Levelling the learning ground for healthcare professionals across the world through SIMBA: a mixed-methods study.

OBJECTIVES: To compare the acceptance, strengths and limitations of Simulation via Instant Messaging-Birmingham Advance (SIMBA) in low/middle-income countries (LMICs) and high-income countries (HICs), on healthcare professionals' professional development and learning. DESIGN: Cross-sectional study. SETTING: Online (either mobile or computer/ laptop or both). PARTICIPANTS: 462 participants (LMICs: 29.7%, n=137 and HICs: 71.3%, n=325) were included. INTERVENTIONS: Sixteen SIMBA sessions were conducted between May 2020 and October 2021. Doctors-in-training solved anonymised real-life clinical scenarios over WhatsApp. Participants completed pre-SIMBA and post-SIMBA surveys. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes were identified using Kirkpatrick's training evaluation model. LMIC and HIC participants' reactions (level 1) and self-reported performance, perceptions and improvements in core competencies (level 2a) were compared using the χ2 test. Content analysis of open-ended questions was performed. RESULTS: Postsession, there were no significant differences in application to practice (p=0.266), engagement (p=0.197) and overall session quality (p=0.101) between LMIC and HIC participants (level 1). Participants from HICs showed better knowledge of patient management (LMICs: 77.4% vs HICs: 86.5%; p=0.01), whereas participants from LMICs self-reported higher improvement in professionalism (LMICs: 41.6% vs HICs: 31.1%; p=0.02). There were no significant differences in improved clinical competency scores in patient care (p=0.28), systems-based practice (p=0.05), practice-based learning (p=0.15) and communication skills (p=0.22), between LMIC and HIC participants (level 2a). In content analysis, the major strengths of SIMBA over traditional methods were providing individualised, structured and engaging sessions. CONCLUSIONS: Healthcare professionals from both LMICs and HICs self-reported improvement in their clinical competencies, illustrating that SIMBA can produce equivalent teaching experiences. Furthermore, SIMBA's virtual nature enables international accessibility and presents potential for global scalability. This model could steer future standardised global health education policy development in LMICs.

Sustained clinical knowledge improvements from simulation experiences with Simulation via Instant Messaging-Birmingham Advance.

BACKGROUND: Simulation via Instant Messaging-Birmingham Advance (SIMBA) delivers simulation-based learning through WhatsApp and Zoom, helping to sustain continuing medical education (CME) for postgraduate healthcare professionals otherwise disrupted by the coronavirus (COVID-19) pandemic. This study aimed to assess whether SIMBA helped to improve clinical knowledge and if this improvement in knowledge was sustained over time. METHODS: Two SIMBA sessions-thyroid and pituitary-were conducted in July-August 2020. Each session included simulation of various real-life cases and interactive discussion. Participants' self-reported confidence, acceptance, and knowledge were measured using surveys and multiple-choice questions pre- and post-simulation and in a 6- to 12-week follow-up period. The evaluation surveys were designed using Moore's 7 Levels of CME Outcomes Framework. RESULTS: A total of 116 participants were included in the analysis. Significant improvement was observed in participants' self-reported confidence in approach to simulated cases (thyroid, n = 37, P < .0001; pituitary, n = 79, P < .0001). Significant improvement in clinical knowledge was observed following simulation (thyroid, n = 37, P < .0001; pituitary, n = 79, P < .0001). For both sessions, retention of confidence and knowledge was seen at 6-12 weeks' follow-up. CONCLUSIONS: SIMBA increased participants' clinical knowledge on simulated cases and this improvement was retained up to 6-12 weeks after the session. Further studies are required to explore long-term retention and whether it translates to improved real-world clinical practice.

Developing a simulation-based learning model for acute medical education during COVID-19 pandemic with Simulation via Instant Messaging - Birmingham Advance (SIMBA).

