of collagens, each with a unique function in tissue architecture. Type XX collagen, however, is poorly characterized, and little is known about its involvement in cancer. We developed an ELISA quantifying type XX collagen, named PRO-C20, using a monoclonal antibody raised against the C-terminus. PRO-C20 and PRO-C1, an ELISA targeting the N-terminal pro-peptide of type I collagen, was measured in sera of 219 patients with various solid cancer types and compared to sera levels of 33 healthy controls. PRO-C20 was subsequently measured in a separate cohort comprising 36 patients with pancreatic ductal adenocarcinoma (PDAC) and compared to 20 healthy controls and 11 patients with chronic pancreatitis. PRO-C20 was significantly elevated in all cancers tested: bladder, breast, colorectal, head and neck, kidney, lung, melanoma, ovarian, pancreatic, prostate, and stomach cancer (p < 0.01−p < 0.0001). PRO-C1 was only elevated in patients with ovarian cancer. PRO-C20 could discriminate between patients and healthy controls with AUROC values ranging from 0.76 to 0.92. Elevated levels were confirmed in a separate cohort of patients with PDAC (p < 0.0001). High PRO-C20 levels (above 2.57 nM) were predictive of poor survival after adjusting for the presence of metastasis, age, and sex (HR: 4.25, 95% CI: 1.52−11.9, p-value: 0.006). Circulating type XX collagen is elevated in sera of patients with various types of cancer and has prognostic value in PDAC. If validated, PRO-C20 may be a novel biomarker for patients with solid tumors and can help understand the ECM biology of cancer.

Introduction: Information on the long-term performance of biosynthetic meshes is scarce. This study analyses the performance of biosynthetic mesh (Phasix™) over 24 months., Methods: A prospective, international European multi-center trial is described. Adult patients with a Ventral Hernia Working Group (VHWG) grade 3 incisional hernia larger than 10 cm 2 , scheduled for elective repair, were included. Biosynthetic mesh was placed in sublay position. Short-term outcomes included 3-month surgical site occurrences (SSO), and long-term outcomes comprised hernia recurrence, reoperation, and quality of life assessments until 24 months., Results: Eighty-four patients were treated with biosynthetic mesh. Twenty-two patients (26.2%) developed 34 SSOs, of which 32 occurred within 3 months (primary endpoint). Eight patients (11.0%) developed a hernia recurrence. In 13 patients (15.5%), 14 reoperations took place, of which 6 were performed for hernia recurrence (42.9%), 3 for mesh infection (21.4%), and in 7 of which the mesh was explanted (50%). Compared to baseline, quality of life outcomes showed no significant difference after 24 months. Despite theoretical resorption, 10.7% of patients reported presence of mesh sensation in daily life 24 months after surgery., Conclusion: After 2 years of follow-up, hernia repair with biosynthetic mesh shows manageable SSO rates and favorable recurrence rates in VHWG grade 3 patients. No statistically significant improvement in quality of life or reduction of pain was observed. Few patients report lasting presence of mesh sensation. Results of biosynthetic mesh after longer periods of follow-up on recurrences and remodeling will provide further valuable information to make clear recommendations., Trial Registration: Registered on clinicaltrials.gov (NCT02720042), March 25, 2016., (© 2021. The Author(s).)

