Demographic trends in the incidence of young-onset colorectal cancer: a population-based study.

BACKGROUND: Evidence is emerging that the incidence of colorectal cancer is increasing in young adults, but the descriptive epidemiology required to better understand these trends is currently lacking. METHODS: A population-based cohort study was carried out including all adults aged 20-49 years diagnosed with colorectal cancer in England between 1974 and 2015. Data were extracted from the National Cancer Registration and Analysis Service database using ICD-9/10 codes for colorectal cancer. Temporal trends in age-specific incidence rates according to sex, anatomical subsite, index of multiple deprivation quintile and geographical region were analysed using Joinpoint regression. RESULTS: A total of 56 134 new diagnoses of colorectal cancer were analysed. The most sustained increase in incidence rate was in the group aged 20-29 years, which was mainly driven by a rise in distal tumours. The magnitude of incident rate increases was similar in both sexes and across Index of Multiple Deprivation quintiles, although the most pronounced increases in incidence occurred in the southern regions of England. CONCLUSION: Colorectal cancer should no longer be considered a disease of older people. Changes in incidence rates should be used to inform future screening policy, preventative strategies and research agendas, as well as increasing public understanding that younger people need to be aware of the symptoms of colorectal cancer.

ANTECEDENTES: Están apareciendo evidencias de que la incidencia del cáncer colorrectal (colorectal cancer, CRC) está aumentando en adultos jóvenes, pero se carece de la epidemiología descriptiva necesaria para comprender mejor estas tendencias. MÉTODOS: Se realizó un estudio de cohortes de base poblacional de todos los adultos de 20 a 49 años diagnosticados de CRC en Inglaterra entre 1974 y 2015. Los datos se extrajeron de la base de datos NCRAS utilizando los códigos ICD9/10 para el CRC. Las tendencias temporales en las tasas de incidencia específicas por edad (incidence rates, IR) según el sexo, la localización anatómica, el quintil del índice de privación múltiple (index of multiple deprivation, IMD) y la región geográfica se analizaron mediante un modelo de regresión joinpoint. RESULTADOS: Se analizaron un total de 56.134 nuevos diagnósticos de CRC. El aumento más sostenido en la IR se produjo en el grupo de edad de 20 a 29 años, principalmente a expensas de un incremento de los tumores distales. La magnitud de los aumentos de IR fue similar en ambos sexos y en los quintiles del IMD, aunque los aumentos más pronunciados en la incidencia se registraron en las regiones del sur de Inglaterra. CONCLUSIÓN: El CRC ya no debe ser considerado una enfermedad de las personas mayores: los cambios en las tasas de incidencia deberán tenerse en cuenta en las futuras políticas de cribado, en las estrategias preventivas y en los proyectos de investigación, así como para aumentar la toma de conciencia de la población de que las personas más jóvenes deben estar al corriente de los síntomas del CRC.

Factors associated with advanced colorectal cancer differ between young and older adults in England: a population-based cohort study.

AIM: Advanced stage presentation of colorectal cancer is associated with poorer survival outcomes, particularly among young adults. This study aimed to determine whether demographic risk factors for advanced stage presentation differed between young and older adults. METHOD: Individual-level data on all incident colorectal cancers in people aged 20 years and above were extracted from the National Cancer Registration and Analysis Service database for the years 2012 to 2015. Patients were divided into two cohorts: young-onset colorectal cancer (YOCC) if aged 20-49 years and older-onset colorectal cancer (OOCC) if aged 50 years and above. Logistic regression was used to identify risk factors for advanced stage presentation, defined as TNM Stage III or IV, in each cohort. RESULTS: There were 7075 (5.2%) patients in the YOCC cohort and 128 345 (94.8%) patients in the OOCC cohort. Tumours in the YOCC cohort were more likely to be at an advanced stage (67.2% vs 55.3%, P < 0.001) and located distally (63.7% vs 55.4%, P < 0.001). No demographic factor was consistently associated with advanced stage presentation in the YOCC cohort. Among the OOCC cohort, increased social deprivation [OR (Index of Multiple Deprivation quintile 5 vs 1) = 1.11 (95% CI 1.07-1.16), P < 0.001], Black/Black British ethnicity [OR (baseline White) = 1.25 (95% CI 1.11-1.40), P < 0.001] and residence in the East Midlands [OR (baseline London) = 1.11 (95% CI 1.04-1.17), P = 0.001] were associated with advanced stage presentation. CONCLUSION: Demographic factors associated with advanced disease were influenced by age. The effects of social deprivation and ethnicity were only observed in older adults and mirror trends in screening uptake. Targeted interventions for high-risk groups are warranted.

