Analysis of an Indian colorectal cancer faecal microbiome collection demonstrates universal colorectal cancer-associated patterns, but closest correlation with other Indian cohorts.

It is increasingly being recognised that changes in the gut microbiome have either a causative or associative relationship with colorectal cancer (CRC). However, most of this research has been carried out in a small number of developed countries with high CRC incidence. It is unknown if lower incidence countries such as India have similar microbial associations.Having previously established protocols to facilitate microbiome research in regions with developing research infrastructure, we have now collected and sequenced microbial samples from a larger cohort study of 46 Indian CRC patients and 43 healthy volunteers.When comparing to previous global collections, these samples resemble other Asian samples, with relatively high levels of Prevotella. Predicting cancer status between cohorts shows good concordance. When compared to a previous collection of Indian CRC patients, there was similar concordance, despite different sequencing technologies between cohorts.These results show that there does seem to be a global CRC microbiome, and that some inference between studies is reasonable. However, we also demonstrate that there is definite regional variation, with more similarities between location-matched comparisons. This emphasises the importance of developing protocols and advancing infrastructure to allow as many countries as possible to contribute to microbiome studies of their own populations.

Feasibility of an Adapted Community-Based Lifestyle Intervention to Prevent Cancer in the Rural South: Healthy Living Partnerships to Prevent Cancer (HELP PC).

Obesity increases risk of cancer onset and promulgates cancer mortality. Healthy Living Partnerships to Prevent Cancer (HELP PC) is an adapted intensive lifestyle intervention that is facilitated by community health workers (CHWs). The primary objective of this one-arm pilot study was to test the feasibility of evaluating HELP PC in a rural community by assessing participant recruitment, retention, and adherence to the intervention. The secondary objectives of this study were to evaluate the feasibility of collecting study measures and analyze intervention effects to inform future studies. Adults of all races and a BMI ≥ 25 kg/m2 who resided in the Dan River Region of Southern Virginia were recruited. Participants received 24 weekly (hour-long) group sessions led by a CHW and two consultations with a registered dietitian (RDN). Seventy-five percent (21/28) of eligible subjects were enrolled (n = 21; mean age = 46 years; 67% African American; 90% female; median BMI = 36.1), and recruitment was completed in 2 weeks. Fifty-two percent (11/21) of participants attended >70% of group sessions (adherence) and 98% of RDN consultations were attended. Eighty-six percent (n=18) of participants completed the 6-month follow-up visit (retention), and showed improvements in moderate physical activity, health literacy, general health, energy, and emotional well-being. Feasibility of HELP PC was established through efficient participant recruitment, modest attendance, high retention, and execution of data collection procedures. Importantly, findings can be applied to advance cancer prevention lifestyle interventions in rural communities.

Exploring the utility and acceptability of Faecal immunochemical testing (FIT) as a novel intervention for the improvement of colorectal Cancer (CRC) surveillance in individuals with lynch syndrome (FIT for lynch study): a single-arm, prospective, multi-centre, non-randomised study.

