[From medication reconciliation to shared medication review: Pilot study integrating support for community pharmacists within a pharmaceutical care pathway]. / De la conciliation médicamenteuse au bilan partagé de médication : étude pilote intégrant un accompagnement des pharmaciens d'officine au sein d'un parcours de soins pharmaceutiques.

INTRODUCTION: Medication reconciliation at hospital and the shared medication review are two complementary activities for securing the medication management of the elderly patient. We are experimenting with a pharmaceutical care pathway including a support approach to promote continuity between these two activities and the initiation of shared medication review. MATERIALS AND METHODS: An admission and discharge medication reconciliation has been set up in a geriatric follow-up care and rehabilitation service. A drug assessment was also carried out during the hospital stay. Support for community pharmacists following conciliation was provided by phone calls. Medication discrepancies at admission and discharge, pharmaceutical interventions (PI) as well as satisfaction and difficulties encountered by community pharmacists were collected. RESULTS: Thirty-three patients were included in the study. On admission, 33% of patients had an unintentional discrepancy and 15% on discharge. On average 1.15 PI per patient were notified. The support was propounded to 13 pharmacists. Eight pharmacists (62%) accepted it. Among them, 5 (62.5%) had never performed a medication review. Lack of time was the main difficulty encountered by pharmacists. DISCUSSION AND CONCLUSION: Our pathway enables to integrate hospital and primary care activities and specifically support the delicate transition between them. This enables to facilitate the implementation of these activities and to maintain a relevant and secure continuity of pharmaceutical care.

[Impact of positive surgical margins on prostate cancer prognosis]. / Impact carcinologique des marges positives après prostatectomie totale.

OBJECTIVE: To examine the impact of positive surgical margins (PSM) after radical prostatectomy (RP) for prostate cancer on oncological results. PATIENTS AND METHODS: We performed a study where all patients who underwent radical prostatectomy between January 2004 and December 2018 for prostate cancer were included. The preoperative, postoperative data and the carcinological results collected were analyzed. Data were analysed using Kaplan-Meier survival analysis and proportional hazards models. RESULTS: A total of 319 patients with a median age of 65 years (IQR : 62-69) were included. The median follow-up was 43.6 months (IQR: 19.4-79.3). The overall rate of PSM was 33.5%. PSM was associated with biochemical recurrence (P<0.001). Overall mortality was not associated with positive margins. A clinical stage> T1c was an independent predictor of PSM on multivariate analysis (P=0.01). CONCLUSION: PSM would increase the risk of biochemical recurrence with no impact on survival. Clinical stage>T1c was an adverse predictor for PSM. LEVEL OF EVIDENCE: 3.

[Impact of antiplatelet and anticoagulant treatments on bleeding complications in patients treated with HoLEP]. / Impact des anticoagulants et antiagrégants sur complications hémorragiques chez les patients traités par HoLEP.

INTRODUCTION: We aimed to assess the impact of antiplatelet and anticoagulation therapy for patients undergoing HoLEP. METHODS: We performed a study during the learning curve on a consecutive series of patients who underwent HoLEP surgery from 2015 to 2018. The patients were divided into 3 groups: a control group, patients with antiplatelet therapy and patients with anticoagulation therapy. RESULTS: A total of 223 patients underwent HoLEP surgery during this period: 124 in the control group, 63 in the antiplatelet group and 36 in the anticoagulant group. In the anticoagulant group, we observe significant differences with the control group for the catheterization time (2.05 days vs 5.17 days; P<0.001), the hospital length of stay (1.5 nights vs 4.49 nights; P<0.001) and complications (8.9% vs 58%; P<0.001). No difference between the control and antiplatelet groups in terms of catheterization time, hospital length of stay and complications (2.05 days vs 2.68 days; 1.5 nights vs 1.6 nights) but variation in terms of complications and bleeding complications (8.9% vs 21%; P<0,001; 8.1% vs 19%; P<0,001) CONCLUSION: Our study shows that HoLEP is therefore associated with a higher risk of bleeding for patients treated with anticoagulation therapy. Complications increase morbidity with longer catheterization time, hospitalization times and higher transfusion's rates, revision surgery and readmission. LEVEL OF EVIDENCE: 3.

