Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains.

Clostridium perfringens is an anaerobic toxin-producing bacterium associated with intestinal diseases, particularly in neonatal humans and animals. Infant gut microbiome studies have recently indicated a link between C. perfringens and the preterm infant disease necrotizing enterocolitis (NEC), with specific NEC cases associated with overabundant C. perfringens termed C. perfringens-associated NEC (CPA-NEC). In the present study, we carried out whole-genome sequencing of 272 C. perfringens isolates from 70 infants across 5 hospitals in the United Kingdom. In this retrospective analysis, we performed in-depth genomic analyses (virulence profiling, strain tracking and plasmid analysis) and experimentally characterized pathogenic traits of 31 strains, including 4 from CPA-NEC patients. We found that the gene encoding toxin perfringolysin O, pfoA, was largely deficient in a human-derived hypovirulent lineage, as well as certain colonization factors, in contrast to typical pfoA-encoding virulent lineages. We determined that infant-associated pfoA+ strains caused significantly more cellular damage than pfoA- strains in vitro, and further confirmed this virulence trait in vivo using an oral-challenge C57BL/6 murine model. These findings suggest both the importance of pfoA+ C. perfringens as a gut pathogen in preterm infants and areas for further investigation, including potential intervention and therapeutic strategies.

Bifidobacterium bacteraemia is rare with routine probiotics use in preterm infants: A further case report with literature review.

Prophylactic administration of oral probiotics is associated with significant reductions in the morbidity and mortality of necrotising enterocolitis in preterm infants. We document the first case of Bifidobacterium longum subsp. infantis sub-clinical bacteraemia, in an extremely low birth weight preterm infant, since introduction of routine probiotic treatment at the Norfolk and Norwich University Hospital 10 years ago. Whole genome comparisons confirmed the isolated strain likely originated from the probiotic product.

Complicaciones posquirúrgicas en un programa de cribado poblacional de cáncer colorrectal: incidencia y factores asociados / Surgical complications in a population-based colorectal cancer screening program: Incidence and associated factors

Introducción: Los programas de cribado de cáncer colorrectal (CCR) producen riesgos, entre ellos los derivados de las cirugías colorrectales. El objetivo de este análisis es evaluar las complicaciones asociadas a la cirugía. Pacientes y métodos: Análisis retrospectivo de los pacientes que requirieron cirugía colorrectal dentro del programa poblacional de cribado de CCR de Galicia (mayo de 2013-junio de 2019). Analizamos la indicación de la cirugía y la tasa de complicaciones intrahospitalarias (levesI-II, gravesIII-V, clasificación Clavien-Dindo) y al alta. Determinamos mediante un análisis multivariante las variables asociadas a su aparición. Resultados: En el periodo analizado, 1.092 pacientes fueron intervenidos (lesión benigna 16,5%, CCR pT1 18,2%, resto CCR 64,6%), por vía laparoscópica en el 69,8% de los casos. Se detectaron complicaciones intrahospitalarias en el 19,2% de los pacientes (leves: 13,4%; graves: 5,9%; fallecimientos: 0,2%) y al alta en 159 (14,6%) pacientes. El sexo masculino se asoció a las complicaciones intrahospitalarias (OR: 2,0; IC95%: 1,3-3,0). Las variables asociadas a las complicaciones graves fueron: sexo masculino (OR: 2,6; IC95%: 1,2-5,5), hospital terciario (OR: 0,5; IC95%: 0,2-0,9) y ECOGI (OR: 0,2; IC95%: 0,05-0,6). Los factores asociados a las complicaciones tras el alta fueron edad ≥60años (OR: 1,5; IC95%: 1,0-2,3), la ubicación rectal (OR: 1,6; IC95%: 1,1-2,3) y complicaciones intrahospitalarias (OR: 2,2; IC95%: 1,5-3,2). Conclusiones: La cirugía es la principal causa de morbimortalidad asociada a un programa de cribado de CCR. Estos resultados deben ser tenidos en cuenta en la toma de decisiones en lesiones candidatas a resección endoscópica.(AU)

