Bacterial and Viral Infection and Sepsis in Kidney Transplanted Patients

Kidney transplanted patients are a unique population with intrinsic susceptibility to viral and bacterial infections, mainly (but not exclusively) due to continuous immunosuppression. In this setting, infectious episodes remain among the most important causes of death, with different risks according to the degree of immunosuppression, time after transplantation, type of infection, and patient conditions. Prevention, early diagnosis, and appropriate therapy are the goals of infective management, taking into account that some specific characteristics of transplanted patients may cause a delay (the absence of fever or inflammatory symptoms, the negativity of serological tests commonly adopted for the general population, or the atypical anatomical presentation depending on the surgical site and graft implantation). This review considers the recent available findings of the most common viral and bacterial infection in kidney transplanted patients and explores risk factors and outcomes in septic evolution

Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: The Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study

BACKGROUND: Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. METHODS: 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m(2)) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute – Common Toxicity Criteria. RESULTS: 55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7–58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent neurological toxicity 6 months after the end of chemotherapy. CONCLUSION: A significant proportion of patients with advanced ovarian cancer treated with first-line carboplatin/paclitaxel suffer long-term residual neuropathy. This issue should be carefully taken into account before considering re-treatment with the same agents in sensitive recurrent disease

Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the SOCRATES retrospective study

<p>Abstract</p> <p>Background</p> <p>Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer.</p> <p>Methods</p> <p>The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000–2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible.</p> <p>Results</p> <p>Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056) and less advanced FIGO stage (p = 0.025). At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024). About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03). Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026), with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04). Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023).</p> <p>Conclusion</p> <p>This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed.</p

Outcomes of pregnancies after kidney transplantation: lessons learned from CKD. A comparison of transplanted, nontransplanted chronic kidney disease patients and low-risk pregnancies: a multicenter nationwide analysis.

BACKGROUND: Kidney transplantation (KT) may restore fertility in CKD. The reasons why materno-foetal outcomes are still inferior to the overall population are only partially known. Comparison with the CKD population may offer some useful insights for management and counselling.Aim of this study was to analyse the outcomes of pregnancy after KT, compared with a large population of non-transplanted CKD patients and with low-risk control pregnancies, observed in Italy the new millennium. METHODS: We selected 121 live-born singletons after KT (Italian study group of kidney in pregnancy, national coverage about 75%), 610 live-born singletons in CKD and 1418 low-risk controls recruited in 2 large Italian Units, in the same period (2000-2014). The following outcomes were considered: maternal and foetal death; malformations; preterm delivery; small for gestational age baby (SGA); need for the neonatal intensive care unit (NICU); doubling of serum creatinine or increase in CKD stage. Data were analysed according to kidney diseases, renal function (staging according to CKD-EPI), hypertension, maternal age, partity, ethnicity. RESULTS: Materno-foetal outcomes are less favourable in CKD and KT as compared with the low-risk population. CKD stage and hypertension are important determinants of results. KT patients with e-GFR >90 have worse outcomes compared with CKD stage 1 patients; the differences level off when only CKD patients affected by glomerulonephritis or systemic diseases ('progressive CKD') are compared with KT. In the multivariate analysis, risk for preterm and early-preterm delivery was linked to CKD stage (2-5 versus 1: RR 3.42 and 3.78) and hypertension (RR 3.68 and 3.16) while no difference was associated with being a KT or a CKD patient. CONCLUSIONS: The materno-foetal outcomes in patients with kidney transplantation are comparable with those of nontransplanted CKD patients with similar levels of kidney function impairment and progressive and/or immunologic kidney diseas

DÉCLINAISONS DE L' « URBANISME COMME SCIENCE ». DISCOURS ET PROJETS : ITALIE ET FRANCE (1920-1940)