[Result of treatment of urinary lithiasis for professional aptitude]. / Traitement de la lithiase urinaire pour aptitude professionnelle : résultats de la prise en charge par urétéroscopie dans une population militaire.

INTRODUCTION: Military people are inapt for presence of urinary stones. In this specific population, the treatment of stones is even more aggressive than for the general population without recommendation. The final decision about aptitude is the responsibility of the military doctor. Whereas, ureteroscopy has its place there and must done by any urologist. METHODS: The purpose of this study was to estimate the results of treatments by ureteroscopy in this population. Success was defined by the complete absence of fragment visualized in the imaging of control operating comment and so the end of the inaptitude time. RESULTS: Between 2009 and 2016, forty-two were treated for ureteral or renal calculi. The population comprises of 93% men, 35 years old on average. The stones were mainly multiple (more 2) and the medium size is 5mm; sixteen (42.9%) was at the left and eight (19%) was bilateral. In 78.8% (78) of the cases there was a stone in renal position whose 50% (39) still at the lower calyx. In total, 5% of the patients were stone-free in 2 sessions on average. The average deadline of inaptitude of the initial consultation in the resumption of work was of 6 months. In 4% of the cases there was a complication operating rank 4. CONCLUSION: This study confirms the feasibility, the weak harmlessness of ureteroscopy and the lesser deadline of inaptitude. Every urologist can treat this specific population. The patient must be informed and accept the treatment because of excluding referential. LEVEL OF EVIDENCE: 4.

[Oncological results of active surveillance in prostate cancer: A retrospective multicentric cohort]. / Résultats oncologiques de la surveillance active dans le cancer de la prostate : série rétrospective multicentrique.

PURPOSE: To report oncological outcomes of patients with prostate cancer undergoing active surveillance according to SURACAP criteria. METHODS: This multicentric study included patients who were initially treated with active surveillance for localized prostate cancer according to the SURACAP criteria. The duration of active surveillance as well as the causes of discontinuing the protocol and the definitive pathological results of patients who further underwent radical prostatectomy were retrospectively evaluated. The predictors of discontinuing active surveillance were assessed using a univariable Cox Model. In addition, the predictive value of initial MRI was assessed for patients who performed such imagery. RESULTS: Between 2007 and 2013, 80 patients were included, with a median age of 64 years [47-74]. Median follow-up was 52.9 months [24-108]. At 5 years follow-up, 43.4% patients were still under surveillance. Among patients that underwent surgery, 17.8% had an extra-capsular extension. The risk of discontinuing was not significantly greater for patients with tumor size of 2 or 3mm versus 1mm (HR=0.9 [0.46-1.75], P=0.763), 2 positives cores versus 1 (HR=0.98 [0.48-2.02], P=0.967), T2a vs. T1c stage (HR=2.18 [0.77-6.18], P=0.133), increased PSA level (HR=1 [0.96-1.15], P=0.975) or the patient's age (HR=1 [0.93-1.16], P=0.966). Among the 50 patients who performed initial MRI, the results of such imagery was not significantly associated to the risk of discontinuing active surveillance MRI (HR=1.49 [0.63-3.52], P=0.36). CONCLUSION: Although this study reveals a high rate of release from active surveillance at 5 years, the rate of extra-capsular tumors reported in the group of patients that underwent surgery is among the lowest in literature. LEVEL OF EVIDENCE: 4.

[Is obesity a barrier to kidney transplantation?]. / L'obésité est-elle un frein à la transplantation rénale ?

