Is the perception of odour pleasantness shared across cultures and ecological conditions? Evidence from Amazonia, East Africa, New Guinea, Malaysia and Poland.

What makes an odour pleasant or unpleasant? The inherent properties of the constituent chemical compounds, or the nose of the beholder, driven by idiosyncratic differences and culture-specific learning? Here, 582 individuals, including Tanzanian Hadza hunter-gatherers, Amazonian Tsimane' horticulturalists, Yali from the Papuan highlands and two industrialized populations (Poles, Malaysians), rated the pleasantness of 15 odour samples. We find considerable similarities in odour assessments across cultures, but our data do not fully support a claim regarding the universality of smell preferences. Despite cross-cultural similarities in olfactory assessments, probably driven by odour properties, we suggest that odour availability in ecological and cultural niches bears an undeniable effect on human odour preferences.

Metabolic-associated fatty liver disease and hepatocellular carcinoma: a prospective study of characteristics and response to therapy.

BACKGROUND AND AIM: The rising incidence of hepatocellular carcinoma (HCC) in Australia is related to increasing rates of metabolic-associated fatty liver disease (MAFLD). This study aimed to prospectively characterize the metabolic profile, lifestyle, biometric features, and response to treatment of HCC patients in an Australian population. METHOD: Multicenter prospective cohort analysis of newly diagnosed HCC patients at six multidisciplinary team meetings over a 2-year period. RESULTS: Three hundred and thirteen (313) newly diagnosed HCC patients with MAFLD (n = 77), MAFLD plus other liver disease (n = 57) (the "mixed" group), and non-MAFLD (n = 179) were included in the study. Alcohol-associated liver disease (ALD) (43%) and MAFLD (43%) were the most common underlying liver diseases. MAFLD-HCC patients were older (73 years vs 67 years vs 63 years), more likely to be female (40% vs 14% vs 20%), less likely to have cirrhosis (69% vs 88% vs 85%), showed higher ECOG, and were less likely to be identified by screening (29% vs 53% vs 45%). Metabolic syndrome was more prevalent in the MAFLD and mixed groups. The severity of underlying liver disease and HCC characteristics were the same across groups. While the MAFLD population self-reported more sedentary lifestyles, reported dietary patterns were no different across the groups. Dyslipidemia was associated with tumor size, and those taking statins had a lower recurrence rate. CONCLUSION: Equal to ALD, MAFLD is now the most common underlying liver disease seen in HCC patients in Australia. Future HCC prevention screening and treatment strategies need to take this important group of patients into consideration.

Validation of the Short Version (TLS-15) of the Triangular Love Scale (TLS-45) across 37 Languages.

Love is a phenomenon that occurs across the world and affects many aspects of human life, including the choice of, and process of bonding with, a romantic partner. Thus, developing a reliable and valid measure of love experiences is crucial. One of the most popular tools to quantify love is Sternberg's 45-item Triangular Love Scale (TLS-45), which measures three love components: intimacy, passion, and commitment. However, our literature review reveals that most studies (64%) use a broad variety of shortened versions of the TLS-45. Here, aiming to achieve scientific consensus and improve the reliability, comparability, and generalizability of results across studies, we developed a short version of the scale-the TLS-15-comprised of 15 items with 5-point, rather than 9-point, response scales. In Study 1 (N = 7,332), we re-analyzed secondary data from a large-scale multinational study that validated the original TLS-45 to establish whether the scale could be truncated. In Study 2 (N = 307), we provided evidence for the three-factor structure of the TLS-15 and its reliability. Study 3 (N = 413) confirmed convergent validity and test-retest stability of the TLS-15. Study 4 (N = 60,311) presented a large-scale validation across 37 linguistic versions of the TLS-15 on a cross-cultural sample spanning every continent of the globe. The overall results provide support for the reliability, validity, and cross-cultural invariance of the TLS-15, which can be used as a measure of love components-either separately or jointly as a three-factor measure.