Background: Laparoscopic enhanced-view totally extraperitoneal retromuscular repair (eTEP-RM) was recently introduced as a new technique for ventral hernia repair. The aim of the current study was to examine the outcomes of laparoscopic eTEP-RM compared with laparoscopic IPOM for patients with primary ventral and incisional hernia., Methods: This was a retrospective cohort study of patients undergoing laparoscopic ventral hernia repair at a single University Hospital from June 2017 to November 2020. Medical charts of all patients subjected to IPOM and eTEP-RM were evaluated to identify patient- and procedure related variables, as well as postoperative 30-day outcomes., Results: A total of 72 patients were included in the study, 43 and 29 of whom underwent IPOM and eTEP-RM repair, respectively. Patient demographics showed no differences in terms of gender, age, smoking and comorbidity. The median age was 57 years and body mass index 30.5 kg/m 2 . The rate of patients with incisional hernia was higher in the IPOM group (39.5% vs. 20.7%, p = 0.154). There was no difference in horizontal and vertical hernia size defect. The duration of surgery was significantly shorter for IPOM (mean 82.4 vs. 103.4 min, p = 0.010), whereas the length of stay was significantly longer after IPOM (median 1 days vs. 0 days (p < 0.001). The rate of patients requiring postoperative transversus abdominis plane (TAP) block or epidural analgesia was significantly higher after IPOM (33% vs. 0%, p = 0.002). A subgroup analysis on patients undergoing primary ventral hernia showed similar results., Conclusion: The study found laparoscopic eTEP-RM safe and effective compared to traditional laparoscopic IPOM. The patients undergoing eTEP-RM had significantly reduced need for additional analgesic treatment and length of stay., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Over the past decade, demethylation inhibitor (DMI) and succinate dehydrogenase inhibitor (SDHI) fungicides have been extensively used to control to septoria tritici blotch, caused by Zymoseptoria tritici on wheat. This has led to the development and selection of alterations in the target-site enzymes (CYP51 and SDH, respectively)., Results: Taking advantage of newly and previously developed qPCR assays, the frequency of key alterations associated with DMI (CYP51-S524T) and SDHI (SDHC-T79N/I, C-N86S and C-H152R) resistance was assessed in Z. tritici-infected wheat leaf samples collected from commercial crops (n = 140) across 14 European countries prior to fungicide application in the spring of 2019. This revealed the presence of a West to East gradient in the frequencies of the most common key alterations conferring azole (S524T) and SDHI resistance (T79N and N86S), with the highest frequencies measured in Ireland and Great Britain. These observations were corroborated by sequencing (CYP51 and SDH subunits) and sensitivity phenotyping (prothioconazole-desthio and fluxapyroxad) of Z. tritici isolates collected from a selection of field samples. Additional sampling made at the end of the 2019 season confirmed the continued increase in frequency of the targeted alterations. Investigations on historical leaf DNA samples originating from different European countries revealed that the frequency of all key alterations (except C-T79I) has been gradually increasing over the past decade., Conclusion: Whilst these alterations are quickly becoming dominant in Ireland and Great Britain, scope still exists to delay their selection throughout the wider European population, emphasizing the need for the implementation of fungicide antiresistance measures. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Introduction: The COVID-19 pandemic has had a global impact on cancer care but the extent to which this has affected the management of colorectal cancer (CRC) in different countries is unknown. CRC management in Denmark was thought to have been relatively less impacted than in other nations during the first wave of the pandemic. The aim of this study was to determine the pandemic's impact on CRC in Denmark., Methods: The Danish national cancer registry identified patients with newly diagnosed with CRC from 1 March 2020 to 1 August 2020 (pandemic interval) and corresponding dates in 2019 (prepandemic interval). Data regarding clinicopathological demographics and perioperative outcomes were retrieved and compared between the two cohorts., Results: Total CRC diagnoses (201 versus 359 per month, P = 0.008) and screening diagnoses (38 versus 80 per month, P = 0.016) were both lower in the pandemic interval. The proportions of patients presenting acutely and the stage at presentation were, however, unaffected. For those patients having surgery, both colonic and rectal cancer operations fell to about half the prepandemic levels: colon (187 (i.q.r. 183-188) to 96 (i.q.r. 94-112) per month, P = 0.032) and rectal cancers (63 (i.q.r. 59-75) to 32 (i.q.r. 28-42) per month, P = 0.008). No difference was seen in surgical practice or postoperative 30-day mortality rate (colon 2.2 versus 2.2 per cent, P = 0.983; rectal 1.0 versus 2.9 per cent, P = 0.118) between the cohorts. Treatment during the pandemic interval was not independently associated with death at 30 or 90 days., Conclusion: The initial wave of the COVID-19 pandemic reduced the number of new diagnoses made and number of operations but had limited impact on technique or outcomes