Pneumomediastinum following intubation in COVID-19 patients: a case series.

The number of patients requiring tracheal intubation rose dramatically in March and April 2020 with the COVID-19 outbreak. Our thoracic surgery department has seen an increased incidence of severe pneumomediastinum referred for surgical opinion in intubated patients with COVID-19 pneumonitis. Here we present a series of five patients with severe pneumomediastinum requiring decompression therapy over a 7-day period in the current COVID-19 outbreak. We hypothesise that the mechanism for this is the aggressive disease pathophysiology with an increased risk of alveolar damage and tracheobronchial injury, along with the use of larger-bore tracheal tubes and higher ventilation pressures. We present this case series in order to highlight the increased risk of this potentially life-threatening complication among the COVID-19 patient cohort and offer guidance for its management to critical care physicians.

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy.

BACKGROUND: Complete tumour response (pCR) to neo-adjuvant chemo-radiotherapy for rectal cancer is associated with a reduction in local recurrence and improved disease-free and overall survival, but is achieved in only 20-30% of patients. Drug repurposing for anti-cancer treatments is gaining momentum, but the potential of such drugs as adjuncts, to increase tumour response to chemo-radiotherapy in rectal cancer, is only just beginning to be recognised. METHODS: A systematic literature search was conducted and all studies investigating the use of drugs to enhance response to neo-adjuvant radiation in rectal cancer were included. 2137 studies were identified and following review 12 studies were extracted for full text review, 9 studies were included in the final analysis. RESULTS: The use of statins or aspirin during neo-adjuvant therapy was associated with a significantly higher rate of tumour downstaging. Statins were identified as a significant predictor of pCR and aspirin users had a greater 5-year progression-free survival and overall survival. Metformin use was associated with a significantly higher overall and disease-free survival, in a subset of diabetic patients. CONCLUSIONS: Aspirin, metformin and statins are associated with increased downstaging of rectal tumours and thus may have a role as adjuncts to neoadjuvant treatment, highlighting a clear need for prospective randomised controlled trials to determine their true impact on tumour response and overall survival.

Nucleon Structure Functions from Operator Product Expansion on the Lattice.

Deep-inelastic scattering, in the laboratory and on the lattice, is most instructive for understanding how the nucleon is built from quarks and gluons. The long-term goal is to compute the associated structure functions from first principles. So far this has been limited to model calculations. In this Letter we propose a new method to compute the structure functions directly from the virtual, all-encompassing Compton amplitude, utilizing the operator product expansion. This overcomes issues of renormalization and operator mixing, which so far have hindered lattice calculations of power corrections and higher moments.

HOSPEX in the antipodes.

The Australian Army recently adopted the British concept of hospital exercise (HOSPEX) as a means of evaluating the capabilities of its deployable NATO Role 2E hospital, the 2nd General Health Battalion. The Australian approach to HOSPEX differs from the original UK model. This article describes the reasons why the Australian Army needed to adopt the HOSPEX concept, how it was adapted to suit local circumstances and how the concept may evolve to meet the needs of the wider Australian Defence Force and our allies.

Successful lung transplant in a child with cystic fibrosis and persistent Blastobotrys rhaffinosifermentans infection.

Fungal respiratory infections in patients with CF are a significant concern both pre- and post-lung transplantation (LTx). Fungal infection is associated with increased mortality post-LTx, and in the past decade, the prevalence of fungal colonization in Canadian pediatric patients with CF has increased. The emergence of novel fungal pathogens is particularly challenging to the transplant community, as little is known regarding their virulence and optimal management. We present a case of a successful double-lung transplant in a pediatric patient with CF who was infected pretransplantation with a novel yeast, Blastobotrys rhaffinosifermentans. This patient was treated successfully with aggressive antifungal therapy post-transplantation, followed by extended fungal prophylaxis. The significance of fungal colonization and infection in children with CF pre- and post-LTx is reviewed.

Appraisal of guidelines developed by the World Health Organization.

