Update on Ankle and Foot Impingement.

Ankle impingement syndromes are a well-recognized cause of chronic ankle symptoms in both the elite athletic and general population. They comprise several distinct clinical entities with associated radiologic findings. Originally described in the 1950s, advances in magnetic resonance imaging (MRI) and ultrasonography have allowed musculoskeletal (MSK) radiologists to further their understanding of these syndromes and the range of imaging-associated features. Many subtypes of ankle impingement syndromes have been described, and precise terminology is critical to carefully separate these conditions and thus guide treatment options. These are divided broadly into intra-articular and extra-articular types, as well as location around the ankle. Although MSK radiologists should be aware of these conditions, the diagnosis remains largely clinical, with plain film or MRI used to confirm the diagnosis or assess a surgical/treatment target. The ankle impingement syndromes are a heterogeneous group of conditions, and care must be taken not to overcall findings. The clinical context remains paramount. Treatment considerations are patient symptoms, examination, and imaging findings, in addition to the patient's desired level of physical activity.

Multicenter Evaluation of the Novel ETEST Fosfomycin for Antimicrobial Susceptibility Testing of Enterobacterales, Enterococcus faecalis, and Staphylococcus Species.

Fosfomycin is a phosphonic acid derivative active against a wide spectrum of Gram-positive and Gram-negative pathogens. It is used for the treatment of uncomplicated urinary tract infections (uUTI) or severe infections by oral or intravenous (i.v.) administration. In order to improve its performance and robustness, the fosfomycin strip, an antibiotic gradient diffusion strip, was redeveloped and evaluated in the multicenter study summarized in this paper. ETEST fosfomycin (ETEST FO) clinical performance was evaluated by three study sites on 152 Enterococcus faecalis, 100 Staphylococcus spp. and 330 Enterobacterales in comparison with the CLSI and EUCAST agar dilution reference method. Referring to FDA performance criteria, the ETEST FO achieved 91.0% of essential (EA) and 99.0% of categorical agreement (CA) for Escherichia coli. In addition, 98.0% EA and 93.4% CA were achieved for E. faecalis, with no very major errors (VME) or major errors (ME). According to EUCAST breakpoints for intravenous fosfomycin use, Enterobacterales and Staphylococcus spp. also met ISO acceptance criteria for EA and CA (EA 91.5%, 94.0%, respectively, and CA 98.0% for both). A VME rate of 8.8% was observed for Enterobacterales but the MICs were within EA. A trend to predict lower MICs for Citrobacter spp., E. coli and Salmonella enterica and to predict higher MICs for Klebsiella pneumoniae MICs was observed, while ETEST FO should not be used for Enterobacter cloacae, because of low EA and a high VME rate. The study results support the efficiency of the novel ETEST FO, making it an easy-to-handle tool as a substitute to the classical agar dilution method.

Comparing practice and outcome of laparoscopic liver resection between high-volume expert centres and nationwide low-to-medium volume centres.

BACKGROUND: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. METHOD: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. RESULTS: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004). CONCLUSION: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.

Interobserver agreement of digital dermatitis M-scores for photographs of the hind feet of standing dairy cattle.

