[Cutaneous, mucosal and systemic pyoderma gangrenosum]. / Pyoderma gangrenosum cutanéomuqueux et systémique.

BACKGROUND: Extracutaneous and mucosal involvement is rare in neutrophilic dermatoses. We report a case of cutaneous-mucosal and systemic pyoderma gangrenosum (PG) revealing myelodysplasic syndrome. CASE REPORT: A 56-year-old man was hospitalised for an inflammatory abdominal plaque with an ulcerated centre that appeared rapidly in a setting of fever of 40 degrees C, odynophagia, weight loss and arthritis of the ankle. Despite surgical abdominal repair and combined dual antibiotics, the patient remained febrile and the ulcer size continued to increase. The edges were raised, purple and necrotic. Examination revealed vegetative legions with a purple edge on the lower lip and tongue. Histological examination of the skin and mucosal biopsy samples was consistent with a diagnosis of PG. A chest-abdomen CT scan showed mesenteric panniculitis and interstitial lung disease. The bone marrow sample revealed an appearance of chronic myelomonocytic leukaemia with myelofibrosis and excessively high blast levels. Systemic corticosteroids rapidly resulted in apyrexia with healing of the cutaneous, mucosal and visceral lesions. The patient presented secondary worsening of his acute myeloid leukaemia type-IV requiring bone marrow rescue. DISCUSSION: Extracutaneous involvement in neutrophilic dermatoses is rare but takes a number of different forms. We report a case of a patient presenting multifocal PG with cutaneous, mucosal, joint, mesenteric and pulmonary involvement. Oral lesions seen in PG generally affect the palate and they are commonly associated with inflammatory intestinal diseases. Our case is original in terms of the inaugural character of the mucosal lesions, their burgeoning appearance and their location on the lips and tongue.

Contribution of CT-assisted navigation and microdebriders to endoscopic sinus surgery in cystic fibrosis.

OBJECTIVE: To demonstrate the interest of CT-assisted navigation and the microdebrider in rhino-sinus surgery for cystic fibrosis. METHODS: A retrospective study included 20 patients with cystic fibrosis who had undergone endoscopic sinus surgery using CT-assisted navigation and microdebrider between 1998 and 2006. RESULTS: Surgery was indicated for the following symptoms resistant to medical management: incapacitating nasal obstruction (n=18, 90%) and headache or periorbital pain (n=14, 70%). At 3 years follow-up, six patients (30%) were symptom-free, six (30%) had required re-operation, and symptoms were well controlled by medication in the other eight (40%). Mean initial bilateral surgery time was 61 min. There were no complications. CONCLUSION: The advent of microdebriders and CT-based navigation has improved endoscopic sinus surgery in cystic fibrosis. It has permitted the control of medication-resistant symptoms, especially nasal obstruction and pain. Precision is satisfactory, with reduced surgery time. No major complications have been observed. Two- or three-step surgery is possible where endoscopic anatomic landmarks have suffered alteration. The resultant control of symptoms encourages extending indications, with repeat procedures, in view of improving patients' quality of life. Further assessment on a larger series will be needed.

[A case of Nasal septum abscess]. / Abcès de la cloison nasale. A propos d'un cas.

INTRODUCTION: Abscess of the nasal septum is a rare and serious infection, because of the complications which it can generate. The authors report a new case of nasal septum abscess probably of dental origin. OBSERVATION: A 47-year-old man consulted for bilateral nasal obstruction and rhinorrhea for 3 days with fever. The clinical examination as well as TDM imagery revealed a septal abscess. The patient underwent surgical drainage associated to triple antibiotherapy, with a good evolution at the end of 10 days. The etiologic assessment suggested dental infection. CONCLUSION: This is a rare and serious infection of the nasal septum. This new case of rare abscess of the nasal septum gives us the opportunity to describe out the various etiologies, their management, and to insist on the preventive treatment of this infection.

[Nasal septal abscess: a case report]. / Abcès de la cloison nasale: à propos d'un cas.

INTRODUCTION: The nasal septum abscess is a rare and serious infection because of the complications which can be generated. The authors report a new case of nasal septum abscess to probably from dental origin. OBSERVATION: A 47 year old man consulted for bilateral nasal obstruction and rhinorrhea for 3 days with an infectious context. The clinical examination as well as the CT scan demonstrated a septal abscess. The patient had a surgical drainage associated with a triple antibiotherapy with favourable evolution at the end of 10 days. The etiologic investigation is in favour of a dental etiology. CONCLUSION: It is about a rare and serious infectious pathology of the nasal septum. We point out its various etiologies, its management, while insisting on the preventive treatment of this affection.

