Malnourished Microbes: Host-Microbiome Interactions in Child Undernutrition.

Childhood undernutrition is a major global health burden that is only partially resolved by nutritional interventions. Both chronic and acute forms of child undernutrition are characterized by derangements in multiple biological systems including metabolism, immunity, and endocrine systems. A growing body of evidence supports a role of the gut microbiome in mediating these pathways influencing early life growth. Observational studies report alterations in the gut microbiome of undernourished children, while preclinical studies suggest that this can trigger intestinal enteropathy, alter host metabolism, and disrupt immune-mediated resistance against enteropathogens, each of which contribute to poor early life growth. Here, we compile evidence from preclinical and clinical studies and describe the emerging pathophysiological pathways by which the early life gut microbiome influences host metabolism, immunity, intestinal function, endocrine regulation, and other pathways contributing to child undernutrition. We discuss emerging microbiome-directed therapies and consider future research directions to identify and target microbiome-sensitive pathways in child undernutrition.

Stromal composition predicts recurrence of early rectal cancer after local excision.

AIMS: After local excision of early rectal cancer, definitive lymph node status is not available. An alternative means for accurate assessment of recurrence risk is required to determine the most appropriate subsequent management. Currently used measures are suboptimal. We assess three measures of tumour stromal content to determine their predictive value after local excision in a well-characterised cohort of rectal cancer patients without prior radiotherapy. METHODS AND RESULTS: A total of 143 patients were included. Haematoxylin and eosin (H&E) sections were scanned for (i) deep neural network (DNN, a machine-learning algorithm) tumour segmentation into compartments including desmoplastic stroma and inflamed stroma; and (ii) digital assessment of tumour stromal fraction (TSR) and optical DNA ploidy analysis. 3' mRNA sequencing was performed to obtain gene expression data from which stromal and immune scores were calculated using the ESTIMATE method. Full results were available for 139 samples and compared with disease-free survival. All three methods were prognostic. Most strongly predictive was a DNN-determined ratio of desmoplastic to inflamed stroma >5.41 (P < 0.0001). A ratio of ESTIMATE stromal to immune score <1.19 was also predictive of disease-free survival (P = 0.00051), as was stromal fraction >36.5% (P = 0.037). CONCLUSIONS: The DNN-determined ratio of desmoplastic to inflamed ratio is a novel and powerful predictor of disease recurrence in locally excised early rectal cancer. It can be assessed on a single H&E section, so could be applied in routine clinical practice to improve the prognostic information available to patients and clinicians to inform the decision concerning further management.

Local excision after (near) complete response of rectal cancer to neoadjuvant radiation: does it add value?

PURPOSE: Neoadjuvant radiotherapy is commonly used in rectal cancer. When used prior to radical surgery in locally advanced disease, up to one-quarter of patients have no residual cancer at surgery suggesting that radical surgery was unnecessary; those with complete clinical response may be managed on a rectal-preserving 'watch-and-wait' pathway. In those receiving radiotherapy for early stage cancer, local excision of small volume residual or recurrent tumour is possible, but its value is unclear. METHODS: Data were collected from two institutions (UK and Denmark) which maintain prospective databases on all patients undergoing local excision by transanal endoscopic microsurgery (TEM). The study group was all patients who had TEM after neoadjuvant radiation for rectal cancer over an 11-year period. RESULTS: Forty-five patients had TEM after neoadjuvant radiation, 18 after short course radiotherapy (SCRT) and 27 after chemoradiotherapy (CRT). Local recurrence occurred in 13 (29%) and distant metastases in 11 (24%). Complete pathological response was noted in 10 (22%), 28% after SCRT and 19% after CRT, p = 0.02. However, local recurrence still occurred in 60% of those with ypT0 after SCRT. The recurrence rate may be higher in those with residual disease at TEM compared with complete responders (40 vs 30%). CONCLUSION: If complete response can be determined clinically, local excision of the scar does not confer benefit, but follow-up should be maintained. If there is regrowth or residual tumour at TEM, further recurrence is common, and the benefits of TEM may not outweigh the risks, except in those unsuitable for radical surgery.

