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Mohamed Saad Younis,1 Eman Abd el rahman Abououf,1 Ali El saeed Ali,1 Sara Mohamed Abd elhady,2 Rita Maher Wassef2 1Medical Parasitology Department, Faculty of Medicine, Benha University, Benha, Egypt; 2Medical Parasitology Department, Faculty of Medicine, Helwan University, Cairo, EgyptCorrespondence: Rita Maher WassefMedical Parasitology Department, Faculty of Medicine, Helwan University, 30 Street 276 New Maadi, Cairo, EgyptTel +201005782994Fax +20225193381Email rita.wassef@med.helwan.edu.egIntroduction: This study aims to assess the efficacy of silver nanoparticles (Ag Nps) alone and combined with metronidazole (Ag Nps + MTZ) as potential alternative therapeutic agents for Blastocystis hominis.Methods: The parasites were challenged with Ag Nps, Ag Nps + MTZ and MTZ. To assess the efficacy of drugs, counting of viable parasites was done after 1, 2, and 3 hours of adding the drugs.Results: Blastocystis hominis count was reduced by 20.72%, 28.23%, and 18.92% after one hour of adding Ag Nps, Ag Nps + MTZ, and MTZ, respectively. Cysts count was further reduced by 51.49%, 61.61%, and 40.78% after 2 hours and by 71.69%, 79.67%, and 62.65% after 3 hours of adding the drugs in the same order, respectively.Conclusion: There was a statistically significant difference (P< 0.05) in the in vitro growth inhibition of the parasite over the different time intervals when using the tested drugs against the control drug.Keywords: Blastocystis hominis, eosin brilliant cresyl blue stain, metronidazole, silver nanoparticles

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., (©2024 The Authors; Published by the American Association for Cancer Research.)

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., (©2023 American Association for Cancer Research.)

Toxoplasmosis is a frequent disease with an estimated prevalence of more than one billion human cases worldwide and over one million new infections each year. It is classified as a neglected tropical disease by the CDC since 2019. The disease may pass unnoticed in healthy individuals but could be fatal in the immunocompromised. Moreover, no effective treatment is available against the chronic form of the disease. Available anti- Toxoplasma drugs are associated with many side effects. Therefore, search for new more reliable, more efficient, and less toxic therapeutic agents is a continuous endeavor. This study assesses the potential use of nitrofurantoin, a compound with well-established antimicrobial properties, as a potential anti- Toxoplasma drug in vivo. It compares its efficacy to the commonly used anti- Toxoplasma agent spiramycin by molecular and histopathological methods in acute and chronic infection. The results demonstrate a significant ability to eliminate the parasite ( P  < 0.001) whether used as mono- or combined therapy with spiramycin in the acute and chronic stages. When compared to the anti- Toxoplasma drug spiramycin, nitrofurantoin achieved similar efficacy in the acute and chronic infection ( P  = 0.65 and P  = 0.096, respectively). However, better results were obtained when using a combination of both drugs ( P  < 0.001). Additionally, nitrofurantoin showed good inhibitory effects on the inflammatory process in the liver, kidney, and uterus of the experimentally infected animals. In conclusion, nitrofurantoin can be considered as a potential anti- Toxoplasma agent. Nevertheless, further studies are recommended before consideration for clinical trials.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Scholar Media Publishing.)

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., (© 2022. The Author(s).)

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)., (Copyright © The ASCRS 2020.)

