Antibiotic therapy in case of positive cultures of kidney transplant preservation fluid: a nationwide survey of prescribing practices.

Our survey aimed to describe current prescribing practices for perioperative antibiotic prophylaxis in French kidney transplant centers. We conducted a nationwide cross-sectional clinical vignette-based survey that we sent via email to hospital practitioners involved in perioperative management of kidney transplant patients (KTR). Nearly half of practitioners contacted (182/427, 42.6%) were respondents. A total of 167 getting enough kidney transplant activity were eligible for the survey. The response rate was 50.7% (68/134) among interns and 33.8% (99/293) among seniors. Positive perfusion fluids (PF) cultures for methicillin-susceptible Staphylococcus aureus were associated with antibiotic prescribing in 35% of cases, with no difference in prescribing in patients with diabetes, obesity, or delayed graft function. Antibiotic prescribing was most frequent with Pseudomonas aeruginosa (67%) and Klebsiella pneumoniae strains producing extended spectrum ß-lactamases (57%). About 77%, 16%, and 13% of respondents, respectively, reported the existence of local practice guidelines for surgical antibiotic prophylaxis, a standardized approach for antibiotic prescribing in case of positive kidney transplant PF cultures, and local practice guidelines for systematical antibiotic prophylaxis in the early post-transplant period. In France, antibiotic prophylaxis practices in the perioperative kidney transplant period are very heterogeneous. To prevent unnecessary prescribing and bacterial resistance, evidence-based practice guidelines should be developed.

Microbiological epidemiology of preservation fluids in transplanted kidney: a nationwide retrospective observational study.

OBJECTIVES: Kidney transplant recipients are at high-risk for donor-derived infections in the early post-transplant period. Transplant preservation fluid (PF) samples are collected for microbiological analysis. In case of positive PF cultures, the risk for the recipient is unknown and there is no consensus for prescribing prophylactic antibiotics. This nationwide observational study aimed to determine the epidemiology of bacterial and fungal agents in kidney transplant PF cultures and identify risk factors associated with positive PF cultures. METHODS: We performed a retrospective observational study on the following data collected from a national database between October 2015 and December 2016: characteristics of donor, recipient, transplantation, infection in donor and PF microbiological data. RESULTS: Of 4487 kidney transplant procedures, including 725 (16.2%, 725/4487) from living donors, 20.5% had positive PF cultures (living donors: 1.8%, 13/725; deceased donors: 24.1%, 907/3762). Polymicrobial contamination was found in 59.9% (485/810) of positive PF cultures. Coagulase-negative staphylococci (65.8%, 533/810) and Enterobacteriaceae (28.0%, 227/810) were the most common microorganisms. Factors associated with an increased risk of positive PF cultures in multivariable analysis were (for deceased-donor kidney transplants): intestinal perforation during procurement (OR 4.4, 95% CI 2.1-9.1), multiorgan procurement (OR 1.4, 95% CI 1.1-1.7) and en bloc transplantation (OR 2.5, 95% CI 1.3-4.9). Use of perfusion pump and donor antibiotic therapy were associated with a lower risk of positive PF cultures (OR 0.4, 95% CI 0.3-0.5 and OR 0.6, 95% CI 0.5-0.7, respectively). CONCLUSION: In conclusion, 24% of deceased-donor PF cultures were positive, and PF contamination during procurement seemed to be the major cause.

Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part I: Phenotypic characterisation.

