The Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination and Infection on Neutralizing Antibodies: A Nation-wide Cross-sectional Analysis.

BACKGROUND: Neutralising antibodies (nAbs) play a critical role in the protection against severe COVID-19. In the era of vaccine boosters and repeated SARS-CoV-2 outbreaks, identifying individuals at risk represents a public health priority. METHODS: Relying on the Monaco COVID Public Health Programme, we evaluated nAbs from July 2021-June 2022 in 8,080 SARS-CoV-2 vaccinated and/or infected children and adults, at their inclusion visit. We stratified by infection status and investigated variables associated with nAbs using a generalised additive model. RESULTS: Infected and vaccinated participants had high and consistent nAbs (>800 IU/mL), which remained stable over time since injection, regardless of the number of vaccine doses, body mass index, sex, or age. By contrast, uninfected participants showed larger variability (two doses [V2] median 157.6; interquartile range [IQR] 43.3-439.1 IU/mL) versus three doses [V3] median 882.5; [829.5-914.8] IU/mL). NAbs decreased by 20% per month after V2 (adjusted ratio 0.80; 95%CI [0.79-0.82]), but remained stable after V3 (adjusted ratio 0.98; 95%CI [0.92-1.05]). CONCLUSIONS: Hybrid immunity provided stable, high and consistent nAbs over time. The benefit of boosters was marked to restore decaying nAbs in uninfected participants. NAbs could identify individuals at risk of severe COVID-19 and provide more targeted vaccine boosters' campaigns.

Correction: Interaction of Saccharomyces boulardii with Salmonella enterica Serovar Typhimurium Protects Mice and Modifies T84 Cell Response to the Infection.

[This corrects the article DOI: 10.1371/journal.pone.0008925.].

Human Health and Ocean Pollution.