Local excision after polypectomy for rectal polyp cancer: when is it worthwhile?

AIM: The optimal management of a polyp cancer that has been removed endoscopically is unclear. Further local excision is often advocated to remove the polyp stalk or scar or to ensure clear margins, but the benefit of this is unclear. The aim of this paper is to determine whether the indications for further local excision can be better defined. METHOD: Data were collected from two institutions (in UK and Denmark) which maintain prospective databases to collect information on all patients undergoing transanal endoscopic microsurgery (TEM). The study group was all patients who had a TEM after macroscopically complete polypectomy for rectal cancer. Data covering an 11-year period were analysed. RESULTS: Sixty three patients had TEM with no residual cancer after macroscopically complete polypectomy. Residual adenoma was found in 23 (37%). A postpolypectomy endoscopy had not detected the residual adenoma in three. Malignant local recurrence occurred in five patients (8%) and distant metastases in another two (3%). Recurrence occurred in 4/23 (17%) when there was residual adenoma in the TEM specimen and in 3/40 (7.5%) where there was scar only, although this did not reach significance. In two instances recurrence was around 10 years after TEM. Those with residual adenoma at TEM tended to have poorer survival. CONCLUSION: Further local excision often reveals no residual cancer despite microscopically involved polypectomy margins. Careful endoscopy is required to assess the polypectomy site as residual tumour can be missed. In the absence of residual adenoma, TEM does not appear to be of benefit, although a small risk of recurrence exists.

Impact of Suture Type on Erosion Rate After Laparoscopic Ventral Mesh Rectopexy: A Case-Matched Study.