Associations between nausea and vomiting in pregnancy, disgust sensitivity, and first-trimester maternal serum free ß-hCG and PAPP-A.

Elevated levels of nausea and vomiting in pregnancy (NVP) and disgust sensitivity have been observed in the first trimester and both are thought to have a protective function for the mother and her fetus. Their aetiology is not clear, however, with previous studies attributing elevated NVP and disgust to various factors including endocrine changes, immunological changes, and psychological variables. To date, no study has directly assessed the relationship between disgust and NVP. Here, we prospectively collected two independent samples (S1 and S2; n1 = 201, n2 = 391) of women in the first trimester of pregnancy, who completed the Index of Nausea, Vomiting, and Retching and the Disgust Scale-Revised. We also measured free ß-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum. Our results did not confirm any association between NVP and disgust; in addition, they indicate that NVP and disgust may have different proximate causes. Disgust sensitivity was significantly negatively correlated with free ß-hCG and (only in S1) with PAPP-A. In contrast, NVP was significantly positively associated with free ß-hCG levels and (only in S1) with PAPP-A. While low hCG levels seem to be an important indicator for activation of the behavioral immune system in the first trimester, increased hCG levels play a role in stronger symptoms of NVP, a result consistent with previous studies. Levels of PAPP-A are likely part of a larger network of immunological and endocrine responses and do not appear to provide sufficient information for predicting women's NVP and disgust sensitivity.

Testing effects of partner support and use of oral contraception during relationship formation on severity of nausea and vomiting in pregnancy.

BACKGROUND: A recent study focusing on dietary predictors of nausea and vomiting in pregnancy (NVP) found that women with higher levels of partner support, and those who had used oral contraception (OC) when they met the father, both tended to report less severe NVP compared with previous non-users or those with less supportive partners. We provide a further test of these factors, using a large sample of women from four countries who retrospectively scored their NVP experience during their first pregnancy. METHODS: We recruited women who had at least one child to participate in a retrospective online survey. In total 2321 women completed our questionnaire including items on demographics, hormonal contraception, NVP, and partner support. We used general linear models and path analysis to analyse our data. RESULTS: Women who had used OC when they met the father of their first child tended to report lower levels of NVP, but the effect size was small and did not survive adding the participant's country to the model. There was no relationship between NVP and partner support in couples who were still together, but there was a significant effect among those couples that had since separated: women whose ex-partner had been relatively supportive reported less severe NVP. Additional analyses showed that women who were older during their first pregnancy reported less severe NVP, and there were also robust differences between countries. CONCLUSIONS: These results provide further evidence for multiple influences on women's experience of NVP symptoms, including levels of perceived partner support.

Analysis of exhaled breath to identify critically ill patients with ventilator-associated pneumonia.

Ventilator-associated pneumonia commonly occurs in critically ill patients. Clinical suspicion results in overuse of antibiotics, which in turn promotes antimicrobial resistance. Detection of volatile organic compounds in the exhaled breath of critically ill patients might allow earlier detection of pneumonia and avoid unnecessary antibiotic prescription. We report a proof of concept study for non-invasive diagnosis of ventilator-associated pneumonia in intensive care (the BRAVo study). Mechanically ventilated critically ill patients commenced on antibiotics for clinical suspicion of ventilator-associated pneumonia were recruited within the first 24 h of treatment. Paired exhaled breath and respiratory tract samples were collected. Exhaled breath was captured on sorbent tubes and then analysed using thermal desorption gas chromatography-mass spectrometry to detect volatile organic compounds. Microbiological culture of a pathogenic bacteria in respiratory tract samples provided confirmation of ventilator-associated pneumonia. Univariable and multivariable analyses of volatile organic compounds were performed to identify potential biomarkers for a 'rule-out' test. Ninety-six participants were enrolled in the trial, with exhaled breath available from 92. Of all compounds tested, the four highest performing candidate biomarkers were benzene, cyclohexanone, pentanol and undecanal with area under the receiver operating characteristic curve ranging from 0.67 to 0.77 and negative predictive values from 85% to 88%. Identified volatile organic compounds in the exhaled breath of mechanically ventilated critically ill patients show promise as a useful non-invasive 'rule-out' test for ventilator-associated pneumonia.