OBJECTIVES: The KCNQ1 gene encodes the KvLQT1 potassium channel, which generates in the human heart the slow component of the cardiac delayed rectifier current, I(Ks). Mutations in KCNQ1 are the most frequent cause of the congenital long QT syndrome. We have previously cloned a cardiac KCNQ1 human isoform, which exerts a strong dominant-negative effect on KvLQT1 channels. We took advantage of this dominant-negative isoform to engineer an in vivo model of KvLQT1 disruption, obtained by overexpressing the dominant-negative subunit under the control of the alpha-myosin heavy chain promoter. RESULTS: Three different transgenic lines demonstrated a phenotype with increasing severity. Functional suppression of KvLQT1 in transgenic mice led to a markedly prolonged QT interval associated with sinus node dysfunction. Transgenic mice also demonstrated atrio-ventricular block leading to occasional Wenckebach phenomenon. The atrio-ventricular block was associated with prolonged AH but normal HV interval in His recordings. Prolonged QT interval correlated with prolonged action potential duration and with reduced K(+) current density in patch-clamp experiments. RNase protection assay revealed remodeling of K(+) channel expression in transgenic mice. CONCLUSIONS: Our transgenic mouse model suggests a role for KvLQT1 channels not only in the mouse cardiac repolarisation but also in the sinus node automaticity and in the propagation of the impulse through the AV node.

Anticipation in Crohn's disease may be influenced by gender and ethnicity of the transmitting parent.

OBJECTIVE: We sought to examine whether anticipation (an earlier age of onset in succeeding generations) is observed in Crohn's disease (CD) patients within the New York metropolitan area, and whether there are differences in the degree of anticipation with respect to gender and ethnicity of the affected parent. METHODS: Sixty-one parent-child pairs both affected by CD were identified; about half of the pairs were of Ashkenazi Jewish descent. An additional 17 pairs of second-degree relatives with CD were also identified. The intergenerational difference in age at diagnosis (AAD) was used to perform regression analysis and the degree of anticipation among subsets of patients separated on the basis of gender and ethnicity of the transmitting parent was determined. RESULTS: The AAD was consistently (90% of the time) lower in the younger member of the 61 parent-child pairs (35.3+/-1.6 yr vs 20.8+/-1.1 yr, p = 0.0001). Furthermore, the degree of anticipation was significantly greater for father-child pairs (20.6+/-3.2 yr) than for mother-child pairs (11.7+/-2.1 yr). However, when the patient population where the parent had an AAD of < 28 was analyzed separately, there was a lack of clear-cut evidence of anticipation in the population as a whole. Only when the population was subdivided by ethnicity was there convincing evidence of anticipation in the Jewish population. CONCLUSION: Ascertainment bias may be responsible for the apparent anticipation observed in the CD population as a whole or in the nonJewish CD subgroup. However, the Jewish CD population displays strong evidence of anticipation even after correction for ascertainment bias.

Interobserver agreement in the staging of rectal cancer using endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: In rectal tumors invasion of the rectal fat and perirectal lymph nodes are generally regarded as independent prognostic factors in most prospective series. There are no studies in the literature concerning interobserver agreement on the staging of rectal cancer by endorectal ultrasonography (EUS). The aim of the present study was to assess interobserver agreement using EUS in the TN staging of rectal cancer. PATIENTS AND METHODS: Thirty-seven patients with rectal cancer were investigated at two centers using EUS as part of the pretherapeutic staging (Olympus EUM-3 or EUM-20). All examinations were videotaped and reviewed six months later by four independent observers who assessed the stage of the tumor (from uT1 to uT4) and lymphatic invasion on a blinded basis. When the tumor was assessed as uT3, the observers specified the degree of involvement of the rectal fat (in millimeters). Interobserver agreement was estimated using the kappa coefficient (k) and the intraclass correlation coefficient (ICC). Agreement was classed as poor (k < 0.40), fair to good (0.40 < or = k < 0.75) or excellent (k < or = 0.75). RESULTS: Agreement was fair for uT1 tumors (k = 0.40) and poor for uT2 tumors (k = 0.20). Agreement was good (k = 0.58; CI 0.51 to 0.65) for uT3 tumors; there was a significant interobserver correlation for the exact measure of the extent of rectal fat (ICC = 0.65). The agreement was also good (k = 0.54, CI 0.47 to 0.61) for metastatic lymph nodes. CONCLUSION: As in the case of esophageal cancer, interobserver agreement on the staging of uT2 tumors is poor with EUS. The evaluation of rectal tumors with a poor prognosis shows good interobserver agreement.