BACKGROUND: There has been increasing concern and scrutiny in the use of mesh for certain pelvic organ prolapse procedures. However, mesh erosion was often associated with sites of suture fixation of the mesh to the rectum or vagina. Thus, in response to this finding, we replaced our suture material with absorbable monofilament suture. OBJECTIVE: The purpose of this study was to compare the rates of mesh-related complications after laparoscopic ventral mesh rectopexy, according to the type of suture used in fixation of mesh. DESIGN: This was retrospective cohort study. SETTINGS: This study was performed at a high-volume, tertiary care center. It was conducted using a prospective database including patients who underwent laparoscopic ventral mesh rectopexy over a 7-year period. PATIENTS: A total of 495 cases were included; 296 (60%) laparoscopic ventral mesh rectopexies were performed using a nonabsorbable suture compared with 199 (40%) with an absorbable suture in a case-matched analysis. In addition, 151 cases of laparoscopic ventral mesh rectopexy with nonabsorbable were matched based on age, sex, and time of follow-up, with an equal number of patients using absorbable monofilament suture. MAIN OUTCOMES MEASURES: Primary outcome was symptomatic mesh erosion after rectopexy. Secondary outcomes included other mesh-related complications and/or reoperations. RESULTS: The erosion rate was 2% (6/495) in the nonabsorbable suture group, including 4 erosions into the rectum and 2 into the vagina. There was no erosion in the group with absorbable suture. This difference was maintained after matching: after a median follow-up of 6 (12) months, there was no erosion in the absorbable suture group versus 3.3% erosion (n = 5) in the nonabsorbable suture group (p = 0.03). LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: Mesh-related complications are reduced using absorbable sutures compared with nonabsorbable sutures when performing laparoscopic ventral mesh rectopexy with synthetic mesh without an increase in rectopexy failures. See Video Abstract at http://links.lww.com/DCR/B49. IMPACTO DEL TIPO DE SUTURA EN LA TASA DE EROSIóN DESPUéS DE LA RECTOPEXIA VENTRAL LAPAROSCóPICA CON MALLA: UN ESTUDIO DE CASOS EMPAREJADOS: Ha habido una creciente preocupación y escrutinio en el uso de la malla para ciertos procedimientos de prolapso de órganos pélvicos. Sin embargo, la erosión de la malla a menudo se asoció con sitios de fijación de sutura de la malla al recto o la vagina. Por lo tanto, en respuesta a este hallazgo, reemplazamos nuestro material de sutura con sutura de monofilamento absorbible.Comparar las tasas de complicaciones relacionadas con la malla después de la rectopexia laparoscópica de malla ventral, de acuerdo al tipo de sutura utilizada en la fijación de la malla.Este fue un estudio de cohorte retrospectivo.Este estudio se realizó en un centro de atención de tercer nivel de alto volumen. Se realizó utilizando una base de datos prospectiva que incluía pacientes que se sometieron a una rectopexia de malla ventral laparoscópica durante un período de 7 años.Se incluyeron un total de 495 casos; 296 (60%) rectopexias de malla ventral laparoscópica utilizando una sutura no reabsorbible en comparación con 199 (40%) con una sutura absorbible en un análisis de casos emparejados. Además, 151 casos de rectopexia ventral laparoscópica con malla no absorbible se emparejaron según la edad, el sexo y el tiempo de seguimiento con un número igual de pacientes que usaban sutura de monofilamento absorbible.La medida de resultado primaria fue la erosión sintomática de la malla después de la rectopexia. La medida de resultado secundarias incluyeron otras complicaciones y/o reoperaciones relacionadas con la malla.La tasa de erosión fue del 2% (6/495) en el grupo de sutura no absorbible; 4 erosiones en el recto y 2 en la vagina. No hubo erosión en el grupo con sutura absorbible. Esta diferencia se mantuvo después del emparejamiento: después de una mediana de seguimiento de 6 (12) meses, no hubo erosión en el grupo de sutura absorbible versus 3.3% de erosión (n = 5) en el grupo de sutura no absorbible (p = 0.03).Este estudio estuvo limitado por su diseño retrospectivo.Las complicaciones relacionadas con la malla se reducen utilizando suturas absorbibles en comparación con las suturas no absorbibles cuando se realiza la rectopexia de malla ventral laparoscópica con malla sintética, sin un aumento en los fracasos de rectopexia. Vea el Resumen del Video en http://links.lww.com/DCR/B49.

The Application of Bacteriophage Diagnostics for Bacterial Pathogens in the Agricultural Supply Chain: From Farm-to-Fork.

Bacteriophages (phages) have great potential not only as therapeutics but as diagnostics. Indeed, they have been developed and used to diagnose and detect bacterial infections, primarily in human clinical settings. The ability to rapidly detect and control bacterial pathogens in agriculture is of primary importance to maintain food security, improve animal health, and prevent the passage of zoonotic pathogens into the human population. Culture-based detection methods are often labor-intensive, and require further confirmatory tests, increasing costs and processing times needed for diagnostics. Molecular detection methods such as polymerase chain reaction are commonly used to determine the safety of food, however, a major drawback is their inability to differentiate between viable and nonviable bacterial pathogens in food. Phage diagnostics have been proven to be rapid, capable of identifying viable pathogens and do not require cultivation to detect bacteria. Phage detection takes advantage of the specificity of interaction between phage and their hosts. Furthermore, phage detection is cost effective, which is vitally important in agricultural supply chains where there is a drive to keep costs down to ensure that the cost of food does not increase. The full potential of phage detection/diagnostics is not wholly realized or commercialized. This review explores the current use and potential future scope of phage diagnostics and their application to various bacterial pathogens across agriculture and food supply chains.

Quality of life after rectal-preserving treatment of rectal cancer.

