Lymphaticovenous anastomosis: Treatment of a persistent breast seroma.

Lymphaticovenous anastomoses are mainly used in secondary limbs lymphedema. They also can be used to treat iatrogenic seroma. This technique was used to treat a patient with a painful breast seroma that appeared after a mastectomy with axillary dissection, resistant to multiple ponctions and persistent 8 months after. Pre operative both lymphoscintigraphy and lympho-MRI have been performed and we identified lymphatic ducts responsible for the seroma. The one involved in the seroma was also the preferential drainage network of the arm. Innoperative, we performed an indocyanine green angiography to map those lymphatic ducts. A total capsulectomy of the breast seroma has been performed. An incision was made in front of lymphatics selected for lymphaticovenous anastomoses on the anterior axilla face. We performed two microscopic lymphaticovenous anastomoses. The patient was followed up at one, three, six months and one year post operative. No recurrence occurred during the follow-up. At six month the arm perimeter reduced of two centimeters. Lymphoscintigraphy and lympho-MRI were performed at six month showing a disappearance of the drainage asymmetry and collateralities of the upper limb; and no measurable volume in projection of the right breast area. Lymphaticovenous anastomoses may be an effective therapeutic solution for resistant seroma after node dissection. Lymphoscintigraphy and lympho IRM are very useful in those cases.

How to manage calcified vessels for head and neck microsurgical reconstruction.

Head and neck reconstructive microsurgery in patients with calcified vessels (atherosclerosis or radiotherapy) is challenging. Preoperative reconstruction planning should meticulously evaluate the pedicle length and caliber aiming to select the most adapted free flap type and to plan the need for harvesting two free flaps or a venous graft. During surgery, end-to-end microanastomosis should be preferred, without artery clamps on calcified vessels and using open-loop sutures, a limited number of microsutures and a round needle with inside-outside directed bites (no atherosclerotic plaque removal). Before declamping, fibrin sealants are used to prevent minor leakage around the anastomosis as well as before wound closure to fix the optimal position of the pedicle avoiding pressure on the vessels or pedicle kinking. Calcified vessels are not a barrier to microsurgery and do not constitute a contraindication. Several options are useful to safely perform microsurgical head and neck reconstruction.

Serious central nervous system side effects of cephalosporins: A national analysis of serious reports registered in the French Pharmacovigilance Database.

INTRODUCTION: Among antibiotics, Central Nervous System (CNS) adverse drug reactions (ADRs) are often under-suspected and overlooked. Cephalosporins are an important cause of drug-induced CNS ADRs but the characteristics of such ADR have not been fully explored. We aimed to characterize the profile of cephalosporins serious CNS ADRs. METHOD: We performed an analysis of serious reports recorded in the French Pharmacovigilance database from 1987 to 2017. RESULTS: A total of 511 serious ADRs reports was analyzed. Patients had a mean age of 67.1 years and were mainly men (52.5%), with a mean creatinine clearance of 32.9 ml/min. The most involved molecules were cefepime (33.1%), ceftriaxone (29.7%), ceftazidime (19.6%), cefotaxime (9%) and cefazoline (2.9%), mostly administered intravenously (87.3%). A CNS history was observed in 25% of the reports (n = 128). Patients exhibited encephalopathy (30.3%), confusional state (19.4%), convulsion (15.1%), myoclonia (9.4%), status epilepticus (9.2%), coma (6.3%) and hallucination (4.3%). The mean time of onset was 7.7 days and the mean duration was 6 days. Cephalosporin plasma levels were recorded for 153 patients (29.9%) and 107 were above the standards including 62 (57.9%) related to renal impairment. Electroencephalograms were performed in 38.2% (n = 195) of the patients and 81% (n = 158) were abnormal. CONCLUSION: This study characterizes an off-target CNS ADRs of several cephalosporins. Ceftriaxone represented a large part of our reports after cefepime and it would be relevant to warn healthcare professionals. Investigations (EEG, though plasma levels and renal function) can be precious tools for clinicians to make a prompt diagnosis and improve patients' outcomes.