According to a comparative approach, this thesis examines the declinations of « urbanism as a science » in Italy and France between the ‘20s and ‘40s of the twentieth century, as well the devices and the establishment of « scientific planning ». These declinations are explored in the intertwining between discourses and projects, through the prism of four major figures : Marcel Poëte, Gaston Bardet, Gustavo Giovannoni and Luigi Piccinato. Poëte and Giovannoni are the initiators ; Bardet and Piccinato the coders of a way of thinking about urban planning that wants to be « autonomous ». A double key question guide this research: historical and epistemological. On the one hand, the study of « urbanism as a science » and its construction with the support of other disciplines ; and secondly, the analysis of cultural and political context within which the planning doctrines are formulated. A double corpus is explored : theoretical texts, the reading of wich proceeds on the basis of a strict chronological and thematic division ; plans and urban projects, to whom the texts are referred.Cette thèse traite, selon une approche comparative, des déclinaisons de l' « urbanisme comme science » en Italie et en France entre les années 20 et 40 du XXe siècle, et des dispositifs et de la mise en place de l'« urbanisme scientifique ». Ces déclinaisons sont considérées dans l'entrelacement entre discours et projets, à travers du prisme de quatre figures majeures : Marcel Poëte, Gaston Bardet, Gustavo Giovannoni et Luigi Piccinato. Poëte et Giovannoni représentent les initiateurs ; Bardet et Piccinato les codificateurs d'une manière de penser l'urbanisme qui se veut « autonome ». Une double problématique guide cette recherche : épistémologique et historique. D’une part, l’étude de l'« urbanisme comme science » et de sa construction avec le concours d'autres disciplines ; d'autre part, l'exploration du cadre – culturel et politique – à l’intérieur duquel les doctrines de l'urbanisme se formulent. Un double corpus est exploré : de textes théoriques, dont la lecture procède sur la base d'un découpage strict au sens chronologique et thématique ; de plans et de projets urbains, auxquels les textes font souvent référence

Une généalogie du savoir disciplinaire : le modèle science dans la construction du discours des urbanistes dans la première moitié du XXe siècle

International audienceAs a heterodox intellectual, Gaston Bardet manages to overcome the boundaries of an eminently pragmatic vision of urban planning and to correlate the thought on the city with the multiple contributions of the human sciences. Even if it does not suggest models literally, he builds a look on the city that adopts the science as an ideal figure. As a virtuous alternative to empiricism dominant in the practice of planners, it aims to establish a conceptual machinery to deal with the chaotic drift of contemporary city. But its recourse to science as a model is anything but linear, with the large use of metaphors, analogies and even allusions. In an intertwining of scientific intentions, mythicization (of the discourse and the planner’s figure), search for spaces of visibility, Bardet’s reflection introduces a radical departure from the ways of thinking the city which were contemporary. This fault remains largely unexplored, and this article intends to cover the first tracks.Intellectuel hétérodoxe, Gaston Bardet parvient à franchir les limites d’une vision éminemment pragmatique de l’urbanisme et à corréler la pensée sur la ville avec les apports multiples des sciences humaines. Même s’il ne bâtit pas des modèles au sens propre, il construit un regard sur l’urbain qui prend comme figure idéale la science : en tant qu’alternative vertueuse à l’empirisme dominant dans la pratique des urbanistes, il vise à constituer un outillage conceptuel pour faire face à la dérive chaotique de la ville contemporaine. Mais son recours à la science comme modèle est tout autre que linéaire, avec l’emploi diffus de métaphores, d’analogies et même d’allusions. Dans un entrelacement d’intentions scientifiques, de visées de mythisation (du discours et de la figure de l’urbaniste), de recherche d’espaces de visibilité, sa réflexion instaure une rupture radicale par rapport aux manières de penser et de faire la ville qui lui étaient contemporaines. Cette faille demeure largement inexplorée, et cet article se propose d’en parcourir des premières pistes

Une généalogie du savoir disciplinaire : le modèle science dans la construction du discours des urbanistes dans la première moitié du XXe siècle