TAP gene transporter polymorphism in inflammatory bowel diseases.

BACKGROUND: Many studies suggest the implication of genetic factors in inflammatory bowel diseases. Despite some associations with HLA genes, the lack of definite data may be due to ethnic variations, clinical heterogeneity, or the involvement of additional susceptibility genes beside or within the major histocompatibility complex (MHC), such as TAP genes. The aim of this study was to analyze in patients with ulcerative colitis (UC) or Crohn's disease (CD) the polymorphism of TAP genes that encode the proteins necessary for the transfer of antigenic peptides through the endoplasmic reticulum membrane. METHODS: One hundred and one UC and 148 CD patients were compared with 173 unrelated healthy controls. Dimorphisms within the TAP1 and TAP2 alleles were analyzed by sequence-specific oligonucleotide typing. RESULTS: No difference was found between patient groups and controls. However, when CD patients were classified on the basis of their responsiveness to steroid therapy, a significant decrease of TAP2 AA (*0101/*0101) genotype was found in CD patients who did not respond to steroid therapy (22.9% versus 43.7% in steroid responder group; Pc < 0.05; odds ratio = 2.6; 95% confidence limits (CL) = 1.2-5.9). These data appear independent of the distribution of HLA DRB1*01 or DRB1*03 alleles despite a significant linkage disequilibrium between these alleles and TAP2A. CONCLUSIONS: This result suggests, despite the absence of arguments favoring a genetic susceptibility to CD, that the TAP2 gene or other genes located on chromosome 6 may be involved in the genetic heterogeneity of CD.

Leiden factor V mutation in four patients with small bowel infarctions.

The Leiden factor V mutation is observed in 20% of unexplained lower limb venous thromboses and involves substitution of the arginine residue at position 506 by glutamine (R506Q). It is known to decrease the anticoagulant activity of activated protein C. This case report describes 4 cases of small bowel infarction (SBI) associated with the presence of this mutation. Two cases of arterial and 2 cases of venous SBI were observed. Extensive assessment excluded the usual causes of SBI and plasma hypercoagulation syndrome (antithrombin III, protein C, and protein S deficiency and myeloproliferative syndrome). An abnormal resistance to activated protein C was observed. Molecular analysis consisting of polymerase chain reaction amplification and digestion with MnlI showed that 2 patients were heterozygous and 2 were homozygous for the R506Q mutation. Despite familial history of thrombosis in only 1 patient, first- and second-degree relatives of 2 patients also had the presence of the mutation. Examination for the presence of abnormal resistance to activated protein C should be part of the etiological assessment of SBI. Its presence may warrant consideration of long-term anticoagulant therapy, especially for patients with shortened small bowel who are treated by home parenteral nutrition with deep venous access.

Significance of interleukin-1beta and interleukin-1 receptor antagonist genetic polymorphism in inflammatory bowel diseases.