Background: Intimidation constitutes a learning barrier for undergraduates and its reporting rate to authorities remains suboptimal., Methods: A randomized controlled trial was conducted to evaluate the effectiveness of three interventions designed to increase reporting by undergraduates during their surgical rotation. As adjuncts to a standardized lecture, participants were assigned to a simulated intimidation scenario, a video of intimidation events, or a control group. Surveys were completed before the interventions, and at the end of the rotation., Results: Of the 119 included participants, 17.6% reported that they had been intimidated during their previous rotation as compared to 37.0% after the surgical rotation. There were no statistically significant differences in the reporting of intimidation between the groups. However, 65.5% of all participants declared feeling more at ease to report intimidation, yet the reporting rate remained low., Conclusion: Intimidation during clerkship persists as a frequent problem although the best method to increase its reporting remains unclear., Competing Interests: Declaration of competing interest Christian Vincelette received doctoral scholarships from the Faculty of Medicine and Health Sciences at Université de Sherbrooke, the Réseau de Recherche en Interventions en Sciences Infirmières (RRISIQ), and from the Canadian Institutes of Health Research (CIHR). Adam Dubrowski received Canada’s Research Chair in Healthcare Simulation. Maureen Thivierge-Southidara received a master scholarship from the Graduate and postdoctoral studies at Université de Montréal. These organizations were not involved in the decision to pursue this research or to submit this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aims: Crohn's disease [CD] and ulcerative colitis [UC] are distinct forms of inflammatory bowel disease. Heterogeneity of HLA-DR+SIRPα + mononuclear phagocytes [MNPs], including macrophages [MΦ], monocyte-derived [Mono] cells, and dendritic cells [DCs], was reported in gut tissue but not yet investigated in mesenteric lymph nodes [MLNs] of IBD patients. We here compared the phenotype, function, and molecular profile of HLA-DR+SIRPα + MNPs in CD and UC MLNs., Methods: Cell distribution, morphology, immune function, and transcriptomic [bulk RNAseq] and high-dimensional protein expression profiles [CyTOF] of HLA-DR+SIRPα + MNPs were examined in MLNs of UC [n = 14], CD [n = 35], and non-IBD [n = 12] patients., Results: Elevated frequencies of CD14+CD64+CD163+ [Mono/MΦ-like] MNPs displaying monocyte/MΦ morphology and phagocytic function were a distinct feature of UC MLNs. In CD, the proportion of CD14-CD64-CD163- [DC-like] cells was augmented relative to Mono/MΦ-like cells; DC-like cells drove naïve T cell proliferation, Th1 polarisation, and Th17 TCM plasticity. Gene expression profile corroborated the nature of DC-like cells, best represented by BTLA, SERPINF, IGJ and, of Mono/MΦ-like cells, defined by CD163, MARCO, MAFB, CD300E, S100A9 expression. CyTOF analysis showed that CD123+ plasmacytoid cells predominated over conventional DCs in DC-like cells. Four CD163+ clusters were revealed in Mono/MΦ-like cells, two of which were enriched in MARCO-CD68dimHLA-DRdim monocyte-like cells and MARCOhiCD68hiHLA-DRhi Mɸ, whose proportion increased in UC relative to CD., Conclusions: Defining the landscape of MNPs in MLNs provided evidence for expansion of CD163+ Mono/MΦ-like cells in UC only, highlighting a distinction between UC and CD, and thus the potential contribution of monocyte-like cells in driving colitis., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The drug targets IL23 and IL12 regulate pathogenicity and plasticity of intestinal Th17 cells in Crohn's disease (CD) and ulcerative colitis (UC), the two most common inflammatory bowel diseases (IBD). However, studies examining Th17 dysregulation in mesenteric lymph nodes (mLNs) of these patients are rare. We showed that in mLNs, CD could be distinguished from UC by increased frequencies of CCR6 + CXCR3 - RORγ + Tbet - CD4 + (Th17) memory T cells enriched in CD62L low effector memory T cells (T EM ), and their differentially expressed molecular profile. Th17 T EM cells (expressing IL17A, IL17F, RORC , and STAT3 ) displayed a higher pathogenic/cytotoxic ( IL23R, IL18RAP , and GZMB, CD160, PRF1 ) gene signature in CD relative to UC, while non-pathogenic/regulatory genes ( IL9, FOXP3, CTLA4 ) were more elevated in UC. In both CD and UC, IL12 but not IL23, augmented IFNγ expression in Th17 T EM and switched their molecular profile toward an ex-Th17 (Th1 * )-biased transcriptomic signature (increased IFNG , and decreased TCF7, IL17A ), suggesting that Th17 plasticity occurs in mLNs before their recruitment to inflamed colon. We propose that differences observed between Th17 cell frequencies and their molecular profile in CD and UC might have implications in understanding disease pathogenesis, and thus, therapeutic management of patients with IBD.