Early and intensive Motor Training for people with spinal cord injuries (the SCI-MT Trial): description of the intervention.

STUDY DESIGN: Descriptive. OBJECTIVES: The primary objective is to describe the intervention that will be provided in a large multi-centre randomised controlled trial titled: Early and Intensive Motor Training for people with Spinal Cord Injuries (the SCI-MT Trial). The secondary objective is to describe the strategies that will be used to operationalise and standardise the Motor Training provided to participants while keeping the intervention person-centred. METHODS: The paper focuses on the rationale and principles of Motor Training for people with spinal cord injuries (SCI). The description of the intervention is based on the Template for Intervention Description and Replication (TIDieR) checklist. Specifically, it addresses the following 6 criteria of the TIDieR checklist: why the effectiveness of Motor Training is being examined; what, how, where and when the Motor Training will be administered; and how much Motor Training will be provided. RESULTS: A detailed intervention manual has been developed to help standardise the delivery of the intervention. CONCLUSIONS: This paper describes the details of a complex intervention administered as part of a large randomised controlled trial. It will facilitate the subsequent interpretation of the trial results and enable the intervention to be reproduced in clinical practice and future trials.

The impact of endoscopic ultrasound on the management and outcome of patients with oesophageal cancer: an update of a systematic review.

AIM: To provide an updated systematic review concerning the impact of endoscopic ultrasound (EUS) in the modern era of oesophageal cancer staging. MATERIALS AND METHODS: To update the previous systematic review, databases including MEDLINE and EMBASE were searched and studies published from 2005 onwards were selected. Studies reporting primary data in patients with oesophageal or gastro-oesophageal junction cancer who underwent radiological staging and treatment, regardless of intent, were included. The primary outcome was the reported change in management after EUS. Secondary outcomes were recurrence rate and overall survival. Two reviewers extracted data from included articles. This study was registered with PROSPERO (CRD42021231852). RESULTS: Eighteen studies with 11,836 patients were included comprising 2,805 patients (23.7%) who underwent EUS compared to 9,031 (76.3%) without EUS examination. Reported change of management varied widely from 0% to 56%. When used, EUS fine-needle aspiration precluded curative treatment in 37.5%-71.4%. Overall survival improvements ranged between 121 and 639 days following EUS intervention compared to patients without EUS. Smaller effect sizes were observed in a randomised controlled trial, compared to larger differences reported in observational studies. CONCLUSION: Current evidence for the effectiveness of EUS in oesophageal cancer pathways is conflicting and of limited quality. In particular, the extent to which EUS adds value to contemporary cross-sectional imaging techniques is unclear and requires formal re-evaluation.

Interobserver Variation in Echocardiographic Measurements and Grading of Tricuspid Regurgitation Based on a Novel Web-Based Assessment Environment.