of CRC care in Denmark., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Plant pathogens cause significant damage to plant products, compromising both quantities and quality. Even though many elements of agricultural practices are an integral part of reducing disease attacks, modern agriculture is still highly reliant on fungicides to guarantee high yields and product quality. The azoles, 14-alpha demethylase inhibitors, have been the fungicide class used most widely to control fungal plant diseases for more than four decades. More than 25 different azoles have been developed for the control of plant diseases in crops and the group has a world market value share of 20-25%. Azoles have proven to provide long-lasting control of many target plant pathogens and are categorized to have moderate risk for developing fungicide resistance. Field performances against many fungal pathogens have correspondingly been stable or only moderately reduced over time. Hence azoles are still, to date, considered the backbone in many control strategies and widely used as solo fungicides or as mixing partners with other fungicide groups, broadening the control spectrum as well as minimizing the overall risk of resistance development. This review describes the historic perspective of azoles, their market shares and importance for production of major crops like cereals, rice, oilseed rape, sugar beet, banana, citrus, and soybeans. In addition, information regarding use in amenity grass, in the wood preservation industry and as plant growth regulators are described. At the end of the review azoles are discussed in a wider context including future threats following stricter requirements for registration and potential impact on human health., Competing Interests: Outside this work, we have the following potential conflicts to declare: LJ and TH have over the years received research grants (paid to the institution) from BASF, Bayer, Syngenta, Corteva, Adama, UPL, Globachem., (Copyright © 2021 Jørgensen and Heick.)

Introduction: The role of blood-based biomarkers in surgical decision-making in patients with localised pancreatic cancer remains unclear. This review aimed to report the utility of blood-based biomarkers focusing on prediction of response to neoadjuvant therapy, prediction of surgical resectability and early relapse after surgery., Materials and Methods: MEDLINE/PubMed, Embase and Web of Science were searched till October 2019. Studies published between January 2000 and September 2019 with a minimum of 20 patients with pancreatic adenocarcinoma, reporting the utility of at least one blood-based biomarker in predicting response to neoadjuvant therapy and predicting surgical resectability or early relapse after surgery were included., Results: A total of 2604 studies were identified, of which 24 comprising of 3367 patients and 12 blood-based biomarkers were included. All included studies were observational. Levels of carbohydrate antigen (CA)19-9 were reported in the majority of the studies. Levels of CA19-9 predicted the response to neoadjuvant therapy and early relapse in 10 studies. CA125 levels above 35 U/ml were predictive of surgical irresectability in two studies. However, marked variation in both timing of sampling and cut-off values was noted between studies., Conclusion: Despite some evidence of potential benefit, the utility of currently available blood-based biomarkers in aiding surgical decision-making in patients undergoing potentially curative treatment for pancreatic cancer is limited by methodological heterogeneity. Standardisation of future studies may allow a more comprehensive analysis of the biomarkers described in this review., Competing Interests: Conflict of interest statement None declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Enhanced recovery after surgery (ERAS) is a well-known approach to optimize the recovery after surgery. Little is known about specific causes of prolonged hospitalization despite enhanced recovery after open incisional hernia repair (OIHR). The purpose of this study was to identify the causes of continued hospitalization on each of the first 5 postoperative days (PODs) after OIHR., Methods: This was a retrospective study of consecutive patients undergoing open AWR at a regional academic hernia center from 2008 to 2018. Patient charts were evaluated using predefined potential causes of continued hospitalization on each of the first five PODs., Results: A total of 388 patients (mean age 60.9 years, 54.6% male, mean BMI 27.9 kg/m 2 ) were included in the study. Mesh placement was either preperitoneal/intraperitoneal (20%) or retromuscular (80%) and 61% of the patients had an epidural catheter. The median length of stay (LOS) in the cohort was four [IQR 2-6] days. On PODs 4 and 5, causes of continued hospital stay were absent bowel function (2% on POD 4, 1% on POD 5), pain (7% on POD 3, 2% on POD 4), lack of mobilization (1% on POD 4, 1% on POD 5), and other causes (urinary retention, high drain output, and complications to the surgery)., Conclusion: Causes for prolonged hospitalization after OIHR were possibly reducible. Future efforts to improve the ERAS regime and reduce LOS after OIHR should focus on pain treatment- and prevention, alternatives to epidural treatment, and well-defined, evidence-based discharge criteria., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS part of Springer Nature.)

