[What follow-up after pediatric cancer ? The SALTO consultation experience]. / Quel suivi après un cancer pédiatrique ? L'expérience de la consultation SALTO.

During the past 50 years, the mortality due to childhood cancers decreased dramatically thanks to improvements in supportive care and the use of multimodal approaches. In this context, the long-term follow up after childhood cancer has become a main concern for pediatric oncologists. The SALTO programme was developed in 2012 at the CHR Citadelle in Liège in order to organize a multidisciplinary long-term follow-up for the patients previously treated in our department for a childhood cancer. The aim of the present study was to review, for the most frequent childhood cancers, the long-term sequellae and the second cancers developed by the patients participating to the SALTO programme in order to define the follow-up needed. Our data confirm the importance of a multidisciplinary long-term follow-up, based on the treatments received and following international guidelines.

Au cours des cinquante dernières années, la mortalité liée aux cancers pédiatriques a fortement diminué grâce à une amélioration des soins de support et à l'utilisation d'approches multimodales. Dans ce contexte, le devenir à long terme des patients guéris d'un cancer pédiatrique est devenu une des préoccupations majeures pour les oncologues pédiatres. Dans cette optique, la consultation SALTO («Suivi À Long Terme en Oncologie¼) a été mise en place en 2012 au CHR de la Citadelle pour assurer le suivi multidisciplinaire des adultes ayant été traités dans notre secteur d'hémato-oncologie pédiatrique. L'objectif de cette étude a été de revoir, pour les cancers pédiatriques les plus fréquents, les séquelles et les tumeurs secondaires présentées par les patients suivis en consultation SALTO afin de préciser les modalités du suivi au long cours après cancer pédiatrique. Nos résultats confirment l'importance d'un suivi multidisciplinaire à long terme adapté aux traitements reçus, sur base de recommandations internationales.

[Multidisciplinary management of the pediatric sickle cell patient in 2019]. / Prise en charge multidisciplinaire du patient drépanocytaire pédiatrique en 2019.

Sickle cell disease is a common genetic disorder that affects haemoglobin. It is manifested by haemolytic anaemia and vaso-occlusive crisis. It can affect all organs and its evolution is unpredictable. The multidisciplinary management of pediatric patients who suffer from it is essential to adapt their treatment and optimize their evolution. One of the major challenges is to succeed the transition to adult medicine. New therapeutic perspectives are in development and look promising.

La drépanocytose est une maladie génétique fréquente qui affecte l'hémoglobine. Elle se manifeste par une anémie hémolytique et des phénomènes vaso-occlusifs. Elle peut toucher tous les organes et son évolution est imprévisible. La prise en charge multidisciplinaire des patients pédiatriques qui en souffrent est essentielle pour optimaliser leur évolution et adapter leur traitement. Un des défis majeurs est de réussir la transition vers la médecine adulte. De nouvelles perspectives thérapeutiques sont en développement.

[A trans-hospital pilot programme for onco-geriatry. The experience of the CHC-Liege]. / Programme pilote trans-hospitalier d'onco-gériatrie.

The authors offered to 296 consecutive cancer patients aged > or = 70 to undergo a joint comprehensive geriatric and oncological assessment. After pluridisciplinary discussion, several reflections have emerged: the need in 15 - 32% of cases to reinforce the role of the paramedical staff; the correlation between age, low clinical indices, alteration of renal function as well as geriatric characteristics; 67% of evaluated cases presented a significant geriatric profile; recommendations for patients' management in relation to their pattern of frailty and health aging (standard, adapted or palliative treatment).

Evaluation of biological rhythms in elderly cancer patients. A complementary translational research within the frame of the trans-hospital pilot program of oncogeriatrics launched at CHC-Liège.

Thanks to the sponsoring of Belgian Cancer Plan, we have launched a trans-hospital project of oncogeriatrics implying any concerned actors from medical (oncology, geriatrics, various specialties) and paramedical staffs (nurses, physiotherapists, ergotherapists, dieteticians, social workers, psychologists…). We aim to recruit 300 consecutive patients aged over 70 and presenting with a new diagnosed cancer. They will benefit from both detailed Comprehensive Geriatrical (CGA) and Oncological (COA) assessments. A multidisciplinary concertation will try to define for each patient an individualized treatment planning taking into account CGA, CGO, co-morbidities, predictive indexes of chemotherapy toxicity (MAX2, i.e.). Detailed records will be obtained in collaboration with the data-management staff. Furthermore, a complementary translational research will include patients for a simple evaluation of their circadian rhythmicities through cortisol titration at 8a.m. and 4p.m. and actometry recordings of the rest-activity rhythms. Future steps could be developed aiming at the restoration of circadian structure disturbances with revalidation (physical exercise, tai-chi, yoga) and resynchronization (melatonin, hydrocortisone, bright light…) programs.

Amyloid precursor protein cross-linking stimulates beta amyloid production and pro-inflammatory cytokine release in monocytic lineage cells.