OBJECTIVE: To appraise the quality of guidelines developed by the World Health Organization (WHO) that were approved by its Guidelines Review Committee (GRC) and identify strengths and weaknesses in the guideline development process. STUDY DESIGN: Cross-sectional. METHODS: Three individuals independently assessed GRC-approved WHO guidelines using the Appraisal of Guidelines for Research and Evaluation II instrument (AGREE II). Scores were standardized across domains and overall quality was determined through consensus. RESULTS: 124 guidelines met inclusion criteria and were assessed. 58 guidelines were recommended for use, 58 were recommended with modifications and eight were not recommended. The highest scoring domains across guidelines were scope and purpose, and clarity of presentation. The recommended guidelines had higher rigor of development and applicability domain scores in comparison to other guidelines. 77% of the guidelines referenced an underlying evidence review and 49% used GRADE to assess the body of evidence or the strength of the recommendation. The domains in need of improvement included stakeholder engagement, editorial independence, and applicability. Guidelines not recommended for use were generally insufficient in their rigor of development. CONCLUSIONS: WHO guidelines need further improvement, most importantly in the rigor of their development (i.e., use of evidence reviews). Other areas for improvement include increased stakeholder engagement, a more explicit process for recommendation formulation and disclosure of interests, discussion of the facilitators, barriers, resource implications, and criteria for monitoring the outcomes of guideline implementation. WHO guidelines can improve through increased transparency, adherence to the WHO Handbook for Guideline Development, and better oversight by the GRC.

The effect of vertical sleeve gastrectomy on food choice in rats.

OBJECTIVE: Diets high in fat are implicated in the development and maintenance of obesity, and obese individuals display greater preferences for high-fat foods than do their lean counterparts. Weight-reduction bariatric surgery is associated with changes in food choice. In particular, after Roux-en-Y gastric bypass (RYGB), humans and rodents select or prefer foods that are lower in fat content. We asked whether a bariatric surgical procedure limited to the stomach, vertical sleeve gastrectomy (VSG), causes a similar reduction of fat intake/preference. RESEARCH DESIGN AND METHODS: Rats received VSG or Sham surgery or remained surgically naïve, and were assessed for food preference using three diet-choice paradigms. Using progressive-ratio (PR) and conditioned taste aversion paradigms, we further asked whether surgically induced changes in food choice are secondary to changes in the reward value of food and/or to the formation of a food aversion. Finally, food choice was compared between VSG- and RYGB-operated rats. RESULTS: VSG rats decreased their intake of dietary fat, and shifted their preference toward lower caloric-density foods. This change in food choice was not associated with changes in motivated responding on a PR schedule for either a fat or a carbohydrate food reinforcer. When VSG and RYGB were compared directly, both procedures caused comparable changes in food choice. The conditioned taste aversion paradigm revealed that VSG rats form an aversion to an intra-gastric oil administration whereas RYGB rats do not. CONCLUSIONS: VSG and RYGB, two anatomically distinct bariatric procedures, produce similar changes in food choice.

Emotional and informational social support from health visitors and breastfeeding outcomes in the UK.

BACKGROUND: Shorter breastfeeding duration is associated with detrimental consequences for infant health/development and maternal health. Previous studies suggest social support is essential in maintaining breast/chest-feeding and helping to improve general infant feeding experiences. Public health bodies therefore work to support breastfeeding in the UK, yet UK breastfeeding rates continue to be one of the lowest globally. With this, a better understanding of the effectiveness and quality of infant feeding support is required. In the UK, health visitors (community public health nurses specialising in working with families with a child aged 0-5 years) have been positioned as one of the key providers of breast/chest-feeding support. Research evidence suggests that both inadequate informational support and poor/negative emotional support can lead to poor breastfeeding experiences and early breastfeeding cessation. Thus, this study tests the hypothesis that emotional support from health visitors moderates the relationship between informational support and breastfeeding duration/infant feeding experience among UK mothers. METHODS: We ran cox and binary logistic regression models on data from 565 UK mothers, collected as part of a 2017-2018 retrospective online survey on social support and infant feeding. RESULTS: Informational support, compared to emotional support, was a less important predictor of both breastfeeding duration and experience. Supportive emotional support with unhelpful or absent informational support was associated with the lowest hazard of breastfeeding cessation before 3 months. Results for breastfeeding experience followed similar trends, where positive experience was associated with supportive emotional and unhelpful informational support. Negative experiences were less consistent; however, a higher probability of negative experience was found when both types of support were reported as unsupportive. CONCLUSIONS: Our findings point to the importance of health visitors providing emotional support to bolster the continuation of breastfeeding and encourage a positive subjective experience of infant feeding. The emphasis of emotional support in our results encourages increased allocation of resources and training opportunities to ensure health visitors are able to provide enhanced emotional support. Lowering health visitors caseloads to allow for personalised care is just one actionable example that may improve breastfeeding outcomes in the UK.