OBJECTIVES: The primary aim of this study was to assess interobserver variability in grading tricuspid regurgitation (TR) severity. The authors' secondary goals were to delineate which transesophageal echocardiographic (TEE) parameters best correlate with severity and how consistent the participants were at grading severity. DESIGN: This was a prospective cohort study of how clinicians evaluated previously acquired TEE images and videos. SETTING: The 19 TEE studies of patients with TR were recorded by 4 senior echocardiographers across 4 US academic institutions. The participants evaluated these cases on a novel, web-based, assessment environment designed specifically for this study. PARTICIPANTS: Twenty-nine fellowship-trained and board-certified cardiologists and cardiothoracic anesthesiologists volunteered to participate in the study as observers from 19 different institutions. INTERVENTIONS: No interventions were performed on the participants. MEASUREMENTS AND MAIN RESULTS: For each case, participants measured the vena contracta (VC), proximal isovelocity surface area (PISA), and jet area before giving a final classification on the severity of TR. Variation was highest for effective regurgitant orifice area and lowest for VC and PISA. The coefficient of variation, defined as the standard deviation from the mean divided by the mean, for all cases of trace, mild, moderate and severe TR were as follows: Jet Area-111%, 46%, 48%, 76%; VC-67%, 44%, 43%, 36%; PISA-52%, 48%, 31%, 35%; and effective regurgitant orifice area-127%, 95%, 66%, 58%. CONCLUSIONS: The interobserver variation in quantifying TEE parameters for TR is high, suggesting these may be difficult to measure reliably in a busy perioperative setting. Of the parameters assessed, VC and PISA radius had the highest interobserver agreement and the highest correlation with severity.

Dexmedetomidine Is an Equal Cost Alternative to Propofol in Transcatheter Aortic Valve Replacement, With Equivalent In-Hospital and 30-Day Outcomes.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR) with monitored anesthesia care (MAC) is well-tolerated and is growing in popularity. Differences in outcomes based on anesthetic agent choice with MAC has received less attention. The authors sought to determine whether differences in outcomes and cost exist based on whether patients receive dexmedetomidine or propofol when undergoing TAVR with MAC. DESIGN: Retrospective cohort study. SETTING: The Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania. PARTICIPANTS: The study comprised 161 patients who underwent TAVR with MAC between May 2014 and March 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A propofol-only (n = 58) group and dexmedetomidine-only (n = 103) group were identified. No differences in in-hospital mortality or complication rate were identified when evaluating for stroke, transfusion, new arrhythmia, cardiac arrest, or bleeding and vascular complications (p > 0.05, all). Thirty-day outcomes were also equivalent, with no differences in mortality, stroke, vascular complication, new arrhythmia, or myocardial infarction (p > 0.05, all). The average amount of epinephrine, norepinephrine, or phenylephrine used intraoperatively was not significantly different. Overall median hospitalization costs were equivalent ($57,554.31 with dexmedetomidine v $58,538.08 with propofol, p = 0.97). CONCLUSIONS: There were no significant differences in in-hospital outcomes, 30-day outcomes, or total cost of the patient's hospitalization, based on the use of dexmedetomidine versus propofol in patients undergoing TAVR.

Digital disruption of dietetics: are we ready?

Digital health is transforming the delivery of health care around the world to meet the growing challenges presented by ageing populations with multiple chronic conditions. Digital health technologies can support the delivery of personalised nutrition care through the standardised Nutrition Care Process (NCP) by using personal data and technology-supported delivery modalities. The digital disruption of traditional dietetic services is occurring worldwide, supporting responsive and high-quality nutrition care. These disruptive technologies include integrated electronic and personal health records, mobile apps, wearables, artificial intelligence and machine learning, conversation agents, chatbots, and social robots. Here, we outline how digital health is disrupting the traditional model of nutrition care delivery and outline the potential for dietitians to not only embrace digital disruption, but also take ownership in shaping it, aiming to enhance patient care. An overview is provided of digital health concepts and disruptive technologies according to the four steps in the NCP: nutrition assessment, diagnosis, intervention, and monitoring and evaluation. It is imperative that dietitians stay abreast of these technological developments and be the leaders of the disruption, not simply subject to it. By doing so, dietitians now, as well as in the future, will maximise their impact and continue to champion evidence-based nutrition practice.

Forgotten fatalities: British military, mining and maritime accidents since 1900.

