A comprehensive review of relevant clinical literature on evidence-based recommendations and existing prediction models specific to lung cancer surgery was undertaken. Preoperative risk assessment parameters such as pulmonary function tests (PFT), cardiopulmonary exercise testing (CPET), Brunelli models, Thoracoscore and frailty were analyzed for predicting postoperative risk of complications.When assessing fitness for surgery, the primarily used PFT parameters such as predictive postoperative forced expiratory volume in one second (FEV1) and diffusion capacity for carbon monoxide (DLCO ) showed conflicting evidence in determining a positive correlation with postoperative mortality. CPET variables predicted higher complication risk when VO2peak < 10ml/kg/min, AT < 11ml/kg/min and ventilation/carbon dioxide production (VE/VCO2) was in range of 34-40. While a cardiac risk index like the Thoracic Revised Cardiac Risk Index (ThRCRI) predicted major cardiovascular compromise, a thoracic risk index like Thoracoscore proved imprecise. Lastly, frailty is used to risk stratify patients in clinical practice but a recognized validated model specific to thoracic surgery is non-existent.When considering patients for lung cancer surgery, some dilemma exists regarding the accuracy of clinical prediction models and their external validation. There is a pressing need for the development of a consolidated clinically robust risk stratification model to predict complications after thoracic resections.

Abstract Introduction We aimed to determine if patients with CHD are at a higher risk of poor outcomes if they have COVID-19, compared to those without CHD. Method A systematic review was executed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. To identify articles related to COVID-19 and CHD, an extensive literature search was performed on EMBASE, Medline, Scopus and Global Health databases using keywords and MeSH terms. Results 12 articles met the inclusion criteria and were included for analysis in this systematic review. Two themes were identified for data extraction: [1] evidence supporting higher risks in CHD patients and [2] evidence against higher risks in CHD patients. After combining the data, there were 99 patients with CHDs out of which 12 required admission to ICU. Conclusions This systematic review suggests that CHD may increase the risk of poor outcomes for those with COVID-19, but also highlights the necessity for more research with larger sample sizes in order to make a more justified conclusion, as the majority of papers that were analysed were case series and case reports. Future research should aim to quantify the risks if possible while accounting for various confounding factors such as age and treatment history.

Coronavirus disease 2019 (COVID‐19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It was first reported in the city of Wuhan, China in 2019, before spreading globally in the following months and causing a pandemic. According to the World Health Organization, as of October 30, 2020, there have been 44,888,869 confirmed cases and 1,178,475 confirmed deaths due to COVID‐19. Patients with COVID‐19 can have a range of different presentations including a fever, headaches, dry cough, fatigue, ageusia, and anosmia. Angiotensin‐converting enzyme 2 (ACE2) is an enzyme that is expressed in the heart, kidneys, intestines, arteries, and most importantly the respiratory tract epithelium. It has been confirmed as the entry point for SARS‐CoV‐2 into host cells. Studies have suggested that it downregulates ACE2 and causes angiotensin‐II levels to accumulate, whose harmful effects can lead to acute respiratory distress syndrome (ARDS). COVID‐19 has been shown to potentially lead to complications in different organ systems in the human body, including the renal and cardiovascular systems (CVSs). In the CVS, these complications include heart failure and arrhythmia. Studies have suggested that patients suffering from underlying comorbidities, including those that are cardiovascular, are more likely to have poor outcomes that include complications, ICU care, and/or death. The prevalence of diabetes mellitus, hypertension, and cardiovascular disease (CVD) appears to be higher in patients with COVID‐19 who have been hospitalized when compared to those without. There are conflicting studies, however, and it is hard to know if COVID‐19 cases have higher severity due to cardiovascular comorbidities and/or whether it increases the risk of myocardial insults. While research is limited, there appears to be some evidence suggesting that congenital heart disease (CHD) patients may have a worse prognosis if they are infected with COVID‐19, than those without CHD. We aim to explore how COVID‐19 affects the CVS, with a focus on CHD and the risk these patients may be exposed to, as well as the changes made regarding consenting them for surgery.

OBJECTIVE:We aimed to examine the literature to determine if both paediatric and adult patients diagnosed with congenital heart disease (CHD) are at a higher risk of poor outcomes if they have the coronavirus disease 2019 (COVID-19), compared to those without CHD.METHODS:A systematic review was executed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. To identify articles related to COVID-19 and CHD, an extensive literature search was performed on EMBASE, Medline, Scopus, and Global Health databases using keywords and MeSH terms.RESULTS:A total of 12 articles met the inclusion criteria and were included for analysis in this systematic review. Two themes were identified for data extraction: evidence supporting higher risks in CHD patients and evidence against higher risks in CHD patients. After combining the data, there were 99 patients with CHDs out of which 12 required admissions to ICU.CONCLUSION:This systematic review suggests that CHD may increase the risk of poor outcomes for those with COVID-19, but also highlights the necessity for more research with larger sample sizes in order to make a more justified conclusion, as the majority of papers that were analysed were case series and case reports. Future research should aim to quantify the risks if possible whilst accounting for various confounding factors such as age and treatment history.