[Mastectomy and immediate reconstruction: Indications, techniques and decision algorithm]. / Mastectomie avec reconstruction mammaire immédiate : indications et techniques, algorithme de décision d'une reconstruction immédiate.

Immediate breast reconstruction indications extend to infiltrating carcinomas, due to new matrix implant coverage techniques and the development of perforator flaps. These techniques allow adjuvant treatments. However, the decision of immediate reconstruction must be discussed with the oncological multidisciplinary team and the benefits/risks must also be evaluated in relation to the morphology of the patients and their co-morbidities. The chosen type of mastectomy: conventional or skin sparing and/or nipple sparing depends on the shape and volume of the breast, the localization of the tumor in the breast and the distance from the nipple areola complex (NAC). We describe an algorithm to allow, in the case of therapeutic mastectomy with or without adjuvant radiotherapy, an immediate reconstruction with implants or free or pedicled flaps.

[Decision algorithm in immediate breast reconstruction]. / Algorithmes décisionnels en reconstruction mammaire immédiate.

Immediate breast reconstruction showed many advantages in terms of aesthetic and functional results and improvement of quality of life when compared to delayed breast reconstruction. Previous radiotherapy or the use of adjuvant treatments such as radiation therapy, or chemotherapy are no longer a contraindication for immediate breast reconstruction. However, it is important to respect certain rules in order to decrease the risk of complications: the choice of reconstruction technique, the management of the skin envelope according to the breast shape you want to create, the time delay between the first and the second stage of reconstruction depending on a possible adjuvant treatment.

[Deep alkali burns: Evaluation of a two-step surgical strategy]. / Les brûlures profondes par agents basiques : évaluation d'une stratégie chirurgicale en deux temps.

INTRODUCTION: Chemical burns are rare but often lead to deep cutaneous lesions. Alkali agents have a deep and long lasting penetrating power, causing burns that evolve over several days. The local treatment for these patients is excision of the wound and split thickness skin graft. Early excision and immediate skin grafting of alkali burns are more likely to be complicated by graft failure and delayed wound healing. We propose a two-step method that delays skin grafting until two-three days after burn wound excision. RESULTS: Our population included 25 controls and 16 cases. Men were predominant with a mean age of 41.9 years. In 78% of cases, burns were located on the lower limbs. The mean delay between the burn and excision was 16.5 days. In cases, the skin graft was performed at a mean of 11.3 days after the initial excision. We did not unveil any significant difference between both groups for the total skin surface affected, topography of the burns and the causal agent. Wound healing was significantly shorter in cases vs controls (37.5 days vs 50.3 days; P<0.025). Furthermore, we observed a decreased number of graft failures in cases vs controls (13.3% vs 46.7%; P=0.059). CONCLUSION: Our study shows the relevance of a two-step surgical strategy in patients with alkali chemical burns. Early excision followed by interval skin grafting is associated with quicker wound healing and decreased rate of graft failure.

Severe neurological disorders and refractory aspergillosis in an adolescent treated by vincristine and voriconazole.

WHAT IS KNOWN AND OBJECTIVE: Voriconazole and vincristine are major therapeutics in paediatric haematology. However, the risk-benefit ratio of the treatment of invasive aspergillosis with voriconazole in patients receiving vincristine-based chemotherapy remains unclear. CASE DESCRIPTION: We report severe peripheral and central neurological disorders in a 14-year-old girl with T-cell acute lymphoblastic leukaemia and pulmonary aspergillosis. The case describes a strong exacerbation by voriconazole of the vincristine-induced neuropathic pains. It shows the high variability of the trough serum concentration of voriconazole leading to antifungal treatment failure and suggests that its own central neurotoxicity could also be potentiated by vincristine. WHAT IS NEW AND CONCLUSION: Given the risk of either insufficient antifungal efficacy or excessive neurological disorders, this case warns on a probable unfavourable risk-benefit profile of voriconazole during vincristine-based chemotherapy in adolescents.