AIM: Rectal-preserving strategies for managing rectal cancer are becoming more common for selected groups of patients. Oncological outcomes are similar, so long as patients are closely followed, and any local recurrence detected and managed promptly. Functional outcomes are now of increasing importance so patients can be appropriately counselled prior to treatment. We examine functional outcomes in patients managed by multimodal organ-preservation approaches allowing comparison of the full range of strategies. MATERIALS AND METHODS: Patients attending for surveillance after any of four rectal-preserving treatments for rectal cancer (radiotherapy [RT], local excision [LE], RT then LE or LE then RT) were asked to complete a questionnaire assessing general quality of life and bowel, urinary and sexual function. RESULTS: 100 patients completed questionnaires: 34 managed by neoadjuvant RT followed by 'watch and wait', 40 by LE, and 26 who had composite treatment (18 LE + RT and eight RT + LE). Questionnaires were completed a median of 10 months (IQ range 6-33) following treatment. The LE only group tended to have better bowel function, while the composite groups fared worse; significant differences were noted in LARS and some bowel symptoms scores. CONCLUSION: Bowel function appears better after LE alone compared with treatment strategies involving RT, and composite treatments have an additive effect on outcome impairment. Overall quality of life outcomes are good, despite the ongoing requirement for surveillance. As these treatments become more common it is important that patients can be better informed before deciding on a management pathway.

A new family of uncultivated bacteria involved in methanogenesis from the ubiquitous osmolyte glycine betaine in coastal saltmarsh sediments.

BACKGROUND: Coastal environments are dynamic and rapidly changing. Living organisms in coastal environments are known to synthesise large quantities of organic osmolytes, which they use to cope with osmotic stresses. The organic osmolyte glycine betaine (GBT) is ubiquitously found in marine biota from prokaryotic Bacteria and Archaea to coastal plants, marine protozoa, and mammals. In intertidal coastal sediment, GBT represents an important precursor of natural methane emissions and as much as 90% of total methane production in these ecosystems can be originated from methanogenesis from GBT and its intermediate trimethylamine through microbial metabolism. RESULTS: We set out to uncover the microorganisms responsible for methanogenesis from GBT using stable isotope labelling and metagenomics. This led to the recovery of a near-complete genome (2.3 Mbp) of a novel clostridial bacterium involved in anaerobic GBT degradation. Phylogenetic analyses of 16S rRNA gene, functional marker genes, and comparative genomics analyses all support the establishment of a novel family Candidatus 'Betainaceae' fam. nov. in Clostridiales and its role in GBT metabolism. CONCLUSIONS: Our comparative genomes and metagenomics analyses suggest that this bacterium is widely distributed in coastal salt marshes, marine sediments, and deep subsurface sediments, suggesting a key role of anaerobic GBT metabolism by this clostridial bacterium in these ecosystems.

Outcomes following completion and salvage surgery for early rectal cancer: A systematic review.

OBJECTIVES: To establish outcomes after completion and salvage surgery following local excision in literature published since 2005, to inform decision-making when offering local excision. BACKGROUND: Local excision of early rectal cancer aims to offer cure while maintaining quality of life through organ preservation. However, some patients will require radical surgery, prompted by unexpected poor pathology or local recurrence. Consistent definition and reporting of these scenarios is poor. We propose the term "salvage surgery" for recurrence after local excision and "completion surgery" for poor pathology. METHODS: Electronic databases were searched in February 2016. Studies since 2005 describing outcomes for radical surgery following local excision of rectal cancer were included. Pooled and average values were obtained. RESULTS: A total of 23 studies included 262 completion and 165 salvage operations. Most completion operations were done within 4 weeks; local recurrence rate was 5% and overall disease recurrence rate was 14%. The majority of salvage operations for local recurrence were within 15 months of local excision, often following adjuvant treatment. Re-do local excision was used in 15%; APR was the most common radical procedure. Further local recurrence was uncommon (3%) but overall disease recurrence rate was 13%. Estimated 5-year survival was in the order of 50%. Heterogeneity was high among the studies. CONCLUSIONS: Patients undergoing local excision must be informed of risks and expected outcomes, but better data on completion and salvage surgery are required to achieve this. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42014014758.