BACKGROUND: Lynch Syndrome (LS) is an inherited cancer predisposition syndrome defined by pathogenic variants in the mismatch repair (MMR) or EPCAM genes. In the United Kingdom, people with LS are advised to undergo biennial colonoscopy from as early as 25 until 75 years of age to mitigate a high lifetime colorectal cancer (CRC) risk, though the consideration of additional surveillance intervention(s) through the application of non-invasive diagnostic devices has yet to be longitudinally observed in LS patients. In this study, we will examine the role of annual faecal immunochemical testing (FIT) alongside biennial colonoscopy for CRC surveillance in people with LS. METHODS/DESIGN: In this single-arm, prospective, non-randomised study, 400 LS patients will be recruited across 11 National Health Service (NHS) Trusts throughout the United Kingdom. Study inclusion requires a LS diagnosis, between 25 and 73 years old, and a routine surveillance colonoscopy scheduled during the recruitment period. Eligible patients will receive a baseline OC-Sensor™ FIT kit ahead of their colonoscopy, and annually for 3 years thereafter. A pre-paid envelope addressed to the central lab will be included within all patient mailings for the return of FIT kits and relevant study documents. A questionnaire assessing attitudes and perception of FIT will also be included at baseline. All study samples received by the central lab will be assayed on an OC-Sensor™ PLEDIA Analyser. Patients with FIT results of ≥6 µg of Haemoglobin per gram of faeces (f-Hb) at Years 1 and/or 3 will be referred for colonoscopy via an urgent colonoscopy triage pathway. 16S rRNA gene V4 amplicon sequencing will be carried out on residual faecal DNA of eligible archived FIT samples to characterise the faecal microbiome. DISCUSSION: FIT may have clinical utility alongside colonoscopic surveillance in people with LS. We have designed a longitudinal study to examine the efficacy of FIT as a non-invasive modality. Potential limitations of this method will be assessed, including false negative or false positive FIT results related to specific morphological features of LS neoplasia or the presence of post-resection anastomotic inflammation. The potential for additional colonoscopies in a subset of participants may also impact on colonoscopic resources and patient acceptability. TRIAL REGISTRATION: Trial Registration: ISRCTN, ISRCTN15740250 . Registered 13 July 2021.

Lynch syndrome screening in colorectal cancer: results of a prospective 2-year regional programme validating the NICE diagnostics guidance pathway throughout a 5.2-million population.

AIMS: Screening all patients newly diagnosed with colorectal cancer (CRC) for possible Lynch syndrome (LS) has been recommended in the United Kingdom since the National Institute for Health and Care Excellence (NICE) released new diagnostics guidance in February 2017. We sought to validate the NICE screening pathway through a prospective regional programme throughout a 5.2-million population during a 2-year period. METHODS AND RESULTS: Pathology departments at 14 hospital trusts in the Yorkshire and Humber region of the United Kingdom were invited to refer material from patients with newly diagnosed CRC aged 50 years or over between 1 April 2017 and 31 March 2019 for LS screening. Testing consisted of immunohistochemistry for MLH1, PMS2, MSH2 and MSH6 followed by BRAF mutation analysis ± MLH1 promoter methylation testing in cases showing MLH1 loss. A total of 3141 individual specimens were submitted for testing from 12 departments consisting of 3061 unique tumours and 2791 prospectively acquired patients with CRC. Defective mismatch repair (dMMR) was observed in 15% of cases. In cases showing MLH1 loss, 76% contained a detectable BRAF mutation and, of the remainder, 77% showed MLH1 promoter hypermethylation. Of the patients included in the final analysis, 81 (2.9%) had an indication for germline testing. CONCLUSION: LS screening using the NICE diagnostics guidance pathway is deliverable at scale identifying significant numbers of patients with dMMR. This information is used to refer patients to regional clinical genetics services in addition to informing treatment pathways including the use of adjuvant/neoadjuvant chemotherapy and immunotherapy.

Luminal Bioavailability of Orally Administered ω-3 PUFAs in the Distal Small Intestine, and Associated Changes to the Ileal Microbiome, in Humans with a Temporary Ileostomy.