INTRODUCTION: Kidney transplantation is the most suitable of ESRD care. The proportion of obese people is increasing in the general population and patients with kidney impairment. It is important to assess the impact of obesity on surgical complications of kidney transplantation. The aim of this retrospective study was to signify the correlation between obesity and the occurrence of postoperative urological complications during the first year. METHODS: We conducted a retrospective study from March 1999 to December 2009. We conducted a chart review of patients undergoing kidney transplantation. The kidneys were taken from cadaveric donors. Data collected included age, weight, height, preoperative BMI; causal nephropathy, smoking, hypertension, diabetes, anticoagulation therapy. Intraoperative data included operative time (DO), cold ischemia. Urological complications were recorded during the first year after the kidney transplantation (vascular anastomotic strictures, ureterovesical stenosis, lymphorrheas, pyelonephritis, hematoma, wound infection). Statistical analysis consisted of a t-test for independent samples and univariate and multivariate logistic regression for the occurrence of complications. RESULTS: Four hundred and twenty-two patients were transplanted in total. We excluded 20 patients. BMI and duration of surgery patients with complications were significantly different from those of patients with no complications (P=0.016 and P=0.039, respectively). Obese (n=48) had more diabetes (12.5% versus 3.7%, P=0.014), were more often smoking (35.4% versus 22%, P=0.012), had a longer DO (203.64minutes versus 182.46minutes, P=0.006), and complications (62.5% versus 50.28%, P=0.03) than patients with a BMI <30 (n=354). After adjusting for age, smoking, DO, diabetes and BMI showed that only BMI was an independent predictor of the occurrence of postoperative complications with P=0.048 and RR=1.058 [CI: 1 to 1.119]. However, there was no more transplantectomy obese (P=0.911). CONCLUSION: Our study showed that there is a significant risk of surgical complications after kidney transplantation in obese patients. But ultimately, this does not affect graft survival because there are no more transplantectomies or return to dialysis. LEVEL OF EVIDENCE: 5.

[The impact of obesity on renal function at one year after kidney transplantation: single-center experience]. / Impact de l'obésité sur la fonction rénale à 1 an chez les transplantés rénaux: expérience mono centrique.

INTRODUCTION: Kidney transplantation is the treatment of choice for ESRD. Several studies have investigated the factors that may affect kidney function at 1 year. The factors mentioned are anemia, hypercholesterolemia, immunosuppressors, etc. We studied the independent predictors of serum creatinine>100µmol/L at 1 year. MATERIALS AND METHODS: We conducted a retrospective study from March 1999 to December 2009. We conducted a chart review of 402 kidney transplant patients. The kidneys were removed from cadaveric donors. Data collected included age, weight, height, preoperative BMI, the causal nephropathy, smoking, hypertension, diabetes, anticoagulation. Intraoperative data included operative time, and cold ischemia. Statistical analysis consisted of a t-test for independent samples comparing the group with a creatinine≤100µmol/L vs>100 group, and univariate and multivariate Cox regression for a serum creatinine>100µmol/L at 1 year and test of correlation between BMI and serum creatinine at 1 year postoperatively. RESULTS: We found a significant difference in BMI and cold ischemia with P=0.008 and P=0.002, respectively. In contrast there was no difference in age, operative time and blood loss, P=0.758, P=0.941 and P=0.963, respectively. Multivariate Cox regression showed that donor age P=0.004 (HR: 1.016 and CI: 1.005-1.027), a recipient age P=0.023 (HR: 0.986 and CI: 0.974-0.998) and BMI P=0.001 (HR: 1.019 and CI: 1.010-1.028) were independent predictors of serum creatinine>100µmol/L at 1 year. The Pearson correlation coefficient r=0.154 (P=0.004) showed a significant correlation between BMI and serum creatinine. CONCLUSION: Our study showed that donor age, recipient age and BMI were independent predictors of renal function>100µmol/L at 1 year. Our results highlight the difficulty of the management of obesity in renal transplant patients. LEVEL OF EVIDENCE: 5.

Generation of region- and species-specific expressed gene probes from somatic cell hybrids.

