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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 mm 2 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., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: Breslow thickness (BT) is the most important histological prognostic feature for melanoma prognosis, but it only captures tumour size in one dimension. Adding a further measurement in a different axis has been shown to improve prognostic value. It seems reasonable that further prognostic value could be obtained by estimating the number of invasive melanoma cells using nuclear count. The aim of this study was to show proof of concept that nuclear count has prognostic value independent of BT., Methods and Results: Melanoma cell nuclei were labelled with SRY-related HMG-box 10 (SOX10) protein, the sections scanned and StarDist machine-learning algorithm used to count nuclei in 102 cases of primary cutaneous melanoma. Prognostic value was assessed using survival analyses. Nuclear count correlated strongly with T category, BT and calculated tumour area (each P < 0.001), suggesting that it was a valid marker of melanoma burden. Nuclear count was a predictor for overall survival in univariable analysis [hazard ratio (HR) = 2.25, confidence interval (CI) = 1.66-3.06, P < 0.001] and multivariable analysis (HR = 2.60, CI = 1.59-4.24, P < 0.001). BT and ulceration were significant in univariable analyses, but not in multivariable models with nuclear count. Models containing nuclear count showed the best fit. Similar results were seen for melanoma-specific and metastasis-free survival. Nuclear count was able to stratify melanomas within a given T stage., Conclusions: This study demonstrated proof of concept that counting melanoma nuclei may be an improved measure of invasive tumour burden compared to BT. Future studies will need to refine methods of nuclear detection and also to confirm its prognostic value., (© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.)

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., Competing Interests: AMT reports grants from Grifols Biotherapeutics, grants from Alpha-1 Foundation, personal fees from CSL Behring, grants and non-financial support from Arrowhead Inc, outside the submitted work. NKO, JH-S, RM, PN, and BN have no conflict of interest to declare., (© 2019 Published by Elsevier Ltd.)

Background: Pulmonary rehabilitation programme for lung surgery patients can reduce the risk of post-operative complications but compliance to programmes can be limited by access to health care. We developed a home-based rehabilitation app and tested its feasibility in patients undergoing lung resection surgery., Methods: A cohort study was conducted over 18 months at a regional thoracic unit. The Fit 4 Surgery app included ten exercises. Patients were instructed to exercise for at least three minutes for each exercise. Data was transmitted back to the researchers remotely. Data was also collected from a contemporaneous group of surgery patients who attended local outpatient-based Chronic Obstructive Pulmonary Disease rehabilitation classes. Quality of Life and outcomes data in the app group were collected. Patients were also interviewed about their experience of the app., Results: App patients had a shorter wait before surgery compared to patients attending rehabilitation classes (24 vs 45 days) but managed four times as many sessions (2 vs 9), improving incremental shuttle walk test distance by 99 ± 83 (p < 0.05) metres before surgery. Five themes were gathered from the interviews., Conclusion: An app based programme of rehabilitation can be delivered in a timely fashion to lung surgery patients with demonstrable physiological benefits; this will need to be confirmed in further clinical trials., Clinical Trial Registration Number: ISRCTN00061628. Registered 27 May 2011.

Background: Mortality following lung cancer resection has been shown to double between 30 and 90 days and readmission following surgery is associated with an increased risk of mortality. The aim of this study was to describe the causes of readmission and mortality and enable the identification of potentially modifiable factors associated with these events., Methods: Prospective cohort study at a United Kingdom tertiary referral centre conducted over 55 months. Binary logistic regression was used to identify factors associated with death within 90 days of surgery., Results: The 30 day and 90 day mortality rates were 1.4% and 3.3% respectively. The most common causes of death were pneumonia, lung cancer and Acute Respiratory Distress Syndrome/Multi Organ Failure. Potentially modifiable risk factors for death identified were: Postoperative pulmonary complications (Odds ratio 6.1), preoperative lymphocyte count (OR 0.25), readmission within 30 days (OR 4.2) and type of postoperative analgesia (OR for intrathecal morphine 4.8). The most common causes of readmission were pneumonia, shortness of breath and pain., Conclusions: Postoperative mortality is not simply due to fixed factors; the impacts of age, gender and surgical procedure on postoperative survival are reduced when the postoperative course of recovery is examined. Perioperative immune function, as portrayed by the occurrence of infection and lower lymphocyte count in the immediate perioperative period, and pain control method are strongly associated with 90 day mortality; further studies in these fields are indicated as are studies of psychological factors in recovery., Clinical Registration Number: ISRCTN00061628., (Copyright © 2019. Published by Elsevier Ltd.)