Background: Pollution - unwanted waste released to air, water, and land by human activity - is the largest environmental cause of disease in the world today. It is responsible for an estimated nine million premature deaths per year, enormous economic losses, erosion of human capital, and degradation of ecosystems. Ocean pollution is an important, but insufficiently recognized and inadequately controlled component of global pollution. It poses serious threats to human health and well-being. The nature and magnitude of these impacts are only beginning to be understood. Goals: (1) Broadly examine the known and potential impacts of ocean pollution on human health. (2) Inform policy makers, government leaders, international organizations, civil society, and the global public of these threats. (3) Propose priorities for interventions to control and prevent pollution of the seas and safeguard human health. Methods: Topic-focused reviews that examine the effects of ocean pollution on human health, identify gaps in knowledge, project future trends, and offer evidence-based guidance for effective intervention. Environmental Findings: Pollution of the oceans is widespread, worsening, and in most countries poorly controlled. It is a complex mixture of toxic metals, plastics, manufactured chemicals, petroleum, urban and industrial wastes, pesticides, fertilizers, pharmaceutical chemicals, agricultural runoff, and sewage. More than 80% arises from land-based sources. It reaches the oceans through rivers, runoff, atmospheric deposition and direct discharges. It is often heaviest near the coasts and most highly concentrated along the coasts of low- and middle-income countries. Plastic is a rapidly increasing and highly visible component of ocean pollution, and an estimated 10 million metric tons of plastic waste enter the seas each year. Mercury is the metal pollutant of greatest concern in the oceans; it is released from two main sources - coal combustion and small-scale gold mining. Global spread of industrialized agriculture with increasing use of chemical fertilizer leads to extension of Harmful Algal Blooms (HABs) to previously unaffected regions. Chemical pollutants are ubiquitous and contaminate seas and marine organisms from the high Arctic to the abyssal depths. Ecosystem Findings: Ocean pollution has multiple negative impacts on marine ecosystems, and these impacts are exacerbated by global climate change. Petroleum-based pollutants reduce photosynthesis in marine microorganisms that generate oxygen. Increasing absorption of carbon dioxide into the seas causes ocean acidification, which destroys coral reefs, impairs shellfish development, dissolves calcium-containing microorganisms at the base of the marine food web, and increases the toxicity of some pollutants. Plastic pollution threatens marine mammals, fish, and seabirds and accumulates in large mid-ocean gyres. It breaks down into microplastic and nanoplastic particles containing multiple manufactured chemicals that can enter the tissues of marine organisms, including species consumed by humans. Industrial releases, runoff, and sewage increase frequency and severity of HABs, bacterial pollution, and anti-microbial resistance. Pollution and sea surface warming are triggering poleward migration of dangerous pathogens such as the Vibrio species. Industrial discharges, pharmaceutical wastes, pesticides, and sewage contribute to global declines in fish stocks. Human Health Findings: Methylmercury and PCBs are the ocean pollutants whose human health effects are best understood. Exposures of infants in utero to these pollutants through maternal consumption of contaminated seafood can damage developing brains, reduce IQ and increase children's risks for autism, ADHD and learning disorders. Adult exposures to methylmercury increase risks for cardiovascular disease and dementia. Manufactured chemicals - phthalates, bisphenol A, flame retardants, and perfluorinated chemicals, many of them released into the seas from plastic waste - can disrupt endocrine signaling, reduce male fertility, damage the nervous system, and increase risk of cancer. HABs produce potent toxins that accumulate in fish and shellfish. When ingested, these toxins can cause severe neurological impairment and rapid death. HAB toxins can also become airborne and cause respiratory disease. Pathogenic marine bacteria cause gastrointestinal diseases and deep wound infections. With climate change and increasing pollution, risk is high that Vibrio infections, including cholera, will increase in frequency and extend to new areas. All of the health impacts of ocean pollution fall disproportionately on vulnerable populations in the Global South - environmental injustice on a planetary scale. Conclusions: Ocean pollution is a global problem. It arises from multiple sources and crosses national boundaries. It is the consequence of reckless, shortsighted, and unsustainable exploitation of the earth's resources. It endangers marine ecosystems. It impedes the production of atmospheric oxygen. Its threats to human health are great and growing, but still incompletely understood. Its economic costs are only beginning to be counted.Ocean pollution can be prevented. Like all forms of pollution, ocean pollution can be controlled by deploying data-driven strategies based on law, policy, technology, and enforcement that target priority pollution sources. Many countries have used these tools to control air and water pollution and are now applying them to ocean pollution. Successes achieved to date demonstrate that broader control is feasible. Heavily polluted harbors have been cleaned, estuaries rejuvenated, and coral reefs restored.Prevention of ocean pollution creates many benefits. It boosts economies, increases tourism, helps restore fisheries, and improves human health and well-being. It advances the Sustainable Development Goals (SDG). These benefits will last for centuries. Recommendations: World leaders who recognize the gravity of ocean pollution, acknowledge its growing dangers, engage civil society and the global public, and take bold, evidence-based action to stop pollution at source will be critical to preventing ocean pollution and safeguarding human health.Prevention of pollution from land-based sources is key. Eliminating coal combustion and banning all uses of mercury will reduce mercury pollution. Bans on single-use plastic and better management of plastic waste reduce plastic pollution. Bans on persistent organic pollutants (POPs) have reduced pollution by PCBs and DDT. Control of industrial discharges, treatment of sewage, and reduced applications of fertilizers have mitigated coastal pollution and are reducing frequency of HABs. National, regional and international marine pollution control programs that are adequately funded and backed by strong enforcement have been shown to be effective. Robust monitoring is essential to track progress.Further interventions that hold great promise include wide-scale transition to renewable fuels; transition to a circular economy that creates little waste and focuses on equity rather than on endless growth; embracing the principles of green chemistry; and building scientific capacity in all countries.Designation of Marine Protected Areas (MPAs) will safeguard critical ecosystems, protect vulnerable fish stocks, and enhance human health and well-being. Creation of MPAs is an important manifestation of national and international commitment to protecting the health of the seas.

Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections.

The yeast Saccharomyces boulardii CNCM I-745 is one of the probiotics recommended for the prevention of antibiotic-associated diarrhea. Studies conducted in vivo and in vitro demonstrated that in the case of infectious diseases there are two potential sites of action of Saccharomyces boulardii CNCM I-745: (1) An action on enteropathogenic microorganisms (adhesion of bacteria and their elimination or an effect on their virulence factors: Toxins, lipopolysaccharide, etc.); and (2) a direct action on the intestinal mucosa (trophic effects, effects on epithelial reconstitution, anti-secretory effects, anti-inflammatory, immunomodulators). Oral administration of Saccharomyces boulardii CNCM I-745 to healthy subjects does not alter their microbiota. However, in the case of diseases associated with the use of antibiotics or chronic diarrhea, Saccharomyces boulardii CNCM I-745 can restore the intestinal microbiota faster. The interaction of Saccharomyces boulardii CNCM I-745 with the innate immune system have been recently demonstrated thus opening up a new therapeutic potential of this yeast in the case of diseases associated with intestinal infections but also other pathologies associated with dysbiosis such as inflammatory diseases.

The Saccharomyces boulardii CNCM I-745 strain shows protective effects against the B. anthracis LT toxin.

The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT) of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax.

Saccharomyces boulardii modifies Salmonella typhimurium traffic and host immune responses along the intestinal tract.

Salmonella enterica serovar Typhimurium (ST) is an enteropathogenic Gram-negative bacterium that causes infection following oral ingestion. ST spreads rapidly along the gastrointestinal tract (GIT) and invades the intestinal epithelium to ultimately reach internal body organs. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is prescribed for prophylaxis of diarrheal infectious diseases. We previously showed that S.b-B prevents weight loss in ST-infected mice and significantly decreases bacterial translocation to the spleen and liver. This study was designed to investigate the effect of S.b-B on ST migration along the GIT and the impact of the yeast on the host's early innate immune responses. Bioluminescent imaging (BLI) was used to evaluate the effect of S.b-B on the progression of luminescent Salmonella Typhimurium (ST-lux) in the GIT of mice pretreated with streptomycin. Photonic emission (PE) was measured in GIT extracts (stomach, small intestine, cecum and colon) at various time periods post-infection (PI). PE analysis revealed that, 45 min PI, ST-lux had migrated slightly faster in the mice treated with S.b-B than in the untreated infected animals. At 90 min PI, ST-lux had reached the cecum in both groups of mice. Adhesion of ST to S.b-B was visualized in the intestines of the mice and probably accounts for (1) the faster elimination of ST-lux in the feces, and (2) reduced translocation of ST to the spleen and liver. In the early phase of infection, S.b-B also modifies the host's immune responses by (1) increasing IFN-γ gene expression and decreasing IL-10 gene expression in the small intestine, and (2) elevating both IFN-γ, and IL-10 mRNA levels in the cecum. BLI revealed that S.b-B modifies ST migration and the host immune response along the GIT. Study findings shed new light on the protective mechanisms of S.b-B during the early phase of Salmonella pathogenesis.

Saccharomyces boulardii does not prevent relapse of Crohn's disease.

