Multi-tissue profiling of oxylipins reveal a conserved up-regulation of epoxide:diol ratio that associates with white adipose tissue inflammation and liver steatosis in obesity.

BACKGROUND: Obesity drives maladaptive changes in the white adipose tissue (WAT) which can progressively cause insulin resistance, type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated liver disease (MASLD). Obesity-mediated loss of WAT homeostasis can trigger liver steatosis through dysregulated lipid pathways such as those related to polyunsaturated fatty acid (PUFA)-derived oxylipins. However, the exact relationship between oxylipins and metabolic syndrome remains elusive and cross-tissue dynamics of oxylipins are ill-defined. METHODS: We quantified PUFA-related oxylipin species in the omental WAT, liver biopsies and plasma of 88 patients undergoing bariatric surgery (female N = 79) and 9 patients (female N = 4) undergoing upper gastrointestinal surgery, using UPLC-MS/MS. We integrated oxylipin abundance with WAT phenotypes (adipogenesis, adipocyte hypertrophy, macrophage infiltration, type I and VI collagen remodelling) and the severity of MASLD (steatosis, inflammation, fibrosis) quantified in each biopsy. The integrative analysis was subjected to (i) adjustment for known risk factors and, (ii) control for potential drug-effects through UPLC-MS/MS analysis of metformin-treated fat explants ex vivo. FINDINGS: We reveal a generalized down-regulation of cytochrome P450 (CYP)-derived diols during obesity conserved between the WAT and plasma. Notably, epoxide:diol ratio, indicative of soluble epoxide hydrolyse (sEH) activity, increases with WAT inflammation/fibrosis, hepatic steatosis and T2DM. Increased 12,13-EpOME:DiHOME in WAT and liver is a marker of worsening metabolic syndrome in patients with obesity. INTERPRETATION: These findings suggest a dampened sEH activity and a possible role of fatty acid diols during metabolic syndrome in major metabolic organs such as WAT and liver. They also have implications in view of the clinical trials based on sEH inhibition for metabolic syndrome. FUNDING: Wellcome Trust (PS3431_WMIH); Duke-NUS (Intramural Goh Cardiovascular Research Award (Duke-NUS-GCR/2022/0020); National Medical Research Council (OFLCG22may-0011); National Institute of Environmental Health Sciences (Z01 ES025034); NIHR Imperial Biomedical Research Centre.

Personalized Prehabilitation Improves Tolerance to Chemotherapy in Patients with Oesophageal Cancer.

BACKGROUND: Prehabilitation programmes aim to optimise patients before and after cancer treatment including surgery. Previous studies in surgical patients demonstrate that prehabilitation improves pre-operative fitness and overcomes the negative impact of neoadjuvant chemotherapy on fitness. The aim of this study was to assess the impact of prehabilitation on the tolerance of neoadjuvant chemotherapy in patients with oesophageal cancer. METHODS: Patients with oesophageal or gastroesophageal junction (GOJ) cancer from two oncology centres were retrospectively included in the present comparative cohort study; one provided a multimodal prehabilitation programme and one did not offer any prehabilitation. Tolerance of chemotherapy, defined as completion of the full chemotherapy regime as per protocol, was compared between the two groups. RESULTS: In terms of participants, 92 patients were included in this study, 47 patients in the prehabilitation cohort and 45 in the control cohort. Compared with the control group, the prehabilitation group demonstrated an improved rate of chemotherapy completion (p = 0.029). In multivariate analysis, participation in prehabilitation was significantly associated with an improved rate of chemotherapy completion. CONCLUSION: The findings of this exploratory study suggest that prehabilitation is associated with better tolerance for chemotherapy. Further research is needed to establish the long-term impact of prehabilitation on oncological outcomes.

Feasibility of Implementation and the Impact of a Digital Prehabilitation Service in Patients Undergoing Treatment for Oesophago-Gastric Cancer.