Dielectric environment and/or random disorder effects on free, charged and localized excitonic states in monolayer WS2.

Excitonic effects play an important role on the optoelectronic behavior of atomically thin two-dimensional (2D) crystals of the WS2 transition metal dichalcogenide. In this paper, neutral and charged exciton behaviors in monolayer WS2 are handled within effective-mass approximation for which the critical parameters are ensured from our ab initio calculations. Firstly, we reveal an exciton series with a novel energy dependence on the orbital angular momentum. Considerable control of the dielectric environment on neutral and charged excitons binding energies is elucidated. We demonstrate that for accepted values of effective masses, the negative and positive trion binding energies should be identical. Secondly, localization of neutral exciton center of mass motion by random potential arising from monolayer defects is also studied. The results obtained are in agreement with available experimental work.

Tracheotomy in children: evolution in indications.

OBJECTIVES: To evaluate the evolution of indications for tracheostomy in children. METHODS: A retrospective review of 46 children undergoing tracheostomy between 1996 and 2001. RESULTS: The indications for tracheostomy were classified in two groups:(1) prolonged ventilator dependence (57%), (2) upper airway obstructions (43%). The average age of the tracheostomy was 3 years and 8 months. This was higher in the first group (5.5 years). Decannulation was accomplished in 52%. The indications for tracheostomy were evaluated and were found to decrease in frequency for upper airway obstructions. An increasing indication was for chronic disorders requiring prolonged ventilator dependence. Complications occurred in 50% of children. Overall mortality was 13-2.7% directly related to the tracheostomy. CONCLUSIONS: Evolving indication has been ventilator dependence. Upper airway obstruction as an indication has diminished in frequency, especially with the concomitant progress of endoscopic techniques.

[Imported malaria in Tunisia]. / Le paludisme d'importation en Tunisie.

Thanks to the national programme of malaria eradication carried out between 1968 and 1972, there has been no active transmission of the parasitosis in Tunisia since the last indigenous case in 1979. Since 1980, with the increase in international exchanges especially with sub-Saharian countries, only imported cases of malaria have been reported in Tunisia. A retrospective and thorough survey of malaria cases diagnosed in the laboratory of parasitology of the Pasteur Institute in Tunis from 1980 to 1995 determined the epidemiological characteristics of this imported parasitosis. All in all, during the sixteen years following eradication, 245 cases were registered. The majority of cases (86.2%) was diagnosed by a systematic control of groups at risk within the national programme of malaria eradication. The remaining 13.8% cases sought medical advice when clinical symptoms appeared after their return from endemic countries. The population most affected by imported malaria were men (sex-ratio: 6.8) aged between 20 and 40 years (76% of cases); 38% were Tunisians having sojourned in an endemic country, essentially students from sub-Saharian Africa. The presumed country of contamination was African in 92.7% of the cases. Entrance into Tunisia by patients was mainly by air; 4% of the registered cases had come by land from Algeria. Sound knowledge of the epidemiological characteristics of imported malaria would make for a better follow-up of the affected population and thus reduce the probability of repeated transmission.

Azacitidine salvage therapy for relapse of myeloid malignancies following allogeneic hematopoietic SCT.

Patients with hematopoietic malignancies relapsing after allogeneic hematopoietic SCT (allo-HSCT) have a poor prognosis. We retrospectively analyzed the patients who received azacitidine in our center in the course of treatment of their post-transplant relapse. We identified 31 patients. Relapse occurred at a median of 3.7 (1.7-37.6) months following allo-HSCT. Patients received a median number of three cycles (1-12) of azacitidine (7 days, 75 mg/m(2) daily). Thirty-nine percent of patients had either a monosomal karyotype or a complex karyotype. Eleven patients (35%) received at least one DLI. Eleven patients responded to azacitidine, with four patients achieving a CR (13%). Median time to best response was 92 (35-247) days, with a median duration of 209 (64-751) days. One-year estimated survival rate was 14%. In conclusion, azacitidine may reinduce durable remissions in very few patients with AML or myelodysplastic syndrome. The toxicity related to azacitidine was high, although it may be difficult to distinguish between treatment-related side effects, namely due to cytopenia and toxicity due to the relapse or disease progression itself. Early administration of azacitidine after transplant followed by DLI should be considered as a pre-emptive therapy for potential relapse in patients with minimal residual disease or high-risk myeloid malignancies.

Management of laryngomalacia.

Laryngomalacia is the most common laryngeal disease of infancy. It is poorly tolerated in 10% of cases, requiring assessment and management, generally surgical. Surgery often consists of supraglottoplasty, for which a large number of technical variants have been described. This surgery, performed in an appropriate setting, relieves the symptoms in the great majority of cases with low morbidity. However, few data are available concerning the objective results: preoperative and postoperative objective assessment of these infants is therefore necessary whenever possible. Noninvasive ventilation (NIV) may be indicated in some infants with comorbid conditions or failing to respond to surgical management.