Introduction: Colorectal cancer (CRC) screening programs produce risks, including those derived from colorectal surgeries. The objective of this analysis is to evaluate the complications associated with the surgery. Patients and methods: Retrospective analysis including patients who required colorectal surgery within the population-based CRC screening program in Galicia (May 2013-June 2019). We analyzed the indication for surgery and the rate of in-hospital (mildI-II, severeIII-V, Clavien-Dindo classification) and at discharge complications. We performed a multivariate analysis to determine the variables independently associated. Results: In the analyzed period, 1092 patients underwent surgery (benign lesion 16.5%, pT1 CRC 18.2%, rest of CRC 64.6%) laparoscopic approach in 69.8% of the cases. In-hospital complications were detected in 19.2% of patients (mild: 13.4%; severe: 5.9%; deaths: 0.2%) and at discharge in 159 (14.6%) patients. Male sex was associated with in-hospital complications (OR: 2.0; 95%CI: 1.3-3.0). The variables associated with severe complications were: male sex (OR: 2.6; 95%CI: 1.2-5.5), tertiary hospital (OR: 0.5; 95%CI: 0.2-0.9) and ECOGI (OR: 0.2; 95%CI: 0.05-0.6). The factors associated with complications after discharge were age ≥60years (OR: 1.5; 95%CI: 1.0-2.3), rectal location (OR: 1.6; 95%CI: 1.1-2.3) and in-hospital complications (OR: 2.2; 95%CI: 1.5-3.2). Conclusions: Surgery is the main cause of morbidity and mortality associated with a CRC screening program. These results must be taken into account in the decision making of lesions that are candidates for endoscopic resection.(AU)

Surgical complications in a population-based colorectal cancer screening program: Incidence and associated factors. / Complicaciones posquirúrgicas en un programa de cribado poblacional de cáncer colorrectal: incidencia y factores asociados.

INTRODUCTION: Colorectal cancer (CRC) screening programs produce risks, including those derived from colorectal surgeries. The objective of this analysis is to evaluate the complications associated with the surgery. PATIENTS AND METHODS: Retrospective analysis including patients who required colorectal surgery within the population-based CRC screening program in Galicia (May 2013-June 2019). We analyzed the indication for surgery and the rate of in-hospital (mildI-II, severeIII-V, Clavien-Dindo classification) and at discharge complications. We performed a multivariate analysis to determine the variables independently associated. RESULTS: In the analyzed period, 1092 patients underwent surgery (benign lesion 16.5%, pT1 CRC 18.2%, rest of CRC 64.6%) laparoscopic approach in 69.8% of the cases. In-hospital complications were detected in 19.2% of patients (mild: 13.4%; severe: 5.9%; deaths: 0.2%) and at discharge in 159 (14.6%) patients. Male sex was associated with in-hospital complications (OR: 2.0; 95%CI: 1.3-3.0). The variables associated with severe complications were: male sex (OR: 2.6; 95%CI: 1.2-5.5), tertiary hospital (OR: 0.5; 95%CI: 0.2-0.9) and ECOGI (OR: 0.2; 95%CI: 0.05-0.6). The factors associated with complications after discharge were age ≥60years (OR: 1.5; 95%CI: 1.0-2.3), rectal location (OR: 1.6; 95%CI: 1.1-2.3) and in-hospital complications (OR: 2.2; 95%CI: 1.5-3.2). CONCLUSIONS: Surgery is the main cause of morbidity and mortality associated with a CRC screening program. These results must be taken into account in the decision making of lesions that are candidates for endoscopic resection.

Overtreatment in nonmalignant lesions detected in a colorectal cancer screening program: a retrospective cohort study.