Human genes expressed in interspecific somatic cell hybrids can be cloned specifically by subtractive cDNA hybridization. This approach is based on the observation that cDNA fragments from noncoding segments of mature human transcripts do not form stable heteroduplexes with their rodent homologues under high-stringency hybridization conditions. Thus, small, oligo-dT primed cDNAs from a rat/human hybrid retaining a fragment of human chromosome 17 were enriched for human sequences by hybridization with RNA from a sister clone containing a smaller human chromosome fragment. The enriched probe was used to screen a human cDNA library, and nine expressed genes from within the non-overlap region were obtained. This method should be useful for cloning active human genes from defined chromosome segments.

Efficient modification of human chromosomal alleles using recombination-proficient chicken/human microcell hybrids.

Targeted modification of human chromosomal alleles by homologous recombination is a powerful approach to study gene function, but gene targeting in mammalian cells is an inefficient process. In contrast, gene targeting in a chicken pre-B cell line, DT40, is highly efficient. We have transferred human chromosome 11 into DT40 cells by microcell fusion, and find that the resulting hybrids are recombination-proficient. In these cells, targeting efficiencies into the chicken ovalbumin locus were > 90% and into the human beta-globin and Ha-ras loci were 10-15%. These modified human chromosomes can be transferred subsequently to mammalian cells for functional tests. This chromosome shuttle system allows for the efficient homologous modification of human chromosomal genes, and for subsequent phenotypic analyses of the modified alleles in different mammalian cell types.

Effect of endocervical inflammation on days to conception in dairy cows.

In contrast to endometritis, now diagnosed by cytological examination, the effect of endocervical inflammation on reproductive performance has been inadequately investigated. In this study, endocervical and endometrial cytological specimens were collected from 168 Holstein cows between 21 and 60 days in milk (DIM) to investigate the prevalence of endocervical inflammation and effect on days to conception. Statistical analyses were stratified based on DIM at examination (<35 vs. ≥35 DIM). Endocervical inflammation with ≥5% neutrophils before 35 DIM (disregarding the level of endometrial inflammation) was associated with decreased hazard of pregnancy within 300 DIM (adjusted hazard ratio, 0.4; 95% confidence interval: 0.3-0.8). A decrease in hazard of pregnancy was observed when >6% neutrophils were counted in endometrial smears (adjusted hazard ratio, 0.4; 95% confidence interval: 0.2-0.7). The study suggested an additive effect of combined endocervical and endometrial inflammation on the hazard of pregnancy within 300 DIM. Using the thresholds of 5% neutrophils for the cervix and 6% neutrophils for the uterus, 11% of the cows examined before 35 DIM presented cervicitis only, 13% were affected by endometritis only, and 32% suffered from both endometrial and endocervical inflammation. The presence (absence) of cervicitis was not indicative of the presence (absence) of endometritis. This study showed that in addition to uterine inflammation, endocervical inflammation in early lactation affects conception. Thus, the global evaluation of genital tract health may be more beneficial for reproductive performance than that of endometrial inflammation.

Clustering of cytokine genes on mouse chromosome 11.

The presence of positionally conserved amino acid residues suggests that the mouse proteins TCA3, P500, MIP1-alpha, MIP1-beta, and JE are members of a single gene family. These proteins are activation specific and can be expressed by both myeloid and lymphoid cells. MIP1-alpha/MIP1-beta and MCAF (the putative human homologue of JE) act as chemotactic and activating agents for neutrophils and macrophages, respectively. The functions of TCA3 and P500 are unknown. We have used interspecies somatic cell hybrids and recombinant inbred mouse strains to show that the genes encoding TCA3, MIP1-alpha, MIP1-beta, and JE (provisionally termed Tca3, Mip-1a, Mip-1b, and Sigje, respectively) map as a cluster on the distal portion of mouse chromosome 11 near the Hox-2 gene complex. DNA sequence analysis indicates that the P500 and TCA3 proteins are encoded by alternative splicing products of one genomic gene. Additionally, the genes encoding TCA3 and JE are found to be strikingly similar with respect to the positions of intron-exon boundaries. Together, these data support the model that the cytokines TCA3, P500, MIP1-alpha, MIP1-beta, and JE are encoded by a single cluster of related genes. The gene encoding IL-5 (Il-5), which acts as a T cell-replacing factor, a B cell growth factor, and an eosinophil differentiation factor, is also mapped to mouse chromosome 11.Il-5 maps approximately 25 cM proximal to the Tca-3 gene and appears tightly linked to a previously described gene cluster that includes Il-3, Il-4, and Csfgm. We discuss the potential relevance of the two cytokine gene clusters described here with particular attention to specific human hematologic malignancies associated with chromosomal aberrations at corresponding locations on human chromosomes 5 and 17.