Background: The effects of the Nuss procedure on chest wall motion and spirometry have previously been described; we aimed to describe the effects of removal of the Nuss bar., Methods: We studied 9 patients just prior to and 6 weeks after Nuss bar removal. Regional chest volume changes, synchrony of respiratory movement and spirometry were recorded using optoelectronic plethysmography (OEP) and compared. Recordings were performed at rest and exercise during cycle ergometry., Results: There were small but statistically significant changes in tidal volumes of the diaphragmatic ribcage compartment during exercise (+ 48 ml, p = 0.038, Cohen's d = 0.12) and percentage contribution of the diaphragmatic ribcage to total tidal volumes at rest (+ 2.7 percentage points, p = 0.038, Cohen's d = 0.12). Synchrony of respiratory movements at rest and during exercise was unchanged following Nuss bar removal. There were no significant changes in spirometry and exercise capacity., Conclusions: The effects of Nuss bar removal on diaphragmatic ribcage motion are detectable but small and unlikely to be of clinical significance. No change in exercise capacity should be expected after Nuss bar removal., Trial Registration: Registered at ClinicalTrials.gov, identifier NCT02958683 , registered 5th August 2016, first patient enrolled July 2016, retrospectively registered.

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.

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.

Purpose: Reconstruction after sternal resection is performed according to surgeon intuition; physiologic evidence for selection of prostheses is lacking. We present our experience of the in vivo function of a novel device for sternal reconstruction., Description: A three-dimensional-printed titanium and porous polyethylene sternal prosthesis was made according to the patient's computed tomographic scan. The titanium arms slot over adjacent ribs and are fixed in place with screws. The porous element allows ingrowth of native tissue while preventing lung herniation around the narrow titanium bars., Evaluation: We performed optoelectronic plethysmography to assess the physiologic function of the device compared with a muscle flap reconstruction. Asynchronous and paradoxical movements of the thoracoabdominal surface were apparent with the muscle flap reconstruction but not with the new device. Considerably higher tidal volumes and a lower respiratory rate achieved the same minute volume with the new device compared with the muscle flap., Conclusions: Rigid sternal reconstruction with a three-dimensional-printed prosthesis demonstrated superior respiratory mechanics compared with reconstruction with an autologous muscle flap., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Receiving information about their disease and treatment is very important to patients with cancer. There is an association between feeling appropriately informed and better quality of life. This audit aimed to estimate patient satisfaction with perioperative information in those undergoing surgery for lung cancer and any change in satisfaction over time., Methods: A questionnaire (EORTC-Info-25) was administered prospectively to patients preoperatively and up to six months postoperatively. The preoperative questionnaire was completed by 292 patients and 88 free text comments were completed. Intrapersonal responses were compared over time., Results: Patients were highly satisfied with information prior to surgery. The overall helpfulness of information did not change over time but satisfaction with the amount of information decreased. Patients who received more information about 'the disease' and 'things you can do to help yourself get well' were less likely to report a drop in satisfaction (Odds Ratio 0.858, 95% Confidence interval 0.765 to 0.961, p = 0.008 and OR 0.102, 95% CI 0.018 to 0.590, p = 0.011 respectively). Free text responses revealed patients most frequently wanted more information on the disease, aftercare and self-care. Suffering complications from surgery was not associated with a change in satisfaction with information postoperatively., Conclusions: Patients want to know more about their diagnosis, but also how to recover and cope with issues once they have gone home after surgery. Postoperative satisfaction with information may improve if patients are given more information on these topics.

Background: Interventional bronchoscopy is effective in the management of patients with symptomatic airway obstruction for both malignant and benign conditions. The main aim of this study is to report our experience with emergency interventional bronchoscopy in patients with symptomatic airway obstruction and identify prognostic factors for survival., Methods: This is a retrospective observational study of patients undergoing emergency interventional bronchoscopy over a 4-year period. Survival times were analyzed separately for patients with benign and malignant airway obstruction by the Kaplan-Meier method., Results: Between June 2009 and July 2013, 168 emergency interventional bronchoscopies were performed in 112 patients for airway obstruction. The median age was 63 years (range, 20 to 86), and 91 patients (54%) patients were female. Seventy-two cases (43%) had airway obstruction due to malignant disease. There were 3 in-hospital deaths (2.7%). Median survival of the study population was 5.6 months (range, 0 to 51) with a median follow-up of 7.3 months (range, 0 to 51). Median survival for patients with malignant airway obstruction was 3.5 months (range, 0 to 21), and 9.8 months (range, 0.1 to 51) for those with benign disease. Airway intervention facilitated palliative chemotherapy in 32 patients (44%) of those with malignant airway obstruction. At multivariate analysis in patients with malignant airway obstruction, presence of stridor (hazard ratio 1.919, 95% confidence interval: 1.082 to 3.404, p = 0.026) and not receiving postprocedure chemotherapy (hazard ratio 2.05, 95% confidence interval: 1.156 to 3.636, p = 0.014) were independent prognostic factors for death., Conclusions: Emergency interventional bronchoscopy for airway obstruction is safe, relieved symptoms, and facilitated palliative chemotherapy, which improved survival., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)