Digital dermatitis (DD) is the leading infectious cause of lameness in dairy cattle, and it affects their welfare and productivity worldwide. At the herd level, DD is often assessed while cows are standing in a milking parlor, and lesions are most commonly evaluated using the M-score. The objective of this study was to examine the interobserver agreement for M-scores of the feet of standing cattle, based on digital color photographs of dairy cattle hind feet. A total of 88 photographs and written descriptors of the M-score were sent to 11 scorers working at 10 different institutions in 5 countries. The scorers received no formal training immediately before scoring the photographs; however, all regularly used the M-score to score DD. The answers for 36 photographs were excluded from the analysis because the photograph either had more than 1 M-stage as mode or not all scorers assigned an M-score to it. The M-scores of the 11 scorers from 52 photographs were available for analysis. Interobserver agreement was tested using Gwet's agreement coefficient (AC1) and the mode was assumed correct. Overall, moderate agreement emerged for the M-score (AC1 = 0.48). For the individual M-stages, almost perfect agreement existed for M0 (AC1 = 0.99), M1 (AC1 = 0.92), and M3 (AC1 = 0.82), and substantial agreement for M2 (AC1 = 0.61), M4 (AC1 = 0.65), and M4.1 (AC1 = 0.71). This outcome indicates the degree of individual variation in M-scoring in this context by unstandardized, experienced European observers, particularly for the M2, M4, and M4.1 stages. Standardized training is likely to improve the consistency of M-scoring and thus the generalizability of future DD research results on this important endemic disease.

Proactive multi-modality treatment of Pancreatic Neuroendocrine Tumours (PNETs): Potential survival benefits.

BACKGROUND/OBJECTIVES: Primary and metastatic pancreatic neuroendocrine tumours (PNET) can be treated with combination of surgery, locoregional and systemic therapy. Survival benefits from individual treatments have been well reported, however, the combined outcome from multimodal treatments are not well described in the literature. We report outcomes in a cohort of PNET patients treated with proactive, multimodality therapy. METHODS: 106 patients were identified from a single tertiary referral centre prospective database. Outcomes of treatment were studied, with the primary end point being death from any cause. RESULTS: Median follow-up was 71 months and overall 5-year survival of 62%. In patients with stage I-III disease (51 patients) estimated 5-year survival was 90%. Median survival in patients with stage IV disease was 51 months with an estimated 5-year survival of 40% in this group. A total of 80 patients (75%) had surgery of which 16% suffered complications requiring intervention. There was no perioperative mortality. CONCLUSIONS: This study demonstrates that proactive multimodal treatment is safe and may confer a survival benefit to patients in this cohort compared to historical data.

Exposure to benzene in a pooled analysis of petroleum industry case-control studies.

Cases of lymphohematopoietic cancer from three petroleum industry cohorts, matched to controls from the respective cohort, were pooled into single study. Average benzene exposure was quantitatively estimated in ppm for each job based on measured data from the relevant country, adjusted for the specific time period, site and job exposure characteristics and the certainty of the exposure estimate scored. The probability of dermal exposure and of peak exposure was also assessed. Before risk was examined, an exposure estimate comparison and rationalisation exercise was performed across the studies to ensure accuracy and consistency of approach. This article evaluates the final exposure estimates and their use in the risk assessments. Overall benzene exposure estimates were low: 90% of participants accumulated less than 20 ppm-years. Mean cumulative exposure was estimated as 5.15 ppm-years, mean duration was 22 years, and mean exposure intensity was 0.2 ppm. 46% of participants were allocated a peak exposure (>3 ppm at least weekly). 40% of participants had a high probability of dermal exposure (based on the relative probability of at least weekly exposure). There were differences in mean intensity of exposure, probability of peak, and/or dermal exposure associated with job category, job site, and decade of exposure. Terminal Operators handling benzene-containing products were the most highly exposed group, followed by Tanker Drivers carrying gasoline. Exposures were higher around 1940-1950 and lower in more recent decades. Overall confidence in the exposure estimates was highest for recently held jobs and for white-collar jobs. We used sensitivity analyses, which included and excluded case-sets on the basis of exposure certainty scores, to inform the risk assessment. The above analyses demonstrated that the different patterns of exposure across the three studies are largely attributable to differences in jobs, site types, and time frames rather than study. This provides reassurance that the previous rationalisation of exposures achieved inter-study consistency and that the data could be confidently pooled.

Propensity score-based analysis of outcomes of laparoscopic versus open liver resection for colorectal metastases.