BACKGROUND: Home-based and supervised prehabilitation programmes are shown to have a positive impact on outcomes in patients with oesophago-gastric (OG) cancer. The primary aim of this study was to establish the feasibility of delivering a digital prehabilitation service. METHODS: Patients undergoing treatment for OG cancer with curative intent were recruited into the study. During the COVID-19 pandemic, patients were offered a digital prehabilitation service. Following the lifting of COVID-19 restrictions, patients were also offered both a hybrid clinic-based in-person service and a digital service. Implementation and clinical metrics from the two prehabilitation models were compared. RESULTS: 31 of 41 patients accepted the digital service (75%). Of the people who started the digital programme, 3 dropped out (10%). Compliance with the weekly touchpoints was 86%, and the median length of programme was 12 weeks. Twenty-six patients enrolled in the in-person service. Two patients dropped out (10%). Average compliance to weekly touchpoints was 71%, and the median length of programme was 10 weeks. In the digital group, sit to stand (STS) increased from 14.5 (IQR 10.5-15.5) to 16 (IQR 16-22); p = 0.02. Median heart rate recovery (HRR) increased from 10.5 (IQR 7.5-14) to 15.5 (IQR 11-20) bpm; p = 0.24. There was a significant drop in distress (median 3 (IQR 0-5) to 1 (IQR 0-2); p = 0.04) and a small drop in anxiety (median 3 (0-5) to 2 (0-3); p = 0.22). There was no difference in the postoperative complication rate and length of hospital stay between the two groups. DISCUSSION: This study has shown that digital prehabilitation can be delivered effectively to patients with OG cancer, with high engagement and retention rates. We observed improvements in some physical and psychological parameters with the digital service, with comparable clinical outcomes to the in-person service.

The effects of prehabilitation on body composition in patients undergoing multimodal therapy for esophageal cancer.

Prehabilitation aims to optimize a patient's functional capacity in preparation for surgery. Esophageal cancer patients have a high incidence of sarcopenia and commonly undergo neoadjuvant therapy, which is associated with loss of muscle mass. This study examines the effects of prehabilitation on body composition during neoadjuvant therapy in esophageal cancer patients. In this cohort study, changes in body composition were compared between esophageal cancer patients who participated in prehabilitation during neoadjuvant therapy and controls who did not receive prehabilitation. Assessment of body composition was performed from CT images acquired at the time of diagnosis and after neoadjuvant therapy. Fifty-one prehabilitation patients and 28 control patients were identified. There was a significantly greater fall in skeletal muscle index (SMI) in the control group compared with the prehabilitation patients (Δ SMI mean difference = -2.2 cm2/m2, 95% CI -4.3 to -0.1, p=0.038). Within the prehabilitation cohort, there was a smaller decline in SMI in patients with ≥75% adherence to exercise in comparison to those with lower adherence (Δ SMI mean difference = -3.2, 95% CI -6.0 to -0.5, P = 0.023). A greater decrease in visceral adipose tissue (VAT) was seen with increasing volumes of exercise completed during prehabilitation (P = 0.046). Loss of VAT during neoadjuvant therapy was associated with a lower risk of post-operative complications (P = 0.017). By limiting the fall in SMI and promoting VAT loss, prehabilitation may have multiple beneficial effects in patients with esophageal cancer. Multi-center, randomized studies are needed to further explore these findings.

Guide to Enhanced Recovery for Cancer Patients Undergoing Surgery: ERAS and Oesophagectomy.

Enhanced Recovery After Surgery (ERAS) protocols are widely used in oesophageal cancer surgery. Multiple studies have demonstrated that ERAS protocols are associated with a shorter length of stay and a reduction in the incidence of post-operative complications after oesophagectomy. However, there is substantial heterogeneity in the content of ERAS protocols and the delivery of these pathways can be challenging. This paper discusses the key recommendations for ERAS protocols in oesophageal cancer surgery and the barriers and facilitating factors for their successful implementation.

Adherence to Pre-operative Exercise and the Response to Prehabilitation in Oesophageal Cancer Patients.

