Paris Descartes University

About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Transplantation. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.

Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

Abstract: As discussed in detail in other chapters of this review, chronic hepatitis B (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) Most HCCs complicate the evolution of an active or inactive cirrhosis However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical region to the other, being much higher in the southern half of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are associated with the cirrhosis This heterogeneity is probably a reflection of different environmental and genetic factors This review will summarize the current knowledge on the mechanisms involved in HBV-related liver carcinogenesis It will show in particular how viruses can be viewed as tools to discover and dissect new cellular pathways involved in cancer development and emphasize the potential synergistic effects between HBV and hepatitis C virus, as well as between viral infections and other environmental factors, such as alcohol

Integrative Genomic Analysis Reveals Somatic Mutations in Pheochromocytoma and Paraganglioma

Abstract: Pheochromocytomas and paragangliomas are neuroendocrine tumors that occur in the context of inherited cancer syndromes in ∼30% of cases and are linked to germline mutations in the VHL, RET, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2 and TMEM127 genes. Although genome-wide expression studies have revealed some of the mechanisms likely to be involved in pheochromocytoma/paraganglioma tumorigenesis, the complete molecular distinction of all subtypes of hereditary tumors has not been solved and the genetic events involved in the generation of sporadic tumors are unknown. With these purposes in mind, we investigated 202 pheochromocytomas/paragangliomas, including 75 hereditary tumors, using expression profiling, BAC array comparative genomic hybridization and somatic mutation screening. Gene expression signatures defined the hereditary tumors according to their genotype and notably, led to a complete subseparation between SDHx- and VHL-related tumors. In tumor tissues, the systematic characterization of somatic genetic events associated with germline mutations in tumor suppressor genes revealed loss of heterozygosity (LOH) in a majority of cases, but also detected point mutations and copy-neutral LOH. Finally, guided by transcriptome classifications and LOH profiles, somatic mutations in VHL or RET genes were identified in 14% of sporadic pheochromocytomas/paragangliomas. Overall, we found a germline or somatic genetic alteration in 45.5% (92/202) of the tumors in this large series of pheochromocytomas/paragangliomas. Regarding mutated genes, specific molecular pathways involved in tumorigenesis mechanisms are identified. Altogether, these new findings suggest that somatic mutation analysis is likely to yield important clues for personalizing molecular targeted therapies.

Comfort and patient-centred care without excessive sedation: the eCASH concept.

Abstract: We propose an integrated and adaptable approach to improve patient care and clinical outcomes through analgesia and light sedation, initiated early during an episode of critical illness and as a priority of care. This strategy, which may be regarded as an evolution of the Pain, Agitation and Delirium guidelines, is conveyed in the mnemonic eCASH—early Comfort using Analgesia, minimal Sedatives and maximal Humane care. eCASH aims to establish optimal patient comfort with minimal sedation as the default presumption for intensive care unit (ICU) patients in the absence of recognised medical requirements for deeper sedation. Effective pain relief is the first priority for implementation of eCASH: we advocate flexible multimodal analgesia designed to minimise use of opioids. Sedation is secondary to pain relief and where possible should be based on agents that can be titrated to a prespecified target level that is subject to regular review and adjustment; routine use of benzodiazepines should be minimised. From the outset, the objective of sedation strategy is to eliminate the use of sedatives at the earliest medically justifiable opportunity. Effective analgesia and minimal sedation contribute to the larger aims of eCASH by facilitating promotion of sleep, early mobilization strategies and improved communication of patients with staff and relatives, all of which may be expected to assist rehabilitation and avoid isolation, confusion and possible long-term psychological complications of an ICU stay. eCASH represents a new paradigm for patient-centred care in the ICU. Some organizational challenges to the implementation of eCASH are identified.

Abusive Head Trauma: Judicial Admissions Highlight Violent and Repetitive Shaking

Abstract: Objective Confessions are uncommon in abusive head trauma (AHT) cases, and there is debate over whether shaking alone can cause the injuries characteristic of AHT. The objective of this article is to correlate legal statements by perpetrators with medical documentation to offer insights into the mechanism of injury. Methods In this retrospective observational study we examined forensic evidence from 112 cases referred for AHT over a 7-year period. We compared 29 cases in which a perpetrator confessed to violence toward the child with 83 cases in which there was no confession. Inclusion criteria were subdural hematoma (SDH) on computed tomography and perpetrator admission of a causal relationship between the violence inflicted and the child's symptoms. Groups were compared by using Student's t test for age and Fisher's exact test for gender, death, fractures, retinal hemorrhages, ecchymoses, symptoms, and SDH patterns. All medical records from birth to diagnosis, imaging studies, and written investigation reports were reviewed. Results All confessions came from forensic investigations. There was no statistically significant difference between the 2 groups for any of the variables studied. Shaking was described as extremely violent (100%) and was repeated (55%) from 2 to 30 times (mean: 10) because it stopped the infant's crying (62.5%). Impact was uncommon (24%). No correlation was found between repeated shaking and SDH densities. Conclusions This unique forensic case series confirms the violence of shaking. The high frequency of habitual AHT is a strong argument for reporting suspected cases to judicial authorities and helps to explain the difficulty in dating the injuries.