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IntroductionPerianal fistula is a burdening disease with an annual incidence of 6–12/100 000 in Western countries. More than 90% of crypto-glandular fistulas originate from perianal abscess. Despite adequate drainage, up to 83% recur or result in an anal fistula, the majority developing within 12 months. There is some evidence that gut-derived bacteria play a role in the development of perianal fistula. Up till now, it is not common practice to routinely administer prophylactic antibiotics to prevent anal fistula development. There is a need for a study to establish whether adding antibiotic treatment to surgical drainage of perianal abscess results in a reduction in perianal fistulas.Methods and analysisThis multicentre, double-blind, randomised, placebo-controlled trial investigates whether addition of antibiotics (ciprofloxacin and metronidazole) to surgical drainage of a perianal abscess is beneficial compared with surgical drainage alone. The primary outcome is the development of a perianal fistula within 1 year. Secondary outcomes include quality of life, treatment costs, need for repeated drainage, patient-reported outcomes and other clinical outcomes. Participants are recruited in one academic and seven peripheral Dutch clinics. To demonstrate a reduction of perianal fistula from 30% to 15% when treated with adjuvant antibiotics with a two-sided alpha of 0.05, a power of 80% and taking a 10% loss to follow-up percentage into account, the total sample size will be 298 participants. Data will be analysed according to the intention-to-treat principle.Ethics and disseminationThe study protocol has been approved by the Medical Ethics Review Committee of the Amsterdam University Medical Centers (nr. 2021_010). Written consent is obtained from each participant prior to randomisation into the study. The results of this trial will be submitted for publication in international peer-reviewed journals, presented at conferences and spread to coloproctological associations.Trial registration numbers2020-004449-35; NCT05385887.

PurposeTo generate and extend the evidence on the clinical validity of an artificial intelligence (AI) algorithm to detect acute pulmonary embolism (PE) on CT pulmonary angiography (CTPA) of patients suspected of PE and to evaluate the possibility of reducing the risk of missed findings in clinical practice with AI-assisted reporting.MethodsConsecutive CTPA scan data of 3316 patients referred because of suspected PE between 24-2-2018 and 31-12-2020 were retrospectively analysed by a CE-certified and FDA-approved AI algorithm. The output of the AI was compared with the attending radiologists’ report. To define the reference standard, discordant findings were independently evaluated by two readers. In case of disagreement, an experienced cardiothoracic radiologist adjudicated.ResultsAccording to the reference standard, PE was present in 717 patients (21.6%). PE was missed by the AI in 23 patients, while the attending radiologist missed 60 PE. The AI detected 2 false positives and the attending radiologist 9. The sensitivity for the detection of PE by the AI algorithm was significantly higher compared to the radiology report (96.8% vs. 91.6%, p < 0.001). Specificity of the AI was also significantly higher (99.9% vs. 99.7%, p = 0.035). NPV and PPV of the AI were also significantly higher than the radiology report.ConclusionThe AI algorithm showed a significantly higher diagnostic accuracy for the detection of PE on CTPA compared to the report of the attending radiologist. This finding indicates that missed positive findings could be prevented with the implementation of AI-assisted reporting in daily clinical practice.Critical relevance statementMissed positive findings on CTPA of patients suspected of pulmonary embolism can be prevented with the implementation of AI-assisted care.Key pointsThe AI algorithm showed excellent diagnostic accuracy detecting PE on CTPA.Accuracy of the AI was significantly higher compared to the attending radiologist.Highest diagnostic accuracy can likely be achieved by radiologists supported by AI.Our results indicate that implementation of AI-assisted reporting could reduce the number of missed positive findings.

IntroductionHaemorrhoidal disease is one of the most common anorectal disorders, which affects nearly half of the general population. Treatment of grade III haemorrhoids consists initially of conservative measures, followed by rubber band ligation and haemorrhoidectomy when unsuccessful. Given the current guidelines and numerous modalities the obvious question which needs to be answered is which treatment is the best for grade III haemorrhoids. There is a need for evaluating treatment from the patient’s point of view and transparency in surgical and non-surgical treatment outcome.Methods and analysisThis multicentre, randomised controlled, non-inferiority trial with cost–utility analysis compares haemorrhoidectomy with rubber band ligation. Patients aged 18 years and older with symptomatic haemorrhoids grade III are recruited. Primary outcome measure is quality of life at 24 months measured with the EQ-5D-5L and in-hospital (in)direct costs and out-of-hospital postoperative costs. A key secondary outcome is recurrence at 1-year postprocedure. Secondary outcomes are complaint reduction with proctology-specific patient-reported outcome measurements (Haemorrhoid Severity Score, ProctoPROM, PROM-HISS, vaizey score), resumption of work, pain and complication rates. Data are collected at seven different time points. Standard postprocedural care is followed.A sample size has been calculated using a one sided alpha of 0.025 and a power of 80% with an SD of 0.15 and a non-inferiority limit of 0.05. With stratification by centre and to adjust for 10% lost to follow-up the total sample size will be 360 patients in total (180 per group).Data will be analysed according to the intention-to-treat and the per-protocol principle.Ethics and disseminationThe protocol has been approved by the Medical Ethics Review Committee of the Amsterdam University Medical Centres, location AMC. Findings will be disseminated in peer-reviewed journals and presented at conferences, whether they are positive, negative or inconclusive.Trial registration numbersNCT04621695, NTR8020