Beta amyloid peptide-containing neuritic plaques are a defining feature of Alzheimer's disease pathology. Beta amyloid are 38-43 residue peptides derived by proteolytic cleavage of amyloid precursor protein. Although much attention has focused on the proteolytic events leading to beta amyloid generation, the function of amyloid precursor protein remains poorly described. Previously, we reported that amyloid precursor protein functions as a pro-inflammatory receptor on monocytic lineage cells and defined a role for amyloid precursor protein in adhesion by demonstrating that beta(1) integrin-mediated pro-inflammatory activation of monocytes is amyloid precursor protein dependent. We demonstrated that antibody-induced cross-linking of amyloid precursor protein in human THP-1 monocytes and primary mouse microglia stimulates a tyrosine kinase-based pro-inflammatory signaling response leading to acquisition of a reactive phenotype. Here, we have identified pro-inflammatory mediators released upon amyloid precursor protein-dependent activation of monocytes and microglia. We show that amyloid precursor protein cross-linking stimulated tyrosine kinase-dependent increases in pro-inflammatory cytokine release and a tyrosine kinase-independent increase in beta amyloid 1-42 generation. These data provide much needed insight into the function of amyloid precursor protein and provide potential therapeutic targets to limit inflammatory changes associated with the progression of Alzheimer's disease.

Temporal course of graviperception in intermittently stimulated cress roots.

Gravitropic bending of Lepidium roots caused by intermittent stimulation lasting approximately 1 h was the same for a particular sum of stimulation intervals and was independent of (i) the length of a single stimulation interval (from 1 to 12.2 s) during which the roots were exposed unilaterally and horizontally, and (ii) rest intervals (from 60 to 300 s) during which roots were horizontally rotated at two revolutions per minute on a clinostat. The same effectiveness of equal sums of short stimulations separated by relatively long rest intervals indicates that the signals into which the stimuli are transduced are: (i) additive; (ii) proportional to the duration of a single stimulation; and (iii) stable for at least 5 min. The perception time is shorter than 1 s, the presentation time is approximately 10 s. The effects of intermittent stimulation fit the hypothesis that the gravity-induced movement of statoliths changes asymmetrically the stress in cytoskeletal actin filaments, thereby inducing gravitropic bending.

Gravity induced changes in intracellular potentials in statocytes of cress roots.

Two glass microelectrodes were inserted from opposite sides of the root cap into statocytes of Lepidium sativum L. immersed in medium with or without cytochalasin D (CD). Intracellular potentials (Eis) of statocytes were measured with reference to an earthed electrode in the bathing solution. In the absence of CD, Ei values were -160 +/- 2 mV (n = 52) in vertical roots. During the recording of Eis, the roots were tilted from the vertical by 45 degrees so that in a tilted root one electrode was on the upper side and the other on the lower side; after 5 min the roots were returned to the vertical. At approximately 64 s after tilting (lasting 5-15 s) there was a transient lowering of Ei (more negative) by an average of 4.7 mV on both the upper and lower sides (n = 52). In some cases, this decrease in Ei was preceded by a transitory increase. Returning the roots to the vertical resulted in a response similar to that obtained by tilting. In roots treated with CD at a concentration of 3 (microM for 1 h, the initial Ei was -145 +/- 2 mV (n = 43), and the lowering of Ei on position change (tilting or returning) was smaller (2.0 mV) in some statocytes (n = 50) and higher (8.1 mV) in others (n = 14) compared to control roots (without and with DMSO). A higher concentration (10 microM) of CD and longer treatment (2 h) further reduced the decrease in Ei (1.1 mV) on position change (n = 26). The observed effects of CD support the hypothesis that statoliths in statocytes are anchored by actin filaments to the plasma membrane and/or to the cortical endoplasmic reticulum. Movement of statoliths during the first step of graviperception may lead to stress changes in actin filaments, affecting the transmembrane potential and also the Ei.

Production of tumour necrosis factor-alpha, interferon-gamma and interleukin-2 by peripheral blood mononuclear cells of subjects suffering from rheumatoid arthritis.

Using radio-immunoassay methods, the production of tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) released by peripheral blood mononuclear cells (PBMC), maintained in culture and stimulated by phytohemagglutinin (PHA), was measured in normal subjects and patients with active or inactive rheumatoid arthritis (RA). Results indicated a dissociation between mitogenic response and secretion of mediators by PBMC under the influence of PHA in both normal controls and in patients with rheumatoid arthritis (RA). While [3H]thymidine incorporation was characterized by a rather bell-shaped curve with increasing concentrations of PHA, IL-2 and TNF-alpha displayed a linear dose-dependent increase. [3H]thymidine uptake by PBMC was in the same range in normal subjects as in patients with active and inactive RA, although cytokine secretion differed. The PBMC of patients with active RA produced less TNF-alpha, IL-2, and IFN-gamma than did those of the controls. In cases of inactive RA, the secretory response varied from subject to subject; mean values did not differ from those of normal subjects, except for those of IL-2 (p less than 0.01). The significance and the clinical relevance of these findings are discussed.