OBJECTIVE: Genetic susceptibility to inflammatory bowel disease is well recognized. There is also increasing evidence for the activation of the mucosal immune system and the production of inflammatory cytokines, i.e., interleukin (IL)-1ra and IL-1beta in the inflammatory bowel disease. The aim of this study was to analyze the IL-1beta and IL-1ra gene polymorphism and linkage disequilibrium coefficient between the different alleles of these genes in patients with Crohn's disease (CD) or ulcerative colitis (UC), according to the severity of the disease. METHODS: Two hundred twenty-eight inflammatory bowel disease patients (87 UC and 141 CD) were included in this study and compared with 113 unrelated controls. The IL-1beta and IL-1ra gene polymorphism was studied after specific amplification of variable regions by PCR. A penta-allelic polymorphism, corresponding to a VNTR region located in intron 2 of the IL-1ra gene, was analyzed, whereas bi-allelic RFLPs displayed by two restriction enzymes (TaqI and AvaI) at position -511 of the IL-1beta gene were analyzed. RESULTS: There was no significant difference of genotype distribution between controls and CD or UC patients. However, surgically treated UC patients were characterized by a higher frequency of genotype IL-1ra 1-2 (39 vs 16%, pc < 0.01) compared with nonoperated UC patients. Moreover, nonoperated UC patients displayed a lower frequency of IL-1ra allele 2 than surgically treated UC patients (14 vs 34%, pc < 0.002) or controls (14 vs 30%, pc < 0.005). Furthermore, simultaneous analysis of the IL-1beta and IL-1ra genes that are located in the same region of chromosome 2 revealed that CD patients carrying the IL-1beta allele 2 were more often noncarriers of IL-1ra allele 2 (p < 0.005). Moreover, UC and CD patients were, characterized by a lower frequency of the association of IL-1ra allele 2 and IL-1beta allele 2 compared with controls (8.3 vs 20.3% and 10.6 vs 20.3%, p < 0.03). CONCLUSIONS: IL-1ra and IL-1beta gene polymorphism analysis from a clinical standpoint might help in defining UC prognosis. However, functional studies at both the circulating and mucosal level with stratification on allele associations, especially IL-1ra allele 2-IL-1beta allele 2 subgroups must be realized before therapeutic implications.

[Gene therapy of a model of glioblastoma in rats using adenovirus vector encoding the HSVtk gene]. / Thérapie génique d'un modèle de glioblastome chez le rat à l'aide d'adénovirus porteurs du gène HSVtk.

Our aim was to test the therapeutic effects of adenovirus-mediated gene therapy in an animal model of brain tumor which was obtained by injection of 9L gliosarcoma cells into the caudate nucleus of rat brains. Seven days after the implantation of tumor cells, adenovirus vectors bearing the Escherichia coli beta galactosidase gene (ADV beta-gal) or the herpes simplex virus thymidine kinase gene (ADVtk) were stereotactically injected in the tumor. Injection of the ADV beta gal resulted in the expression of the marker gene in 61% of the animals. Transfer of the ADVtk was followed, 3 days later, by intraperitoneal injection of ganciclovir (GCV) for 10 days. A control group was treated with saline instead of GCV. We observed a significant regression of the tumors in 50% of the rats treated with ADVtk and GCV as compared with control animals. In 4 cases out of 6, the tumor completely disappeared after treatment. These results demonstrate the potential efficacy of adenovirus-mediated transfer of the HSVtk gene following by GCV administration for the treatment of glioblastomas.

[Primary pericardial thymoma: an unusual etiology of neoplastic pericarditis]. / Thymome primitif du péricarde: une étiologie inhabituelle de péricardite néoplasique.

We present a case of a primary pericardic thymoma, revealed by a pericardic effusion. This ectopic localisation is very unusual; neoplastic pericarditis are usually due to metastasis of carcinomas or lymphomas. Sometimes, they are secondary to pericardic invasion by mediastinal malignant thymomas or a metastasis of thymomas. Our patient presented a single pericardic localisation of thymoma without any other site. We discuss ectopic localisations of thymic tissue and thymomas and the diagnostic usefulness of the MIC 2 antibody.

[Giant hyperplastic polyposis with adenomatous tissue]. / Polypose hyperplasique géante à composante adénomateuse.

Hyperplastic polyps are the most common type of colorectal polyps. They are usually multiple and localized in the rectosigmoid area. They are easily recognized by their small size (< 10 mm), sessile form, smooth-surface and translucid appearance. Typically, these polyps have no malignant potential. We report the case of a 68-year-old man who had multiple rectosigmoid polyps, some of them having macroscopic features of adenomatous polyps. Because of the occurrence of bleeding after endoscopic polypectomy of two polyps corresponding to adenomas at examination, because of the multiplicity of these polyps and their localization in diverticulosis, a left colectomy followed by coloanal anastomosis was performed. Histologic examination of the surgical specimen revealed the hyperplastic nature of all polyps with, in two of them, a focus of adenomatous tissue.

Histological discrimination of idiopathic inflammatory bowel disease from other types of colitis.