BACKGROUND: There is a need for high-level evidence regarding the added value of laparoscopic (LLR) compared with open (OLR) liver resection. The aim of this study was to compare the surgical and oncological outcomes of patients with colorectal liver metastases (CRLM) undergoing LLR and OLR using propensity score matching to minimize bias. METHODS: This was a single-centre retrospective study using a prospective database of patients undergoing liver resection for CRLM between August 2004 and April 2015. Co-variates selected for matching included: number and size of lesions, tumour location, extent and number of resections, phase of surgical experience, location and lymph node status of primary tumour, perioperative chemotherapy, unilobar or bilobar disease, synchronous or metachronous disease. Prematching and postmatching analyses were compared. Surgical and oncological outcomes were analysed. RESULTS: Some 176 patients undergoing LLR and 191 having OLR were enrolled. After matching, 133 patients from each group were compared. At prematching analysis, patients in the LLR group showed a longer overall survival (OS) and higher R0 rate than those in the OLR group (P = 0·047 and P = 0·030 respectively). Postmatching analyses failed to confirm these results, showing similar OS and R0 rate between the LLR and OLR group (median OS: 55·2 versus 65·3 months respectively, hazard ratio 0·70 (95 per cent c.i. 0·42 to 1·05; P = 0·082); R0 rate: 92·5 versus 86·5 per cent, P = 0·186). The 5-year OS rate was 62·5 (95 per cent c.i. 45·5 to 71·5) per cent) for OLR and 64·3 (48·2 to 69·5) per cent for LLR. Longer duration of surgery, lower blood loss and morbidity, and shorter postoperative stay were found for LLR on postmatching analysis. CONCLUSION: Propensity score matching showed that LLR for CRLM may provide R0 resection rates and long-term OS comparable to those for OLR, with lower blood loss and morbidity, and shorter postoperative hospital stay.

Target validation of the inosine monophosphate dehydrogenase (IMPDH) gene in Cryptosporidium using Phylomer(®) peptides.

Cryptosporidiosis, a gastroenteric disease characterised mainly by diarrheal illnesses in humans and mammals is caused by infection with the protozoan parasite Cryptosporidium. Treatment options for cryptosporidiosis are limited, with the current therapeutic nitazoxanide, only partly efficacious in immunocompetent individuals. The parasite lacks de novo purine synthesis, and is exclusively dependant on purine salvage from its host. Inhibition of the inosine 5' monophosphate dehydrogenase (IMPDH), a purine salvage enzyme that is essential for DNA synthesis, thereby offers a potential drug target against this parasite. In the present study, a yeast-two-hybrid system was used to identify Phylomer peptides within a library constructed from the genomes of 25 phylogenetically diverse bacteria that targeted the IMPDH of Cryptosporidium parvum (IMPcp) and Cryptosporidium hominis (IMPch). We identified 38 unique interacting Phylomers, of which, 12 were synthesised and screened against C. parvum in vitro. Two Phylomers exhibited significant growth inhibition (81.2-83.8% inhibition; P < 0.05), one of which consistently exhibited positive interactions with IMPcp and IMPch during primary and recapitulation yeast two-hybrid screening and did not interact with either of the human IMPDH proteins. The present study highlightsthe potential of Phylomer peptides as target validation tools for Cryptosporidium and other organisms and diseases because of their ability to bind with high affinity to target proteins and disrupt function.

HLA similarities indicate shared genetic risk in 21-hydroxylase autoantibody positive South African and United States Addison's disease.