BACKGROUND: Prehabilitation is thought to reduce post-operative respiratory complications by optimising fitness before surgery. This prospective, single-centre study aimed to establish the effect of pre-operative exercise on cardiorespiratory fitness in oesophageal cancer patients and characterise the effect of adherence and weekly physical activity on response to prehabilitation. METHODS: Patients received a personalised, home-based pre-operative exercise programme and self-reported their adherence each week. Cardiorespiratory fitness (pVO2max and O2 pulse) was assessed at diagnosis, following completion of neoadjuvant chemotherapy (NAC) and immediately before surgery. Study outcomes included changes in fitness and post-operative pneumonia. RESULTS: Sixty-seven patients with oesophageal cancer underwent prehabilitation followed by surgery between January 2016 and December 2018. Fitness was preserved during NAC and then increased prior to surgery (pV02max Δ = +2.6 ml min-1, 95% CI 1.2-4.0 p = 0.001; O2 pulse Δ = +1.4 ml beat-1 95% CI 0.5-2.3 p = 0.001). Patients with higher baseline fitness completed more physical activity. Regression analyses found adherence was associated with improvement in fitness immediately before surgery (p = 0.048), and the amount of physical activity completed was associated with the risk of post-operative pneumonia (p = 0.035). CONCLUSION: Pre-operative exercise can maintain cardiorespiratory fitness during NAC and facilitate an increase in fitness before surgery. Greater exercise volumes were associated with a lower risk of post-operative pneumonia, highlighting the importance progressing exercise programmes throughout prehabilitation. Patients with high baseline fitness completed more physical activity and may require less supervision to reach their exercise goals. Further research is needed to explore stratified approaches to prehabilitation.

The Impact of Prehabilitation on Post-operative Outcomes in Oesophageal Cancer Surgery: a Propensity Score Matched Comparison.

BACKGROUND: Patients undergoing oesophageal cancer surgery are often frail with a high risk of post-operative complications. Prehabilitation has been shown to reduce post-operative complications in specific patient populations but evidence in oesophageal cancer patients is inconclusive. METHODS: Between January 2016 and April 2019, all patients with resectable oesophageal cancer who underwent curative treatment at a specialist tertiary centre participated in a personalised, home-based, multimodal prehabilitation programme. Post-operative complications and hospital stay in this group were compared to a control sample. Propensity score matching was used to control for differences in baseline characteristics. RESULTS: Seventy-two patients who completed prehabilitation and 39 control patients were studied; following propensity score matching, there were 38 subjects in each group. In comparison to matched controls, patients in the prehabilitation group had a lower incidence of post-operative pneumonia (prehabilitation = 26%; control = 66%; p = 0.001) and a shorter length of stay (prehabilitation = median 10 days, IQR 8-17 days; control = median 13 days, IQR 11-20 days; p = 0.018). On multivariate regression analysis, participation in prehabilitation was associated with a 77% lower incidence of post-operative pneumonia (OR 0.23, 95% CI 0.09 to 0.55 p = 0.001). There was no significant difference in the incidence of overall complications or severe complications. CONCLUSION: Prehabilitation was associated with a lower incidence of post-operative pneumonia and shorter hospital length of stay following oesophagectomy. This model of home based, personalised, and supervised prehabilitation is effective and relevant to centralised cancer services.

Temporal trends, patterns, and predictors of preterm birth in California from 2007 to 2016, based on the obstetric estimate of gestational age.