Purpose: The purpose of the study was to delineate parental concept of road safety in the state of Qatar, integrate parental thoughts and ideas into public safety, and share our data with authorities to assist in implementing campaigns against speeding in a country with a high rate of motor vehicle accidents., Methods: A cross-sectional prospective study was conducted at Hamad Medical Corporation (HMC), the only tertiary care and academic hospital in the state of Qatar. Parents of children younger than 18 years of age and residents of the State of Qatar were offered an interview survey., Results: A total of 200 questionnaires were completed (response rate = 98%). Approximately 80% of parents were in between 20 and 40 years of age, and 61% of them were females. Almost 40% of participating families reside outside of the city of Doha. Interestingly, only 1 in 2 parents thought their children were safe while riding with them in the car. Moreover, only 47% of parents always used car seats, seatbelts, and proper restraints. This is inspite that nearly 82% of parents felt that these restraints protect children in case of an accident. Parents were also asked of the best place to receive information regarding road safety. Almost 50% preferred to receive the information through social media, whereas 44.3% opted for local television. Role modeling was also assessed and it showed that 85% of parents believed that the most effective way in teaching children and young people to use roads in a safe way is to always provide a positive role model when using the roads., Conclusion: A large proportion of residents in the state of Qatar perceive that children are not safe while commuting in roads. Social media, a space where most of our community inhabit, seems to be the best setting to target our people., Competing Interests: There are no conflicts of interest.

Screening of toxoplasmosis in cancer patients is mandatory especially before starting treatment to guard against life-threatening disseminated disease. Diagnosis of toxoplasmosis rely mainly on serology. The most widely used method for detection of anti- Toxoplasma gondii ( T . gondii ) antibodies is the enzyme linked immunosorbent assay (ELISA), being available and reliable. Immunochromatographic tests (ICT) attracted a lot of attention recently being one of the high quality, rapid and easy to perform tests. Available data comparing the performance of ICT versus ELISA techniques have yielded inconsistent results and none compared their performance among the immunocompromised cancer patients. Therefore, we designed this study to compare the performance of a new ICT (the OnSite Toxo IgG/IgM Combo Rapid test) and ELISA techniques for the detection of anti- T. gondii antibody as a tool for screening for toxoplasmosis among cancer patients in Cairo-Egypt. Among 180 cancer patients, a total of 110 patients (61.1%) were positive for anti- T. gondii antibodies by one or both methods. Agreement between both methods was found in 78.8% of the samples. By using ELISA technique as a gold standard test for the detection of anti- T. gondii antibodies , our results showed 87.5% specificity and 74% sensitivity of ICT technique. Moreover, our results proved that ICT is more sensitive in detecting lower level of antibodies than ELISA, that makes it preferable as a screening test for the immunocompromised patients., Competing Interests: Compliance with ethical standardsAuthors certify that they have no financial, academic, commercial, political or personal associations that might pose a conflict of interest with the submitted article.

Background: Toxoplasmosis is one of the most important cosmopolitan life-threatening diseases in immune-compromised patients. It is caused by an intracellular protozoon: Toxoplasma gondii (T. gondii). The parasite can cause pneumonia, encephalitis or disseminated disease in immune-deficient patients and dangerous congenital anomalies in infants born to mothers infected during early pregnancies. The present study aims to evaluate the prevalence of toxoplasmosis in Egyptian cancer patients and to correlate the prevalence with type of malignancy and the different cancer treatment modalities. Materials and Methods: Blood samples from 150 cancer patients and 50 control subjects have been examined for presence of anti-toxoplasma antibodies using a lateral flow chromatographic immunoassay. Results: Among cancer patients included in this study, the prevalence of anti- T.gondii antibodies was 20% for IgG and 4% for IgM, while in the control group it was 8% and 2% in the same order. This difference was statistically significant for IgG (P =0.003) but not for IgM (P = 0.44). Patients with solid organ tumors treated with chemotherapy had the highest prevalence rate of toxoplasmosis (28%). It was also found higher in males (26%) than females (10%) and higher among urban (18%) than rural dwellers (16%). Conclusion: Cancer patients showed a significantly higher rate of infection with T. gondii than their cross-matched control. For that reason, we recommend the inclusion of a screening test for toxoplasmosis in their routine workup., (Creative Commons Attribution License)

