Nonoperative management protocol for locally advanced rectal cancer.

AIM: The standard treatment for low rectal cancer is preoperative chemoradiotherapy followed by surgery with low anterior resection with diverting ileostomy or abdominoperineal resection, both of which have significant long-term effects on bowel and sexual function. Due to the high morbidity of surgery, there has been increasing interest in nonoperative management for low rectal cancer. The aim of this work is to conduct a pan-Canadian Phase II trial assessing the safety of nonoperative management for low rectal cancer. METHOD: Patients with Stage II or III low rectal cancer completing chemoradiotherapy according to standard of care at participating centres will be assessed for complete clinical response 8-14 weeks following completion of chemoradiotherapy. Subjects achieving a clinical complete response will undergo active surveillance including endoscopy, imaging and bloodwork at regular intervals for 24 months. The primary outcome will be the rate of local regrowth 2 years after chemoradiotherapy. Nonoperative management will be considered safe (i.e. as effective as surgery to achieve local control) if the rate of local regrowth is ≤30% and surgical salvage is possible for all local regrowths. Secondary outcomes will include disease-free and overall survival. CONCLUSION: The results will be highly clinically relevant, as it is expected that nonoperative management will be safe and lead to widespread adoption of nonoperative management in Canada. This change in practice has the potential to decrease the number of patients requiring surgery and the costs associated with surgery and long-term surgical morbidity.

Diverticulitis: A Review of Current and Emerging Practice-Changing Evidence.

Acute diverticulitis represents a common colorectal emergency seen in the Western world. Over time, management of this condition has evolved. This review aims to highlight recent evidence and update current recommendations. Notable evidence has emerged in certain aspects of diverticulitis. This includes disease pathogenesis, as emerging data suggest a potentially greater role for the microbiome and genetic predisposition than previously thought. Acute management has also seen major shifts, where traditional antibiotic treatment may no longer be necessary for acute uncomplicated diverticulitis. Following successful medical management of acute diverticulitis, indications for elective sigmoidectomy have decreased. The benefit of emergency surgery remains for peritonitis, sepsis, obstruction, and acute diverticulitis in certain immunocompromised patients. Routine colonoscopy, once recommended after all acute diverticulitis episodes, has been shown to be beneficial for cancer exclusion in a distinct patient population. Despite advances in research, certain entities remain poorly understood, such as smoldering diverticulitis and symptomatic uncomplicated diverticular disease. As research in the field expands, paradigm shifts will shape our understanding of diverticulitis, influencing how clinicians approach management and educate patients.

Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines.

OBJECTIVE: Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing. DESIGN: The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo. RESULTS: Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii. Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1α, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery. CONCLUSION: Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.

[Access to donor human milk in Switzerland and CHUV's first human milk bank in Romandy : issues and perspectives]. / Pédiatrie - Accès au lait de donneuses en Suisse et création de la première banque de lait maternel romande au CHUV : enjeux et perspectives.

Mother's own milk (MOM) is ideal for infant growth and health. When MOM is unavailable, donor human milk (DHM), rather than infant formula, is recommended for at-risk, preterm or sick neonates (NN), in view of its protective effects. Human milk banks (HMB) collect, secure, process and distribute DHM. In Switzerland, there is insufficient and unequal access to DHM in the absence of a national policy framework. With the support of the State of Vaud, the CHUV and the Interregional Blood Transfusion of the Swiss Red Cross will open the first HMB in Romandy in 2022. This HMB offers an innovative system in Switzerland, based on complementary expertise, in order to guarantee the quality and safety of DHM and to support the promotion of breastfeeding and human milk donation.

Le lait maternel (LM) est idéal pour la croissance et la santé des nourrissons. En l'absence de LM, le lait de donneuses (LD) est préférable au lait artificiel pour les nouveau-nés (NN) à risques, prématurés ou présentant certaines pathologies, au vu de ses effets protecteurs. Les banques de lait (BL) collectent, sécurisent, traitent et distribuent le LD. Il existe en Suisse une insuffisance et une inégalité d'accès au LD, faute de cadre national. Avec le soutien de l'État de Vaud, le CHUV et la Transfusion interrégionale de la Croix-Rouge suisse ouvriront en 2022 la première BL romande. Cette BL propose un système novateur en Suisse, fondé sur une complémentarité d'expertises, afin d'optimiser la qualité et la sécurité du LD et de soutenir la promotion de l'allaitement et du don.

The role of butyrate in surgical and oncological outcomes in colorectal cancer.