BACKGROUND: Preterm birth (PTB) is associated with increased infant mortality, and neurodevelopmental abnormalities among survivors. The aim of this study is to investigate temporal trends, patterns, and predictors of PTB in California from 2007 to 2016, based on the obstetric estimate of gestational age (OA). METHODS: A retrospective cohort study evaluated 435,280 PTBs from the 5,137,376 resident live births (8.5%) documented in the California Birth Statistical Master Files (BSMF) from 2007 to 2016. The outcome variable was PTB; the explanatory variables were birth year, maternal characteristics and health behaviors. Descriptive statistics and logistic regression analysis were used to identify subgroups with significant risk factors associated with PTB. Small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) infants were identified employing gestational age based on obstetric estimates and further classified by term and preterm births, resulting in six categories of intrauterine growth. RESULTS: The prevalence of PTB in California decreased from 9.0% in 2007 to 8.2% in 2014, but increased during the last 2 years, 8.4% in 2015 and 8.5% in 2016. Maternal age, education level, race and ethnicity, smoking during pregnancy, and parity were significant risk factors associated with PTB. The adjusted odds ratio (AOR) showed that women in the oldest age group (40-54 years) were almost twice as likely to experience PTB as women in the 20- to 24-year reference age group. The prevalence of PTB was 64% higher in African American women than in Caucasian women. Hispanic women showed less disparity in the prevalence of PTB based on education and socioeconomic level. The analysis of interactions between maternal characteristics and perinatal health behaviors showed that Asian women have the highest prevalence of PTB in the youngest age group (< 20 years; AOR, 1.40; 95% confidence interval (CI), 1.28-1.54). Pacific Islander, American Indian, and African American women ≥40 years of age had a greater than two-fold increase in the prevalence of PTB compared with women in the 20-24 year age group. Compared to women in the Northern and Sierra regions, women in the San Joaquin Valley were 18%, and women in the Inland Empire and San Diego regions 13% more likely to have a PTB. Women who smoked during both the first and second trimesters were 57% more likely to have a PTB than women who did not smoke. Compared to women of normal prepregnancy weight, underweight women and women in obese class III were 23 and 33% more likely to experience PTB respectively. CONCLUSIONS: Implementation of public health initiatives focusing on reducing the prevalence of PTB should focus on women of advanced maternal age and address race, ethnic, and geographic disparities. The significance of modifiable maternal perinatal health behaviors that contribute to PTB, e.g. smoking during pregnancy and prepregnancy obesity, need to be emphasized during prenatal care.

Recent trends, risk factors, and disparities in low birth weight in California, 2005-2014: a retrospective study.

BACKGROUND: Low birth weight (LBW) is a leading risk factor for infant morbidity and mortality in the United States. There are large disparities in the prevalence of LBW by race and ethnicity, especially between African American and White women. Despite extensive research, the practice of clinical and public health, and policies devoted to reducing the number of LBW infants, the prevalence of LBW has remained unacceptably and consistently high. There have been few detailed studies identifying the factors associated with LBW in California, which is home to a highly diverse population. The aim of this study is to investigate recent trends in the prevalence of LBW infants (measured as a percentage) and to identify risk factors and disparities associated with LBW in California. METHODS: A retrospective cohort study included data on 5,267,519 births recorded in the California Birth Statistical Master Files for the period 2005-2014. These data included maternal characteristics, health behaviors, information on health insurance, prenatal care use, and parity. Logistic regression models identified significant risk factors associated with LBW. Using gestational age based on obstetric estimates (OA), small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) infants were identified for the periods 2007-2014. RESULTS: The number of LBW infants declined, from 37,603 in 2005 to 33,447 in 2014. However, the prevalence of LBW did not change significantly (6.9% in 2005 to 6.7% in 2014). The mean maternal age at first delivery increased from 25.7 years in 2005 to 27.2 years in 2014. The adjusted odds ratio showed that women aged 40 to 54 years were twice as likely to have an LBW infant as women in the 20 to 24 age group. African American women had a persistent 2.4-fold greater prevalence of having an LBW infant compared with white women. Maternal age was a significant risk factor for LBW regardless of maternal race and ethnicity or education level. During the period 2017-2014, 5.4% of the singleton births at 23-41 weeks based on OE of gestational age were SGA infants (preterm SGA + term SGA). While all the preterm SGA infants were LBW, both preterm AGA and term SGA infants had a higher prevalence of LBW. CONCLUSIONS: In California, during the 10 years from 2005 to 2014, there was no significant decline in the prevalence of LBW. However, maternal age was a significant risk factor for LBW regardless of maternal race and ethnicity or education level. Therefore, there may be opportunities to reduce the prevalence of LBW by reducing disparities and improving birth outcomes for women of advanced maternal age.

Poor performance in incremental shuttle walk and cardiopulmonary exercise testing predicts poor overall survival for patients undergoing esophago-gastric resection.

