[Melanoma : the patient's care pathway. From diagnosis to therapy]. / Le mélanome : le trajet de soins du patient. Le mélanome : le trajet de soins du patient Du diagnostic au traitement Du diagnostic au traitement.

The management of melanoma is a typical example of a pluridisciplinary approach, in order to provide the patient with a rapid and adequate treatment plan after the initial diagnosis. Both in the domains of dermatology, pathology and oncology, enormous progress has been made. Recent advances permit a rapid access to diagnostic techniques using teledermoscopy, an improved diagnostic accuracy using dermoscopy, pre-interventional high-frequency ultrasound and optical coherence tomography, a determination of risk factors using immunohistochemistry and genetic analyses on the pathology samples. Furthermore, the development of immunotherapies, in particular the anti-PD1 antibodies, and the directed therapies, therapies permitting an increased number of patients to experience an increased survival with an acceptable tolerance profile in the event of metastatic lesions. This article describes the patient's care pathway, from the initial diagnosis, staging, to an eventual treatment and follow-up.

Le traitement du mélanome est un exemple type de collaboration multidisciplinaire, afin de pouvoir garantir au patient une prise en charge rapide dès le moment de la détection de la lésion. Tant au niveau dermatologique, anatomopathologique et oncologique, d'énormes progrès ont eu lieu ces dernières années. Ils permettent un accès au diagnostic de plus en rapide par la télédermoscopie, une précision diagnostique accrue par la dermoscopie, l'ultrason à haute fréquence et la tomographie par cohérence optique, une détermination des facteurs de risque immunohistochimiques et génétiques sur les analyses anatomo-pathologiques ainsi que le recours à des immunothérapies, notamment les anti-PD1, et à des traitements ciblés. Ces nouveaux traitements permettent souvent une plus longue survie du patient, avec un profil de tolérance acceptable en cas de lésions métastatiques. Cet article reprend le trajet de soins du patient, du diagnostic initial et du staging au traitement éventuel avec son suivi.

[Locally advanced and metastatic cutaneous squamous cell carcinoma treated with cemiplimab]. / Carcinome spinocellulaire cutané localement avancé et métastatique traité par cémiplimab.

The treatment of locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) essentially relies on surgery and eventually radiotherapy of the treated site and afferent lymph nodes. Unfortunately, some cases are no candidates for surgery or radiotherapy and a systemic treatment may be indicated. Chemotherapies are only partially efficacious and associated with potential toxicities. A recent study evaluating the efficacy and tolerance of cemiplimab, a PD1 antagonist for locally advanced and metastatic cSCC demonstrated an objective response rate of 49 % and 47 % for locally advanced and metastatic cSCC, while maintaining a response of at least 6 months of 63 % and 60 %, respectively. We present a clinical case of a patient with a locally advanced cSCC of the forehead with bone resorption and cervical lymphadenopathies. After failure of multiple surgical interventions and radiotherapies, he responded partially to cemiplimab immunotherapy with a good safety profile.

Le traitement du carcinome spinocellulaire cutané (cSCC) localement avancé et/ou métastatique repose essentiellement sur la chirurgie et, éventuellement, sur une radiothérapie de la zone chirurgicale et de l'aire ganglionnaire afférente. Malheureusement, certains cas ne sont plus opérables ou accessibles à la radiothérapie et un traitement systémique est alors indiqué. Les chimiothérapies sont peu efficaces et potentiellement toxiques. Une étude récente évaluant l'efficacité et la tolérance du cémiplimab, un antagoniste PD1, dans les cSCC localement avancés et métastatiques, démontre une réponse objective confirmée de 49 % et de 47 %, respectivement, avec un maintien de la réponse d'au moins 6 mois de 63 % et de 60 %, respectivement. Nous présentons le cas d'un patient avec un cSCC localement avancé au niveau du front, avec effraction osseuse et adénopathies cervicales, ayant eu de multiples chirurgies et radiothérapies. Il a présenté une réponse partielle au cémiplimab avec un profil de tolérance satisfaisant.

Proton-Stabilized Photochemically Reversible E/ Z Isomerization of Spiropyrans.