BACKGROUND: Although colorectal cancer (CRC) screening programs reduce CRC incidence and mortality, they are associated with risks in healthy subjects. However, the risk of overtreatment and overdiagnosis has not been determined yet. The aim of this study was to report the surgery rates in patients with nonmalignant lesions detected within the first round of a fecal immunochemical test (FIT) based CRC screening program and the factors associated with it. METHODS: We included in this analysis all patients with nonmalignant lesions detected between May 2013 and June 2019 in the Galician (Spain) CRC screening program. We calculated surgery rate according to demographic variables, the risk classification according to the colonoscopy findings (European guidelines for quality assurance), the endoscopist's adenoma detection rate (ADR) classified into quartiles and the hospital's complexity level. We determined which variables were independently associated with surgery rate and expressed the association as Odds Ratio and its 95% confidence interval (CI). RESULTS: We included 15,707 patients in the analysis with high (19.9%), intermediate (26.9%) low risk (23.3%) adenomas and normal colonoscopy (29.9%) detected in the analyzed period. Colorectal surgery was performed in 162 patients (1.03, 95% CI 0.87-1.19), due to colonoscopy complications (0.02, 95% CI 0.00-0.05) and resection of colorectal benign lesions (1.00, 95% CI 0.85-1.16). Median hospital stay was 6 days with 17.3% patients developing minor complications, 7.4% major complications and one death. After discharge, complications developed in 18.4% patients. In benign lesions, an endoscopic resection was performed in 25.4% and a residual premalignant lesion was detected in 89.9%. The variables independently associated with surgery in the multivariable analysis were age (≥60 years = 1.57, 95% CI 1.11-2.23), sex (female = 2.10, 95% CI 1.52-2.91), the European guidelines classification (high risk = 67.94, 95% CI 24.87-185.59; intermediate risk = 5.63, 95% CI 1.89-16.80; low risk = 1.43; 95% CI 0.36-5.75), the endoscopist's ADR (Q4 = 0.44, 95% CI 0.28-0.68; Q3 = 0.44, 95% CI 0.27-0.71; Q2 = 0.71, 95% CI 0.44-1.14) and the hospital (tertiary = 0.54, 95% CI 0.38-0.79). CONCLUSIONS: In a CRC screening program, the surgery rate and the associated complications in patients with nonmalignant lesions are low, and related to age, sex, endoscopic findings, endoscopist's ADR and the hospital's complexity.

pT1 Colorectal Cancer Detected in a Colorectal Cancer Mass Screening Program: Treatment and Factors Associated with Residual and Extraluminal Disease.

The aim of this study is to describe the treatment of pT1 colorectal cancer (CRC) in a mass screening program, the surgery-related complications and the factors associated with residual disease after endoscopic resection and extraluminal disease after surgery. We included in this retrospective analysis all the pT1 CRC detected in the Galician CRC screening program between May 2013 and June 2019. We determined which variables were independently associated with the outcomes of the study through a multivariable logistic regression analysis. We included 370-354 pT1 N0(X), 16 pT1N1- out of the 971 CRC detected; 277 (74.9%) were resected endoscopically and 162 (43.8%) were not referred to surgery. There were surgical complications in 30.7% and 16.3% of the patients during hospitalization and after discharge. Residual disease was detected in 12 (4.3%) after endoscopic resection and extraluminal disease in 18 (8.6%) patients after surgery. The variables independently associated with initial endoscopic resection were a pedunculated morphology (OR 33.1, 95% CI 4.3-254), a diameter ≥ 20 mm (OR 3.94, 95% CI 1.39-11.18) and a Site-Morphology-Size-Access score < 9 (OR 428, 95% CI 42-4263). The variables related with surgery rescue were a piecemeal resection (OR 4.48, 95% CI 1.48-13.6), an infiltrated/nonevaluable resection border (OR 7.44, 95% CI 2.12-26.0), a non-well-differentiated histology (OR 4.76, 95% CI 1.07-20.0), vascular infiltration (OR 8.24, 95% CI 2.72-25.0) and a Haggitt 4 infiltration of the submucosa (OR 5.68, 95% CI 2.62-12.3). Residual disease after endoscopic resection was associated with an infiltrated/nonevaluable resection border (OR 34.9, 95% CI 4.08-298), a non-well-differentiated histology (OR 6.67, 95% CI 1.05-50.0), and the vascular infiltration of the submucosa (OR 7.61, 95% CI 1.55-37.4). The variables related with extraluminal disease after surgical resection were no endoscopic resection (OR 4.34, 95% CI 1.26-14.28), a non-well-differentiated histology (OR 4.35, 95% CI 1.39-14.29) and the lymphatic infiltration of the submucosa (OR 4.8, 95% CI 1.32-17.8). In a CRC screening program, although most of pT1 CRC are candidates for endoscopic treatment, surgery is a safe procedure. We have defined some easy to evaluate variables that can be used in the decision-making process.