STUDY QUESTION What prevents the fall in anti-Müllerian hormone (AMH) levels in polycystic ovary syndrome (PCOS) and what are the consequences of this for follicle progression in these ovaries? SUMMARY ANSWER Exposure of granulosa cells (GCs) to high levels of androgens, equivalent to that found in PCOS, prevented the fall in AMH and was associated with dysregulated AMH-SMAD signalling leading to stalled follicle progression in PCOS. WHAT IS KNOWN ALREADY In normal ovaries, AMH exerts an inhibitory role on antral follicle development and a fall in AMH levels is a prerequisite for ovulation. Levels of AMH are high in PCOS, contributing to the dysregulated follicle growth that is a common cause of anovulatory infertility in these women. STUDY DESIGN, SIZE, DURATION Human KGN-GC (the cell line that corresponds to immature GC from smaller antral follicles (AF)) were cultured with a range of doses of various androgens to determine the effects on AMH production. KGN-GC were also treated with PHTPP (an oestrogen receptor β (ERβ) antagonist) to examine the relationship between AMH expression and the ratio of ERα:ERβ. The differential dose-related effect of AMH on gene expression and SMAD signalling was investigated in human granulosa-luteal cells (hGLC) from women with normal ovaries, with polycystic ovarian morphology (PCOM) and with PCOS. KGN-GC were also cultured for a prolonged period with AMH at different doses to assess the effect on cell proliferation and viability. PARTICIPANTS/MATERIALS, SETTING, METHODS AMH protein production by cells exposed to androgens was measured by ELISA. The effect of PHTPP on the mRNA expression levels of AMH, ERα and ERβ was assessed by real-time quantitative PCR (qPCR). The influence of AMH on the relative mRNA expression levels of aromatase, AMH and its receptor AMHRII, and the FSH and LH receptor (FSHR and LHR) in control, PCOM and PCOS hGLCs was quantified by qPCR. Western blotting was used to assess changes in levels of SMAD proteins (pSMAD-1/5/8; SMAD-4; SMAD-6 and SMAD-7) after exposure of hGLCs from healthy women and women with PCOS to AMH. The ApoTox-Glo Triplex assay was used to evaluate the effect of AMH on cell viability, cytotoxicity and apoptosis. MAIN RESULTS AND THE ROLE OF CHANCE Testosterone reduced AMH protein secreted from KGN-GC at 10-9-10-7 M (P < 0.05; P < 0.005, multiple uncorrected comparisons Fishers least squares difference), but at equivalent hyperandrogenemic levels no change was seen in AMH levels. 5α-DHT produced a significant dose-related increase in AMH protein secreted into the media (P = 0.022, ANOVA). Increasing the mRNA ratio of ERα:ERβ produced a corresponding increase in AMH mRNA expression (P = 0.015, two-way ANOVA). AMH increased mRNA levels of aromatase (P < 0.05, one-way ANOVA) and FSHR (P < 0.0001, one-way ANOVA) in hGLCs from women with PCOM, but not from normal cells or PCOS (normal n = 7, PCOM n = 5, PCOS n = 4). In contrast to hGLCs from ovulatory ovaries, in PCOS AMH reduced protein levels (cell content) of stimulatory pSMAD-1/5/8 and SMAD-4 but increased inhibitory SMAD-6 and -7 (P < 0.05, normal n = 6, PCOS n = 3). AMH at 20 and 50 ng/ml decreased KGN-GC cell proliferation but not viability after 8 days of treatment (P < 0.005, two-way ANOVA). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Luteinised GC from women undergoing IVF have a relatively low expression of AMH/AMHRII but advantageously continue to display responses inherent to the ovarian morphology from which they are collected. To compensate, we also utilised the KGN cell line which has been characterised to be at a developmental stage close to that of immature GC. The lack of flutamide influence on testosterone effects is not in itself sufficient evidence to conclude that the effect on AMH is mediated via conversion to oestrogen, and the effect of aromatase inhibitors or oestrogen-specific inhibitors should be tested. The effect of flutamide was tested on testosterone but not DHT. WIDER IMPLICATIONS OF THE FINDINGS Normal folliculogenesis and ovulation are dependent on the timely reduction in AMH production from GC at the time of follicle selection. Our findings reveal for the first time that theca-derived androgens may play a role in this model but that this inhibitory action is lost at levels of androgens equivalent to those seen in PCOS. The AMH decline may either be a direct effect of androgens or an indirect one via conversion to oestradiol and acting through the upregulation of ERα, which is known to stimulate the AMH promoter. Interestingly, the ability of GCs to respond to this continually elevated AMH level appears to be reduced in cells from women with PCOS due to an adaptive alteration in the SMAD signalling pathway and lower expression of AMHRII, indicating a form of 'AMH resistance'. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Thomas Addison Scholarship, St Georges Hospital Trust. The authors report no conflict of interest in this work and have nothing to disclose. TRIAL REGISTRATION NUMBER N/A.