BACKGROUND & AIMS: Saccharomyces boulardii is a probiotic yeast that has been shown to have beneficial effects on the intestinal epithelial barrier and digestive immune system. There is preliminary evidence that S boulardii could be used to treat patients with Crohn's disease (CD). We performed a randomized, placebo-controlled trial to evaluate the effects of S boulardii in patients with CD who underwent remission during therapy with steroids or aminosalicylates. METHODS: We performed a prospective study of 165 patients who achieved remission after treatment with steroids or salicylates; they were randomly assigned to groups given S boulardii (1 g/day) or placebo for 52 weeks. The primary end point was the percentage of patients in remission at week 52. Time to relapse, Crohn's disease activity index scores, and changes in parameters of inflammation were secondary end points. RESULTS: CD relapsed in 80 patients, 38 in the S boulardii group (47.5%) and 42 in the placebo group (53.2%, a nonsignificant difference). The median time to relapse did not differ significantly between patients given S boulardii (40.7 weeks) vs placebo (39.0 weeks). There were no significant differences between groups in mean Crohn's disease activity index scores or erythrocyte sedimentation rates or in median levels of C-reactive protein. In a post hoc analysis, nonsmokers given S boulardii were less likely to experience a relapse of CD than nonsmokers given placebo, but this finding requires confirmation. CONCLUSIONS: Although the probiotic yeast S boulardii is safe and well tolerated, it does not appear to have any beneficial effects for patients with CD in remission after steroid or salicylate therapies.

Modification of Salmonella Typhimurium motility by the probiotic yeast strain Saccharomyces boulardii.

BACKGROUND: Motility is an important component of Salmonella enterica serovar Typhimurium (ST) pathogenesis allowing the bacteria to move into appropriate niches, across the mucus layer and invade the intestinal epithelium. In vitro, flagellum-associated motility is closely related to the invasive properties of ST. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is widely prescribed for the prophylaxis and treatment of diarrheal diseases caused by bacteria or antibiotics. In case of Salmonella infection, S.b-B has been shown to decrease ST invasion of T84 colon cell line. The present study was designed to investigate the impact of S.b-B on ST motility. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed on human colonic T84 cells infected by the Salmonella strain 1344 alone or in the presence of S.b-B. The motility of Salmonella was recorded by time-lapse video microscopy. Next, a manual tracking was performed to analyze bacteria dynamics (MTrackJ plugin, NIH image J software). This revealed that the speed of bacterial movement was modified in the presence of S.b-B. The median curvilinear velocity (CLV) of Salmonella incubated alone with T84 decreased from 43.3 µm/sec to 31.2 µm/sec in the presence of S.b-B. Measurement of track linearity (TL) showed similar trends: S.b-B decreased by 15% the number of bacteria with linear tract (LT) and increased by 22% the number of bacteria with rotator tract (RT). Correlation between ST motility and invasion was further established by studying a non-motile flagella-deficient ST strain. Indeed this strain that moved with a CLV of 0.5 µm/sec, presented a majority of RT and a significant decrease in invasion properties. Importantly, we show that S.b-B modified the motility of the pathogenic strain SL1344 and significantly decreased invasion of T84 cells by this strain. CONCLUSIONS: This study reveals that S.b-B modifies Salmonella's motility and trajectory which may account for the modification of Salmonella's invasion.

Interaction of Saccharomyces boulardii with Salmonella enterica serovar Typhimurium protects mice and modifies T84 cell response to the infection.

BACKGROUND: Salmonella pathogenesis engages host cells in two-way biochemical interactions: phagocytosis of bacteria by recruitment of cellular small GTP-binding proteins induced by the bacteria, and by triggering a pro-inflammatory response through activation of MAPKs and nuclear translocation of NF-kappaB. Worldwide interest in the use of functional foods containing probiotic bacteria for health promotion and disease prevention has increased significantly. Saccharomyces boulardii is a non-pathogenic yeast used as a probiotic in infectious diarrhea. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we reported that S. boulardii (Sb) protected mice from Salmonella enterica serovar Typhimurium (ST)-induced death and prevented bacterial translocation to the liver. At a molecular level, using T84 human colorectal cancer cells, we demonstrate that incubation with Sb before infection totally abolished Salmonella invasion. This correlates with a decrease of activation of Rac1. Sb preserved T84 barrier function and decreased ST-induced IL-8 synthesis. This anti-inflammatory effect was correlated with an inhibitory effect of Sb on ST-induced activation of the MAPKs ERK1/2, p38 and JNK as well as on activation of NF-kappaB. Electron and confocal microscopy experiments showed an adhesion of bacteria to yeast cells, which could represent one of the mechanisms by which Sb exerts its protective effects. CONCLUSIONS: Sb shows modulating effects on permeability, inflammation, and signal transduction pathway in T84 cells infected by ST and an in vivo protective effect against ST infection. The present results also demonstrate that Sb modifies invasive properties of Salmonella.

