[Artificial nutrition in advanced palliative situations : Issues and recommendations]. / Nutrition artificielle en situation palliative avancée : quels enjeux et quelles recommandations ?

This article focuses on the recommendations and issues of artificial nutrition (AN) in advanced palliative situations. In oncological situations, stages of cachexia and performance indexes help guide the decision-making process regarding the indications for AN. AN is usually not recommended in low performance indexes (Karnofsky ≤50 %, ECOG ≥ 3) nor in refractory cachexia. In some cases, a time-limited therapeutic trial may be suggested, with its effectiveness assessed by measurable goals. In advanced dementia, AN is not recommended. Often at the source of an AN request, the emotional aspect deserves to be explored in order to assess the patient's and his/her family's expectations and fears.

Cet article s'intéresse aux recommandations et aux enjeux de la nutrition artificielle (NA) en situation palliative avancée. En situation oncologique, les stades de cachexie et les indices de performance permettent d'orienter le processus décisionnel quant aux indications de la NA. Cette dernière est en général contre- indiquée lors d'indice de performance bas (Karnofsky ≤ 50 %, ECOG/ Eastern Cooperative Oncology Group ≥ 3) et lors de cachexie réfractaire. Dans certains cas, un essai thérapeutique d'un temps limité peut être proposé, dont l'efficacité est évaluée par des objectifs mesurables. En situation de démence avancée, la NA n'est pas recommandée. Souvent à l'origine d'une demande de NA, l'aspect émotionnel mérite d'être exploré afin d'évaluer les angoisses et les (faux) espoirs du patient et de ses proches.

Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers.

BACKGROUND AND AIMS: Carriage of rs738409:G in patatin-like phospholipase domain containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with carriage of PNPLA3 rs738409:G. This study explores the risk associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC. APPROACH AND RESULTS: Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including 1,031 with alcohol-related cirrhosis and HCC, 1,653 with alcohol-related cirrhosis without HCC, 2,588 alcohol misusers with no liver disease, and 899 healthy controls. Genetic associations with the risks for developing alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for developing both cirrhosis (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.72-0.88; P = 8.13 × 10-6 ) and HCC (OR, 0.77; 95% CI, 0.68-0.89; P = 2.27 × 10-4 ), whereas carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR, 1.70; 95% CI, 1.54-1.88; P = 1.52 × 10-26 ) and HCC (OR, 1.77; 95% CI, 1.58-1.98; P = 2.31 × 10-23 ). These associations remained significant after adjusting for age, sex, body mass index, type 2 diabetes, and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women, but the protective effect against the subsequent development of HCC was only observed in men (ORallelic , 0.75; 95% CI, 0.64-0.87; P = 1.72 × 10-4 ). CONCLUSIONS: Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population.

Correction: Genetic Variants in PNPLA3 and TM6SF2 Predispose to the Development of Hepatocellular Carcinoma in Individuals With Alcohol-Related Cirrhosis.

Author Pierre Deltenre, MD should appear in the author list in position 25, between Felix Braun and Thomas Berg. He should also have a PhD degree added to his name.

Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis.

OBJECTIVES: Variants in patatin-like phospholipase domain-containing 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), and membrane bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) are risk factors for the development of alcohol-related cirrhosis. Within this population, PNPLA3 rs738409 is also an established risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to explore possible risk associations of TM6SF2 rs58542926 and MBOAT7 rs641738 with HCC. METHODS: Risk variants in PNPLA3, TM6SF2, and MBOAT7 were genotyped in 751 cases with alcohol-related cirrhosis and HCC and in 1165 controls with alcohol-related cirrhosis without HCC. Association with the risk of developing HCC was analyzed using multivariate logistic regression. RESULTS: The development of HCC was independently associated with PNPLA3 rs738409 (ORadjusted 1.84 [95% CI 1.55-2.18], p = 1.85 × 10-12) and TM6SF2 rs58542926 (ORadjusted 1.66 [1.30-2.13], p = 5.13 × 10-05), using an additive model, and controlling the sex, age, body mass index, and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (ORadjusted 1.04 [0.88-1.24], p = 0.61) was not significant. The population-attributable fractions were 43.5% for PNPLA3 rs738409, 11.5% for TM6SF2 rs58542926, and 49.9% for the carriage of both the variants combined. CONCLUSIONS: Carriage of TM6SF2 rs58542926 is an additional risk factor for the development of HCC in people with alcohol-related cirrhosis. Carriage of both PNPLA3 rs738409 and TM6SF2 rs58542926 accounts for half of the attributable risk for HCC in this population. Genotyping will allow for more precise HCC risk-stratification of patients with alcohol-related cirrhosis, and genotype-guided screening algorithms would optimize patient care.

For Better or Worse: The Effect of Prismatic Adaptation on Auditory Neglect.

Patients with auditory neglect attend less to auditory stimuli on their left and/or make systematic directional errors when indicating sound positions. Rightward prismatic adaptation (R-PA) was repeatedly shown to alleviate symptoms of visuospatial neglect and once to restore partially spatial bias in dichotic listening. It is currently unknown whether R-PA affects only this ear-related symptom or also other aspects of auditory neglect. We have investigated the effect of R-PA on left ear extinction in dichotic listening, space-related inattention assessed by diotic listening, and directional errors in auditory localization in patients with auditory neglect. The most striking effect of R-PA was the alleviation of left ear extinction in dichotic listening, which occurred in half of the patients with initial deficit. In contrast to nonresponders, their lesions spared the right dorsal attentional system and posterior temporal cortex. The beneficial effect of R-PA on an ear-related performance contrasted with detrimental effects on diotic listening and auditory localization. The former can be parsimoniously explained by the SHD-VAS model (shift in hemispheric dominance within the ventral attentional system; Clarke and Crottaz-Herbette 2016), which is based on the R-PA-induced shift of the right-dominant ventral attentional system to the left hemisphere. The negative effects in space-related tasks may be due to the complex nature of auditory space encoding at a cortical level.