Human Slan DCs have been studied in patients with psoriasis, rheumatoid arthritis, cancer, and autoimmune diseases. In this study, we investigated the frequency, phenotype, and function of Slan DCs in blood, colon, as well as mLNs of patients with IBD. We first show that the frequency of circulating CD14(dull)Slan DCs was reduced in CD patients refractory to immunosuppressive drugs or TNF-α blockers relative to untreated CD, UC, and healthy subjects. In blood of CD patients, Slan DCs expressed CD172a, as detected by CD47 fusion protein binding, when compared with its lack of expression in control subjects. Next, we demonstrate that CD172a(+)Slan DCs that produced IL-1β and TNF-α accumulated in mLNs and colons of CD patients. The CD172a(+)Slan DCs up-regulated their expression of CD14 in CD tissues and the proinflammatory cytokines were produced in CD14(bright)CD172a(+)Slan DCs. By contrast, no difference was noted in the frequency of Slan DCs between inflamed, noninflamed colonic mucosa of UC patients and control, non-IBD donors. Finally, the percentage of cytokine-producing Slan DCs also augmented in response to TLR2 and NOD2 in in vitro stimulation in PBMCs of CD, but not UC, patients. In conclusion, we propose that proinflammatory CD14(bright)CD172a(+)Slan DCs are a distinguishing feature between CD and UC, as these cells accumulate uniquely in mLNs and colonic mucosa of CD patients. Thus, Slan DCs may contribute to CD immunopathogenesis., (© Society for Leukocyte Biology.)

In mice, the transfer of CD172a(+) (SIRP-α) dendritic cells (DCs) elicits T cell-driven colitis, whereas treatment with CD47-Fc protein, a CD172a-binding agent, confers protection. The aim of this study was to elucidate the nature and functional properties of human CD172a(+) DCs in chronic intestinal inflammation. Here, we show that CD172a(+)CD11c(+) cells accumulate in the mesenteric lymph nodes (mLNs) and inflamed intestinal mucosa in patients with Crohn's disease (CD). These cells are distinct from resident DCs and may coexpress markers typically associated with monocyte-derived inflammatory DCs such as CD14 and/or DC-SIGN, E-Cadherin, and/or CX3CR1. Spontaneous IL-1β and TNF production by HLA-DR(+) cells in CD tissues is restricted to those expressing CD172a. An avidity-improved CD47 fusion protein (CD47-Var1) suppresses the release of a wide array of inflammatory cytokines by CD172a(+) cells, which may include HLA-DR(-)CD172a(+) neutrophils, in inflamed colonic explant cultures and impairs the ability of HLA-DR(+)CD172a(+) cells to activate memory Th17 but not Th1 responses in mLNs. In conclusion, targeting CD172a(+) cells may represent novel therapeutic perspectives for patients with CD.

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.

Methionine sulphoxide reductase A (MSRA) that reduces methionine-S-sulphoxide back to methionine constitutes a catalytic antioxidant mechanism to prevent oxidative damage at multiple sub-cellular loci. This study examined the relative importance of protection of the cytoplasm and mitochondria by MSRA using A-10 vascular smooth muscle cells, a cell type that requires a low level of reactive oxygen species (ROS) for normal function but is readily damaged by higher concentrations of ROS. Adenoviral over-expression of human MSRA variants, targeted to either mitochondria or the cytoplasm, did not change basal viability of non-stressed cells. Oxidative stress caused by treatment with the methionine-preferring oxidizing reagent chloramine-T decreased cell viability in a concentration-dependent manner. Cytoplasmic MSRA preserved cell viability more effectively than mitochondrial MSRA and co-application of S-methyl-L-cysteine, an amino acid that acts as a substrate for MSRA when oxidized, further increased the extent of protection. This suggests an important role for an MSRA catalytic antioxidant cycle for protection of the cytoplasmic compartment against oxidative damage.