Genetic similarities between patients from the United States and South African (SA) Addison's Disease (AD) strengthen evidence for genetic association. SA-AD (n = 73), SA healthy controls (N = 78), and US-AD patients (N = 83) were genotyped for DQA1, DQB1, DRB1, and HLA-B alleles. Serum was tested for the quantity of 21OH-AA and IFNα-AA at the Barbara Davis Center. Although not as profound as in US-AD, in SA-AD 21OH-AA + subjects the predominantly associated risk haplotypes were DRB1*0301-DQB1*0201 (DR3), DRB1*04xx-DQB1*0302 (DR4), and the combined DR3/4 genotype. DQB1*0302 associated DRB1*04xx haplotypes conferred higher risk than those DRB1*04xx haplotypes associated with other DQB1 alleles. We found negative association in 21OH-AA + SA-AD for DQA1*0201-DQB1*0202 and DQA1*0101-DQB1*0501 vs SA controls, and positive association for DQA1*0401-DQB1*0402 vs US-AD. Apart from the class II DR3 haplotype, HLA-B8 did not have an independent effect; however together DR3 and HLA-B8 conferred the highest risk vs 21OH-AA negative SA-AD and SA-controls. HLA-B7 (often with DR4) conferred novel risk in 21OH-AA + SA-AD vs controls. This study represents the first comparison between South African and United States AD populations utilizing genotyping and serology performed at the same center. SA-AD and US-AD 21OH-AA + patients share common HLA risk haplotypes including DR4 (with HLA-B7) and DR3 (with HLA-B8), strengthening previously described HLA associations and implicating similar genetic etiology.

Mediation of the solar wind termination shock by non-thermal ions.

Broad regions on both sides of the solar wind termination shock are populated by high intensities of non-thermal ions and electrons. The pre-shock particles in the solar wind have been measured by the spacecraft Voyager 1 (refs 1-5) and Voyager 2 (refs 3, 6). The post-shock particles in the heliosheath have also been measured by Voyager 1 (refs 3-5). It was not clear, however, what effect these particles might have on the physics of the shock transition until Voyager 2 crossed the shock on 31 August-1 September 2007 (refs 7-9). Unlike Voyager 1, Voyager 2 is making plasma measurements. Data from the plasma and magnetic field instruments on Voyager 2 indicate that non-thermal ion distributions probably have key roles in mediating dynamical processes at the termination shock and in the heliosheath. Here we report that intensities of low-energy ions measured by Voyager 2 produce non-thermal partial ion pressures in the heliosheath that are comparable to (or exceed) both the thermal plasma pressures and the scalar magnetic field pressures. We conclude that these ions are the >0.028 MeV portion of the non-thermal ion distribution that determines the termination shock structure and the acceleration of which extracts a large fraction of bulk-flow kinetic energy from the incident solar wind.

Mood disturbance in glioma patients.

Patients diagnosed with primary brain tumors such as glioma experience psychological distress throughout the illness trajectory. Determining which patient characteristics are associated with more severe mood disturbance throughout the illness trajectory can help identify patients at risk and assist in developing targeted interventions based on these factors. Adult glioma patients were eligible for participation. Data collection tools included an investigator completed clinician assessment tool, patient completed demographic form and the Profile of mood states-short form. A multiple regression model was used to describe the relationship between the patient groups and clinical factors. The study enrolled 186 glioma patients of various tumor grades, who were categorized in three groups (newly diagnosed, on-treatment, follow-up) based on disease status at time of visit. Newly diagnosed patients experienced more total mood disturbance than all the other groups. Characteristics associated with more severe mood disturbance varied by patient group: newly diagnosed patients who were not on corticosteroids and were not married were more likely to have higher mood disturbance [R(2) = 0.27, F (2, 29) = 5.31, p < 0.02]. For those on treatment, the use of concomitant medications, having more than 1 recurrence and low income predicted higher mood disturbance [R(2) = 0.417, F (4, 67) = 11.98, p < 0.001]. For those not on active treatment, female sex, anti-depressant use and having a lower income was associated with higher mood disturbance [R(2) = 0.183, F (3, 55) = 4.11, p < 0.02]. Additionally, when compared to other cancer groups, glioma patients reported similar mood disturbance to those with breast cancer. Factors other than disease characteristics are associated with higher mood disturbance and vary according to current disease status. The use of concomitant medications, demographic factors, recurrence and income are associated with mood disturbance and interventions may need to be tailored to these underlying factors.