Simulation-based learning (SBL) is well-established in medical education and has gained popularity, particularly during the COVID-19 pandemic when in-person teaching is infeasible. SBL replicates real-life scenarios and provides a fully immersive yet safe learning environment to develop clinical competency. Simulation via Instant Messaging - Birmingham Advance (SIMBA) is an exemplar of SBL, which we previously showed to be effective in endocrinology and diabetes. Previous studies reported the efficacy of SBL in acute medicine. We studied SIMBA as a learning intervention for healthcare professionals interested in acute medicine and defined our aims using the Kirkpatrick model: (i) develop an SBL tool to improve case management; (ii) evaluate experiences and confidence before and after; and (iii) compare efficacy across training levels.Three sessions were conducted, each representing a PDSA cycle (Plan-Do-Study-Act), consisting of four cases and advertised to healthcare professionals at our hospital and social media. Moderators facilitated progression through 25 min simulations and adopted patient and clinical roles as appropriate. Consultants chaired discussion sessions using relevant guidelines. Presimulation and postsimulation questionnaires evaluated self-reported confidence, feedback and intended changes to clinical practice.Improvements were observed in self-reported confidence managing simulated cases across all sessions. Of participants, 93.3% found SIMBA applicable to clinical practice, while 89.3% and 88.0% felt SIMBA aided personal and professional development, respectively. Interestingly, 68.0% preferred SIMBA to traditional teaching methods. Following participant feedback, more challenging cases were included, and we extended the time for simulation and discussion. The transcripts were amended to facilitate more participant-moderator interaction representing clinical practice. In addition, we refined participant recruitment over the three sessions. In cycle 1, we advertised incentives: participation counted towards teaching requirements, certificates and feedback. To rectify the reduction in participants in cycle 2, we implemented new advertisement methods in cycle 3, including on-site posters, reminder emails and recruitment of the defence deanery cohort.

SARS-CoV-2 positivity in offspring and timing of mother-to-child transmission: living systematic review and meta-analysis.

OBJECTIVES: To assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring. DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Major databases between 1 December 2019 and 3 August 2021. STUDY SELECTION: Cohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal). RESULTS: 472 studies (206 cohort studies, 266 case series and case reports; 28 952 mothers, 18 237 babies) were included. Overall, 1.8% (95% confidence interval 1.2% to 2.5%; 140 studies) of the 14 271 babies born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 592 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 14 had confirmed mother-to-child transmission: seven in utero (448 assessed), two intrapartum (18 assessed), and five during the early postnatal period (70 assessed). Of the 800 SARS-CoV-2 positive babies with outcome data, 20 were stillbirths, 23 were neonatal deaths, and eight were early pregnancy losses; 749 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 2.4, 95% confidence interval 1.3 to 4.4), maternal death (14.1, 4.1 to 48.0), maternal admission to an intensive care unit (3.5, 1.7 to 6.9), and maternal postnatal infection (5.0, 1.2 to 20.1) were associated with SARS-CoV-2 positivity in offspring. Positivity rates using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.3%) in studies from North America to 5.7% (3.2% to 8.7%) in studies from Latin America and the Caribbean. CONCLUSION: SARS-CoV-2 positivity rates were found to be low in babies born to mothers with SARS-CoV-2 infection. Evidence suggests confirmed vertical transmission of SARS-CoV-2, although this is likely to be rare. Severity of maternal covid-19 appears to be associated with SARS-CoV-2 positivity in offspring. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178076. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

SIMBA: using Kolb's learning theory in simulation-based learning to improve participants' confidence.

BACKGROUND: Simulation via Instant Messaging- Birmingham Advance (SIMBA) delivers simulation-based learning (SBL) through WhatsApp® and Zoom® based on Kolb's experiential learning theory. This study describes how Kolb's theory was implemented in practice during SIMBA adrenal session. METHODS: SIMBA adrenal session was conducted for healthcare professionals and replicated Kolb's 4-stage cycle: (a) concrete experience-online simulation of real-life clinical scenarios, (b) reflective observation-discussion and Q&A following simulation, (c) abstract conceptualisation-post-session MCQs, and (d) active experimentation-intentions to implement the acquired knowledge in future practice. Participants' self-reported confidence levels for simulated and non-simulated cases pre- and post-SIMBA were analysed using Wilcoxon Signed-Rank test. Key takeaway and feedback were assessed quantitatively and qualitatively in a thematic analysis. RESULTS: Thirty-three participants were included in the analysis. A Wilcoxon signed-rank test showed that the SIMBA session elicited a statistically significant change in participants' self-reported confidence in their approach to Cushing's syndrome (Z = 3.873, p = 0.0001) and adrenocortical carcinoma (Z = 3.970, p < 0.0001). 93.9% (n = 31/33) and 84.8% (n = 28/33) strongly agreed/agreed the topics were applicable to their clinical practice and accommodated their personal learning style, respectively. 81.8% (n = 27/33) reported increase in knowledge on patient management, and 75.8% (n = 25/33) anticipated implementing learning points in their practice. CONCLUSIONS: SIMBA effectively adopts Kolb's theory to provide best possible experience to learners, highlighting the advantages of utilising social media platforms for SBL in medical education. The ability to conduct SIMBA sessions at modest cost internationally paves way to engage more healthcare professionals worldwide.

Clinical and biochemical profile of 786 sequential episodes of diabetic ketoacidosis in adults with type 1 and type 2 diabetes mellitus.