[Aplasia cutis congenita: Update and management]. / Aplasia cutis congenita : mise au point et prise en charge.

Congenital skin aplasia, or aplasia cutis congenita (ACC) is a rare congenital disease. It is characterized by the absence of skin at birth, localized or widespread, of one or several areas. This condition commonly involve the scalp but can also involve more rarely the trunk or limbs. However it is most frequently an isolated disorder, it can be associated with other anomalies, such as the Adams-Oliver syndrome, the association with a fetus papyraceus or with an epidermolysis bullosa. Many hypothesis have been suggested: vascular, genetic, traumatic, pharmacological or an anomaly in the neural tube closure process, but the exact mechanism is still unknown. Morbidity and mortality of this malformation depends on the affected area and the size of the defect. The main risk is the infection, hemorrhage and thrombosis in the case of a scalp defect with an underlying bone defect, the exposure of the meninges and the superior sagittal sinus. The initial management of ACC will therefore involve several plastic surgery techniques, from more simple to more complex, using conservative wound care to flaps techniques. Other techniques can be performed later, in the management of ACC sequelae, such as skin expansion for scarring alopecia.

[Non syndromic craniosynostosis]. / Les craniosténoses non syndromiques.

Craniosynostosis are rare congenital malformations of the skull resulting from the premature fusion of one or several cranial sutures. Prevalence is considered in approximately 1 on 2000 births. Non syndromic craniosynostosis (NSC) or isolated form are the most frequent forms (85 % of the cases). They are classified most of the time according to the synostotic suture(s) and the engendered cranial deformation: sagittal synostosis or scaphocephaly, metopic synostosis or trigonocephaly, bicoronal synostosis or brachycephaly, coronal synostosis or plagiocephaly and oxycephaly. Although the multifactorial origin is commonly admitted, the precise mechanisms which lead to the premature fusion of a suture, remain incompletely resolute. The main risks are the intracranial high blood pressure and its consequences on the psychomotor development, the visual or respiratory infringement which can require a surgery in emergency. The treatment is realized by multidisciplinary teams allowing to provide a strategy adapted to every situation. The decision-making process depends on patient's age, on the type and severity of the craniosynostosis, and on the patient's health. This surgery is ideally performed before the age of 1 year and indication only in morphological purpose is widely recognized to avoid any social damage to the child. The follow-up is essential and is made throughout the growth in particular to detect a recurrence or the evolution towards a complex form of craniosynostosis.

[Rational use of distraction osteogenesis in craniofacial surgery]. / Utilisation rationnelle de la distraction osseuse en chirurgie craniofaciale.

Distraction osteogenesis, initially developed by Ilizarov for limb, is the tissular extension caused by the progressive space of the osseous pieces following an osteotomy. Distraction is osteogenesic and histogenic. Twenty-five years ago, at the instigation of McCarthy, this technique was used to handle the craniofacial malformations in the various floors of the face : mandibular, mediofacial and cranial. The most wide-spread protocols respect a latency period from 0 to 7 days, a rhythm of distraction from 1 to 2mm a day in 2 at 4 times and a period of consolidation from 4 to 8 weeks. Distraction is the result of the inventiveness of the pioneers then the work to always adapt to the multiple complex clinical situations. The surgeon has to choose between internal or external materials allowing a mono- or multi-vectorial extension, in osseous and/or dental anchoring. The mandibular distraction is very effective for the treatment of the secondary obstructive syndromes in the unilateral or bilateral severe hypomandibular malformations. She also allows desobstruction of the superior airways within the framework of the mediofacial hypoplasies as well as the secondary treatment of the growth defects in cleft lips and palates. Finally, the distraction osteogenesis enhanced reliability of the fronto-facial advancement in early and secondary treatment of craniofaciosynostosis. This is a real support of the facial growth, which has to be included in a plan of global treatment.