Background: National screening programmes increase the proportion of T1 colorectal cancers. Local excision may be possible, but the risk of lymph node metastases (LNMs) could jeopardize long-term outcomes. The aim of the present study was to review the association between histopathological findings and LNMs in T1 colorectal cancer., Methods: A systematic literature search was conducted using PubMed,Embase, and Cochrane online databases. Studies investigating the association between one or more histopathological factors and LNMs in patients who underwent resection for T1 colorectal cancer were included., Results: Sixteen observational studies were included in the meta-analysis, including a total of 10 181 patients, of whom 1 307 had LNMs. Lymphovascular invasion (odds ratio (OR) 7.42; P < 0.001), tumour budding (OR 4.00; P < 0.001), depth of submucosal invasion, whether measured as at least 1000 µm (OR 3.53; P < 0.001) or Sm2-3 (OR 2.12; P = 0.020), high tumour grade (OR 3.75; P < 0.001), polypoid growth pattern (OR 1.59; P = 0.040), and rectal location of tumour (OR 1.36; P = 0.003) were associated with LNMs., Conclusion: Distinct histopathological factors associated with nodal metastases in T1 colorectal cancer can aid selection of patients for local excision or major excisional surgery., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Type XI collagen has been associated with tumor fibrosis and aggressiveness in patients with pancreatic ductal adenocarcinoma (PDAC). The propeptide on Type XI collagen is released into the circulation after proteolytic processing at either amino acid 253 or 511. This allows for a noninvasive biomarker approach to quantify Type XI collagen production. We developed two ELISA-based biomarkers, targeting the two enzymatic cleavage sites (PRO-C11-253 and PRO-C11-511). In a discovery cohort including serum from patients with PDAC (n = 39, Stages 1-4), chronic pancreatitis (CP, n = 12) and healthy controls (n = 20), PRO-C11-511, but not PRO-C11-253, was significantly upregulated in patients with PDAC and CP compared to healthy controls. Furthermore, PRO-C11-511 levels >75th percentile were associated with poor overall survival (OS) (HR, 95% CI: 3.40, 1.48-7.83). The PRO-C11-511 biomarker potential was validated in serum from 686 patients with PDAC. Again, high levels of PRO-C11-511 (>75th percentile) were associated with poor OS (HR, 95% CI: 1.68, 1.40-2.02). Furthermore, PRO-C11-511 remained significant after adjusting for clinical risk factors (HR, 95% CI: 1.50, 1.22-1.86). In conclusion, quantifying serum levels of Type XI collagen with PRO-C11-511 predicts poor OS in patients with PDAC. This supports that Type XI collagen is important for PDAC biology and that PRO-C11-511 has prognostic noninvasive biomarker potential for patients with PDAC., (© 2021 UICC.)