The locus control region activates serpin gene expression through recruitment of liver-specific transcription factors and RNA polymerase II.

The human serine protease inhibitor (serpin) gene cluster at 14q32.1 comprises 11 serpin genes, many of which are expressed specifically in hepatic cells. Previous studies identified a locus control region (LCR) upstream of the human alpha1-antitrypsin (alpha1AT) gene that is required for gene activation, chromatin remodeling, and histone acetylation throughout the proximal serpin subcluster. Here we show that the LCR interacts with multiple liver-specific transcription factors, including hepatocyte nuclear factor 3beta (HNF-3beta), HNF-6alpha, CCAAT/enhancer binding protein alpha (C/EBPalpha), and C/EBPbeta. RNA polymerase II is also recruited to the locus through the LCR. Nongenic transcription at both the LCR and an upstream regulatory region was detected, but the deletion of the LCR abolished transcription at both sites. The deletion of HNF-3 and HNF-6 binding sites within the LCR reduced histone acetylation at both the LCR and the upstream regulatory region and decreased the transcription of the alpha1AT, corticosteroid binding globulin, and protein Z-dependent protease inhibitor genes. These results suggest that the LCR activates genes in the proximal serpin subcluster by recruiting liver-specific transcription factors and components of the general transcription machinery to regulatory regions upstream of the alpha1AT gene.

[Necrosis of the glans penis: a complication of an injection of buprenorphin in a opioid abuser]. / Nécrose du gland après injection volontaire de buprénorphine dans un contexte de toxicomanie aux opioïdes.

Necrosis of the penis glans is commonly described after circumcision or strangulation. We report the case of a patient, opioid abuser, who presented an isolated glans necrosis after an injection of buprenorphin. The buprenorphin (Subutex) is a sublingual partial mu-opioid agonist used for the treatment of heroin dependance. Its intravenous or subcutaneous abuse is associated with local infection. The patient require a surgical intervention. After the failure of a mucosal graft, a soft skin graft was done.

North atlantic deep-sea fertility.

Observations have been made on two cruises in the North Atlantic in which large numbers of microscopic, unicellular flagellates have been found throughout the aphotic zone below 1000 meters. Preliminary measurements also indicate the uptake of dissolved organic substances, suggestive of an apparently viable, actively metabolizing community at these depths.

Multigene family for sarcomeric myosin heavy chain in mouse and human DNA: localization on a single chromosome.

Cloned myosin heavy chain DNA probes from rat and human were hybridized to restriction endonuclease digests of genomic DNA from somatic cell hybrids and their parental cells. The mouse myosin heavy chain genes detectable by this assay were located on chromosome 11, and three different human sarcomeric myosin heavy chain genes were mapped to the short arm of chromosome 17. A synteny between myosin heavy chain and two unrelated markers, thymidine kinase and galactokinase, was found to be preserved in the rodent and human genomes.

Participation of the human beta-globin locus control region in initiation of DNA replication.