Saccharomyces boulardii inhibits inflammatory bowel disease by trapping T cells in mesenteric lymph nodes.

BACKGROUND & AIMS: Saccharomyces boulardii is a nonpathogenic yeast used for treatment of diarrhea. We used a mice model of inflammatory bowel disease (IBD) to analyze the effects of S boulardii on inflammation. METHODS: Lymphocyte-transferred SCID mice, displaying IBD, were fed daily with S boulardii. Weight loss and inflammatory status of the colon were monitored. Nuclear factor-kappaB activity was assessed in the colon. The CD4(+) T-cell production of interferon (IFN) gamma was evaluated by enzyme-linked immunosorbent assay, and a comprehensive reverse-transcription polymerase chain reaction (RT-PCR) analysis for both colon and mesenteric lymph nodes was performed. Finally, we analyzed cell migration mechanisms in vitro and in vivo. RESULTS: S boulardii treatment inhibits IBD. S boulardii induces an accumulation of IFN-gamma-producing T-helper 1 cells within the mesenteric lymph nodes correlated with a diminution of CD4(+) T-cell number and IFN-gamma production by CD4+ T cells within the colon. The influence of S boulardii treatment on cell accumulation in mesenteric lymph nodes was also observed in normal BALB/c mice and involves modifications of lymph node endothelial cell adhesiveness by a yeast secretion product. CONCLUSIONS: S boulardii has a unique action on inflammation by a specific alteration of the migratory behavior of T cells, which accumulate in mesenteric lymph nodes. Therefore, S boulardii treatment limits the infiltration of T-helper 1 cells in the inflammed colon and the amplification of inflammation induced by proinflammatory cytokines production. These results suggest that S boulardii administration may have a beneficial effect in the treatment of IBD.

Saccharomyces boulardii prevents TNF-alpha-induced apoptosis in EHEC-infected T84 cells.

Induction of apoptosis and necrosis by enterohemorrhagic Escherichia coli (EHEC) has been reported in vivo and in vitro, but features of cell death were not noted in those reports. Since tumor necrosis factor-alpha (TNF-alpha) has been implicated in the apoptosis of invasive bacteria, we investigated the role of this cytokine in EHEC-induced apoptosis. We hypothesize that the probiotic yeast strain Saccharomyces boulardii that interferes with EHEC-induced pro-inflammatory pathways delays EHEC-induced apoptosis. By 6 h of infection, flow cytometry analysis of T84 cells demonstrated that 40% of cells were FITC-annexin-V-positive and 40% of cells incorporated both annexin and propidium iodide (PI). Simultaneously, western blot analysis demonstrated that procaspases-8 and -3 were cleaved. Fragmentation of internucleosomal DNA revealed evidence of apoptotic leader formation after 8 and 9 h of infection. Procaspase-9 activation and 3',3-dihexyloxacarbocyanine iodide (DiOC(6)) incorporation were observed at 3 h of infection. In cells preincubated with S. boulardii and infected with EHEC in the presence of yeast, the quantities of procaspases-8, -9 and -3 did not vary, and no DNA fragmentation was observed. The TNF-alpha transcript level and the level of secreted TNF-alpha increased considerably (P<0.001vs control cells) at 6 h of infection in EHEC-alone-infected cells, but were significantly reduced in cells infected in the presence of S. boulardii (P<0.001vs EHEC-alone-infected cells). The presence of anti-TNF-alpha antibody during infection reduced by 30% the level of FITC-annexin V-positive cells. Altogether, these findings demonstrated that: (i) EHEC infection stimulated TNF-alpha synthesis that is implicated in apoptosis of T84 cells; and (ii) S. boulardii induced a decrease in TNF-alpha and related apoptosis in EHEC-infected T84 cells.