AIMS: To assess the value of histology in diagnosing inflammatory bowel disease (IBD) in colorectal biopsy specimens. METHODS: Retrospective, double blind evaluation of colorectal biopsy specimens from 41 patients with colitis (28 with ischaemic colitis and 13 with acute self-limited colitis) and 84 patients with IBD (42 with Crohn's disease and 42 with ulcerative colitis). RESULTS: The features distinguishing IBD from other forms of colitis included distorted architecture, lymphocyte and plasma cell infiltrate, excess of polymorphonuclear leucocytes, polymorphonuclear cryptitis, crypt abscesses, and basal lymphoid aggregates. The features discriminating between Crohn's disease and ulcerative colitis included an irregular or villous surface, distorted architecture, decrease in mucus content, and polymorphonuclear cryptitis. Using multivariate analysis, 90% of patients with Crohn's disease and 71% of those with ulcerative colitis were correctly classified, the former being strongly defined by epithelioid granulomas, microgranulomas and isolated giant cells, and the latter best defined by an irregular or villous surface, decrease in mucus content and crypt atrophy. CONCLUSIONS: Examination of colorectal biopsy specimens is a reliable method for diagnosing IBD. In the absence of epithelioid granulomas, microgranulomas and isolated giant cells a diagnosis of Crohn's disease is based on the absence of histological criteria favouring ulcerative colitis. The histological spectrum of indeterminate colitis remains to be clarified.

Synthesis of novel inhibitors of the HIV-1 protease: difunctional enols of simple N-protected amino acids.

A series of enol HIV-1 protease inhibitors which show competitive inhibition and the structure-activity relationship study which led to the design of these compounds are reported. By systematically modifying simple amino acids, Boc-Phe enol and Boc-Tyr enol derivatives yield nanomolar Kiapp values (Kiapp = 0.485 microM and Kiapp = 0.425 microM, respectively). These enols are of low molecular weight (< 500 g/mol) and of non-peptidic nature. The enols are synthesized in a one step chemical synthesis and modifications to increase their potency could easily be performed. Boc-Phe enol and Boc-Tyr enol showed low inhibitory effect on pepsin, Kiapps of 23 and 149 microM, respectively, and Boc-Phe enol showed a Kiapp of 20 microM for cathepsin D. Neither of these two compounds inhibited renin (< 10% inhibition at 200 microM).

[Intraductal mucin-secreting tumors of the pancreas. Nosologic discussion of two cases of villous tumor of Wirsung's duct and a case of mucinous ductal ectasia]. / Les tumeurs mucosécrétantes intracanalaires du pancréas. Discussion nosologique à propos de deux cas de tumeur villeuse du canal de Wirsung et d'un cas d'ectasie canalaire mucineuse.

Intraductal mucin-producing tumors of the pancreas are rare, recently described tumors; they have a better prognosis than usual ductal carcinomas of the pancreas. We report two cases of villous tumor of the main pancreatic duct and one case of mucinous ductal ectasia, with histochemical and immunohistochemical study.

[Cystic tumors and endocrine tumor of the pancreas. An unusual association]. / Tumeurs kystiques et tumeur endocrine du pancréas. Une association exceptionnelle.

Cystadenomas and cystadenocarcinomas are the most common cystic tumors of the pancreas. Their inner lining contains neuroendocrine cells that may, in rare cases, produce a systemic syndrome. Similarly, digestive or pancreatic endocrine tumors have been reported in association with cystic tumors of the pancreas. We report a case of cystadenocarcinoma of the pancreas head, associated with a serous cystadenoma and an endocrine tumor of the body of the pancreas. In a 70 year old patient, jaundiced due to obstruction of the extra-hepatic bile ducts, the abdominal ultrasound and CT scan showed a hypoechogenic hypodense lesion of the pancreas head resulting in an enlargement of the common bile duct and pancreatic duct. Echoendoscopy confirmed the diagnosis and gave additional information; it showed that the cephalic lesion was heterogeneous, with anechogene spaces separated by coarse echogenic septae associated to a solid contingent. Also detected by echoendoscopy was a cystic lesion containing thin septae and a contiguous hypoechogenic nodule of the body of the pancreas. Histology of the specimen following total pancreatectomy revealed a cephalic cystadenocarcinoma associated with a serous cystadenoma and a non-secreting endocrine tumor of the body region. This observation highlights the usefulness of echoendoscopy in the work-up of cystic lesions of the pancreas; indeed, the tumors of the body of the pancreas were not detected by others methods. Furthermore, there are reports in literature on endocrine secretion syndromes secondary to digestive endocrine tumors or neuroendocrine cells in the lining of cystic tumors of the pancreas.