Unexpectedly long half-life of metformin elimination in cases of metformin accumulation.

INTRODUCTION: In a study of the oral administration of a single dose of metformin to healthy participants, the estimated half-life (t½ ) for the elimination of the drug from erythrocytes was found to be 23.4 h (compared with 2.7 h for metformin in plasma). However, these pharmacokinetic indices have not been well defined in metformin accumulation. METHODS: We systematically reviewed all the data on plasma and erythrocyte metformin assays available in our centre. We then selected patients with a plasma metformin concentration ≥ 5 mg/l and in whom the metformin concentration had been remeasured once or more at least 5 days after admission. RESULTS: Twelve patients met the aforementioned criteria. All but one of these patients displayed generally severe lactic acidosis on admission (mean ± sd pH and lactate: 6.88 ± 0.35 and 14.8 ± 6.56 mmol/l, respectively) and 11 were treated with dialysis. The mean ± sd time interval between the first and last blood sample collections for metformin measurement was 8.3 ± 3.2 days (range 5-14 days). Five days after the first sample had been collected, metformin was still detectable in plasma and in erythrocytes in all patients. Metformin remained detectable for up to 13 days (both in plasma and in erythrocytes). The estimated mean terminal t½ for metformin in plasma and erythrocytes was 51.9 and 43.4 h, respectively. CONCLUSIONS: The prolonged elimination of accumulated metformin (even after dialysis therapy) challenges the traditional view that the drug clears rapidly because of a short half-life in plasma.

[Massive panniculectomy and bilateral subtotal mastectomy in a case of calciphylaxis: A case report and up date]. / Dermolipectomie abdominale et mastectomie bilatérale subtotale dans le cadre d'une calciphylaxie: à propos d'un cas et mise au point.

Calciphylaxis or calcific arteriolopathy is a rare, life-threatening obstructive pathology of the small cutaneous and subcutaneous vessels. It mainly affects patients with chronic renal failure but it also has been described in patients with normal renal function. The principal risks factors apart from renal failure and phosphocalcic metabolism imbalance are: the female sex, obesity, peripheral vascular disease, diabetes and oral anti-coagulation. We present a very rare case of abdominal, mammarian and upper thighs calciphylaxis in a patient with normal renal function. She presented a severe obesity with a recent important loss of weight and had been treated by oral anticoagulants for a long time. She benefited of a multidisciplinary approach with dermatologists, plastic surgeons and anesthesists permitting a recovery in fourteen weeks. Multidisciplinary approach is necessary but the place of the surgery is not well defined. We report a case in which early and wide surgical approach permitted to obtain a favourable evolution of the pathology. Then, we propose a therapeutic strategy after review of the literature.

[Cell therapy for stroke: from myth to reality]. / La thérapie cellulaire de l'accident vasculaire cérébral ischémique : du mythe à la réalité

INTRODUCTION: Stroke is one of the leading causes of death and disability worldwide. Intravenous recombinant tissue plasminogen activator is the only available therapy for acute ischemic stroke, but its use is limited by a narrow therapeutic window and cannot stimulate endogenous repair and regeneration of damaged brain tissue. Stem cell-based approaches hold much promise as potential novel treatments to restore neurological function after stroke. STATE OF THE ART: In this review, we summarize data from preclinical and clinical studies to investigate the potential application of stem cell therapies for treatment of stroke. Stem cells have been proposed as a potential source of new cells to replace those lost due to central nervous system injury, as well as a source of trophic molecules to minimize damage and promote recovery. Various stem cells from multiple sources can generate neural cells that survive and form synaptic connections after transplantation in the stroke-injured brain. Stem cells also exhibit neurorevitalizing properties that may ameliorate neurological deficits through stimulation of neurogenesis, angiogenesis and inhibition of inflammation. PERSPECTIVES/CONCLUSION: Performed in stroke, cell therapy would decrease brain damage and reduce functional deficits. After the damage has been done, it would still improve neurological functions by activating endogenous repair. Nevertheless, many questions raised by experimental studies particularly related to long-term safety and technical details of cell preparation and administration must be resolved before wider clinical use.