Septoria tritici blotch (STB) caused by the fungal pathogen Zymoseptoria tritici and powdery mildew (PM) caused by Blumeria graminis f.sp tritici ( Bgt ) are among the forefront foliar diseases of wheat that lead to a significant loss of grain yield and quality. Resistance breeding aimed at developing varieties with inherent resistance to STB and PM diseases has been the most sustainable and environment-friendly approach. In this study, 175 winter wheat landraces and historical cultivars originated from the Nordic region were evaluated for adult-plant resistance (APR) to STB and PM in Denmark, Estonia, Lithuania, and Sweden. Genome-wide association study (GWAS) and genomic prediction (GP) were performed based on the adult-plant response to STB and PM in field conditions using 7,401 single-nucleotide polymorphism (SNP) markers generated by 20K SNP chip. Genotype-by-environment interaction was significant for both disease scores. GWAS detected stable and environment-specific quantitative trait locis (QTLs) on chromosomes 1A, 1B, 1D, 2B, 3B, 4A, 5A, 6A, and 6B for STB and 2A, 2D, 3A, 4B, 5A, 6B, 7A, and 7B for PM adult-plant disease resistance. GP accuracy was improved when assisted with QTL from GWAS as a fixed effect. The GWAS-assisted GP accuracy ranged within 0.53-0.75 and 0.36-0.83 for STB and PM, respectively, across the tested environments. This study highlights that landraces and historical cultivars are a valuable source of APR to STB and PM. Such germplasm could be used to identify and introgress novel resistance genes to modern breeding lines., 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., (Copyright © 2021 Alemu, Brazauskas, Gaikpa, Henriksson, Islamov, Jørgensen, Koppel, Koppel, Liatukas, Svensson and Chawade.)

Azole resistance is an emerging problem in patients with aspergillosis. The role of fungicides for resistance development and occurrence is not fully elucidated. EUCAST reference MICs of 17 fungicides (11 azoles and 6 others), five azole fungicide metabolites and four medical triazoles were examined against two reference and 28 clinical isolates of A. fumigatus , A. flavus and A. terreus with ( n = 12) and without ( n = 16) resistance mutations. Eight/11 azole fungicides were active against wild-type A. fumigatus , A. flavus and A. terreus , including four (metconazole, prothioconazole-desthio, prochloraz and imazalil) with low MIC 50 (≤2 mg/L) against all three species and epoxiconazole, propiconazole, tebuconazole and difenoconazole also against wild-type A. terreus . Mefentrifluconazole, azole metabolites and non-azole fungicides MICs were >16 mg/L against A. fumigatus although partial growth inhibition was found with mefentrifluconazole. Moreover, mefentrifluconazole and axozystrobin were active against wild-type A. terreus . Increased MICs (≥3 dilutions) were found for TR 34 /L98H, TR 34 (3) /L98H, TR 46 /Y121F/T289A and G432S compared to wild-type A. fumigatus for epoxiconazole, propiconazole, tebuconazole, difenoconazole, prochloraz, imazalil and metconazole (except G432S), and for prothioconazole-desthio against TR 46 /Y121F/T289A, specifically. Increased MICs were found in A. fumigatus harbouring G54R, M220K and M220R alterations for five, one and one azole fungicides, respectively, compared to MICs against wild-type A. fumigatus . Similarly, increased MICs wer found for A. terreus with G51A, M217I and Y491H alterations for five, six and two azole fungicides, respectively. Azole fungicides showed activity against wild-type A. fumigatus , A. terreus and A. flavus , but not against all mutant isolates, suggesting the environmental route of azole resistance may have a role for all three species.