BACKGROUND: Oral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut. OBJECTIVES: We investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum. METHODS: Ileostomy fluid (IF) and blood were obtained at baseline, after first capsule dosing (median 2 h), and at a similar time after final dosing on day 28, in 11 individuals (median age 63 y) with a temporary ileostomy. Fatty acids were measured by LC-tandem MS. The ileal microbiome was characterized by 16S rRNA PCR and Illumina sequencing. RESULTS: There was a mean 6.0 ± 9.8-fold and 6.6 ± 9.6-fold increase in ileal EPA and DHA concentrations (primary outcome), respectively, at 28 d, which was associated with increased RBC ω-3 PUFA content (P ≤ 0.05). The first oral dose did not increase the ileal ω-3 PUFA concentration except in 4 individuals, who displayed high luminal EPA and DHA concentrations, which reduced to concentrations similar to the overall study population at day 28, suggesting physiological adaptation. Bacteroides, Clostridium, and Streptococcus were abundant bacterial genera in the ileum. Ileal microbiome variability over time and between individuals was large, with no consistent change associated with acute ω-3 PUFA dosing. However, high concentrations of EPA and DHA in IF on day 28 were associated with higher abundance of Bacteroides (r2 > 0.86, P < 0.05) and reduced abundance of other genera, including Actinomyces (r2 > 0.94, P < 0.05). CONCLUSIONS: Oral administration of ω-3 PUFAs leads to increased luminal ω-3 PUFA concentrations and changes to the microbiome, in the ileum of individuals with a temporary ileostomy. This study is registered on the ISRCTN registry as ISRCTN14530452.

Health Disparities among Lesbian, Gay, Bisexual, and Transgender (LGBT) Adults in Nashville, Tennessee.

OBJECTIVES: Health disparities for lesbian, gay, bisexual, and transgender (LGBT) adults are well documented, but LGBT health data at the municipal and county levels are lacking, especially in the southern United States. The objective of this study was to compare access to care, health outcomes, and behavioral risk factors between LGBT and non-LGBT adults in Nashville and Davidson County, Tennessee. METHODS: Data for this study came from a randomly selected, population-based sample of LGBT (n = 128) and non-LGBT (n = 1583) adults in Nashville. Multivariable logistic regression models were used to compare health outcomes between LGBT and non-LGBT Nashvillians while adjusting for demographic characteristics and socioeconomic status. RESULTS: LGBT Nashvillians were more likely to be uninsured (odds ratio [OR] 3.96, 95% confidence interval [CI] 1.72-9.10), report unmet medical care needs because of cost (OR 2.20, 95% CI 1.14-4.25), exhibit worse mental health outcomes (eg, frequent mental distress; OR 4.53, 95% CI 2.33-8.80), and report high-risk behaviors for human immunodeficiency virus (OR 9.47, 95% CI 3.96-22.62) compared with non-LGBT Nashvillians. CONCLUSIONS: To achieve health equity for LGBT individuals at the municipal level, Nashville and Tennessee should consider multifaceted approaches to expanding health insurance coverage and nondiscrimination protections and address mental health and human immunodeficiency virus risks among vulnerable populations.

Human Germline Genome Editing.

With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input.

Calorie-Containing Recovery Drinks Increase Recreational Runners' Voluntary Energy and Carbohydrate Intake, with Minimal Impact on Fluid Recovery.

This study assessed voluntary dietary intake when different beverages were provided within a recovery area following recreational exercise. Participants completed two 10-km runs 1 week apart. Immediately after the first run, "beer drinkers" (n = 54; mean ± SD: age = 23.9 ± 5.8 years, body mass [BM] = 76 ± 13 kg) randomly received low-alcohol beer (Hahn Ultra® [Lion Co.], 0.9% alcohol by volume) or sports drink (SD; Gatorade® [PepsiCo]), whereas "nonbeer drinkers" (n = 78; age = 21.8 ± 2.2 years, BM = 71 ± 13 kg) received water or SD. Participants remained in a recovery area for 30-60 min with fluid consumption monitored. The following week, participants received the alternate beverage. Participants recorded all food/fluid consumed for the remainder of both trial days (diary and photographs). Fluid balance was assessed via BM change and urine specific gravity. Paired t tests were used to assess differences in hydration and dietary variables. No differences were observed in preexercise urine specific gravity (∼1.01) or BM loss (∼2%) between intervention groups (ps > .05). Water versus SD: No difference in acute fluid intake was noted (water = 751 ± 259 ml, SD = 805 ± 308 ml, p = .157). SD availability influenced total energy and carbohydrate intakes (water = 5.7 ± 2.5 MJ and 151 ± 77 g, SD = 6.5 ± 2.7 MJ and 187 ± 87 g, energy p = .002, carbohydrate p < .001). SD versus beer: SD availability resulted in greater acute fluid intake (SD = 1,047 ± 393 ml, beer = 850 ± 630 ml; p = .004), which remained evident at the end of trial days (SD = 3,337 ± 1,100 ml, beer = 2,982 ± 1,191 ml; p < .01). No differences in dietary variables were observed. Next day, urine specific gravity values were not different between water versus SD. However, a small difference was detected between SD versus beer (SD = 1.021 ± 0.009, beer = 1.016 ± 0.008, p = .002). Consuming calorie-containing drinks postexercise appears to increase daily energy and carbohydrate intake but has minimal impact on next-day hydration.