Butyrate is a short-chain fatty acid produced by colonic gut bacteria as a result of fermentation of dietary fibers. In the colon, butyrate is a major energy substrate and contributes to the nutritional support and proliferation of a healthy mucosa. It also promotes the intestinal barrier function by enhancing mucus production and tight junctions. In addition to its pro-proliferative effect in healthy colonocytes, butyrate inhibits the proliferation of cancer cells. The antineoplastic effect of butyrate is associated with the inhibitory effect of butyrate on histone deacetylase (HDAC) enzymes, which promote carcinogenesis. Due to the metabolic shift of cancer cells toward glycolysis, unused butyrate accumulates and inhibits procarcinogenic HDACs. In addition, recent studies suggest that butyrate may improve the healing of colonic tissue after surgery in animal models, specifically at the site of reconnection of colonic ends, anastomosis, after surgical resection. Here, we review current evidence on the impact of butyrate on epithelial integrity and colorectal cancer and present current knowledge on data that support its potential applications in surgical practice.

Crohn's Disease after Proctocolectomy and IPAA for Ulcerative Colitis.

BACKGROUND: Proctocolectomy with IPAA is considered curative for ulcerative colitis. However, signs of Crohn's disease can develop postoperatively in some cases. OBJECTIVE: Our aim was to document the postoperative diagnosis of Crohn's disease, to identify potential preoperative predictive factors, and to review the evolution of patients on treatment. DESIGN: This is a retrospective cohort study. SETTINGS: This study was conducted at a tertiary care center in Montreal, Canada. PATIENTS: A total of 301 patients underwent an IPAA for ulcerative colitis between 1985 and 2014. MAIN OUTCOME MEASURES: The primary outcome was the cumulative incidence of the postoperative diagnosis of Crohn's disease. RESULTS: During a median follow-up of 68 months, Crohn's disease was diagnosed at a median time of 77 months (8-270) in 38 patients (12.6%). The cumulative incidence of Crohn's disease was 7.5% at 5 years postoperatively and gradually increased to 17.7% and 33.0% at 10 and 20 years. The following predictive factors for Crohn's disease were observed on univariate analysis: current tobacco smoking at surgery (HR 3.56 (95% CI, 1.54-8.22)), suspicion of indeterminate colitis (HR 3.50 (95% CI, 1.69-7.24)), presence of mouth ulcers before surgery (HR 2.16 (95% CI, 1.03-4.53)), and age at diagnosis of ulcerative colitis (HR 0.94 (95% CI, 0.90-0.97)). Suspicion of indeterminate colitis (HR 3.18 (95% CI 1.46-6.93); p = 0.004) and age at diagnosis (HR 0.95 (95% CI, 0.91-0.99); p = 0.018) remained statistically significant on multivariate analysis. Postoperative inflammatory disease was controlled by medical therapy in most patients. Removal of the pouch was necessary in 16% of patients with Crohn's disease. LIMITATIONS: This was a retrospective single-center study. CONCLUSIONS: Diagnosis of Crohn's disease can occur at a distance from surgery with an increasing cumulative incidence over time. Preoperative predictive factors are few and should not determine candidacy for surgery. Therapeutic options are identical to those available for treatment of typical Crohn's disease and allow a favorable evolution in most patients. See Video Abstract at http://links.lww.com/DCR/B372. BROTE DE CROHN DESPUS DE UNA PROCTOCOLECTOMA CON ANASTOMOSIS DE RESERVORIO LEOANAL EN CASOS DE COLITIS ULCEROSA: ANTECEDENTES:La proctocolectomía con reservorio ileo-anal se considera curativa para la colitis ulcerosa. Sin embargo, signos de enfermedad de Crohn pueden desarrollarse después de la operación en algunos casos.OBJETIVO:Nuestro objetivo fue documentar el diagnóstico postoperatorio de la enfermedad de Crohn, identificar posibles factores predictivos preoperatorios y revisar la evolución de los pacientes con tratamiento.DISEÑO:Estudio retrospectivo de cohortes.AJUSTES:Centro de atención terciaria en Montreal, Canadá.PACIENTES:301 pacientes portadores de un reservorio íleo-anal realizados por colitis ulcerosa entre 1985 y 2014.PRINCIPALES MEDIDAS DE RESULTADO:Acumulación de la incidencia en el diagnóstico postoperatorio de enfermedad de Crohn.RESULTADOS:Durante una media de 68 meses de seguimiento, la enfermedad de Crohn fué diagnosticada en un tiempo medio de 77 meses (8-270) en 38 pacientes (12,6%). La acumulación de incidencia de la enfermedad de Crohn fue del 7,5% a los 5 años después de la operación y aumentó gradualmente a 17,7 y 33,0% a los 10 y 20 años. Los siguientes factores predictivos para la enfermedad de Crohn se observaron en el análisis univariado: tabaquismo activo al momento de la cirugía (cociente de riesgo (HR) 3.56 (intervalo de confianza del 95% (IC) 1.54-8.22)), sospecha de colitis indeterminada (HR 3.50 (IC del 95% 1.69-7.24)), presencia de úlceras en la boca antes de la cirugía (HR 2.16 (IC 95% 1.03-4.53)) y edad al diagnóstico de colitis ulcerosa (HR 0.94 (IC 95% 0.90-0.97)). La sospecha de colitis indeterminada (HR 3.18 (IC 95% 1.46-6.93), p = 0.004) y la edad al momento del diagnóstico (HR 0.95 (IC 95% 0.91-0.99), p = 0.018) permanecieron estadísticamente significativos en el análisis multivariado. La reacción inflamatoria intestinal postoperatoria fue controlada con tratamiento médico en la mayoría de los pacientes. El retiro del reservorio íleo-anal fue necesario en 16% de los pacientes con enfermedad de Crohn.LIMITACIONES:Estudio retrospectivo de centro único.CONCLUSIONES:El diagnóstico de la enfermedad de Crohn puede ocurrir a distancia de la cirugía con la acumulación de incidencia creciente con el tiempo. Los factores predictivos preo-peratorios son pocos y no pueden determinar la candidatura para la cirugía. Las opciones terapéuticas son idénticas a las disponibles para el tratamiento de la enfermedad de Crohn típica y permiten una evolución favorable en la mayoría de los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B372. (Traducción-Dr. Xavier Delgadillo).