Effects of Saccharomyces boulardii on fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition.

AIM: Diarrhea is a significant problem in patients on total enteral nutrition (TEN) and may involve changes in intestinal short chain fatty acids or microflora. Recent studies suggest that the probiotic yeast Saccharomyces boulardii (Sb) may decrease its incidence. The aim of this study was to assess the effects of Sb on fecal flora and short-chain fatty acids (SCFA) in patients on long-term TEN. METHODS: Ten patients (3 females, 7 males, 59+/-5.5 years), on TEN for a median of 13 mo (1-125), and 15 healthy volunteers (4 females, 11 males, 32+/-2.0 years) received Sb (0.5 g bid PO) for 6 d. Two stool samples were taken before, on the last 2 d and 9-10 d after treatment, for SCFA measurement and for culture and bacterial identification. Values (mean+/-SE) were compared using sign tests and ANOVA. RESULTS: Fecal butyrate levels were lower in patients (10.1+/-2.9 mmol/kg) than in controls (19.2+/-3.9, P = 0.02). Treatment with Sb increased total fecal SCFA levels in patients (150.2+/-27.2 vs 107.5+/-18.2 mmol/kg, P = 0.02) but not in controls (129.0+/-28.6 vs 113.0+/-15.2 mmol/kg, NS). At the end of treatment with Sb, patients had higher fecal butyrate (16.0+/-4.4 vs 10.1 [2.9] mmol/kg, P = 0.004). Total SCFAs remained high 9 d after treatment was discontinued. Before the treatment, the anaerobe to aerobe ratio was lower in patients compared to controls (2.4+/-2.3 vs 69.8+/-1.8, P = 0.003). There were no significant changes in the fecal flora of TEN patients. CONCLUSION: Sb-induced increase of fecal SCFA concentrations (especially butyrate) may explain the preventive effects of this yeast on TEN-induced diarrhea.

Gallbladder motility and gut hormone plasma levels in subjects with and without gallstones.

Hormonal control of gallbladder motility is still unclear in patients with cholelithiasis. In a case-control study, we determined the characteristics of gallbladder emptying evaluated sonographically and the hormone levels of somatostatin, gastrin, and pancreatic polypeptide, before and after a fatty meal in 10 gallstone patients compared with 20 healthy subjects. Patients with lithiasis had a larger residual volume (median 12,0 ml vs 6,5 ml; P = 0.01) and a lower gallbladder ejection fraction (43% vs 70%, P = 0.02) than healthy subjects. During fasting, plasma pancreatic polypeptide concentrations were significantly higher in lithiasis patients (P < 0.03). In contrast, no differences between the two groups of patients were observed during the post prandial period. Somatostatin and gastrin plasma levels were similar in the two groups. Lastly, the serum bile salt levels were in the normal range and were not different between groups both during fasting and postprandial states. We conclude that large basal plasma concentrations of pancreatic polypeptide, a gut peptide inducing gallbladder relaxation, may constitute a factor facilitating lithogenesis.

Lactobacillus casei DN-114 001 inhibits the increase in paracellular permeability of enteropathogenic Escherichia coli-infected T84 cells.