Objectives The purpose of this study was to evaluate the incremental value of artificial intelligence (AI) compared to the diagnostic accuracy of radiologists alone in detecting incidental acute pulmonary embolism (PE) on routine portal venous contrast-enhanced chest computed tomography (CT). Methods CTs of 3089 consecutive patients referred to the radiology department for a routine contrast-enhanced chest CT between 27–5-2020 and 31–12-2020, were retrospectively analysed by a CE-certified and FDA-approved AI algorithm. The diagnostic performance of the AI was compared to the initial report. To determine the reference standard, discordant findings were independently evaluated by two readers. In case of disagreement, another experienced cardiothoracic radiologist with knowledge of the initial report and the AI output adjudicated. Results The prevalence of acute incidental PE in the reference standard was 2.2% (67 of 3089 patients). In 25 cases, AI detected initially unreported PE. This included three cases concerning central/lobar PE. Sensitivity of the AI algorithm was significantly higher than the outcome of the initial report (respectively 95.5% vs. 62.7%, p  < 0.001), whereas specificity was very high for both (respectively 99.6% vs 99.9%, p  = 0.012). The AI algorithm only showed a slightly higher amount of false-positive findings (11 vs. 2), resulting in a significantly lower PPV (85.3% vs. 95.5%, p  = 0.047). Conclusion The AI algorithm showed high diagnostic accuracy in diagnosing incidental PE, detecting an additional 25 cases of initially unreported PE, accounting for 37.3% of all positive cases. Clinical relevance statement Radiologist support from AI algorithms in daily practice can prevent missed incidental acute PE on routine chest CT, without a high burden of false-positive cases. Key Points • Incidental pulmonary embolism is often missed by radiologists in non-diagnostic scans with suboptimal contrast opacification within the pulmonary trunk. • An artificial intelligence algorithm showed higher sensitivity detecting incidental pulmonary embolism on routine portal venous chest CT compared to the initial report. • Implementation of artificial intelligence support in routine daily practice will reduce the number of missed incidental pulmonary embolism.

BackgroundA medical-psychiatric unit (MPU) is a special ward where staff is trained in caring for patients with psychiatric or behavioural problems that need hospitalisation for physical health problems. It is well known that these patients are at higher risk of complications and have a longer length of stay resulting in higher costs than patients without psychiatric comorbidity. The objective of this study was to analyse the trauma patient population of the first 10 years of existence of the MPU in a level I trauma center.Patients and methodsA retrospective analysis was performed in 2-year cohorts from 2006 to 2016. All trauma patients admitted to the MPU were compared with the overall trauma patient population in VUmc. Data (psychiatric diagnosis, substance abuse, trauma scores, surgical interventions, complications, mortality) were extracted from individual patient notes and the Regional Trauma Registry.Results258 patients were identified. 36% of all patients had a history of previous psychiatric admission and 30% had attempted suicide at least once in their lifetime. Substance abuse was the most common psychiatric diagnosis (39%), with psychotic disorder (28%) in second place. The median hospital stay was 21 days. Median MPU length of stay was 10 days (range 1–160). Injuries were self-inflicted in 57%. The most common mechanism of injury was fall from height with intentional jumping in second place. Penetrating injury rate was 24% and 33% had an ISS ≥ 16, compared to 5% and 15%, respectively, in the overall trauma patient population. The most common injuries were those of the head and neck. Complication rate was 49%.ConclusionTrauma patients that were admitted to the MPU of an urban level I trauma center had serious psychiatric comorbidity as well as high injury severity. Penetrating injury was much more common than in the overall trauma patient population. A high complication rate was noted. The high psychiatric comorbidity and the complicated care warrants combined psychiatric and somatic (nursing) care for this subpopulation of trauma patients. This should be taken into account in the prehospital triage to a trauma center. The institution of a MPU in level I trauma centers is recommended.