[Novelties 2016 in pediatrics]. / Pédiatrie.

Nutrition is central in pediatric care : essential for growth and development, it plays also a role in the prevention of many diseases.Even if breastfeeding is highly recommended, its implementation may be difficult in particular for premature and ill newborns. The creation of a specific unit for breastfeeding support in neonatology allows to help mothers willing to nurse and to improve the rate of breastfeeding for these vulnerable infants.Eating disorders represent an important challenge for patient care. Early detection and rapid management of anorexia is essential for the prognosis. This article describes the challenges and the practical process underlying the development of a practical guideline to manage children and adolescents hospitalized for anorexia.

La nutrition est un thème central en pédiatrie : essentielle pour la croissance et le développement de l'enfant, elle joue également un rôle dans la prévention de nombreuses maladies.Bien que fortement recommandée, la mise en place de l'allaitement peut être difficile en particulier chez les nouveau-nés prématurés ou malades. La création d'une unité de soutien à l'allaitement en néonatologie a permis d'offrir un soutien aux mères souhaitant allaiter et d'améliorer le taux de lactation. Les troubles du comportement alimentaire représentent un important challenge de prise en charge. Une détection et une prise en charge rapide de l'anorexie sont essentielles pour le pronostic. Cet article décrit les enjeux et le processus parcouru pour élaborer un guide de prise en charge des enfants et adolescent(e)s hospitalisé(e)s pour une anorexie.

Frequency and predictors of stroke after acute myocardial infarction: specific aspects of in-hospital and postdischarge events.