INTRODUCTION: We explored the clinical and biochemical differences in demographics, presentation and management of diabetic ketoacidosis (DKA) in adults with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: This observational study included all episodes of DKA from April 2014 to September 2020 in a UK tertiary care hospital. Data were collected on diabetes type, demographics, biochemical and clinical features at presentation, and DKA management. RESULTS: From 786 consecutive DKA, 583 (75.9%) type 1 diabetes and 185 (24.1%) type 2 diabetes episodes were included in the final analysis. Those with type 2 diabetes were older and had more ethnic minority representation than those with type 1 diabetes. Intercurrent illness (39.8%) and suboptimal compliance (26.8%) were the two most common precipitating causes of DKA in both cohorts. Severity of DKA as assessed by pH, glucose and lactate at presentation was similar in both groups. Total insulin requirements and total DKA duration were the same (type 1 diabetes 13.9 units (9.1-21.9); type 2 diabetes 13.9 units (7.7-21.1); p=0.4638). However, people with type 2 diabetes had significantly longer hospital stay (type 1 diabetes: 3.0 days (1.7-6.1); type 2 diabetes: 11.0 days (5.0-23.1); p<0.0001). CONCLUSIONS: In this population, a quarter of DKA episodes occurred in people with type 2 diabetes. DKA in type 2 diabetes presents at an older age and with greater representation from ethnic minorities. However, severity of presentation and DKA duration are similar in both type 1 and type 2 diabetes, suggesting that the same clinical management protocol is equally effective. People with type 2 diabetes have longer hospital admission.

Utility of Simulation via Instant Messaging - Birmingham Advance (SIMBA) in medical education during COVID-19 pandemic.

BACKGROUND: Simulation via Instant Messaging - Birmingham Advance (SIMBA) aimed to improve clinicians' confidence in managing various clinical scenarios during the COVID-19 pandemic. METHODS: Five SIMBA sessions were conducted between May and August 2020. Each session included simulation of scenarios and interactive discussion. Participants' self-reported confidence, acceptance, and relevance of the simulated cases were measured. RESULTS: Significant improvement was observed in participants' self-reported confidence (overall n = 204, p<0.001; adrenal n = 33, p<0.001; thyroid n = 37, p<0.001; pituitary n = 79, p<0.001; inflammatory bowel disease n = 17, p<0.001; acute medicine n = 38, p<0.001). Participants reported improvements in clinical competencies: patient care 52.0% (n = 106/204), professionalism 30.9% (n = 63/204), knowledge on patient management 84.8% (n = 173/204), systems-based practice 48.0% (n = 98/204), practice-based learning 69.6% (n = 142/204) and communication skills 25.5% (n = 52/204). CONCLUSION: SIMBA is a novel pedagogical virtual simulation-based learning model that improves clinicians' confidence in managing conditions across various specialties.

Effect of COVID-19 on the clinical course of diabetic ketoacidosis (DKA) in people with type 1 and type 2 diabetes.

OBJECTIVE: COVID-19 in people with diabetes is associated with a disproportionately worse prognosis. DKA is an acute complication of diabetes with a mortality rate of approximately 0.67%. Little is known about the natural history of DKA in the presence of COVID-19. This study aimed to explore the effects of COVID-19 on presentation, clinical course and outcome in patients presenting with DKA. DESIGN: Retrospective cohort study. METHODS: All patients treated for DKA between 1 March 2020 and 30 May 2020 were included. Patients were categorised as COVID-positive or COVID-negative based on the swab test. A pre-COVID group was established using data from 01 March 2019 to 30 May 2019 as external control. Data regarding demographics, diabetes type, pH, bicarbonate, lactate, glucose, DKA duration, complications and outcome were collected. RESULTS: A total of 88 DKA episodes were included in this study. There was no significant difference in the severity or duration of DKA between the three groups. COVID-positive T1DM were more hyperglycaemic on admission compared to COVID-negative and pre-COVID patients. There was an over representation of T2DM in COVID-positive patients with DKA than in pre-COVID or COVID-negative groups. CONCLUSION: COVID-19 appears to influence the natural history of DKA differently in T1DM and T2DM. Patients with T1DM and COVID-19 presented with more hyperglycaemia (60 mmol/L (35.9-60.0) vs 31.4 mmol/L (28.0-39.1) vs 24 mmol/L (20.2-33.75), respectively). Patients with T2DM were unusually presenting in DKA when infected with COVID-19 with greater ICU need and higher mortality rates. A collaborative, multi-centre study is needed to provide more definitive results.