Probiotics are living microorganisms which, when ingested in adequate amounts, exert health benefits toward the host. For instance, probiotics might act through reinforcement of the intestinal epithelial barrier function. The goal of the present study was to determine whether Lactobacillus casei DN-114 001 could abrogate the increase in paracellular permeability induced by enteropathogenic Escherichia coli. We used the human colon T84 cell line infected with a wild-type enteropathogenic E. coli (strain E2348/69). Paracellular permeability was followed by monitoring transepithelial electrical resistance variations and by observing zonula occludens-1 distribution. Two infection procedures were used: co-incubation (the pathogenic and probiotic strains were simultaneously incubated with T84 cells) and post-infection (the probiotic was added in the presence of pathogenic bacteria 3 h after the beginning of the infection). We also investigated the effect of L. casei on enteropathogenic E. coli adhesion. L. casei DN-114 001 inhibited, in a dose-dependent-manner, the decrease in enteropathogenic E. coli-induced transepithelial electrical resistance and zonula occludens-1 redistribution using two different infection procedures. However, L. casei did not inhibit pathogenic strain adhesion. L. casei DN-114 001 inhibited the increase in EPEC-induced paracellular permeability. This property could partially explain the previously observed health benefits of this probiotic for human natural defenses, such as those associated with prevention of diarrhea.

Reduced medication dependency and improved symptoms and quality of life 12 months after enteryx implantation for gastroesophageal reflux.

BACKGROUND: The need is well recognized for additional data on endoluminal therapies for gastroesophageal reflux disease (GERD). This prospective multicenter clinical trial was designed to assess safety and effectiveness of Enteryx, a nonresorbable copolymer implanted into the lower esophagus, in reducing usage of proton pump inhibitors (PPIs) and improving reflux symptoms and quality of life. METHODS: Enteryx implantation was performed under fluoroscopic visualization without general anesthesia in 93 patients with symptomatic GERD responsive to and relapsing upon cessation of PPI therapy. Subjective and objective data were collected up to 12 months postprocedure. The criterion for treatment success was reduction in PPI dosage of > or =50%. RESULTS: At 12 months, treatment success was attained in 86% (confidence interval, 77%-93%) of 74 evaluable patients and elimination of PPI therapy in 65% (confidence interval, 53%-76%). The treatment success rate by intent-to-treat analysis was 69% (confidence interval, 58%-78%). Reflux-related heartburn (P < 0.0001), regurgitation symptoms (P = 0.0005), and physical (P < 0.0001) and mental quality of life (P = 0.0012) scores improved. The most frequent complications were chest pain (77%), dysphagia/odynophagia (27%), and sensation of fever (26%). CONCLUSIONS: Enteryx implantation provides an effective and safe alternative for management of gastroesophageal reflux, reducing medication dependency and symptoms and enhancing quality of life.

Serum fibrosis markers can detect large oesophageal varices with a high accuracy.

OBJECTIVES: The aim of this study was to determine the value of serum fibrosis markers for the diagnosis of oesophageal varices in alcoholic patients. METHODS: Fifty-four sets of clinical and biochemical data, including serum markers of fibrosis, obtained from 146 heavy alcohol drinkers (106 men, 40 women; mean age 49.2+/-9.0 years) without any history of variceal bleeding were analysed. Gastroscopy and liver biopsy were performed in all patients. Multivariate analysis was performed to identify the markers best correlated with oesophageal varices. RESULTS: Fifty-nine patients (40.4%) had severe fibrosis (3+) and 48 (32.9%) had oesophageal varices (all grades considered together). In multivariate analysis, a prothrombin index below 60%, alkaline phosphatase activity over 110 IU/l, and hyaluronate over 100 g/l were the best markers for the prediction of oesophageal varices. The diagnostic accuracy for medium to large oesophageal varices using these three factors was 86%. Eight patients (16.7%) with oesophageal varices presented no or moderate fibrosis (F<3): one patient (12.5%) had an alkaline phosphatase level >110 IU/l. However, all eight of these patients had small oesophageal varices. CONCLUSIONS: These three non-invasive markers correctly predict the presence or absence of medium to large oesophageal varices in 86% of alcoholic patients.

[Is combined treatment with interferon alpha and ribavirin for 3 months enough in selected patients with a genotype 2 or 3 hepatitis C virus?]. / Un traitement combiné par interféron-alpha et ribavirine pendant 3 mois pourrait-il suffire chez des malades sélectionnés infectés par un virus de l'hépatite C de génotype 2 ou 3?