Aesthetic Medicine Nurses and Qualified Nonmedical Practitioners: Our Role and Requirements as Aesthetic Medicine Adapts to Worldwide Changes and Needs.

Aesthetic medicine nursing is a highly skilled specialty, which continues to evolve. A survey of 197 experienced aesthetic medicine nurses practicing in eight countries revealed shortcomings in the current approach to their education, training, and registration. Education and training are currently self-identified and self-funded and are often provided by the companies that manufacture or distribute the products used in aesthetic medicine treatments. Accreditation and registration schemes are not mandatory, and an international professional governing body is lacking to facilitate international cooperation and sharing of best practice. There is a need for an academic, coherent, and comprehensive approach to the training and education of aesthetic medicine nurses that will equip them with the knowledge and experience to not only administer treatments and attain natural looking results but also prevent, recognize, and manage any potential complications associated with such treatments.

A Nutrition Recovery Station Following Recreational Exercise Improves Fruit Consumption but Does Not Influence Fluid Recovery.

Immediate postexercise access to fruit/fluid via a recovery "station" is a common feature of mass participation sporting events. Yet little evidence exists examining their impact on subsequent dietary intake. The aim of this study was to determine if access to fruit/water/sports drinks within a recovery station significantly alters dietary and fluid intakes in the immediate postexercise period and influences hydration status the next morning. 127 (79 males) healthy participants (M ± SD, age = 22.5 ± 3.5y, body mass (BM) = 73 ± 13kg) completed two self-paced morning 10km runs separated by 1 week. Immediately following the first run, participants were randomly assigned to enter (or not) the recovery station for 30min. All participants completed the alternate recovery option the following week. Participants recorded BM before and after exercise and measured Urine Specific Gravity (USG) before running and again the following morning. For both trial days, participants also completed 24h food and fluid records via a food diary that included photographs. Paired-sample t tests were used to assess differences in hydration and dietary outcome variables (Recovery vs. No Recovery). No difference in preexercise USG or BM change from exercise were observed between treatments (p's > .05). Attending the recovery zone resulted in a greater total daily fluid (Recovery = 3.37 ± 1.46L, No Recovery = 3.16 ± 1.32L, p = .009) and fruit intake (Recovery = 2.37 ± 1.76 servings, No Recovery = 1.55 ± 1.61 servings, p > .001), but had no influence on daily total energy (Recovery = 10.15 ± 4.2MJ, No Recovery = 10.15 ± 3.9MJ), or macronutrient intakes (p > .05). Next morning USG values were not different between treatments (Recovery = 1.018 ± 0.007, No Recovery = 1.019 ± 0.009, p > .05). Recovery stations provide an opportunity to modify dietary intake which promote positive lifestyle behaviors in recreational athletes.

EUS-guided through the needle microbiopsy: a useful adjunct in the investigation of pancreatic cystic lesions.