Plasma osteopontin as a biomarker of prostate cancer aggression: relationship to risk category and treatment response.

BACKGROUND: High plasma osteopontin (OPN) has been linked to tumour hypoxia, metastasis, and poor prognosis. This study aims to assess whether plasma osteopontin was a biomarker of increasing progression within prostate cancer (PCa) prognostic groups and whether it reflected treatment response to local and systemic therapies. METHODS: Baseline OPN was determined in men with localised (n=199), locally recurrent (n=9) and castrate-resistant, metastatic PCa (CRPC-MET; n=37). Receiver-operating curves (ROC) were generated to describe the accuracy of OPN for distinguishing between localised risk groups or localised vs metastatic disease. We also measured OPN pre- and posttreatment, following radical prostatectomy, external beam radiotherapy (EBRT), androgen deprivation (AD) or taxane-based chemotherapy. RESULTS: The CRPC-MET patients had increased baseline values (mean 219; 56-513 ng ml(-1); P<0.0001) compared with the localised, non-metastatic group (mean 72; 12-438 ng ml(-1)). The area under the ROC to differentiate localised vs metastatic disease was improved when OPN was added to prostate-specific antigen (PSA) (0.943-0.969). Osteopontin neither distinguished high-risk PCa from other localised PCa nor correlated with serum PSA at baseline. Osteopontin levels reduced in low-risk patients after radical prostatectomy (P=0.005) and in CRPC-MET patients after chemotherapy (P=0.027), but not after EBRT or AD. CONCLUSION: Plasma OPN is as good as PSA at predicting treatment response in CRPC-MET patients after chemotherapy. Our data do not support the use of plasma OPN as a biomarker of increasing tumour burden within localised PCa.

The open abdomen and temporary abdominal closure systems--historical evolution and systematic review.

AIM: Several techniques for temporary abdominal closure have been developed. We systematically review the literature on temporary abdominal closure to ascertain whether the method can be tailored to the indication. METHOD: Medline, Embase, the Cochrane Central Register of Controlled Trials and relevant meeting abstracts until December 2009 were searched using the following headings: open abdomen, laparostomy, VAC (vacuum assisted closure), TNP (topical negative pressure), fascial closure, temporary abdominal closure, fascial dehiscence and deep wound dehiscence. The data were analysed by closure technique and aetiology. The primary end-points included delayed fascial closure and in-hospital mortality. The secondary end-points were intra-abdominal complications. RESULTS: The search identified 106 papers for inclusion. The techniques described were VAC (38 series), mesh/sheet (30 series), packing (15 series), Wittmann patch (eight series), Bogotá bag (six series), dynamic retention sutures (three series), zipper (15 series), skin only and locking device (one series each). The highest facial closure rates were seen with the Wittmann patch (78%), dynamic retention sutures (71%) and VAC (61%). CONCLUSION: Temporary abdominal closure has evolved from simple packing to VAC based systems. In the absence of sepsis Wittmann patch and VAC offered the best outcome. In its presence VAC had the highest delayed primary closure and the lowest mortality rates. However, due to data heterogeneity only limited conclusions can be drawn from this analysis.

Importance of Fungicide Seed Treatment and Environment on Seedling Diseases of Cotton.

The importance of fungicide seed treatments on cotton was examined using a series of standardized fungicide trials from 1993 to 2004. Fungicide seed treatments increased stands over those from seed not treated with fungicides in 119 of 211 trials. Metalaxyl increased stands compared to nontreated seed in 40 of 119 trials having significant fungicide responses, demonstrating the importance of Pythium spp. on stand establishment. Similarly, PCNB seed treatment increased stands compared to nontreated seed for 44 of 119 trials with a significant response, indicating the importance of Rhizoctonia solani in stand losses. Benefits from the use of newer seed treatment chemistries, azoxystrobin and triazoles, were demonstrated by comparison with a historic standard seed treatment, carboxin + PCNB + metalaxyl. Little to no stand improvement was found when minimal soil temperatures averaged 25°C the first 3 days after planting. Stand losses due to seedling pathogens increased dramatically as minimal soil temperatures decreased to 12°C and rainfall increased. The importance of Pythium increased dramatically as minimal soil temperature decreased and rainfall increased, while the importance of R. solani was not affected greatly by planting environment. These multi-year data support the widespread use of seed treatment fungicides for the control of the seedling disease complex on cotton.