BACKGROUND AND PURPOSE: Stroke is a serious complication after acute myocardial infarction (AMI) and is closely associated with decreased survival. This study aimed to investigate the frequency, characteristics, and factors associated with in-hospital and postdischarge stroke in patients with AMI. METHODS: Eight thousand four hundred eighty-five consecutive patients admitted to a cardiology intensive care unit for AMI, between January 2001 and July 2010. Stroke/transient ischemic attack were collected during 1-year follow-up. RESULTS: One hundred twenty-three in-hospital strokes were recorded: 65 (52.8%) occurred on the first day after admission for AMI, and 108 (87%) within the first 5 days. One hundred six patients (86.2%-incidence rate 1.25%) experienced in-hospital ischemic stroke, and 14 patients (11.4%-incidence rate 0.16%) were diagnosed with an in-hospital hemorrhagic stroke. In-hospital ischemic stroke subtypes according to the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification showed that only 2 types of stroke were identified more frequently. As expected, the leading subtype of in-hospital ischemic stroke was cardioembolic stroke (n=64, 60%), the second was stroke of undetermined pathogenesis (n=38, 36%). After multivariable backward regression analysis, female sex, previous transient ischemic attack (TIA)/stroke, new-onset atrial fibrillation, left ventricular ejection fraction (odds ratio per point of left ventricular ejection fraction), and C-reactive protein were independently associated with in-hospital ischemic stroke. When antiplatelet and anticoagulation therapy within the first 48 hours was introduced into the multivariable model, we found that implementing these treatments (≥1) was an independent protective factor of in-hospital stroke. In-hospital hemorrhagic stroke was dramatically increased (5-fold) when thrombolysis was prescribed as the reperfusion treatment. However, the different parenteral anticoagulants were not predictors of risk in univariable analysis. Finally, only 45 postdischarge strokes were recorded. Postdischarge stroke subtypes showed a more heterogeneous distribution of mechanisms. The annual rate of stroke post-AMI remained stable throughout the 10-year study period. CONCLUSIONS: The present study describes specific predictors of in-hospital and postdischarge stroke in patients with AMI. It showed a marked increase in the risk of death, both during hospitalization and in the year after AMI. After hospital discharge, stroke remains a rare event and is mostly associated with high cardiovascular risk.

Human basophils interact with memory T cells to augment Th17 responses.

Basophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3- or IL-33-activated basophils amplified IL-17 release in effector memory T cells (T(EM)), central memory T cells (T(CM)), and CCR6(+) CD4 T cells. More specifically, basophils promoted the emergence of IL-17(+)IFN-γ(-) and IL-17(+)IFN-γ(+), but not IL-17(-)IFN-γ(+) CD4 T cells in T(EM) and T(CM). Mechanistic analysis revealed that the enhancing effect of IL-17 production by basophils in T(EM) involved the ERK1/2 signaling pathway, occurred in a contact-independent manner, and was partially mediated by histamine via H(2) and H(4) histamine receptors. The results of the present study reveal a previously unknown function for basophils in augmenting Th17 and Th17/Th1 cytokine expression in memory CD4 T cells. Because basophils accumulated in inflamed inflammatory bowel disease tissues, we propose that these cells are key players in chronic inflammatory disorders beyond Th2.

The gut barrier as a gatekeeper in colorectal cancer treatment.

Colorectal cancer (CRC) is highly prevalent and is a major cause of cancer-related deaths worldwide. The incidence rate of CRC remains alarmingly high despite screening measures. The main curative treatment for CRC is a surgical resection of the diseased bowel segment. Postoperative complications usually involve a weakened gut barrier and a dissemination of bacterial proinflammatory lipopolysaccharides. Herein we discuss how gut microbiota and microbial metabolites regulate basal inflammation levels in the gut and the healing process of the bowel after surgery. We further elaborate on the restoration of the gut barrier function in patients with CRC and how this potentially impacts the dissemination and implantation of CRC cells in extracolonic tissues, contributing therefore to worse survival after surgery.

Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery.

PURPOSE: Anastomotic leak (AL) is a major complication in colorectal cancer surgery and consists of the leakage of intestinal content through a poorly healed colonic wound. Colorectal cancer recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence and that improving anastomotic healing may prevent local implantation and metastatic dissemination of cancer cells. EXPERIMENTAL DESIGN: We investigated the association between AL and postoperative outcomes in patients with colorectal cancer. Using mouse models of poor anastomotic healing, we assessed the processes of local implantation and dissemination of cancer cells. The effect of dietary supplementation with inulin and 5-aminosalicylate (5-ASA), which activate PPAR-γ in the gut, on local anastomotic tumors was assessed in mice undergoing colonic surgery. Inulin and 5-ASA were also assessed in a mouse model of liver metastasis. RESULTS: Patients experiencing AL displayed lower overall and oncologic survival than non-AL patients. Poor anastomotic healing in mice led to larger anastomotic and peritoneal tumors. The microbiota of patients with AL displays a lower capacity to activate the antineoplastic PPAR-γ in the gut. Modulation of gut microbiota using dietary inulin and 5-ASA reinforced the gut barrier and prevented anastomotic tumors and metastatic spread in mice. CONCLUSIONS: Our findings reinforce the hypothesis that preventing AL is paramount to improving oncologic outcomes after colorectal cancer surgery. Furthermore, they pave the way toward dietary targeting of PPAR-γ as a novel way to enhance healing and diminish cancer recurrence.

Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon.