OBJECTIVE: Endoscopic ultrasound-guided through-the-needle microbiopsy (EUS-TTNB) forceps is a recent development that facilitates sampling of the walls of pancreatic cystic lesions (PCL) for histological analysis. We aimed to assess the impact of EUS-TTNB and its influence on patient management in a tertiary pancreas centre. DESIGN: A prospective database of consecutive patients who underwent EUS-TTNB from March 2020 to August 2022 at a tertiary referral centre was retrospectively analysed. RESULTS: Thirty-four patients (22 women) were identified. Technical success was achieved in all cases. Adequate specimens for histological diagnosis were obtained in 25 (74%) cases. Overall, EUS-TTNB led to a change in management in 24 (71%) cases. Sixteen (47%) patients were downstaged, with 5 (15%) discharged from surveillance. Eight (24%) were upstaged, with 5 (15%) referred for surgical resection. In the 10 (29%) cases without change in management, 7 (21%) had confirmation of diagnosis with no change in surveillance, and 3 (9%) had insufficient biopsies on EUS-TTNB. Two (6%) patients developed post-procedural pancreatitis, and 1 (3%) developed peri-procedural intracystic bleeding with no subsequent clinical sequelae. CONCLUSION: EUS-TTNB permits histological confirmation of the nature of PCL, which can alter management outcomes. Care should be taken in patient selection and appropriately consented due to the adverse event rate.

Impact of FADS gene variation and dietary fatty acid exposure on biochemical and anthropomorphic phenotypes in a Hispanic/Latino cohort.

Introduction: Polyunsaturated fatty acids (PUFA) and highly unsaturated fatty acid (HUFA) synthetic products and their signaling metabolites play vital roles in immunity, inflammation, and brain development/function. Frequency differences of variants within the fatty acid desaturase (FADS) gene cluster affect levels of HUFAs, their biologically active products, and numerous physiological phenotypes. Fundamental questions remain regarding the impact of this genetic variation on the health of Hispanic/Latino populations. Methods: Data and biospecimens (plasma, red blood cells, buffy coat-derived DNA) from 135 participants (83.7% female) were used to assess the relationship(s) between dietary PUFA levels, a FADS haplotype tagging SNP, rs174537, and the capacity of Hispanic/Latino populations to generate HUFAs in plasma and RBC as well as its potential impact on anthropomorphic phenotypes. Results: The dietary habits of the cohort showed that participant diets contained a high ratio (9.3 ± 0.2, mean ± SEM) of linoleic acid (n-6) to alpha-linolenic acid (n-3) and also contained extremely low levels of n-3 HUFAs (eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA), both features of the Modern Western Diet. Compared to African and European American cohorts, the frequency of the TT rs174537 genotype was highly enriched (53% of subjects) in this Hispanic/Latino cohort and was strongly associated with lower circulating HUFA levels. For example, plasma levels of arachidonic acid (ARA: 20:4, n-6) and EPA (20:5, n-3) were 37% and 23%, respectively, lower in the TT versus the GG genotype. HUFA biosynthetic efficiency, as determined by metabolic product to precursor ratios, was highly dependent (p < 0.0001) on the rs174537 genotype (GG > GT > TT) for both circulating n-6 and n-3 HUFAs. In contrast, the RBC Omega-3 Index (EPA + DHA) was extremely low (2.89 ± 1.65, mean ± sd) in this population and independent of rs174537 genotype. Importantly, the rs174537 genotype was also related to female height with TT genotype participants being 4.5 cm shorter (p = 0.0001) than the GG + GT participants. Discussion: Taken together, this study illustrates that dietary PUFA + HUFA × FADS gene- interactions place a large proportion (>50%) of Hispanic/Latino populations at high risk of a deficiency in both circulating and cellular levels of n-3 HUFAs.

A retrospective study evaluating silver-impregnated dressings on cesarean wound healing.