Role of oxygen in wound healing: a review of evidence.

OBJECTIVE: To review the evidence regarding the influence of oxygen as an intrinsic factor on cutaneous wound healing. METHOD: A literature search was performed using Ovid and the Cochrane Database with the search terms: 'Wound healing', 'Oxygen', 'Collagen', 'Angiogenesis', 'Inflammation' and 'Surgical Site Infection'. Human and animal studies were included if relevant and examined for methodological quality. RESULTS: There are no meta-analyses of the use of oxygen in wound healing and only two randomised controlled trials (RCTs). Studies vary in methodological quality. The majority of the data comes from animal models. In total 1568 studies on wound healing and oxygen were found. CONCLUSION: Oxygen is vital throughout wound healing, especially in the inflammatory and proliferative phases. Research suggests that patient supplementation with oxygen could enhance bacterial killing and angiogenesis, reduce surgical site infection rates and increase wound tensile strength, facilitating improved healing. CONFLICT OF INTEREST: None.

Dynamic postural stability in pregnant fallers and non-fallers.

OBJECTIVE: To compare dynamic postural stability in pregnant women who have fallen during their pregnancies with those who have not, and with a group of non-pregnant women. DESIGN: The study was both longitudinal and cross-sectional. A cohort of pregnant women were followed through their second and third trimesters. A non-pregnant control group was used for comparison. SETTING: University-based laboratory. POPULATION: A total of 81 women (41 pregnant and 40 controls) participated. Twenty-nine pregnant women completed the protocol. METHODS: Data were collected on the pregnant women in the middle of their second and third trimesters. Pregnant women were surveyed about their daily activities, exercise participation, and fall history. Postural reaction time and centre of pressure (COP) movement data, in response to translational perturbations, were collected using a force plate. A mixed-model analysis of variants (ANOVA) was performed on each of the dependent variables (alpha = 0.05). Chi-square analysis was performed to determine if exercise participation altered the likelihood of a subject experiencing a fall (alpha = 0.05). MAIN OUTCOME MEASURES: Reaction time, initial sway, total sway, and sway velocity. RESULTS: Fifty-two percent of our pregnant subjects experienced a fall. Initial sway response, total sway, and sway velocity were smaller in the pregnant fallers than in the non-fallers and control participants (P < 0.05). Thirty-one of the pregnant subjects participated in regular exercise. Sedentary pregnant women were more likely to experience a fall than those who exercised. CONCLUSIONS: Dynamic balance is altered in pregnant women who have fallen compared with non-fallers and controls. Exercise may play a role in fall prevention in pregnant women.

Observer accuracy in the detection of pulmonary nodules on CT: effect of cine frame rate.

AIM: To assess the effect of cine frame rate on the accuracy of the detection of pulmonary nodules at computed tomography (CT). MATERIALS AND METHODS: CT images of 15 consecutive patients with (n = 13) or without (n = 2) pulmonary metastases were identified. Initial assessment by two thoracic radiologists provided the "actual" or reference reading. Subsequently, 10 radiologists [board certified radiologists (n = 4) or radiology residents (n = 6)] used different fixed cine frame rates for nodule detection. Within-subjects analysis of variance (ANOVA) was used to evaluate the data. RESULTS: Eighty-nine nodules were identified by the thoracic radiologists (median 8, range 0-29 per patient; median diameter 9 mm, range 4-40 mm). There was a non-statistically significant trend to reduced accuracy at higher frame rates (p=0.113) with no statistically significant difference between experienced observers and residents (p = 0.79). CONCLUSION: The accuracy of pulmonary nodule detection at higher cine frame rates is reduced, unrelated to observer experience.

Dynamic heterogeneity: rapid generation of metastatic variants in mouse B16 melanoma cells.

The ability of clonally derived lines of B16F1 and B16F10 melanoma cells to form experimental metastases in C57BL mice after intravenous injection was examined. Luria- Delbruck fluctuation analysis was applied to the results obtained with parallel subclones grown to small population sizes before testing for metastatic ability. The analysis demonstrated that variant cells capable of forming experimental metastases were generated in B16F1 cell populations at an effective rate of about 1.3 X 10(-5) per cell per generation while in B16F10 cell populations the effective rate of production was about 5 X 10(-5) per cell per generation. These results are consistent with a dynamic heterogeneity model of tumor progression. They suggest that the majority of cells in both lines are effectively nonmetastatic and that the higher metastatic ability of the B16F10 population may be due in part to a higher rate of generation of metastatic variants.