Spiropyrans undergo Cspiro-O bond breaking to their ring-open protonated E-merocyanine form upon protonation and irradiation via an intermediate protonated Z-merocyanine isomer. We show that the extent of acid-induced ring opening is controlled by matching both the concentration and strength of the acid used and with strong acids full ring opening to the Z-merocyanine isomer occurs spontaneously allowing its characterization by 1H NMR spectroscopy as well as UV/vis spectroscopy, and reversible switching between Z/ E-isomerization by irradiation with UV and visible light. Under sufficiently acidic conditions, both E- and Z-isomers are thermally stable. Judicious choice of acid such that its p Ka lies between that of the E- and Z-merocyanine forms enables thermally stable switching between spiropyran and E-merocyanine forms and hence pH gating between thermally irreversible and reversible photochromic switching.

[Retrospective study of epidemiological and clinical characteristics of pediatric burns in the CHU Liège Burn Center]. / Admission des enfants au Centre des Brûlés du CHU de Liège : étude rétrospective épidémiologique et clinique.

In Belgium, epidemiological data are rare, and most often extrapolated, for burn injuries, especially in the pediatrician population. The purpose of this study was to obtain data for the pediatrician population in Liege. It retrospectively analyzed burns in the pediatrician population treated in the Burn Center Liege, during five years. Overall 844 patients (379 girls, 465 boys) were included for the first part of this study (burns localization and etiology, sex ratio, age), with a mean age of 4.2 years old. Over this five years period, the number of pediatrician patients admitted increased by 47 %. The most frequent burn site was the hand (32.8 %) and the burn cause was scalds (49.4 %). For the second part of the study (hospitalisation and treatment duration, hypertrophic scars), 712 patients were included (321 girls and 391 boys). Hypertrophic scars were found in 9.27 %. Our results show that burn injury is more often found in boys, and this injury occurs mostly in children under 5 years of age.

Les données épidémiologiques pour les traumatismes par brûlures en Belgique sont rares, et issues d'extrapolations, particulièrement pour la population pédiatrique. Cette étude a pour but d'obtenir des chiffres propres à la population pédiatrique liégeoise. Il s'agit d'une étude rétrospective des brûlures dans la population pédiatrique prise en charge par le Centre des Brûlés de Liège sur une période de 5 ans. Dans la première partie de l'étude (localisation et nature des brûlures, sex ratio et âge moyen), 844 patients (379 filles et 465 garçons) ont été inclus avec un âge moyen de 4,2 ans. Au fil des années, le nombre de contacts pédiatriques a augmenté de 47 %. Le site de brûlure le plus fréquemment constaté est la main (32,8 %) et la cause principale de brûlure est le contact avec des liquides chauds (49,4 %). Dans la seconde partie (durée de pansement, d'hospitalisation et apparition de cicatrice hypertrophique), 712 patients ont été pris en compte (321 filles et 391 garçons). Une cicatrice hypertrophique a été observée chez 9,3 % des patients. Nos résultats montrent que les garçons sont plus souvent victimes de ce type de traumatisme et que ce dernier survient principalement chez l'enfant de moins de 5 ans.

Boron difluorides with formazanate ligands: redox-switchable fluorescent dyes with large stokes shifts.

The synthesis of a series of (formazanate)boron difluorides and their 1-electron reduction products is described. The neutral compounds are fluorescent with large Stokes shifts. DFT calculations suggest that a large structural reorganization accompanies photoexictation and accounts for the large Stokes shift. Reduction of the neutral boron difluorides occurs at the ligand and generates the corresponding radical anions. These complexes are non-fluorescent, allowing switching of the emission by changing the ligand oxidation state.

Writing and erasing hidden optical information on covalently modified cellulose paper.

An unprecedented strategy for preparing photoresponsive cellulose paper enabling the storage of short-lived optical data by covalent photopatterning is disclosed. An ab initio design hinting that the covalent grafting of coumarins on the paper could yield valuable photoresponsive units was first performed. Second, light sensitive paper that can be reversibly altered upon irradiation at a specific wavelength was prepared by covalent surface functionalization with coumarins. Third, the validity of this strategy is demonstrated using the photolithography of several gripping patterns such as a dynamic QR code.

A methodological evaluation of volumetric measurement techniques including three-dimensional imaging in breast surgery.