Clinical manifestations, prevalence, risk factors, outcomes, transmission, diagnosis and treatment of COVID-19 in pregnancy and postpartum: a living systematic review protocol.

INTRODUCTION: Rapid, robust and continually updated evidence synthesis is required to inform management of COVID-19 in pregnant and postpartum women and to keep pace with the emerging evidence during the pandemic. METHODS AND ANALYSIS: We plan to undertake a living systematic review to assess the prevalence, clinical manifestations, risk factors, rates of maternal and perinatal complications, potential for mother-to-child transmission, accuracy of diagnostic tests and effectiveness of treatment for COVID-19 in pregnant and postpartum women (including after miscarriage or abortion). We will search Medline, Embase, WHO COVID-19 database, preprint servers, the China National Knowledge Infrastructure system and Wanfang databases from 1 December 2019. We will supplement our search with studies mapped by Cochrane Fertility and Gynaecology group, Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), COVID-19 study repositories, reference lists and social media blogs. The search will be updated every week and not be restricted by language. We will include observational cohort (≥10 participants) and randomised studies reporting on prevalence of COVID-19 in pregnant and postpartum women, the rates of clinical manifestations and outcomes, risk factors in pregnant and postpartum women alone or in comparison with non-pregnant women with COVID-19 or pregnant women without COVID-19 and studies on tests and treatments for COVID-19. We will additionally include case reports and series with evidence on mother-to-child transmission of SARS-CoV-2 in utero, intrapartum or postpartum. We will appraise the quality of the included studies using appropriate tools to assess the risk of bias. At least two independent reviewers will undertake study selection, quality assessment and data extraction every 2 weeks. We will synthesise the findings using quantitative random effects meta-analysis and report OR or proportions with 95% CIs and prediction intervals. Case reports and series will be reported as qualitative narrative synthesis. Heterogeneity will be reported as I2 and τ2 statistics. ETHICS AND DISSEMINATION: Ethical approval is not required as this is a synthesis of primary data. Regular updates of the results will be published on a dedicated website (https://www.birmingham.ac.uk/research/who-collaborating-centre/pregcov/index.aspx) and disseminated through publications, social media and webinars. PROSPERO REGISTRATION NUMBER: CRD42020178076.

Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.

OBJECTIVE: To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 6 October 2020, along with preprint servers, social media, and reference lists. STUDY SELECTION: Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19. DATA EXTRACTION: At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly. RESULTS: 192 studies were included. Overall, 10% (95% confidence interval 7% to 12%; 73 studies, 67 271 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (41%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to have symptoms (odds ratio 0.28, 95% confidence interval 0.13 to 0.62; I2=42.9%) or report symptoms of fever (0.49, 0.38 to 0.63; I2=40.8%), dyspnoea (0.76, 0.67 to 0.85; I2=4.4%) and myalgia (0.53, 0.36 to 0.78; I2=59.4%). The odds of admission to an intensive care unit (odds ratio 2.13, 1.53 to 2.95; I2=71.2%), invasive ventilation (2.59, 2.28 to 2.94; I2=0%) and need for extra corporeal membrane oxygenation (2.02, 1.22 to 3.34; I2=0%) were higher in pregnant and recently pregnant than non-pregnant reproductive aged women. Overall, 339 pregnant women (0.02%, 59 studies, 41 664 women) with confirmed covid-19 died from any cause. Increased maternal age (odds ratio 1.83, 1.27 to 2.63; I2=43.4%), high body mass index (2.37, 1.83 to 3.07; I2=0%), any pre-existing maternal comorbidity (1.81, 1.49 to 2.20; I2=0%), chronic hypertension (2.0, 1.14 to 3.48; I2=0%), pre-existing diabetes (2.12, 1.62 to 2.78; I2=0%), and pre-eclampsia (4.21, 1.27 to 14.0; I2=0%) were associated with severe covid-19 in pregnancy. In pregnant women with covid-19, increased maternal age, high body mass index, non-white ethnicity, any pre-existing maternal comorbidity including chronic hypertension and diabetes, and pre-eclampsia were associated with serious complications such as admission to an intensive care unit, invasive ventilation and maternal death. Compared to pregnant women without covid-19, those with the disease had increased odds of maternal death (odds ratio 2.85, 1.08 to 7.52; I2=0%), of needing admission to the intensive care unit (18.58, 7.53 to 45.82; I2=0%), and of preterm birth (1.47, 1.14 to 1.91; I2=18.6%). The odds of admission to the neonatal intensive care unit (4.89, 1.87 to 12.81, I2=96.2%) were higher in babies born to mothers with covid-19 versus those without covid-19. CONCLUSION: Pregnant and recently pregnant women with covid-19 attending or admitted to the hospitals for any reason are less likely to manifest symptoms such as fever, dyspnoea, and myalgia, and are more likely to be admitted to the intensive care unit or needing invasive ventilation than non-pregnant women of reproductive age. Pre-existing comorbidities, non-white ethnicity, chronic hypertension, pre-existing diabetes, high maternal age, and high body mass index are risk factors for severe covid-19 in pregnancy. Pregnant women with covid-19 versus without covid-19 are more likely to deliver preterm and could have an increased risk of maternal death and of being admitted to the intensive care unit. Their babies are more likely to be admitted to the neonatal unit. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178076. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 1 September 2020 (BMJ 2020;370:m3320), and previous updates can be found as data supplements (https://www.bmj.com/content/370/bmj.m3320/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.

