[News drugs and evolution towards personalized treatment for cystic fibrosis]. / Avancées thérapeutiques et évolution vers une médecine personnalisée pour les patients atteints de mucoviscidose.

Cystic fibrosis is a genetic disorder responsible for the production of a defective transmembrane protein. In recent years, new protein modulators have been developed. They aim to treat the underlying cause of the disease. The results on the biomarkers of the function of the CFTR protein and on the clinical outcomes are very encouraging. However, there is an individual heterogeneity in the response to modulators within a same genotype. Furthermore, clinical trials focus on the most common mutations in the CFTR gene, in particular DF508. Intestinal organoids, a new model of ex vivo study, could offer a quick approach to increase access to effective treatment for all patients with cystic fibrosis regardless of their CFTR genotype. Organoids could enable personalized treatment of cystic fibrosis.

La mucoviscidose est une maladie génétique responsable de la production d'une protéine transmembranaire défectueuse. Au cours des dernières années, se sont développés des traitements modulateurs ciblant les défauts spécifiques de la protéine causés par les mutations du gène CFTR. Les résultats sur les biomarqueurs de la fonction de la protéine CFTR et sur les paramètres cliniques sont très encourageants. Cependant, une hétérogénéité individuelle dans la réponse aux modulateurs est observée. De plus, les essais cliniques se focalisent sur les mutations les plus fréquentes du gène, en particulier DF508. Les organoïdes intestinaux, un nouveau modèle d'étude ex vivo, pourraient offrir une approche rapide pour majorer l'accès à un traitement efficace à tous les patients, quel que soit leur génotype CFTR. Les tests in vitro sur les organoïdes rendent possible l'évolution vers une médecine personnalisée pour les patients atteints de mucoviscidose.

[Lung transplantation benefits for terminal lung diseases]. / Apport de la greffe pulmonaire dans les pathologies respiratoires terminales.

Lung transplantation is an established treatment of pulmonary diseases at an advanced stage. The purpose of our study is to present the benefits, indications and complications of this surgical procedure in the CHU of Liège. The cohort includes 14 patients transplanted between 2005 and 2009, and who were inserted in a pulmonary rehabilitation programme at the university hospital of Liège. The criteria of assessment are the values of respiratory function tests at rest and exercise, and quality of life. Inherent complications related to this type of surgical operation have been collected. We found a dramatic improvement in pulmonary function tests performed at rest both immediately after the transplantation and after 6 months. Likewise exercise capacity was already increased shortly after the transplantation and further improved 6 months later. As for health related quality of life, parameters that improved the most were dyspnoea and global quality of life, and the improvement was already maximal immediately after the transplantation. Our retrospective study confirms the data of the literature, namely an improvement of respiratory function, effort capacity and quality of life after lung transplantation.

Skin immunoglobulin deposition following intravenous immunoglobulin therapy in toxic epidermal necrolysis.

Human intravenous immunoglobulins (IVIg) which contain anti-CD95 antibodies have been proposed to treat toxic epidermal necrolysis (TEN). Presently, there is no evidence that IVIg reach the keratinocytes in TEN patients. The aim of this study was to assess the Ig distribution in the serum, blister fluid and skin of six consecutive TEN patients treated with IVIg (1 g/kg/day) for 3 days. They were compared with five TEN patients who only received supportive therapy. In all patients, IgA, IgM and IgG concentrations were measured in the serum and blister fluid using an immuno-nephelometric method. Immunohistochemistry was performed on skin biopsies taken from both TEN clinically involved and uninvolved skin to search for IgG deposits. On admission, the IgG concentrations were significantly higher in both TEN serum and TEN blister fluid compared with their respective IgA and IgM contents. The IgG, IgA and IgM concentrations in blister fluid were significantly lower than their respective serum concentrations. The serum and blister fluid IgG concentrations, but not that of IgA and IgM, were markedly increased at the completion of the IVIg treatment. By contrast, they remained unchanged in the TEN patients that were untreated with IVIg. In the IVIg-treated patients, the IgG intraepidermal deposits raised markedly in both TEN-involved and uninvolved skin. This was not the case in patients who did not receive IVIg. These results suggest that IVIg perfusions brought a prominent increase in IgG concentration in the serum, blister fluid and epidermis of both TEN-involved and clinically uninvolved skin. The presence of potentially protective IgG in TEN epidermis following IVIg treatment could help limiting the disease progression.