Breast surgery currently remains very subjective and each intervention depends on the ability and experience of the operator. To date, no objective measurement of this anatomical region can codify surgery. In this light, we wanted to compare and validate a new technique for 3D scanning (LifeViz 3D) and its clinical application. We tested the use of the 3D LifeViz system (Quantificare) to perform volumetric calculations in various settings (in situ in cadaveric dissection, of control prostheses, and in clinical patients) and we compared this system to other techniques (CT scanning and Archimedes' principle) under the same conditions. We were able to identify the benefits (feasibility, safety, portability, and low patient stress) and limitations (underestimation of the in situ volume, subjectivity of contouring, and patient selection) of the LifeViz 3D system, concluding that the results are comparable with other measurement techniques. The prospects of this technology seem promising in numerous applications in clinical practice to limit the subjectivity of breast surgery.

[The perforator pedicled propeller flap for distal tibial exposure: two case reports]. / Couverture de pertes de substance du tibia distal par lambeau pédiculé perforant en hélice: deux cas cliniques.

Distal lower leg soft tissue defect is frequently a challenge to repair, particularly on the tibial crest. The coverage of this kind of lesion has some limitations because of regional minimal blood supply and paucity of local soft-tissue flaps. The perforator pedicled propeller (PPP) method tries to find a new place in lower leg reconstruction in bringing similar tissues at the recipient site and avoiding long and difficult free flap transfer or muscular sacrifice. The authors report on the use of PPP method for a tibial crest exposure after trauma and for a soft tissue defect with osteomyelitis on the tibial crest.

Theoretical study of the tautomerism in the one-electron oxidized guanine-cytosine base pair.

Ionizing radiation on DNA mainly generates one-electron oxidized guanine-cytosine base pair (G(+·):C), and in the present paper we study all possible tautomers of G(+·):C by using ab initio approaches. Our calculations reveal that the tautomeric equilibrium follows a peculiar path, characterized by a stepwise mechanism: first the proton in the central hydrogen bond N1(G)-H1-N3(C) migrates from guanine to cytosine, and then the cytosine cation releases one proton from its amino group. During this second step, water acts as a proton acceptor, localizing the positive charge on one of the water molecules interacting with the guanine radical. In agreement with experimental findings, the computed energy barriers show that the deprotonation of the cytosine cation is the speed-limiting step in the tautomeric equilibrium. The influence of the number of water molecules incorporated in the theoretical model is analyzed in detail. The evolution of electronic properties along the reaction path is also discussed on the basis of partial atomic charges and spin density distributions. This work demonstrates that water indeed plays a crucial role in the tautomeric equilibra of base pairs.

Shoulder function after latissimus dorsi transfer in breast reconstruction.

BACKGROUND/AIMS: Latissimus dorsi (LD) transfer in the case of breast reconstruction remains frequently used because this muscle provides a good size source of tissue in reconstructive surgery. Given that, the consequences of the LD removal on shoulder function and the actual loss of maximal strength developed must be investigated. METHODS: Twenty women (50 ± 7.5 years old) were evaluated before surgery, 3 and 6 months after an unilateral transfer of a pedicle flap of LD muscle used for breast reconstruction. Women performed a bilateral shoulder isokinetic assessment [for the internal rotators (IRs) and external rotators and for the abductor and adductor (ADD) muscles] allowing the establishment of bilateral muscular deficit status and the study of agonist/antagonist muscle ratios. The algofunctional and clinical status of the shoulders was analysed by the means of Constant score and specific shoulder clinical tests. The women did not perform any specific strengthening of muscle shoulder after surgery. RESULTS: The isokinetic assessment showed a muscle weakness 3 and 6 months after LD transfer, mainly on the ADDs (33 ± 9% at 6 months) and on the IRs (16 ± 11% at 6 months). The Constant score significantly decreased after surgery on the operated shoulder. Women with a Constant score impairment showed pain during specific shoulder clinical tests. We also found a correlation between Constant score impairment and internal rotators weakness or rotator muscle imbalance. CONCLUSION: Given those results, we could advocate a specific shoulder strengthening after LD transfer, focused mainly on the IRs and ADDs.

[Giant lipoma on the back]. / Lipome géant dorsal.

Solitary lipoma is the most frequent soft tissue tumor, often appearing between 40 and 60 years of age. It is described as "giant" beyond 1 kg of weight and 10 cm of diameter. Its volume is the source of a good many problems in social life (camouflage, difficulties to dress) and causes multiple health problems such as pain, difficulties to sleep, compressions of nerves or vital structures, infections, etc. The diagnosis is primarily clinical. However, it is necessary to systematically exclude a malignant process. Surgical biopsy is recommended if the diagnosis cannot be asserted by the clinic or an imagery. The therapeutic attitude is abstention in case of small volume without functional impairment. Otherwise, total surgical excision is indicated with pathological analysis. We describe the clinical history of a patient suffering from a giant dorsal lipoma.