Escherichia coli that harbor the polyketide synthase (pks) genomic island produce colibactin and are associated with sporadic colorectal cancer development. Given the considerable prevalence of pks+ bacteria in healthy individuals, we sought to identify strategies to limit the growth and expansion of pks+ E. coli. We found that culture supernatants of the probiotic strain E. coli Nissle 1917 were able to inhibit the growth of the murine pathogenic strain pks+ E. coli NC101 (EcNC101). We performed a nontargeted analysis of the metabolome in supernatants from several E. coli strains and identified putrescine as a potential postbiotic capable of suppressing EcNC101 growth in vitro. The effect of putrescine supplementation was then evaluated in the azoxymethane/dextran sulfate sodium mouse model of colorectal cancer in mice colonized with EcNC101. Putrescine supplementation inhibited the growth of pks+ E. coli, reduced the number and size of colonic tumors, and downmodulated the release of inflammatory cytokines in the colonic lumen. Additionally, putrescine supplementation led to shifts in the composition and function of gut microbiota, characterized by an increase in the Firmicutes/Bacteroidetes ratio and enhanced acetate production. The effect of putrescine was further confirmed in vitro using a pks+ E. coli strain isolated from a patient with colorectal cancer. These results suggest that probiotic-derived metabolites can be used as an alternative to live bacteria in individuals at risk of developing colorectal cancer due to the presence of pks+ bacteria in their colon. SIGNIFICANCE: Putrescine supplementation inhibits the growth of cancer-promoting bacteria in the gut, lowers inflammation, and reduces colon cancer development. The consumption of healthy foods rich in putrescine may be a potential prophylactic approach for individuals at risk of developing colorectal cancer due to the presence of pks+ bacteria in their colon.

Safety and clinical efficacy of EUS-guided pelvic abscess drainage.

Background and Objectives: EUS is a potential alternative for the drainage of abscesses. The aim of this study was to determine if EUS-guided pelvic abscess drainage is technically feasible, safe, and a valid option for abscess resolution. Methods: We conducted a retrospective review from 2002 to 2020 at a single quaternary institution. EUS-guided pelvic abscess drainage via the transrectal route was performed in all patients with or without drain/stent placement. Technical and clinical success of EUS-guided pelvic abscess drainage was analyzed. Descriptive analyses and Fisher exact test were performed. Results: Sixty consecutive patients were included in the study (53.5% male; mean age, 53.8 ± 17.9 years). Pelvic abscesses occurred mainly postoperatively (33 cases; 60.0%) and from complicated diverticulitis (14 cases; 23.3%). Mean diameter was 6.5 ± 2.4 cm (80% unilocular). Drainage was performed with EUS-guided stent placement (double-pigtail plastic or lumen-apposing metal) in 74.5% of cases and with aspiration alone for the remainder. Technical success occurred in 58 cases (97%). Of those with long-term follow-up after EUS-guided pelvic abscess drainage (n = 55; 91.7%), complete abscess resolution occurred in 72.7% of all cases. Recurrence occurred in 8 cases (14.5%) and persisted in 7 patients (12.5%), 7 of which were successfully retreated with EUS-guided pelvic abscess drainage. Accounting for these successful reinterventions, the overall rate of abscess resolution was 85.5%. Abscess resolution rate improved with drain placement (83%). Accounting for 7 repeat EUS-guided pelvic abscess drainages, overall abscess resolution improved. Two deaths occurred (3.4%) because of sepsis from failed source control in patients who had previously failed medical, radiological, and surgical treatment. Conclusions: EUS-guided pelvic abscess drainage is technically feasible, safe, and an effective alternative to radiological or open surgical drainage. It also offers favorable clinical outcomes in different clinical situations.

Periodontal disease: a new factor associated with the presence of multiple complex coronary lesions.

BACKGROUND AND AIM: Periodontal disease, including bone loss, is thought to be involved in coronary artery disease. Multiple complex coronary lesions relate to multifocal destabilization of coronary plaques. We investigated whether bone loss could be associated with the presence of multiple complex coronary lesions. METHODS: This cross-sectional study included 150 patients with recent myocardial infarction (<1 month). Multiple complex coronary lesions were determined at coronary angiography. A panoramic dental X-ray including bone loss >50% was performed. Patients with no or simple complex lesions were compared to patients with multiple complex lesions. RESULTS: Over 20% of patients had multiple complex coronary lesions. Patients with multiple complex lesion were less likely to be women and more likely to have multivessel disease or elevated C-reactive protein (CRP) than patients with no or single complex lesion. Bone loss >50% tended to be more frequent in patients with multiple complex lesions (p = 0.063). In multivariate analysis, multivessel disease, gender and CRP were associated with multiple complex lesion. Bone loss >50% increased the risk of multiple complex lesion. CONCLUSION: Bone loss was associated with complex multiple coronary lesions, beyond systemic inflammation. These findings may bear important clinical implications for the prevention and treatment of coronary artery disease.