OBJECTIVE: This retrospective study was designed to assess the effectiveness of silver-impregnated dressings in reducing postoperative wound care visits. DESIGN: A retrospective chart review of 72 patients was conducted to compare the effectiveness of silver-impregnated dressings with traditional wound dressings in reducing additional postoperative visits associated with surgical site infections (SSIs) in patients undergoing cesarean delivery: Prior to October 1, 2009, incisions of 36 women were covered with gauze pads. Subsequent to that date, Silverlon dressings (Cura Surgical, Geneva, Illinois) were applied to the wounds of the remaining 36 women. MAIN RESULTS: Two patients whose incisions were covered with a gauze pad and 2 patients who received the silver-impregnated dressings developed an SSI requiring additional wound care visits. Silver-impregnated dressings did not significantly reduce the rate of wound care-related postoperative visits, but the experimental group had a higher rate of comorbidities. CONCLUSIONS: Although there was no observed difference in the number of women requiring additional wound care visits, the significantly greater number of comorbidities noted in the silver-impregnated dressing group should have theoretically placed them at increased risk for SSIs and additional postoperative wound care visits, suggesting that silver-impregnated dressings may have more of a protective effect than is appreciated in this study. A randomized prospective study is planned to further assess its usefulness in decreasing the incidence of wound infections along with its potential benefits regarding wound appearance.

Neural Correlates of Positive Emotion Processing That Distinguish Healthy Youths at Familial Risk for Bipolar Versus Major Depressive Disorder.

OBJECTIVE: Familial risk for bipolar disorder (BD) or major depressive disorder (MDD) may lead to differential emotion processing signatures, resulting in unique neural vulnerability. METHOD: Healthy offspring of a parent with BD (n = 29, "BD-risk") or MDD (n = 44, "MDD-risk") and healthy control youths without any personal or family psychopathology (n = 28, "HC") aged 8 to 17 years (13.64 ± 2.59 years) completed an implicit emotion-perception functional magnetic resonance imaging task. Whole-brain voxelwise and psychophysiological interaction analyses examined neural differences in activation and connectivity during emotion processing. Regression modeling tested for neural associations with behavioral strengths and difficulties and conversion to psychopathology at follow-up (3.71 ± 1.91 years). RESULTS: BD-risk youth showed significantly reduced bilateral putamen activation, and decreased connectivity between the left putamen and the left ventral anterior cingulate cortex (vACC) and the right posterior cingulate cortex (PCC) during positive-valence emotion processing compared to MDD-risk and HC (Z >2.3; p <.001). Decreased left putamen-right PCC connectivity correlated with subsequent peer problems in BD-risk (ß = -2.90; p <.05) and MDD-risk (ß = -3.64; p < .05) groups. Decreased left (ß = -0.09; p < .05) and right putamen activation (ß = -0.07; p = .04) were associated with conversion to a mood or anxiety disorder in BD-risk youths. Decreased left putamen-right PCC connectivity was associated with a higher risk of conversion in BD-risk (HR = 8.28 , p < .01) and MDD-risk (HR = 2.31, p = .02) groups. CONCLUSION: Reduced putamen activation and connectivity during positive emotion processing appear to distinguish BD-risk youths from MDD-risk and HC youths, and may represent a marker of vulnerability.

Stay in treatment: Predicting dropout from pediatric weight management study protocol.

INTRODUCTION: Childhood obesity is a serious public health concern. Multidisciplinary pediatric weight management programs have been deemed effective. However, effectiveness of these programs is impacted by attrition, limiting health benefits to children, and inefficiently utilizing scarce resources. METHODS: We have developed a model (the Outcomes Forecasting System, OFS) that isolates variables associated with attrition from pediatric weight management, with the potential to forecast participant dropout. In Aim 1, we will increase the power and precision of the OFS and then validate the model through the consistent acquisition of key patient, family, and treatment data, from three different weight management sites. In Aim 2, external validity will be established through the application of the OFS at a fourth pediatric weight management program. Aim 3 will be a pilot clinical trial, incorporating an intervention built on the results of Aims 1 and 2 and utilizing the OFS to reduce attrition. DISCUSSION: A greater understanding of the patient, family, and disease-specific factors that predict dropout from pediatric weight management can be utilized to prevent attrition. The goal of the current study is to refine the OFS to a level of precision and efficiency to be a valuable tool to any weight management program. By identifying the most pertinent factors driving attrition across weight management sites, new avenues for treatment will be identified. This study will result in a valuable forecasting tool that will be applicable for diverse programs and populations, decrease program costs, and improve patient retention, adherence, and outcomes. CLINICALTRIALSGOV IDENTIFIER: NCT04364282.