Background: Major abdominal surgery in older and frail patients is associated with considerable morbidity and mortality. Plasma albumin is routinely measured in the clinic and has been proposed as an indicator of frailty. This study aimed to investigate if plasma albumin is a predictor of mortality in older patients undergoing open abdominal surgery., Materials and Methods: We conducted a single-center, register-based retrospective study of patients, aged ⩾60 years who underwent one of 81 open abdominal surgical procedures. Patients operated on during the period from January 1 st , 2000 to May 31 st , 2013 were consecutively identified in the Danish National Patient Registry. Plasma albumin was measured within 30 days prior to surgery and the primary endpoint was 30-day postoperative mortality., Results: 3,639 patients were included of whom 68.2% underwent emergency surgery. The rate of severe hypoalbuminemia (plasma albumin < 28 g/L) was 43.4%. Preoperative plasma albumin was lower in patients with a fatal 30-day outcome (mean 20.6 g/L vs 30.1 g/L in survivors, p < 0.0001). Other independent predictive parameters of 30-day mortality were age, male sex, and emergency surgery. We present an algorithm including these four variables for the prediction of 30-day mortality for patients aged ⩾60 years undergoing open abdominal surgery., Conclusion: Preoperative plasma albumin is a predictor of 30-day mortality in patients above 60 years of age following open abdominal surgery. Assessment of plasma albumin in conjunction with other risk factors such as age, sex, and surgical priority may improve preoperative decision-making.

Background: In hospitalized patients, abnormal plasma electrolyte concentrations are frequent and have been linked to poor outcomes following acute surgery. The aim of this study was to assess whether preoperative plasma levels of potassium, sodium, and creatinine at the time of admission were associated with 30-day mortality in patients following open abdominal surgery., Methods: This was a single-center register-based retrospective study. By means of electronic search in a maintained surgery database, all patients (n = 4177) aged ≥ 60 years old undergoing open surgery in our department from January 2000 to May 2013 were identified. Plasma was assessed within 30 days prior to surgery. The primary endpoint was 30-day postoperative mortality. The association between mortality and plasma levels of potassium, sodium, and creatinine were examined using Cox proportional hazard models., Results: A total of 3690 patients were included in the study cohort. The rates of abnormal preoperative plasma levels were 36, 41, and 38% for potassium, sodium, and creatinine, respectively. The overall 30 day mortality was 20%. A predictive algorithm for 30 day mortality following abdominal surgery was constructed by means of logistic regression showing excellent distinction between patients with and without a fatal postoperative outcome., Conclusion: Apart from demographic factors (age, sex, and emergency surgery), preoperative imbalance in potassium, sodium and creatinine levels were significant independent predictors of early mortality following open abdominal surgery.

Wheat ( Triticum aestivum L.) is one of the world's staple food crops and one of the most devastating foliar diseases attacking wheat is powdery mildew (PM). In Denmark only a few specific fungicides are available for controlling PM and the use of resistant cultivars is often recommended. In this study, two Chinese wheat landraces and two synthetic hexaploid wheat lines were used as donors for creating four multi-parental populations with a total of 717 individual lines to identify new PM resistance genetic variants. These lines and the nine parental lines (including the elite cultivars used to create the populations) were genotyped using a 20 K Illumina SNP chip, which resulted in 8,902 segregating single nucleotide polymorphisms for assessment of the population structure and whole genome association study. The largest genetic difference among the lines was between the donors and the elite cultivars, the second largest genetic difference was between the different donors; a difference that was also reflected in differences between the four multi-parental populations. The 726 lines were phenotyped for PM resistance in 2017 and 2018. A high PM disease pressure was observed in both seasons, with severities ranging from 0 to >50%. Whole genome association studies for genetic variation in PM resistance in the populations revealed significant markers mapped to either chromosome 2A, B, or D in each of the four populations. However, linkage disequilibrium between these putative quantitative trait loci (QTL) were all above 0.80, probably representing a single QTL. A combined analysis of all the populations confirmed this result and the most associated marker explained 42% of the variation in PM resistance. This study gives both knowledge about the resistance as well as molecular tools and plant material that can be utilised in marker-assisted selection. Additionally, the four populations produced in this study are highly suitable for association studies of other traits than PM resistance., Competing Interests: The study was performed in a collaboration between Aarhus University and the plant breeding company Nordic Seed A/S. NN, PS, JA, AJ, and JO were employed by company Nordic Seed A/S. 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 © 2021 Nordestgaard, Thach, Sarup, Rodriguez-Algaba, Andersen, Hovmøller, Jahoor, Jørgensen and Orabi.)