INTRODUCTION: Esophageal and gastric cancer have a poor prognosis and surgical intervention is associated with considerable morbidity, highlighting the need for careful preoperative assessment. The Incremental Shuttle Walk Test (ISWT) and Cardiopulmonary exercise testing (CPET) can assess preoperative fitness. This study aims to investigate their correlation with both postoperative respiratory complications and overall survival. PATIENTS AND METHODS: Patients were identified who underwent esophageal or gastric resections for cancer between 2010 and 2014 and had ISWT and/or CPET assessments. Tumor differentiation, stage, postoperative respiratory complications, and outcome were documented and then correlated with the results of the preoperative fitness assessments. RESULTS: Neither the ISWT result, anaerobic threshold (AT) nor VO2 Max correlated well with perioperative complications. However, ISWT (p < 0.001), AT (p < 0.001) and VO2 Max (p < 0.001) all correlated strongly with overall survival. No patient with a score of less than 350 m on ISWT survived beyond 3 years. In a subset of patients with ISWT results both pre and post chemotherapy (n = 49), those that had an improvement in result had a 19% incidence of post-operative respiratory complications compared to 45% where the result did not change or declined, though due to small numbers this only approached significance (p = 0.08). CONCLUSION: ISWT and CPET can be useful preoperative tools to predict overall survival for patients undergoing esophago-gastric resection. Furthermore, patients that improve their functional status during chemotherapy seem to do better than those where it remains static or declines.

Enhanced recovery protocols after oesophagectomy.

The feasibility and safety of enhanced recovery protocols (ERP) have been demonstrated in a large number of surgical specialties. Several studies have shown improved post-operative outcomes and economic benefit from the use of ERPs in oesophageal cancer surgery. However, these improvements are not always translated more widely into clinical practice due to variation in protocols, poor compliance and failure to implement a robust implementation strategy. ERP implementation strategies should reflect the fact that these are complex interventions that are influenced by a wide range of social, organizational and cultural factors.

Grit and burnout in UK doctors: a cross-sectional study across specialties and stages of training.

PURPOSE OF THE STUDY: Grit is characterised by the ability to persevere during difficulties and maintain a sustained effort over an extended period of time. Throughout their careers, doctors will experience many periods of stress and difficulty. This may result in burnout, defined by the presence of exhaustion and disengagement from work. This study aims to characterise the relationship between grit and burnout in doctors and to establish whether there are differences between specialties and levels of training. STUDY DESIGN: A multicentre cross-sectional survey by questionnaire was used. Participants were recruited from training days and an online medical forum. The survey consisted of the Short Grit Scale and the Oldenburg Burnout Inventory, which examine levels of grit and burnout, respectively. RESULTS: 548 responses were collected. We found a weak negative correlation between grit and burnout in UK doctors (r=-0.243, p<0.001). Hospital consultants had significantly higher grit scores than trainees. The highest level of burnout was found among general practitioners (GPs). When GPs were analysed separately, the correlation between grit and resilience was not seen. CONCLUSIONS: An understanding of an individual's level of grit may be used to identify doctors at a greater risk of burnout. As a high level of grit is associated with less burnout, interventions to improve grit through resilience training should be examined. Further research is needed to understand how grit levels change during a doctor's career and why GPs experience higher levels of burnout.

Multiple thoracic duct cysts: an unusual CT finding.

Thoracic duct cysts in the mediastinum are rare. We report the case of a 66-year-old gentleman who was found to have multiple small thoracic duct cysts during investigation of a retrosternal thyroid goitre. Multiple paraoesphageal swellings were seen on a computed tomographic scan in the upper posterior mediastinum. The largest was 2 cm and they were continuous with the thoracic duct. This is this first reported case of multiple thoracic duct cysts. Previous cases are of a single large swelling, the majority of which were surgically excised. Small asymptomatic cysts such as the case we present are suitable for conservative management.

Management of a bilobed testicle in a 12-year-old boy.

A bilobed testicle is an extremely rare congenital malformation, with only five cases published to date. We present the case of a 12-year-old boy with a bilobed testicle. With so few cases available, much of what is known about the management of this condition is based on cases of polyorchidism and the complications associated with this, including malignancy and torsion. Whilst surgery may play a role in some patients, uncomplicated cases can be managed conservatively. There is no long-term data on the outcome of conservative management but we propose this patient can be discharged if no further changes are identified after 18 months.