Microbiome Analysis of More Than 2,000 NHS Bowel Cancer Screening Programme Samples Shows the Potential to Improve Screening Accuracy.

PURPOSE: There is potential for fecal microbiome profiling to improve colorectal cancer screening. This has been demonstrated by research studies, but it has not been quantified at scale using samples collected and processed routinely by a national screening program. EXPERIMENTAL DESIGN: Between 2016 and 2019, the largest of the NHS Bowel Cancer Screening Programme hubs prospectively collected processed guaiac fecal occult blood test (gFOBT) samples with subsequent colonoscopy outcomes: blood-negative [n = 491 (22%)]; colorectal cancer [n = 430 (19%)]; adenoma [n = 665 (30%)]; colonoscopy-normal [n = 300 (13%)]; nonneoplastic [n = 366 (16%)]. Samples were transported and stored at room temperature. DNA underwent 16S rRNA gene V4 amplicon sequencing. Taxonomic profiling was performed to provide features for classification via random forests (RF). RESULTS: Samples provided 16S amplicon-based microbial profiles, which confirmed previously described colorectal cancer-microbiome associations. Microbiome-based RF models showed potential as a first-tier screen, distinguishing colorectal cancer or neoplasm (colorectal cancer or adenoma) from blood-negative with AUC 0.86 (0.82-0.89) and AUC 0.78 (0.74-0.82), respectively. Microbiome-based models also showed potential as a second-tier screen, distinguishing from among gFOBT blood-positive samples, colorectal cancer or neoplasm from colonoscopy-normal with AUC 0.79 (0.74-0.83) and AUC 0.73 (0.68-0.77), respectively. Models remained robust when restricted to 15 taxa, and performed similarly during external validation with metagenomic datasets. CONCLUSIONS: Microbiome features can be assessed using gFOBT samples collected and processed routinely by a national colorectal cancer screening program to improve accuracy as a first- or second-tier screen. The models required as few as 15 taxa, raising the potential of an inexpensive qPCR test. This could reduce the number of colonoscopies in countries that use fecal occult blood test screening.

The colorectal cancer-associated faecal microbiome of developing countries resembles that of developed countries.

BACKGROUND: The incidence of colorectal cancer (CRC) is increasing in developing countries, yet limited research on the CRC- associated microbiota has been conducted in these areas, in part due to scarce resources, facilities, and the difficulty of fresh or frozen stool storage/transport. Here, we aimed (1) to establish a broad representation of diverse developing countries (Argentina, Chile, India, and Vietnam); (2) to validate a 'resource-light' sample-collection protocol translatable in these settings using guaiac faecal occult blood test (gFOBT) cards stored and, importantly, shipped internationally at room temperature; (3) to perform initial profiling of the collective CRC-associated microbiome of these developing countries; and (4) to compare this quantitatively with established CRC biomarkers from developed countries. METHODS: We assessed the effect of international storage and transport at room temperature by replicating gFOBT from five UK volunteers, storing two in the UK, and sending replicates to institutes in the four countries. Next, to determine the effect of prolonged UK storage, DNA extraction replicates for a subset of samples were performed up to 252 days apart. To profile the CRC-associated microbiome of developing countries, gFOBT were collected from 41 treatment-naïve CRC patients and 40 non-CRC controls from across the four institutes, and V4 16S rRNA gene sequencing was performed. Finally, we constructed a random forest (RF) model that was trained and tested against existing datasets from developed countries. RESULTS: The microbiome was stably assayed when samples were stored/transported at room temperature and after prolonged UK storage. Large-scale microbiome structure was separated by country and continent, with a smaller effect from CRC. Importantly, the RF model performed similarly to models trained using external datasets and identified similar taxa of importance (Parvimonas, Peptostreptococcus, Fusobacterium, Alistipes, and Escherichia). CONCLUSIONS: This study demonstrates that gFOBT, stored and transported at room temperature, represents a suitable method of faecal sample collection for amplicon-based microbiome biomarkers in developing countries and suggests a CRC-faecal microbiome association that is consistent between developed and developing countries.