BACKGROUND: Comparative long-term trends in fatal accident rates in the UK's most hazardous occupations have not been reported. AIMS: To compare trends in fatal accident rates in six of the most hazardous occupations (the three armed forces, merchant shipping, sea fishing and coal mining) and the general British workforce during peacetime years since 1900. METHODS: Examinations of annual mortality reports, returns, inquiry files and statistics. The main outcome measure was the fatal accident rate per 100 000 population employed. RESULTS: These six occupations accounted for ~40% of all fatal accidents in the British workforce. Fatal accident rates were highest in merchant shipping to 1914 (400-600 per 100 000) and in the Royal Air Force and sea fishing by the early 1920s (around 300 per 100 000). Since the 1950s sea fishing has remained the most hazardous occupation (50-200). Widespread reductions in fatal accident rates for each occupation have been greatest in recent years in the three armed forces and merchant shipping. Compared with the general workforce, relative risks of fatalities have increased in recent decades in all these occupations except shipping. CONCLUSIONS: All six occupations still have high fatal accident rates. The greatly increased fatalities in sea fishing generally and in the Royal Air Force during its early years reflect, for different reasons, cultures of extreme risk-taking in these two sectors. Reductions in fatality rates in the armed forces over the last 20 years are due largely to decreases in land transport accidents.

Characterization of on-target adverse events caused by TRK inhibitor therapy.

BACKGROUND: The tropomyosin receptor kinase (TRK) pathway controls appetite, balance, and pain sensitivity. While these functions are reflected in the on-target adverse events (AEs) observed with TRK inhibition, these AEs remain under-recognized, and pain upon drug withdrawal has not previously been reported. As TRK inhibitors are approved by multiple regulatory agencies for TRK or ROS1 fusion-positive cancers, characterizing these AEs and corresponding management strategies is crucial. PATIENTS AND METHODS: Patients with advanced or unresectable solid tumors treated with a TRK inhibitor were retrospectively identified in a search of clinical databases. Among these patients, the frequency, severity, duration, and management outcomes of AEs including weight gain, dizziness or ataxia, and withdrawal pain were characterized. RESULTS: Ninety-six patients with 15 unique cancer histologies treated with a TRK inhibitor were identified. Weight gain was observed in 53% [95% confidence interval (CI), 43%-62%] of patients and increased with time on TRK inhibition. Pharmacologic intervention, most commonly with glucagon-like peptide 1 analogs or metformin, appeared to result in stabilization or loss of weight. Dizziness, with or without ataxia, was observed in 41% (95% CI, 31%-51%) of patients with a median time to onset of 2 weeks (range, 3 days to 16 months). TRK inhibitor dose reduction was the most effective intervention for dizziness. Pain upon temporary or permanent TRK inhibitor discontinuation was observed in 35% (95% CI, 24%-46%) of patients; this was more common with longer TRK inhibitor use. TRK inhibitor reinitiation was the most effective intervention for withdrawal pain. CONCLUSIONS: TRK inhibition-related AEs including weight gain, dizziness, and withdrawal pain occur in a substantial proportion of patients receiving TRK inhibitors. This safety profile is unique relative to other anticancer therapies and warrants careful monitoring. These on-target toxicities are manageable with pharmacologic intervention and dose modification.

Nanotoxicology of an Elastin-like Polypeptide Rapamycin Formulation for Breast Cancer.

The clinical utility of rapamycin (Rapa) is limited by solubility, bioavailability, and side effects. To overcome this, our team recently reported an elastin-like polypeptide (ELP) nanoparticle with high affinity, noncovalent drug binding, and integrin-mediated cellular uptake. Given the scarcity of pharmacology/toxicology studies of ELP-based drug carriers, this article explores safety and efficacy of ELP-Rapa. ELP-Rapa nanoparticles tested negative for hemolysis, did not interfere in plasma coagulation nor in platelet function, and did not activate the complement. Upon incubation with HepG2 cells, ELP-Rapa revealed significant cellular uptake and trafficking to acidic organelles, consistent with lysosomes. Internalized ELP-Rapa nanoparticles increased oxidative stress 4-fold compared to free drug or free ELP controls. However, mice bearing orthotopic hormone receptor positive BT-474 breast tumors, given a high dose (∼10-fold above therapeutic dose) of 1 month administration of ELP-Rapa, did not induce hepatotoxicity. On the other hand, tumor growth and mTOR signaling were suppressed without affecting body weight. Nanoparticles assembled using ELP technology appear to be a safe and efficient strategy for delivering Rapa.