Intermolecular proton transfer in microhydrated guanine-cytosine base pairs: a new mechanism for spontaneous mutation in DNA.

Accurate calculations of the double proton transfer (DPT) in the adenine-thymine base pair (AT) were presented in a previous work [J. Phys. Chem. A 2009, 113, 7892.] where we demonstrated that the mechanism of the reaction in solution is strongly affected by surrounding water. Here we extend our methodology to the guanine-cytosine base pair (GC), for which it turns out that the proton transfer in the gas phase is a synchronous concerted mechanism. The O(G)-H-N(C) hydrogen bond strength emerges as the key parameter in this process, to the extent that complete transfer takes place by means of this hydrogen bond. Since the main effect of the molecular environment is precisely to weaken this bond, the direct proton transfer is not possible in solution, and thus the tautomeric equilibrium must be assisted by surrounding water molecules in an asynchronous concerted mechanism. This result demonstrates that water plays a crucial role in proton reactions. It does not act as a passive element but actually catalyzes the DPT.

Effects of hydration on the proton transfer mechanism in the adenine-thymine base pair.

We report the first density functional study of water catalytic effect in the double proton transfer (DPT) taking place in the adenine-thymine (AT) base pair. To gain more insight regarding the accuracy of several theoretical methods, the ability of various functionals and models for describing the geometry of this system has first been checked. According to our results, BP86/6-311++G(d,p) is the best option for describing the solvation effects in AT when applied to a two-water-molecule-featuring model. The two possible mechanisms for DPT in solution are explored: in the first one, water molecules only remain passive elements, whereas in the second one they are directly included in the reaction path. For the noncatalyzed mechanism, the stable structures constitute the canonical form of the base pair and the first proton transfer product. Nevertheless, by involving the two water molecules in the reaction, we found three stable species: canonical base pair, first proton transfer product, and double proton transfer product. Although the thermodynamic analysis confirms that AT does not contribute to spontaneous mutation through proton transfer catalyzed by surrounding water, our results suggest that microhydration may play a crucial role for DPT reaction in others DNA or RNA basis pair.

Type 1 diabetes and idiopathic retroperitoneal fibrosis: case report.

Retroperitoneal fibrosis is characterized by the presence of a retroperitoneal tissue, consisting of chronic inflammation and marked fibrosis, which entraps the retroperitoneal organs. In two-thirds of cases, the retroperitoneal fibrosis is idiopathic. The pathogenic mechanism is not clearly identified. We report a case of idiopathic retroperitoneal fibrosis associated with type 1 diabetes mellitus. A 61-year-old woman with C peptide negative insulindependent diabetes developed retroperitoneal fibrosis revealed by bilateral hydronephrosis. Anti-GAD 65 antibodies were positive. There were no signs of autoimmune pancreatitis: no steatorrhea, normal IgG4 isotype levels, and absence of pancreas morphological abnormalities.

[Issues of France's "Leonetti Act": Involvement of amyotrophic lateral sclerosis patients in prior discussions concerning respiratory support and end-of-life care]. / Les enjeux de la loi Leonetti: participation des patients atteints de sclérose latérale amyotrophique à une discussion anticipée sur la réanimation respiratoire et les soins de fin de vie.

In accordance with the principle of personal autonomy, expert consensus statements on amyotrophic lateral sclerosis (ALS) recommend early engagement with terminal-phase patients on the type of symptomatic treatment to be administered in the event of respiratory failure, since decompensation progresses too rapidly to allow time for a discussion. The French Parliamentary Act on Patients' Rights and End-of-Life Care (dated 22 April 2005) grants individuals the right to refuse unreasonable treatment and obliges physicians to take account of any prior instructions given by a person before he/she became incapable of communicating. The provision of prior instructions is a very reassuring situation for the physician: the autonomous patient indicates his or her choice of end-of-life care. However, there are two pitfalls which must be avoided: (i) holding a discussion for the sole purpose of obtaining prior instructions and (ii) not acknowledging the patient's vulnerability. The present study dealt with 35 ALS patients for whom the question of either intensive care or palliative end-of-life care remained open. Even though the great majority of these individuals were keen to know their exact state of health, 48% refused to consider this circumstance and only 20% expressed prior instructions. These results prompted us to question the ethical dimension of the concept of autonomy beyond its founding formulation: can one envisage an incapacity to confront oneself with the existential question of possible death? In 80% of cases, the physician will have to take a care decision in the absence of any prior instructions from the patient. This amounts to more than respecting a person's autonomy and involves exercising medical responsibility.