Simulated management of inferior vena cava injury during robotic paraaortic lymphadenectomy utilizing the porcine model.

Injury of the inferior vena cava is an infrequent but serious complication of paraaortic lymphadenectomy. Training in the management of this injury might be enhanced through animate simulation. Our objective was to assess a simulated animal model for training in intraoperative management of inferior vena cava injury in the context of robotic paraaortic lymphadenectomy. We used a female domestic pig to create an injury of the inferior vena cava, which was then managed two ways with robotically assisted surgery. Edited videos of the two models were assessed by 32 senior learners and 23 attending faculty. The assessments included key competencies and domains of fidelity. A scale of poor, fair, or good was utilized. The injury and management simulated those seen in humans, both anatomically and surgically, although deficiencies were noted. Specifically, a reduced rapidity of bleeding and a related greater ease of control contributed to lower ratings for some aspects of fidelity. Fidelity and addressing the key competency of suture repair also received some lower ratings, particularly from vascular surgeons and their trainees. The porcine model for simulation of inferior vena cava injury during robotically assisted paraaortic lymphadenectomy may be useful for training purposes.

Detecting direct oral anticoagulants in trauma patients using liquid chromatography-mass spectrometry: A novel approach to medication reconciliation.

BACKGROUND: Accurate medication reconciliation in trauma patients is essential but difficult. Currently, there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS)-based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival. METHODS: Plasma samples were collected from 356 patients who provided informed consent including 10 healthy controls, 19 known positive or negative controls, and 327 trauma patients older than 65 years who were evaluated at our large, urban level 1 trauma center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban, and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage were compared with LCMS results to determine overall accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the assay. RESULTS: Of 356 patients, 39 (10.96%) were on DOACs: 21 were on apixaban, 14 on rivaroxaban, and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.05% (PPV, 92.50%; NPV, 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.10% (PPV, 86.36%; NPV 99.40%). There were three false-positive results and two false-negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity. CONCLUSION: This LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients. LEVEL OF EVIDENCE: Diagnostic Test, level III.

Effects of overwintering temperatures on the escape response in cunner (Tautogolabrus adspersus).

Cunner (Tautogolabrus adspersus) are a temperate labrid species that inhabit the Western Atlantic and experience temperatures ranging from 0°C to 25°C. During autumn, once temperatures drop below 10°C in Long Island Sound, cunner find shelter and enter a state of quiescence. Previous work has shown that acclimation to low temperatures limits the performance of locomotor musculature, which significantly lowers steady swimming capabilities. We aimed to understand how the escape response (C-start) might be impacted by temperatures experienced by cunner in Long Island Sound over the course of a year. Escape responses were recorded at 250 frames/s at 20°C, 15°C, 10°C, and 5°C. Average peak velocities and accelerations were faster in fish acclimated to 20°C than to 5°C and 10°C. Despite taking a similar turn angle to 10°C and 15°C fish, the 5°C treatment group took longer to complete the C-start, which might make them more susceptible to predation at this temperature. Based on these results it appears that the escape response is reduced at cold temperatures. Previous research has shown that locomotor musculature performance is significantly reduced at cold temperatures, which could explain the results seen here. The decrease in escape performance at cold temperatures could explain their state of extended torpor as the slowed C-start at these cold temperatures might make them more susceptible to predation.