The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

Predicting Postoperative Lung Function Following Lung Cancer Resection: A Systematic Review and Meta-analysis.

BACKGROUND: Lung resection remains the gold standard treatment for early stage lung cancer; prediction of postoperative lung function is a key selection criterion for surgery with the aim of determining risk of postoperative dyspnoea. We aimed to identify the different prediction techniques used, and compare their accuracy. METHODS: A systematic review and meta-analysis sought to synthesise studies conducted that assess prediction of postoperative lung function up to 18/02/2018 (n = 135). PROBAST was used to assess risk of bias in studies, 17 studies were judged to be at low risk of bias. FINDINGS: Meta-analysis revealed CT volume and density measurement to be the most accurate (mean difference 71 ml) and precise (standard deviation 207 ml) of the reported techniques used for predicting FEV1; evidence for predicting gas transfer was lacking. INTERPRETATION: The evidence suggests using CT volume and density is the preferred technique in the prediction of postoperative FEV1. Further studies are required to ensure that the methods and thresholds we propose are linked to patient reported outcomes. FUNDING: Salary support for NKO, RM, PN, BN, and AMT was provided by University Hospitals Birmingham NHS Foundation Trust.

Cardioplegia in paediatric cardiac surgery: a systematic review of randomized controlled trials.

OBJECTIVES: Cardioplegia is the primary method for myocardial protection during cardiac surgery. We conducted a systematic review of randomized controlled trials of cardioplegia in children to evaluate the current evidence base. METHODS: We searched MEDLINE, CENTRAL and LILACS and manually screened retrieved references and systematic reviews to identify all randomized controlled trials comparing cardioplegia solutions or additives in children undergoing cardiac surgery published in any language; secondary publications and those reporting inseparable adult data were excluded. Two or more reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. RESULTS: We identified 26 trials randomizing 1596 children undergoing surgery; all were single-centre, Phase II trials, recruiting few patients (median 48, interquartile range 30-99). The most frequent comparison was blood versus crystalloid in 10 (38.5%) trials, and the most common end points were biomarkers of myocardial injury (17, 65.4%), inotrope requirements (15, 57.7%) and length of stay in the intensive care unit (11, 42.3%). However, the heterogeneity of patients, interventions and reported outcome measures prohibited meta-analysis. Overall risk of bias was high in 3 (11.5%) trials, unclear in 23 (88.5%) and low in none. CONCLUSIONS: The current literature on cardioplegia in children contains no late phase trials. The small size, inconsistent use of end points and low quality of reported trials provide a limited evidence base to inform practice. A core outcome set of clinically important, standardized, validated end points for assessing myocardial protection in children should be developed to facilitate the conduct of high-quality, multicentre trials. PROSPERO registration: CRD42017080205.

Randomized controlled trials in children's heart surgery in the 21st century: a systematic review.

OBJECTIVES: Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children's heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. METHODS: We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. RESULTS: We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28-82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). CONCLUSIONS: The recent literature in children's heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice.

A case of a retained drain tip following intercostal drain insertion: avoiding a 'never event'.

Pleural effusions are commonly drained with Seldinger intercostal drains. One uncommon but serious risk of drain insertion is that of a foreign body being retained in the pleural cavity following removal. We report a case in which the tip of the drain was retained in the pleural space following difficult insertion of a Seldinger intercostal drain in a district general hospital. Prompt recognition and clear patient communication are important at the occurrence of an unusual complication. Surgical removal of the foreign body was performed following transfer. We report this case to raise awareness that insertion and withdrawal of drains over the guidewire during insertion may damage the drain and highlight the need for doctors who insert chest drains to perform a count of instruments during ward or clinic-based procedures as well as those performed in theatres. We now include removable parts of chest drains in our theatre instrument count.