Reactive oxygen species contribute to ageing of the vascular system and development of cardiovascular disease. Methionine-S-sulphoxide, an oxidized form of methionine, is repaired by the enzyme methionine sulphoxide reductase A (MSRA). The enzyme, targeted to mitochondria or the cytosol by alternative splicing, is vital for oxidative stress resistance. This study was designed to examine the endogenous expression and intracellular localization of MSRA in rat aortic vascular smooth muscle cells (VSMCs). We detected robust MSRA immunoreactivity exclusively in mitochondria. Sequence analysis of msrA transcripts revealed the presence of a novel mitochondrial splice variant, msrA2a, in cultured rat VSMCs as well as in aortic tissue preparations. The enzymatic activity of a recombinant MSRA2a protein was confirmed by the reduction of methionine sulphoxide in a model substrate peptide. We conclude that multiple MSRA variants participate in the repair of oxidized proteins in VSMC mitochondria, but that other protective mechanisms may exist in the cytoplasmic compartment.

Surgery in cirrhotic patients is associated with high morbidity and mortality related to portal hypertension and liver insufficiency. Therefore, preoperative portal decompression is a logical approach to facilitate abdominal surgery and hopefully to improve postoperative survival. The present study evaluated the clinical outcomes of 18 patients (mean age 58 years) with cirrhosis (seven alcoholics and 11 nonalcoholics) who underwent transjugular intrahepatic portosystemic shunt (TIPS) placement before antrectomy (n=5), colectomy (n=10), small-bowel resection (n=1), pancreatectomy (n=1) and nephrectomy (n=1). TIPS was performed a mean (+/-SD) of 72+/-21 days before surgery and induced a marked mean decrease in portohepatic gradient from 21.4+/-3.9 mmHg to 8.4+/-3.4 mmHg. Cirrhotic patients (n=17) who underwent elective abdominal surgery without preoperative TIPS placement were used as the control group. Both groups were matched for age, etiology of cirrhosis, indications for surgery, type of surgery and coagulation parameters. The mean Pugh score was significantly higher in the TIPS group (7.7 versus 6.2). No significant differences were observed for operative blood loss, postoperative complications, duration of hospitalization and one-month (83% versus 88%) or one-year (54% versus 63%) cumulative survival rate. Analysis using the Cox proportional hazards model showed that neither TIPS placement nor preoperative Pugh score were independent predictors for survival. The present study suggests that preoperative TIPS placement does not improve postoperative evolution after abdominal surgery in cirrhotic patients with good or moderately impaired liver function.

Methionine-directed oxidation of the human Slo1 potassium channel (hSlo1) shifts the half-activation voltage by -30 mV and markedly slows channel deactivation at low concentrations of intracellular Ca2+ ([Ca2+]i). We demonstrate here that the contemporaneous mutation of M536, M712 and M739 to leucine renders the channel functionally insensitive to methionine oxidation caused by the oxidant chloramine-T (Ch-T) without altering other functional characteristics. Coexpression with the auxiliary beta1 subunit fails to restore the full oxidative sensitivity to this triple mutant channel. The Ch-T effect is mediated specifically by M536, M712 and M739 because even small changes in this residue combination interfere with the ability to remove the oxidant sensitivity following mutation. Replacement of M712 or M739, but not M536, with the hydrophilic residue glutamate largely mimics oxidation of the channel and essentially removes the Ch-T sensitivity, suggesting that M712 and M739 may be part of a hydrophobic pocket disrupted by oxidation of non-polar methionine to the more hydrophilic methionine sulfoxide. The increase in wild-type hSlo1 open probability caused by methionine oxidation disappears at high [Ca2+]i and biophysical modelling of the Ch-T effect on steady-state activation implicates a decrease in the allosteric coupling between Ca2+ binding and the pore. The dramatic increase in open probability at low [Ca2+]i especially within the physiological voltage range suggests that oxidation of M536, M712 or M739 may enhance the Slo1 BK activity during conditions of oxidative stress, such as those associated with ischaemia-reperfusion and neurodegenerative disease, or in response to metabolic cues.