International audienceAs a heterodox intellectual, Gaston Bardet manages to overcome the boundaries of an eminently pragmatic vision of urban planning and to correlate the thought on the city with the multiple contributions of the human sciences. Even if it does not suggest models literally, he builds a look on the city that adopts the science as an ideal figure. As a virtuous alternative to empiricism dominant in the practice of planners, it aims to establish a conceptual machinery to deal with the chaotic drift of contemporary city. But its recourse to science as a model is anything but linear, with the large use of metaphors, analogies and even allusions. In an intertwining of scientific intentions, mythicization (of the discourse and the planner’s figure), search for spaces of visibility, Bardet’s reflection introduces a radical departure from the ways of thinking the city which were contemporary. This fault remains largely unexplored, and this article intends to cover the first tracks.Intellectuel hétérodoxe, Gaston Bardet parvient à franchir les limites d’une vision éminemment pragmatique de l’urbanisme et à corréler la pensée sur la ville avec les apports multiples des sciences humaines. Même s’il ne bâtit pas des modèles au sens propre, il construit un regard sur l’urbain qui prend comme figure idéale la science : en tant qu’alternative vertueuse à l’empirisme dominant dans la pratique des urbanistes, il vise à constituer un outillage conceptuel pour faire face à la dérive chaotique de la ville contemporaine. Mais son recours à la science comme modèle est tout autre que linéaire, avec l’emploi diffus de métaphores, d’analogies et même d’allusions. Dans un entrelacement d’intentions scientifiques, de visées de mythisation (du discours et de la figure de l’urbaniste), de recherche d’espaces de visibilité, sa réflexion instaure une rupture radicale par rapport aux manières de penser et de faire la ville qui lui étaient contemporaines. Cette faille demeure largement inexplorée, et cet article se propose d’en parcourir des premières pistes

New perspectives in the treatment of advanced or metastatic gastric cancer

Metastatic gastric cancer remains an incurable disease, with a relative 5-year survival rate of 7%-27%. Chemotherapy, which improves overall survival (OS) and quality of life, is the main treatment option. Meta-analysis has demonstrated that the best survival results obtained in earlier randomized studies were achieved with three-drug regimens containing a fluoropyrimidine, an anthracycline, and cisplatin (ECF). Although there has been little progress in improving median OS times beyond the 9-mo plateau achievable with the standard regimens, the availability of newer agents has provided some measure of optimism. A number of new combinations incorporating docetaxel, oxaliplatin, capecitabine, and S-1 have been explored in randomized trials. Some combinations, such as epirubicin-oxaliplatin-capecitabine, have been shown to be as effective as (or perhaps more effective than) ECF, and promising early data have been derived for S-1 in combination with cisplatin. One factor that might contribute to extending median OS is the advancement whenever possible to second-line cytotoxic treatments. However, the biggest hope for significant survival advances in the near future would be the combination of new targeted biological agents with existing chemotherapy first-line regimens

Hepatocarcinoma: from pathogenic mechanisms to target therapy

Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. It is currently estimated that there are 14,000–18,000 new cases of hepatocellular carcinoma in the United States each year. It is often difficult to identify individuals at risk for HCC. The main associated diseases are chronic hepatitis B and chronic hepatitis C viral infections. While a significant number of potential mutations have been generated including p53 and Insulin-like Growth Factor, our understanding of the molecular mechanisms driving the genesis and progression of HCC remain limited. HCC screening is recommended in high-risk patients. High-risk patients include virtually all patients with cirrhosis and some HBV-infected patients irrespective of cirrhosis (>40 years in men and >50 years in women). A diagnostic approach to HCC has been developed incorporating serology, cytohistology, and radiological characteristics. A precise staging of the disease may help decide on prognosis as well as choice of therapy with the greatest survival potential. Liver transplantation, in theory, is the optimal therapeutic option for HCC; it simultaneously removes the tumor and underlying cirrhosis thus minimizing the risk of HCC recurrence. When it is impossible for this to be performed, percutaneous ablation, chemoembolization, chemotherapy and the newer molecular therapies can be used. Sorafenib is the only drug registered today for the treatment of advanced HCC