Treatment of a groin lymphatic fistula with negative pressure wound therapy.

INTRODUCTION: Groin lymphatic fistulas are a troublesome finding after limb revascularization surgery. Its management represents a difficult task for the clinician. REPORT: We report our experience in the treatment of such a condition with negative-pressure wound therapy (NPWT) in a 70-year-old man which benefited from extra-anatomic prosthetic axillofemoral bypass. After a week of treatment, the fistula dried up and closure was obtained with simple suture under local anaesthesia. Follow-up at 9 months showed stable coverage without any sign of leakage. DISCUSSION: This study depicts NPWT as an effective non-invasive treatment in the management of groin lymphocutaneous fistula.

[Analgesia for wound dressing by continuous peripheral nerve block]. / Analgésie par blocs nerveux périphériques continus dans le cadre des soins de plaies cutanées.

We present the case of a patient with a circumferential venous ulcer at the level of the calf. She is hospitalized for surgical treatment by continuous aspiration dressing and coverage with skin graft. This patient presents a history of chronic pain, on which classical medications have few effects and are accompanied by side effects. After discussion with the patient, a double continuous peripheral nervous block (femoral and sciatic nerve) is set up to improve the tolerance to wound dressing. This technique presents favorable antalgic results. The indications and the different techniques of block performance (by electrostimulation or echo-guided) are described. The infectious risks related to the presence of catheter near cutaneous wounds are clarified according to recent data of literature. The relevance of these techniques in correlation with the development of chronic pain and on the trophicity of the wounds are also discussed.

The consensus of the surgical treatment of burn injuries in Belgium.

On the occasion of the twentieth anniversary of the 'Belgian Association of Burn Injuries' an inventory was made of all surgical techniques used in the five largest Belgian burn centres in order to draw up a consensus document. A questionnaire covering the whole treatment of severely burned patients was sent to the surgeons of each burn unit, ranging from emergency treatment, through diagnostic techniques, burn surgery and post-healing treatment (scars, contractures). During the past decade, several (often expensive) new techniques have been commercialised, resulting in a wide variety of treatment modalities in the different centres. For the majority of bums, however, a similar protocol is followed: the superficial burns are treated conservatively and the deep burns surgically. Nevertheless, burns of indeterminate depth are susceptible to variations in their treatment. There are also different therapeutic options for the deepest burns, from the use of donor skin to dermal substitutes as well as cultured keratinocytes. The writing of this consensus required intense communication on the different therapeutic modalities, as well as an increased exchange of experiences, which could lead to an improvement in the quality of burn treatment in Belgium.

Delayed reepithelialization and scarring deregulation following drug-induced toxic epidermal necrolysis.

A 51-year-old Caucasian woman developed severe drug-induced toxic epidermal necrolysis (TEN) due to allopurinol. The withdrawal of the culprit drug was unfortunately delayed, and dramatic retardation of reepithelialization was observed. At that stage of disease evolution, an inflammatory cell infiltrate was present in the dermis. Coverage of eroded lesions by frozen cultured keratinocyte allografts failed to hasten reepithelialization compared to ungrafted sites. This unusual protracted TEN evolution was followed by the development of extensive hypertrophic and keloid scars. Several biopsies were taken over 6 months. The histologic presentation of the grafted and ungrafted eroded scar tissues looked similar. Both the number and size of the Factor XIIIa-positive dermal dendrocytes, as well as the number of alpha-actin-positive myofibroblasts showed a marked increase between weeks 2 and 12 after grafting. They were reduced after 6 months when the scarring process was stabilized. alpha1 [IV] collagen was never expressed over the eroded scars. Similar to burn patients, delayed reepithelialization might be a risk factor for abnormal scarring in TEN. Cultured keratinocyte allograft apparently offered no improvement in reepithelialization and did not prevent abnormal scarring in this TEN patient.