Bladder substitutes, bile acids and the risk of colorectal cancer: an experimental study.

There is a large body of evidence relating the causation of colon cancer to bile acids. Using an animal model, we attempted to address the question, i.e., the incidences of carcinogenesis in the colon as consequences of resection of different bowel segments, predominantly employed in the construction of various forms of intestinal bladder substitutes. 60 male Wistar rats were operated. Group 1 served as control, in group 2, 20 cm of terminal ileum was resected, and rats in group 3 underwent resection of the distal 10 cm of the ileum and 7 cm of the proximal colon. All rats were killed 6 months after surgery and the colon was removed. After examination under 40-fold magnification, in the absence of tumors, 3 biopsies were performed at predetermined positions and underwent histological processing. Even if no tumor was found it would be incorrect to conclude that these results would have an appeasing relevance. The complex and highly different fecal bile acid profiles of the rat compared to man makes it impossible in this context to draw analogies between the rat model and human colonic carcinogenesis. Furthermore, 6 months of observation in the rat might be too short for 'spontaneous' colonic carcinogenesis. Nevertheless, there exists evidence from epidemiological studies to implicate bile acids as an etiological factor in the development and growth of colorectal cancer. Therefore, the importance of colorectal cancer in urologic surgery patients must be kept in perspective. In this direction, further studies are required besides the application of known appropriate preventive measures.

[Neuroendocrine carcinoma of the esophagus. Case report with immunohistochemical study]. / Carcinome neuroendocrine de l'oesophage. Rapport d'un cas avec étude immunohistochimique.

The authors report a case of neuroendocrine carcinoma of the lower third of the esophagus. Immunohistochemical study revealed that most tumor cells expressed neuron specific enolase, chromogranin A, carcinoembryonic antigen and glucagon. They insist on the usefulness of this study on biopsies in order to guide therapeutic decision.

[Villous tumors of the Wirsung's duct and pancreatic intraductal adenocarcinoma: interrelation or accidental association?]. / Tumeurs villeuses du canal de Wirsung et adénocarcinome pancréatique intra-canalaire: filiation ou association fortuite?

Villous neoplasms of the main pancreatic duct are uncommon. Two cases of neoplasm of the main cephalic pancreatic duct in 61- and 42-year-old patients presenting with long standing (10 and 12 years) history of abdominal pain are reported. In both cases, duodenal fistula was present and mucus was observed by endoscopy at the fistula and major papilla levels. Endoscopic retrograde pancreatography showed a stricture of the main pancreatic duct in the pancreatic head. In one case, with incomplete stricture, pancreatic ducts disclosed typical features of chronic obstructive pancreatitis and contained mucus casts. Histologic examination of total and proximal duodenopancreatectomy showed a villous neoplastic pattern with focal malignant changes within the main pancreatic duct. The adjacent pancreatic tissue showed signs of stromal invasion without lymph node or nervous infiltration. Glandular parenchyma was atrophic in the pancreatic body and tail, with extensive fibrosis, and the pancreatic duct depicted signs of nonpapillary hyperplasia. Histochemical study disclosed a predominant sialomucin secretion by villous adenoma and sulfomucin secretion by epithelial cells lining the accessory or main caudal pancreatic ducts. These results lead us to suggest a possible relationship between villous adenoma of ducts and pancreatic adenocarcinoma.