Supportive relationships between students and their educational faculty and staff can foster positive outcomes such as students’ involvement and development. However, research investigating how students perceive the quality of their relationships with educational faculty/staff (i.e., relationship quality) so far remains scarce. This study’s aim was to gain more insight into the construct of relationship quality in higher education using a qualitative approach. Students’ descriptions of their positive ( n = 294) and negative relationship experiences ( n = 395) were collected using a critical incident technique (final sample N = 513 critical incidents) followed by a template analysis with a priori themes (i.e., relationship quality dimensions: trust in honesty, trust in benevolence, satisfaction, affective commitment, affective conflict). Results indicated that students most often mentioned trust in honesty and trust in benevolence. Affective conflict was not always explicitly mentioned in negative experiences, nor satisfaction in positive experiences. Descriptions of trust in benevolence ( n = 355) were equally distributed over positive and negative incidents. However, trust in honesty was more often referred to in negative ( n = 145) than in positive incidents ( n = 51). The results indicated that students considered timely response to assignments and emails important, and teachers showing interest and attention. The study’s findings provide a new view of how students might positively and negatively perceive the quality of their relationship with educational faculty and staff. This study adds to the theoretical and practical implications of relationship quality research in higher education and how relational aspects are important for students.

Four healthy volunteers were infected with 50 Necator americanus infective larvae (L3) in a controlled human hookworm infection trial and followed for 52 weeks. The kinetics of fecal egg counts in volunteers was assessed with Bayesian multilevel analysis, which revealed an increase between weeks 7 and 13, followed by an egg density plateau of about 1000 eggs/g of feces. Variation in egg counts was minimal between same-day measurements but varied considerably between days, particularly during the plateau phase. These analyses pave the way for the controlled human hookworm model to accelerate drug and vaccine efficacy studies.

Extracellular vesicles (EVs) are small nanometre-sized vesicles that are circulating in blood. They are released by multiple cells, including tumour cells. We hypothesized that circulating EVs contain protein kinases that may be assessed as biomarkers during treatment with tyrosine kinase inhibitors. EVs released by U87 glioma cells, H3255 and H1650 non-small-cell lung cancer (NSCLC) cells were profiled by tandem mass spectrometry. Total AKT/protein kinase B and extracellular signal regulated kinase 1/2 (ERK1/2) levels as well as their relative phosphorylation were measured by western blot in isogenic U87 cells with or without mutant epidermal growth factor receptor (EGFRvIII) and their corresponding EVs. To assess biomarker potential, plasma samples from 24 healthy volunteers and 42 patients with cancer were used. In total, 130 different protein kinases were found to be released in EVs including multiple drug targets, such as mammalian target of rapamycin (mTOR), AKT, ERK1/2, AXL and EGFR. Overexpression of EGFRvIII in U87 cells results in increased phosphorylation of EGFR, AKT and ERK1/2 in cells and EVs, whereas a decreased phosphorylation was noted upon treatment with the EGFR inhibitor erlotinib. EV samples derived from patients with cancer contained significantly more protein (p=0.0067) compared to healthy donors. Phosphorylation of AKT and ERK1/2 in plasma EVs from both healthy donors and patients with cancer was relatively low compared to levels in cancer cells. Preliminary analysis of total AKT and ERK1/2 levels in plasma EVs from patients with NSCLC before and after sorafenib/metformin treatment (n=12) shows a significant decrease in AKT levels among patients with a favourable treatment response (p<0.005). Phosphorylation of protein kinases in EVs reflects their phosphorylation in tumour cells. Total AKT protein levels may allow monitoring of kinase inhibitor responses in patients with cancer.

To compare results from messenger RNA (mRNA)-based TargetPrint testing with those from immunohistochemistry (IHC) and in situ hybridization (ISH) conducted according to local standard procedures at hospitals worldwide. Tumor samples were prospectively obtained from 806 patients at 22 hospitals. The mRNA level of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was assessed by TargetPrint quantitative gene expression readouts. IHC/ISH assessments were performed according to local standards at the participating hospitals. TargetPrint readout showed a high concordance with IHC/ISH of 95 % (kappa 0.81) for ER, 81 % (kappa 0.56) for PR, and 94 % (kappa 0.76) for HER2. The positive/negative agreement between TargetPrint and IHC for ER, PR, and HER2 was 96 %/87 %, 84 %/74 %, and 74 %/98 %, respectively. The concordance rate in IHC/ISH results between hospitals varied: 88–100 % for ER (kappa 0.50–1.00); 50–100 % for PR (kappa 0.20–1.00); and 90–100 % for HER2 (kappa 0.59–1.00). mRNA readout of ER, PR, and HER2 status by TargetPrint was largely comparable to local IHC/ISH analysis. However, there was substantial discordance in IHC/ISH results between different hospitals. When results are discordant, the use of TargetPrint would improve the reliability of hormone receptor and HER2 results by prompting retesting in a reference laboratory.