Lifestyle information and commercial weight management groups to support maternal postnatal weight management and positive lifestyle behaviour: the SWAN feasibility randomised controlled trial.

OBJECTIVES: To assess feasibility of a future randomised controlled trial (RCT) of clinical and cost-effectiveness of lifestyle information and commercial weight management groups to support postnatal weight management to 12 months post-birth. DESIGN: Two-arm feasibility trial, with nested mixed-methods process evaluation. SETTING: Inner-city unit, south England. POPULATION: Women with body mass indices (BMIs) ≥25 kg/m2 at pregnancy booking or normal BMIs (18.5-24.9 kg/m2 ) identified with excessive gestational weight gain at 36 weeks of gestation. METHODS: Randomised to standard care plus commercial weight management sessions commencing 8-16 weeks postnatally or standard care only. MAIN OUTCOMES: Feasibility outcomes included assessment of recruitment, retention, acceptability and economic data collation. Primary and secondary end points included difference between groups in weight 12 months postnatally compared with booking (proposed primary outcome for a future trial), diet, physical activity, smoking, alcohol, mental health, infant feeding, NHS resource use. RESULTS: In all, 193 women were randomised: 98 intervention and 95 control; only four women had excessive gestational weight gain. A slightly greater weight change was found among intervention women at 12 months, with greatest benefit. Among women attending ten or more weight management sessions. There was >80% follow up to 12 months, low risk of contamination and no group differences in trial completion. CONCLUSION: It was feasible to recruit and retain women with BMIs ≥25 kg/m2 to an intervention to support postnatal weight management; identification of excessive gestational weight gain requires consideration. Economic modelling could inform out-of-trial costs and benefits in a future trial. A definitive trial is an important next step. TWEETABLE ABSTRACT: A feasibility RCT of postnatal weight support showed women with BMIs ≥25 kg/m2 can be recruited and followed to 12 months postnatally.

Are interventions in reproductive medicine assessed for plausible and clinically relevant effects? A systematic review of power and precision in trials and meta-analyses.