Prevalence of pks + bacteria and enterotoxigenic Bacteroides fragilis in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer deaths worldwide. CRC patients present with an increase in pathogens in their gut microbiota, such as polyketide synthase-positive bacteria (pks +) and enterotoxigenic Bacteroides fragilis (ETBF). The pks + Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). ETBF is a procarcinogenic bacterium producing the B. fragilis toxin (bft) that promotes colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. METHODS: Fecal samples were collected from healthy controls (N = 62) and CRC patients (N = 94) from the province of Québec (Canada), and a bacterial DNA extraction was performed. Fecal DNA samples were then examined for the presence of the pks island gene and bft using conventional qualitative PCR. RESULTS: We found that a high proportion of healthy controls are colonized by pks + bacteria (42%) and that these levels were similar in CRC patients (46%). bft was detected in 21% of healthy controls and 32% of CRC patients, while double colonization by both pks + bacteria and ETBF occurred in 8% of the healthy controls and 13% of the CRC patients. Most importantly, we found that early-onset CRC (< 50 years) patients were significantly less colonized with pks + bacteria (20%) compared to late-onset CRC patients (52%). CONCLUSIONS: Healthy controls had similar levels of pks + bacteria and ETBF colonization as CRC patients, and their elevated levels may place both groups at greater risk of developing CRC. Colonization with pks + bacteria was less prevalent in early-compared to late-onset CRC.

Oxidative stress and myocardial gene alterations associated with Doxorubicin-induced cardiotoxicity in rats persist for 2 months after treatment cessation.

The molecular mechanisms underlying doxorubicin (DOX)-induced cardiomyopathy include alterations in cardiomyocytes' oxidative stress status and in gene expression. Although such alterations have been reported during in vivo DOX treatment of animals, it remains to be clarified whether they persist after treatment cessation. To address this question, rats were injected with either saline (1 ml/kg/day i.p; control) or DOX (1 mg/kg/day i.p.) for 10 days, and 70 days later cardiac functional parameters were evaluated in vivo by left ventricular catheterization. Hearts were also harvested for histological analyses as well as measurements of oxidative stress parameters by various techniques and gene expression by quantitative polymerase chain reaction of markers of cardiac pathological remodeling, namely atrial natriuretic factor, myosin heavy chain ß, vascular endothelial growth factor A (VEGF-A), and sarcoplasmic reticulum Ca(+2) ATPase. Compared with controls, DOX-treated rats displayed marked alterations in most parameters even 2 months after cessation of treatment. These included 1) lower left ventricular contractility (+dP/dt), 2) increased levels of plasma and myocardial oxidative stress markers, namely thiobarbituric acid reactive substances or dihydroethidium fluorescence, and 3) markedly altered transcript levels for all measured markers of cardiac remodeling, except VEGF-A. These changes correlated significantly with +dP/dt values assessed in the two groups of animals. In conclusion, this study demonstrated that as many as 2 months after cessation of DOX treatment cardiac alterations persisted, reflecting increased oxidative stress and pathological remodeling, the latter being linked to the development of contractile dysfunction.

[Angiotensin converting enzyme inhibitor and calcium antagonist combination. Which place in patients with a stable coronary artery disease?]. / L'association inhibiteur de l'enzyme de conversion et antagoniste calcique. Quelle place chez le patient coronarien stable ?

Cardiovascular diseases are one of the main causes of early morbidity and mortality within occidental world as well as in developing countries where they become a growing burden of public health. North-American recommendations and the ones of the European Society of Cardiology underline that medical treatment, risk factor management and life-style modifications are cornerstone of the treatment. Thanks to their impact on prognosis, angiotensin converting enzyme (ACE) inhibitors are obvious in stable coronary patients. Recently, some large trials have supported the benefits of combining calcium antagonist, amlodipine, and ACE inhibitor, perindopril, in patients with high cardiovascular risk, stable coronary patients or hypertensive patients. This combination has synergistic properties on blood pressure control and target-organ protection, thus reducing cardiovascular events over the long term.