Because of the current economic situation, ambulatory surgery has become a "modus vivendi" for the surgeon. The aim of this study is to examine the feasibility of anal ambulatory surgery and the results obtained over a period of 12 months. 141 consecutive patients underwent anal surgery: 108 on an ambulatory basis (77%) and 33 were admitted to the hospital (23%). The reasons for admitting the patients were the complexity of the operation in 19 (8 sphincteroplasty, 5 complex fistulae, 3 recto-vaginal fistulae...) emergency procedures in 9 and miscellaneous reasons in 5 patients. All 108 patients operated on an ambulatory basis could be discharged at the end of the day but two, one for urinary retention and another because he underwent a more extensive procedure than first planned. Three more had urinary retention; they were catheterized and discharged on the same day. The four patients (3 women and 1 man) developed urinary retention following spinal anesthesia. Three patients (2.7%) had to come back to the emergency room in the first 24 hours for bleeding from the operative site. One of them had to be transfused and reoperated for hemostasis. In conclusion, ambulatory anal surgery is feasible in a large proportion of cases (77%) with a low rate of complications (7.4%) and low rate of unexpected hospital admission (2.7%). In a specialized colorectal unit, 23% of patients required hospitalization for a longer stay.

Multiple small bowel resections for obstructive symptoms caused by Crohn's disease can lead to a short bowel and malabsorption. Preservation of intestinal length is possible by the use of strictureplasty. Between August 1983 and March 1993, ninety strictureplasties were performed in 25 patients. They were 13 males and 12 females with a mean age of 37 years. Fourteen (56%) previously had small bowel resection for Crohn's disease. A mean number of 4.3 strictureplasties per patient were performed. Concomitant resection of bowel with active disease was performed in 18 patients (72%). In this series, no perioperative death occurred and one patient developed an enterocutaneous fistula. The overall complication rate was 8%. Postoperatively, 18 patients (72%) were completely relieved of symptoms, 6 were improved (24%) and one became worst (4%). After a 27 month follow-up period, the symptoms recurred in 13 patients (52%); three had no treatment, 7 had medical treatment and 3 required reoperation (12%). Our results support the safety and the use of strictureplasty for stenotic bowel lesions associated with Crohn's disease.

Surgical repair of the anal sphincters after previous trauma is generally successful. In earlier publications, a protective colostomy was recommended but in most recent series colostomy is omitted. We have been through both phases and this is the first comparative study done on 82 consecutive repairs: 45 with colostomy from 1977 to 1986 (Group I) and 37 without colostomy from 1986 to 1992 (Group II). Causes of trauma were obstetrical: 50, surgical: 24 and violence: 5. Apart from colostomy related morbidity, postoperative complication rates were similar in the two groups. Results were graded excellent, good, fair or poor according to continence to solids, to liquids and soiling. Good and excellent results were obtained in 82% (Group I) and 87% (Group II) after a mean follow-up duration of 42 and 23 months respectively. Furthermore there was no difference between Group I and II in the rate of good/excellent results for cases who had undergone prior repairs (98% v. 100%) and also when the duration of incontinence was more than 10 years (71% v. 83%). We conclude that colostomy is not a determinant factor in the outcome and is therefore not required, avoiding all colostomy related morbidity and disability.

Hepatic encephalopathy is a major complication of portal-systemic shunts with an incidence ranging up to 52%. A small fraction of these patients are refractory to medical therapy. Shunt ligation and colonic procedures are the main surgical approaches. The goal of the latter is to diminish the colonic absorption of nitrogenous substances which are involved in the pathophysiology of hepatic encephalopathy. Six patients, whose average age was 55.7 +/- 2.6 years, were operated for severe postshunt encephalopathy requiring 4.3 +/- 0.9 admissions for a total duration of 76 +/- 26 days over 1-11 years. One patient had undergone a splenoral shunt and 5 had a portacaval shunt. One ligation of the shunt and 5 colon exclusions were performed. The average postoperative hospital stay was 21.5 +/- 3.9 days. The mean follow-up was 47 +/- 20 months. The patient with the shunt ligation remains free of encephalopathy 94 months after the procedure and has not bled from his esophageal varices. Among the 5 colon exclusion patients, there were 1 death and 3 complications. Three patients were completely relieved of their hepatic encephalopathy. One of those 3 died of a subarachnoid hemorrhage 28 months after the surgery. The fourth still needs medication to control a persistent, although improved, encephalopathy that required 2 further hospitalizations. Colon exclusion is a useful intervention in very selected cases. It has a lower operative mortality than total colectomy and the advantage over shunt ligation of not reestablishing hypertension in the portal system.

Experimental use of cyclosporine in animal models following small intestinal transplantation is reviewed. The authors' techniques for monitoring allografts and harvesting the small bowel in humans for transplantation purposes are described.