Simulation via instant messaging-Birmingham advance (SIMBA) model helped improve clinicians' confidence to manage cases in diabetes and endocrinology.

BACKGROUND: Simulation-based learning (SBL) has been increasingly used in both undergraduate and postgraduate medical training curricula. The aim of Simulation via Instant Messaging-Birmingham Advance (SIMBA) is to create a simple virtual learning environment to improve trainees' self-reported confidence in diabetes and Endocrinology. METHODS: This study was done as part of the continuous professional development for Health Education England West Midlands speciality trainees in diabetes and Endocrinology. Standardized transcripts of anonymized real-life endocrinology (endocrine session) and diabetes cases (diabetes session) were used in the simulation model. Trainees interacted with moderators through WhatsApp® in this model. All cases were then discussed in detail by a consultant endocrinologist with reference to local, national and international guidelines. Trainee acceptance rate and improvement in their self-reported confidence levels post-simulation were assessed. RESULTS: 70.8% (n = 17/24) and 75% (n = 18/24) strongly agreed the simulation session accommodated their personal learning style and the session was engaging. 66.7% (n = 16/24) strongly felt that the simulation was worth their time. In the endocrine session, there was a significant improvement in trainees' confidence in the management of craniopharyngioma (p = 0.0179) and acromegaly (p = 0.0025). There was a trend towards improved confidence levels to manage Cushing's disease and macroprolactinoma. In diabetes session, there was a significant improvement in trainees' confidence to interpret continuous glucose monitor readings (p = 0.01). There was a trend towards improvement for managing monogenic diabetes, hypoglycaemic unawareness and interpreting Libre readings. Overall, there was a significant improvement in trainees' confidence in managing cases that were discussed post-simulation. CONCLUSION: SIMBA is an effective learning model to improve trainees' confidence to manage various diabetes and endocrine case scenarios. More sessions with a variety of other speciality case scenarios are needed to further assess SIMBA's effectiveness and application in other areas of medical training.

Meta-analysis of prognostic factors of overall survival in patients undergoing oesophagectomy for oesophageal cancer.

INTRODUCTION: Currently, the American Joint Commission on Cancer (AJCC) staging system is used for prognostication for oesophageal cancer. However, several prognostically important factors have been reported but not incorporated. This meta-analysis aimed to characterize the impact of preoperative, operative, and oncological factors on the prognosis of patients undergoing curative resection for oesophageal cancer. METHODS: This systematic review was performed according to PRISMA guidelines and eligible studies were identified through a search of PubMed, Scopus, and Cochrane CENTRAL databases up to 31 December 2018. A meta-analysis was conducted with the use of random-effects modeling to determine pooled univariable hazard ratios (HRs). The study was prospectively registered with the PROSPERO database (Registration: CRD42018157966). RESULTS: One-hundred and seventy-one articles including 73,629 patients were assessed quantitatively. Of the 122 factors associated with survival, 39 were significant on pooled analysis. Of these. the strongly associated prognostic factors were 'pathological' T stage (HR: 2.07, CI95%: 1.77-2.43, P < 0.001), 'pathological' N stage (HR: 2.24, CI95%: 1.95-2.59, P < 0.001), perineural invasion (HR: 1.54, CI95%: 1.36-1.74, P < 0.001), circumferential resection margin (HR: 2.17, CI95%: 1.82-2.59, P < 0.001), poor tumor grade (HR: 1.53, CI95%: 1.34-1.74, P < 0.001), and high neutrophil:lymphocyte ratio (HR: 1.47, CI95%: 1.30-1.66, P < 0.001). CONCLUSION: Several tumor biological variables not included in the AJCC 8th edition classification can impact on overall survival. Incorporation and validation of these factors into prognostic models and next edition of the AJCC system will enable personalized approach to prognostication and treatment.