STUDY QUESTION: How much statistical power do randomised controlled trials (RCTs) and meta-analyses have to investigate the effectiveness of interventions in reproductive medicine? SUMMARY ANSWER: The largest trials in reproductive medicine are unlikely to detect plausible improvements in live birth rate (LBR), and meta-analyses do not make up for this shortcoming. WHAT IS KNOWN ALREADY: Effectiveness of interventions is best evaluated using RCTs. In order to be informative, these trials should be designed to have sufficient power to detect the smallest clinically relevant effect. Similar trials can subsequently be pooled in meta-analyses to more precisely estimate treatment effects. STUDY DESIGN, SIZE, DURATION: A review of power and precision in 199 RCTs and meta-analyses from 107 Cochrane Reviews was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS: Systematic reviews published by Cochrane Gynaecology and Fertility with the primary outcome live birth were identified. For each live birth (or ongoing pregnancy) meta-analysis and for the largest RCT in each, we calculated the power to detect absolute improvements in LBR of varying sizes. Additionally, the 95% CIs of estimated treatment effects from each meta-analysis and RCT were recorded, as these indicate the precision of the result. MAIN RESULTS AND THE ROLE OF CHANCE: Median (interquartile range) power to detect an improvement in LBR of 5 percentage points (pp) (e.g. 25-30%) was 13% (8-21%) for RCTs and 16% (9-33%) for meta-analyses. No RCTs and only 2% of meta-analyses achieved 80% power to detect an improvement of 5 pp. Median power was high (85% for trials and 93% for meta-analyses) only in relation to 20 pp absolute LBR improvement, although substantial numbers of trials and meta-analyses did not achieve 80% power even for this improbably large effect size. Median width of 95% CIs was 25 pp and 21 pp for RCTs and meta-analyses, respectively. We found that 28% of Cochrane Reviews with LBR as the primary outcome contain no live birth (or ongoing pregnancy) data. LARGE-SCALE DATA: The data used in this study may be accessed at https://osf.io/852tn/?view_only=90f1579ce72747ccbe572992573197bd. LIMITATIONS, REASONS FOR CAUTION: The design and analysis decisions used in this study are predicted to overestimate the power of trials and meta-analyses, and the size of the problem is therefore likely understated. For some interventions, it is possible that larger trials not reporting live birth or ongoing pregnancy have been conducted, which were not included in our sample. In relation to meta-analyses, we calculated power as though all participants were included in a single trial. This ignores heterogeneity between trials in a meta-analysis, and will cause us to overestimate power. WIDER IMPLICATIONS OF THE FINDINGS: Trials capable of detecting realistic improvements in LBR are lacking in reproductive medicine, and meta-analyses are not large enough to overcome this deficiency. This situation will lead to unwarranted pessimism as well as unjustified enthusiasm regarding reproductive interventions, neither of which are consistent with the practice of evidence-based medicine or the idea of informed patient choice. However, RCTs and meta-analyses remain vital to establish the effectiveness of fertility interventions. We discuss strategies to improve the evidence base and call for collaborative studies focusing on the most important research questions. STUDY FUNDING/COMPETING INTEREST(S): There was no specific funding for this study. KS and SL declare no conflict of interest. AV consults for the Human Fertilisation and Embryology Authority (HFEA): all fees are paid directly to AV's employer. JW declares that publishing research benefits his career. SR is a Statistical Editor for Human Reproduction. JW and AV are Statistical Editors for Cochrane Gynaecology and Fertility. DRB is funded by the NHS as Scientific Director of a clinical IVF service. PROSPERO REGISTRATION NUMBER: None.

Propensity score analysis of 18-FDG PET/CT-enhanced staging in patients undergoing surgery for esophageal cancer.

PURPOSE: PET/CT is now integral to the staging pathway for potentially curable esophageal cancer (EC), primarily to identify distant metastases undetected by computed tomography. The aim of this study was to analyze the effect of PET/CT introduction on survival and assess patterns of recurrence after esophagectomy. METHODS: A longitudinal cohort of EC patients staged between 1998 and 2016 were considered for inclusion. After co-variate adjustment using propensity scoring, a cohort of 496 patients (273 pre-PET/CT and 223 post-PET/CT) who underwent esophagectomy [median age 63 years (31-80), 395 males, 425 adenocarcinomas, 71 squamous cell carcinomas, 325 neoadjuvant therapy] were included. The primary outcome measure was overall survival (OS) based on intention to treat. RESULTS: Three-year OS pre-PET/CT was 42.5% compared with 57.8% post-PET/CT (Chi2 6.571, df 1, p = 0.004). On multivariable analysis, pT stage (HR 1.496 [95% CI 1.28-1.75], p < 0.0001), pN stage (HR 1.114 [95% CI 1.04-1.19], p = 0.001) and PET/CT staging (HR 0.688 [95% CI 0.53-0.89] p = 0.004) were independently associated with OS. Recurrent cancer was observed in 125 patients (51.4%) pre-PET/CT, compared with 74 patients post-PET/CT (37.8%, p = 0.004), and was less likely to be distant recurrence after PET/CT introduction (39.5 vs. 27.0%, p = 0.006). CONCLUSIONS: Enhanced PET/CT staging is an important modality and independent factor associated with improved survival in patients undergoing esophagectomy for cancer.