Clinical effectiveness of mindfulness-based music therapy on improving emotional regulation in blind older women: A randomized controlled trial.

Background: This study aimed to investigate clinical effectiveness of a structured eight-week mindfulness-based music therapy (MBMT) program on improving mood regulation in older women with blindness. This investigation compared a MBMT group with a mindfulness intervention (MI) group and a control group. Methods: Ninety-two older females with blindness from a residential setting in Hong Kong were recruited and randomly allocated to a MBMT (n = 31), MI (n = 30), or control (n = 31) group. Psychological measurements regarding mood regulation and general mood states (namely, Difficulties in Emotion Regulation Scale [DERS], Geriatric Depression Scale [GDS], and Depression Anxiety Stress Scales-21), were taken at pretest and posttest. Outcome assessors were blinded to group assignment. Results: Data was analyzed based on intention-to-treat basis. At posttest, DERS scores in the MBMT group (mean differences and 95% confidence interval: 12.1, 5.5 to 18.8) and the MI group (7.2, 0.5 to 13.8) were lower than that in the control group. GDS scores in the MBMT group (2.9, 1.7 to 4.0) and the MI group (1.7, 0.6 to 2.9) were lower than those in the control group. Compared with the MI group, the MBMT group improved emotional awareness sub-scores in DERS (2.1, 0.2 to 4.1) and appeared to lower depression in GDS scores (1.1, -0.0 to 2.3; p = 0.053). Conclusion: MBMT seems more beneficial than MI alone for improving emotional regulation in older women with blindness. The combination of mindfulness and music can generate a synergetic effect by enhancing both attention and appraisal components within the emotional-regulation process. Trial registration: ClinicalTrials.gov, NCT05583695.

Sodium chloride concentration affects yield, quality, and sensory acceptability of vacuum-tumbled marinated broiler breast fillets.

The objective of this experiment was to determine the effect of sodium chloride concentration on yield, instrumental quality, and sensory acceptability of broiler breast meat that was vacuum tumbled with a 15% solution (over green weight) for 30 min. Different concentrations (0, 0.25, 0.50, 0.75, 1.00, 1.25, and 1.50%) of NaCl (salt) and 0.35% sodium tripolyphosphate were included in the marinade solution. After marinating, breast fillets were evaluated for marination yields, pH, surface color, cooking loss, tenderness, expressible moisture, proximate composition, purge loss, sodium content, and sensory acceptability. As salt concentration increased, CIE L* decreased linearly, with a concentration of 0.75% having lower (P < 0.05) CIE L* values when compared with the control, 0, and 0.25% NaCl treatments. In addition, there was a linear and quadratic decrease (P < 0.05) in shear force as salt concentration increased, with no further decrease (P < 0.05) when greater than 0.75% NaCl was used. Cooking yield increased (P < 0.05) as the salt concentration increased to 1.0%. All marinated treatments were preferred (P < 0.05) over the control treatment, and all treatments marinated with at least 0.50% sodium chloride had an average rating of like moderately. Cluster analysis indicated that consumer groups varied in their preference of broiler breast meat treatments and that samples that were marinated with between 0.5 to 1.0% NaCl were acceptable to the majority of consumers. Marination with 0.75% NaCl was sufficient to maximize yields and decrease lightness (L*) in vacuum-tumbled, marinated broiler breast that is sold raw, but 1.0% NaCl could be used in a precooked product because it minimizes cook loss. In addition, use of 0.50% NaCl had minimal effects on yields, color, and sensory acceptability when compared with products that were marinated with greater concentrations of NaCl.

Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas.