Peginterferon plus ribavirin for 24 weeks is the recommended treatment, for previously untreated patients infected by genotype 2 or 3 hepatitis C virus. We report 2 patients with genotype 3 and 2a, with a sustained virological response, after bitherapy with interferon plus ribavirin with 16 and 14 weeks respectively. Thus in selected patients having genotype 2 or 3, and other predictive factors of a sustained virological response, shorter bitherapy could be enough and improve the effectiveness/tolerance ratio.

Nitric oxide-releasing non steroidal anti-inflammatory drugs: a new generation of anti-tumoral molecules.

Colorectal cancer is the second most common cause of cancer-related mortality in the west. The high incidence and mortality make effective prevention an important public-health and economic issue. The regular intake of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with decreased incidence of certain types of cancer particularly those with an inflammatory component, and then are among the few agents known to be chemopreventive. Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are new chemical entities obtained by adding a nitric oxide-releasing moiety to classical molecules. This new class of molecules has been demonstrated to be much more safe than NSAIDs due to their ability to reduce gastric toxicity. They could therefore represent an alternative to classical NSAIDs treatment. In this review, we sumarise the recent findings in the mechanisms and pathways involved in the antitumoral effects of both NSAIDs and NO-NSAIDs as well as the clinical trials performed with these compounds.

Effects of fatty acids on the growth of Caco-2 cells.

Epidemiological studies suggest that polyunsaturated fatty acids may protect against colorectal neoplasia. In order to explore this observation, cell proliferation and viability, lipid composition, membrane fluidity, and lipid peroxidation were measured in Caco-2 cells after 48h incubation with various fatty acids. Saturated and monounsaturated fatty acids incorporated less well in the membranes than polyunsaturated fatty acids (PUFAs). All of the PUFAs tested had an inhibitory effect on cell proliferation/viability whereas the saturated and monounsaturated fatty acids did not. Addition of palmitic acid had no significant effect on membrane fluidity whereas unsaturated fatty acids increased membrane fluidity in a dose-dependent manner. PUFAs strongly increased tumor cell lipid peroxidation in a dose-dependent manner. Saturated and monounsaturated fatty acids increased lipid peroxidation in this cell line only at high concentration. Preincubation of Caco-2 cells with vitamin E prevented the inhibition of proliferation/viability, the elevation of the MDA concentration and the increased membrane fluidity induced by PUFAs. Our data indicate that PUFAs are potent inhibitors of the growth of colon cancer cells in vitro.

[Transposition of an American-designed comprehensive medical student examination within the framework of the forthcoming French nationwide comprehensive examination. A preliminary study]. / Intérêt de transposer un examen américain dans le cadre du futur examen national classant validant français. Etude préliminaire.

Medical training is undergoing extensive revision in France. A nationwide comprehensive clinical competency examination will be administered for the first time in 2004, relying exclusively on essay-questions. Unfortunately, these questions have psychometric shortcomings, particularly their typically low reliability. High score reliability is mandatory in a high-stakes context. The National Board of Medical Examiners-designed multiple choice-questions (MCQ) are well adapted to assess clinical competency with a high reliability score. The purpose of this study was to test the hypothesis that French medical students could take an American-designed and French-adapted comprehensive clinical knowledge examination with this MCQ format. Two hundred and eighty five French students, from four Medical Schools across France, took an examination composed of 200 MCQs under standardized conditions. Their scores were compared with those of American students. This examination was found assess French students' clinical knowledge with a high level of reliability. French students' scores were slightly lower than those of American students, mostly due to a lack of familiarity with this particular item format, and a lower motivational level. Another study is being designed, with a larger group, to address some of the shortcomings of the initial study. If these preliminary results are replicated, the MCQ format might be a more defendable and sensible alternative to the proposed essay questions.