The human beta-globin locus control region (LCR) controls the transcription, chromatin structure, and replication timing of the entire locus. DNA replication was found to initiate in a transcription-independent manner within a region located 50 kilobases downstream of the LCR in human, mouse, and chicken cells containing the entire human beta-globin locus. However, DNA replication did not initiate within a deletion mutant locus lacking the sequences that encompass the LCR. This mutant locus replicated in the 3' to 5' direction. Thus, interactions between distantly separated sequences can be required for replication initiation, and factors mediating this interaction appear to be conserved in evolution.

Two NF1 translocations map within a 600-kilobase segment of 17q11.2.

Balanced translocations, each involving chromosome 17q11.2, have been described in two patients with von Recklinghausen neurofibromatosis (NF1). To better localize the end points of these translocation events, and the NF1 gene (NF1) itself, human cosmids were isolated and mapped in the immediate vicinity of NF1. One cosmid probe, c11-1F10, demonstrated that both translocation breakpoints, and presumably NF1, are contained within a 600-kilobase Nru I fragment.

From individual to collective displacements in heterogeneous environments.

Animal displacement plays a central role in many ecological questions. It can be interpreted as a combination of components that only depend on the animal (for example a random walk) and external influences given by the heterogeneity of the environment. Here we treat the case where animals switch between random walks in a homogeneous 2D environment and its 1D boundary, combined with a tendency for wall-following behaviour (thigmotactism) that is treated as a Markovian process. In the first part we use mesoscopic techniques to derive from these assumptions a set of partial differential equations (PDE) with specific boundary conditions and parameters that are directly given by the individual displacement parameters. All assumptions and approximations made during this derivation are rigorously validated for the case of exploratory behaviour of the ant Messor sanctus. These PDE predict that the stationary density ratio between the 2D (centre) and 1D (border) environment only depends on the thigmotactic component, not on the size of the centre or border areas. In the second part we test this prediction with the same exploratory behaviour of M. sanctus, in particular when many ants move around simultaneously and may interact directly or indirectly. The prediction holds when there is a low degree of heterogeneity (simple square arena with straight borders), the collective behaviour is "simply" the sum of the individual behaviours. But this prediction breaks down when heterogeneity increases (obstacles inside the arena) due to the emergence of pheromone trails. Our approach may be applied to study the effects of animal displacement in any environment where the animals are confronted with an alternation of 2D space and 1D borders as for example in fragmented landscapes.

[Ilio-ureteral fistula: a life-threatening complication of an iliac Candida-infected pseudoaneurysm. A case report]. / Fistule ilio-urétérale: complication redoutable d'un faux anévrisme iliaque infecté à Candida. A propos d'un cas.

Arterio-ureteral fistula is a rare condition difficult to diagnose. The usual presentation associates acute paroxysmal hematuria with well-identified history and risk factors. We report the case of an 84-year-old man with a life-threatening complication of an ilio-ureteral fistula complicating an anastomotic iliac pseudoaneurysm after prothetic iliofemoral surgery, due to a fungic infection by Candida. After reporting the clinical case and the emergency surgical treatment, we present a review of the literature.

Human matrix attachment regions are necessary for the establishment but not the maintenance of transgene insulation in Drosophila melanogaster.

Human matrix attachment regions (MARs) can insulate transgene expression from chromosomal position effects in Drosophila melanogaster. To gain insight into the mechanism(s) by which chromosomal insulation occurs, we studied the expression phenotypes of Drosophila transformants expressing mini-white transgenes in which MAR sequences from the human apoB gene were arranged in a variety of ways. In agreement with previous reports, we found that a single copy of the insulating element was not sufficient for position-independent transgene expression; rather, two copies were required. However, the arrangement of the two elements within the transgene was unimportant, since chromosomal insulation was equally apparent when both copies of the insulator were upstream of the mini-white reporter as when the transcription unit was flanked by insulator elements. Moreover, experiments in which apoB 3' MAR sequences were removed from integrated transgenes in vivo by site-specific recombination demonstrated that MAR sequences were required for the establishment but not for the maintenance of chromosomal insulation. These observations are not compatible with the chromosomal loop model in its simplest form. Alternate mechanisms for MAR function in this system are proposed.