Although low-grade gliomas (LGG) have a less aggressive course than do high-grade gliomas, the outcome of these tumours is ultimately fatal in most patients. Both the tumour and its treatment can cause disabling morbidity, particularly of cognitive functions. Because many patients present with seizures only, with no other signs and symptoms, maintenance of quality of life and function constitutes a particular challenge in LGG. The slow growth pattern of most LGG, and the rare radiological true responses despite a favourable clinical response to treatment, interferes with the use of progression-free survival as the primary endpoint in trials. Overall survival as an endpoint brings logistical challenges, and is sensitive to other non-investigational salvage therapies. Clinical trials for LGG need to consider other measures of patient benefit such as cognition, symptom burden, and seizure activity, to establish whether improved survival is reflected in prolonged wellbeing. This Review investigates clinical and imaging endpoints in trials of LGG, and provides response assessment in neuro-oncology (RANO) criteria for non-enhancing tumours. Additionally, other measures for patients with brain tumours that assess outcome are described. Similar considerations are relevant for trials of high-grade gliomas, although for these tumours survival is shorter and survival endpoints generally have more value than they do for LGG.

Effect of elliptic handle shape on grasping strategies, grip force distribution, and twisting ability.

A generic torque model for various handle shapes has been developed and evaluated using experimental data. Twelve subjects performed maximum isometric torques using circular and elliptic cylinders in medium and large sizes (circular: r = 25.4, 38.1 mm; elliptic: semi-major/minor axes = 30.9/19.3, 47.1/27.8 mm) finished with aluminium and rubber, in two opposite directions. Torque, grip force distribution, and finger position were recorded. Maximum torques were 25%, 7%, and 31% greater for the elliptic, large-size, and rubber-finished cylinders than for the circular, medium-size, and aluminium-finished cylinders, respectively. Greater torque for the elliptic cylinders was associated with 58% greater normal force that the subjects could generate for the elliptic than circular cylinders. The model suggests that greater torques for the large-size and rubber cylinders are related to long moment arms and greater frictional coupling at the hand-cylinder interface, respectively. Subjects positioned their hands differently depending on torque direction to maximise their normal force and torque generation. STATEMENT OF RELEVANCE: Desirable handle features for torque generation may be different from those for grip only. Design of handles per advantageous handle features (e.g., shape, size, and surface) may help increase people's torque strength and contribute to increased physical capacity of people.

Development and Interrogation of a Transcriptomic Resource for the Giant Triton Snail (Charonia tritonis).

Gastropod molluscs are among the most abundant species that inhabit coral reef ecosystems. Many are specialist predators, along with the giant triton snail Charonia tritonis (Linnaeus, 1758) whose diet consists of Acanthaster planci (crown-of-thorns starfish), a corallivore known to consume enormous quantities of reef-building coral. C. tritonis are considered vulnerable due to overexploitation, and a decline in their populations is believed to have contributed to recurring A. planci population outbreaks. Aquaculture is considered one approach that could help restore natural populations of C. tritonis and mitigate coral loss; however, numerous questions remain unanswered regarding their life cycle, including the molecular factors that regulate their reproduction and development. In this study, we have established a reference C. tritonis transcriptome derived from developmental stages (embryo and veliger) and adult tissues. This was used to identify genes associated with cell signalling, such as neuropeptides and G protein-coupled receptors (GPCRs), involved in endocrine and olfactory signalling. A comparison of developmental stages showed that several neuropeptide precursors are exclusively expressed in post-hatch veligers and functional analysis found that FFamide stimulated a significant (20.3%) increase in larval heart rate. GPCRs unique to veligers, and a diversity of rhodopsin-like GPCRs located within adult cephalic tentacles, all represent candidate olfactory receptors. In addition, the cytochrome P450 superfamily, which participates in the biosynthesis and degradation of steroid hormones and lipids, was also found to be expanded with at least 91 genes annotated, mostly in gill tissue. These findings further progress our understanding of C. tritonis with possible application in developing aquaculture methods.

Clinical relevant pancreatic fistula after pancreatoduodenectomy: when negative amylase levels tell the truth.

Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940-0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81-0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five.