The long-term analgesic efficacy of a single-shot fascia iliaca compartment block in burn patients undergoing skin-grafting procedures.

In a previous study, we assessed the efficacy of a continuous fascia iliaca compartment block (FICB) in reducing the pain at thigh autograft skin donor sites. However, a continuous local anesthetic infusion may cause toxicity or infection. In this prospective, randomized double-blind study, we compared the analgesic efficacy of FICB when given as a single shot vs continuous infusion during the 72-hour postoperative period up to the first dressing change (1dc). After ethical committee approval and informed consent, 81 adults (with 1% to 20% total burn surface area) who were scheduled for split-skin graft harvest procedures of the thigh underwent the FICB procedure before general or spinal anesthesia. Via FICB, patients received a bolus of 40 ml followed by 10 ml/hr consisting of either ropivacaine 0.2% for bolus and infusion (continuous, n = 27), or ropivacaine 0.2% for bolus and saline for infusion (single-shot, n = 27), or saline for both bolus and infusion (control, n = 27) until 1dc. Postoperative analgesia consisted of morphine via a patient-controlled analgesia device. We compared cumulative morphine consumption, static and dynamic pain scores, and side effects related to morphine or ropivacaine during the 72 hours up to 1dc. A single block had the same morphine sparing-effect as the continuous technique. Both techniques were equally effective in diminishing dynamic pain and reducing the side effects normally associated with morphine. However, patients receiving a single block experienced less residual paresia and were more satisfied with their pain-relief treatment than those who received a continuous infusion. A single-shot FICB is an easy, inexpensive, and efficient method for diminishing pain at thigh donor sites during a 72-hour postoperative period and has limited side effects and no residual paresia.

An unusual cause of burn injury: skin exposure to monochloroacetic acid.

Chemical burns can be complicated by the absorption of some of the toxic products through the skin and a subsequent systemic toxicity. We report here the case of a 3-year-old child who was accidentally exposed to monochloroacetic acid and sent to our burn unit with second-degree burn wounds. Regardless of the entry route, monochloroacetic is rapidly and very effectively absorbed and induces a severe toxic syndrome. In the case of skin resorption, the severity of the intoxication is directly related to the area of the contaminated skin contaminated with fatalities when the exposure level reaches more than 5% of the body surface. In the case of a chemical burn with a suspicion of systemic toxicity or in case of burn with an unusual product, the correct attitude is to contact a poison information center, to immediately wash the exposed skin, and to start treating the systemic toxicity as soon as possible. The availability of specific antidotes in the case of unusual poisoning can be a problem.

A study of the influence of body weight and height on military parachute landing injuries.

The weights and heights of 1,880 male military parachutists were recorded, and landing injury rates were calculated according to the weights and heights of the jumpers. Only the weight significantly influenced the injury rate. The set of data (weight, injury rate) are best fitted with a parabola of the form: y = 43.14 - 1.22x + 0.01x2. The concept of the maximal operating weight of a parachute is discussed with its implications for medical standards and for jumps with extra equipment.

A study of some factors influencing military parachute landing injuries.

In a retrospective study of 201,977 jumps, carried out by male military parachutists, over a 10-year period, landing injury rates were calculated according to the time of jump (day or night), the type of parachute, and meteorological data. Also, the wind speed, temperature, and the relative humidity at ground level were taken into account. The two types of parachutes used were both static line deployed, non-steerable canopies. The landing injury rate was found to be influenced by the darkness, surface area of the parachute, wind speed, and possibly temperature when higher than 25 degrees C. The influence of surface wind was best described by two segments of line with a cut-off point. The wind speed at the cut-off point is 12.75 k (6.56 m X s-1) for day jumps and 6.75 k (3.47 m X s-1) for night jumps.