Priming of late endothelial progenitor cells with erythropoietin before transplantation requires the CD131 receptor subunit and enhances their angiogenic potential.

BACKGROUND: Endothelial colony-forming cells (ECFCs) are promising candidates for cell therapy of ischemic diseases. Erythropoietin (EPO) is a cytokine that promotes angiogenesis after ischemic injury. EPO receptors (EPORs) classically include two EPOR subunits, but may also associate with the ß-common chain (CD131) in a newly identified receptor involved in EPO cytoprotective effects. OBJECTIVE: The aim was to take advantage of the proangiogenic properties of EPO to enhance ECFC graft efficiency. We postulated that priming ECFCs by adding epoietin α in culture medium prior to experiments might increase their angiogenic properties. We also explored the role of the CD131 subunit in EPO priming of ECFCs. METHODS AND RESULTS: By western blotting on cord blood ECFC lysates, we showed that EPOR and CD131 expression increased significantly after EPO priming. These proteins coimmunoprecipitated and colocalized, suggesting that they are covalently bound in ECFCs. EPO at 5 IU mL(-1) significantly stimulated proliferation, wound healing, migration and tube formation of ECFCs. EPO priming also increased ECFC resistance to H2 O2-induced apoptosis and survival in vivo. Similarly, in vivo studies showed that, as compared with non-primed ECFC injection, 5 IU mL(-1) EPO-primed ECFCs, injected intravenously 24 h after hindlimb ischemia in athymic nude mice, increased the ischemic/non-ischemic ratios of hindlimb blood flow and capillary density. These effects were all prevented by CD131 small interfering RNA transfection, and involved the phosphoinositide 3-kinase-Akt pathway. CONCLUSION: These results highlight the potential role of EPO-primed ECFCs for cell-based therapy in hindlimb ischemia, and underline the critical role of CD131 as an EPO coreceptor.

Circulating lipoprotein-associated phospholipase A2 in high-grade carotid stenosis: a new biomarker for predicting unstable plaque.

OBJECTIVE: To test plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with high-grade carotid stenosis according to plaque histology. METHODS: This cross-sectional single-centre study included patients with ≥70% North American Symptomatic Carotid Endarterectomy Trial (NASCET) carotid stenosis, who were treated surgically. Serum Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) were determined on the day of surgery. Histopathological analysis classified carotid plaque as stable or unstable, according to AHA classification. RESULTS: Of the 42 patients (mean age 70.4 ± 10.5 years; 67% men), neurological symptoms were present in 16 (38%). Unstable plaques were found in 23 (55%). Median plasma level of Lp-PLA2 was significantly higher in patients with unstable plaque compared to those with stable plaque (222.4 (174.9-437.5) interquartile range (IQR) 63.5 vs. 211.1 (174.9-270.6) IQR 37.2 ng ml(-1); p = 0.02). Moreover, median Lp-PLA2 level were higher in asymptomatic patients with unstable plaque (226.8 ng ml(-1) (174.9-437.5) IQR 76.8) vs. stable plaque (206.9 ng ml(-1) (174.9-270.6) IQR 33.7; p = 0.16). Logistic regression showed that only the neurological symptoms (OR = 30.9 (3.7-244.6); p < 0.001) and the plasma Lp-PLA2 level (OR = 1.7 (1.1-12.3); p = 0.03) were independently associated with unstable carotid plaque as defined by histology. CONCLUSIONS: This study showed that circulating Lp-PLA2 was increased in patients with high-grade carotid stenosis and unstable plaque. Lp-PLA2 may be a relevant biomarker to guide for invasive therapy in asymptomatic patients with carotid artery disease.