Pathophysiology and diagnostic approach to laryngomalacia in infants.

Laryngomalacia is defined as collapse of supraglottic structures during inspiration. It is the most common laryngeal disease of infancy. Laryngomalacia presents in the form of stridor, a high-pitched, musical, vibrating, multiphase inspiratory noise appearing within the first 10 days of life. Signs of severity are present in 10% of cases: poor weight gain (probably the most contributive element), dyspnoea with permanent and severe intercostal or xyphoid retraction, episodes of respiratory distress, obstructive sleep apnoea, and/or episodes of suffocation while feeding or feeding difficulties. The diagnosis is based on systematic office flexible laryngoscopy to confirm laryngomalacia and exclude other causes of supraglottic obstruction. Rigid endoscopy under general anaesthesia is only performed in the following cases: absence of laryngomalacia on flexible laryngoscopy, presence of laryngomalacia with signs of severity, search for any associated lesions prior to surgery, discrepancy between the severity of symptoms and the appearance on flexible laryngoscopy, and/or atypical symptoms (mostly aspirations). The work-up must be adapted to each child; however, guidelines recommend objective respiratory investigations in infants presenting signs of severity.

Escalated lymphodepletion followed by donor lymphocyte infusion can induce a graft-versus-host response without overwhelming toxicity.

Treatment of relapse of hematological malignancies following allogeneic hematopoietic SCT (allo-HSCT) remains very challenging and relies usually on the readministration of chemotherapy combined with donor lymphocyte infusion (DLI). To enhance DLI effectiveness, lymphodepletion (LD) with fludarabine (Flu) and/or CY before the injection of lymphocytes is an attractive modality to modify the immune environment, leading possibly to suppression of regulatory T cells (T(reg)) and exposing the patient to cytokine activation. However, LD before DLI may lead to induction of deleterious GVHD. To avoid inducing overwhelming toxicity, we proceeded by escalating doses of both LD and DLI. Eighteen patients with various non-CML hematological malignancies who relapsed following allo-HSCT were treated with chemotherapy and LD-DLI or LD-DLI upfront. T-cell subpopulation and DC levels as well as cytokine plasma levels (IL-7, IL-15) were measured before and following LD-DLI. Cumulative incidence of acute grade II-IV GVHD was 29.4% similar to that reported in patients receiving DLI without LD. In addition, Flu alone with low dose of DLI was not associated with severe GHVD. CY/Flu at the respective doses of 600 mg/m(2) on day 1 and Flu 25 mg/m(2)/day on days 1-3 did not result in a marked decrease of T(reg) cells, nor in endogenous IL-7 and IL-15 production. However, a peripheral expansion of DCs was observed. These findings suggest that the escalated dose procedure appears safe and prevent overwhelming toxicity. A dose-limiting toxicity has not yet been reached.

Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation.

This single centre study assessed the incidence, kinetics and predictive factors of EBV reactivation and EBV-related lymphoproliferative diseases (LPD) in 33 consecutive patients who received a reduced intensity conditioning (RIC) before umbilical cord blood transplantation (UCBT). During the first 6 months after UCBT, weekly all patients were DNA-PCR screened in the peripheral blood for EBV reactivation and were clinically monitored for clinical features attributable to EBV. The cumulative incidences of EBV reactivation (defined as an EBV load >1000 EBV copies per 10(5) cells measured at least once during follow-up) at 6 months and 2 years after UCBT were 9 (95% confidence interval (CI), 2-22%) and 17% (95% CI, 6-33%), respectively. In 28 patients (85%), the EBV load remained negative at all times, and none of these patients experienced any sign of LPD. Five patients (15%) experienced at least one EBV reactivation episode. EBV reactivation was observed at a median of 132 days (range, 85-438) after UCBT. Two patients developed EBV-related LPD (cumulative incidence, 6% at 3 years). With a median follow-up of 468 days (range, 92-1277) post UCBT, the OS was 62% at 3 years. Five patients died of disease progression and seven patients died of transplant-related complications, including one case of EBV-related LPD. Univariate analysis did not identify any significant risk factor associated with EBV reactivation. We conclude that patients undergoing RIC UCBT are at risk for EBV reactivation, with the need for close EBV monitoring and the use of preemptive rituximab treatment as some cases may progress to life-threatening LPD.

Features of Epstein-Barr Virus (EBV) reactivation after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation.

This single centre study assessed the incidence, kinetics and predictive factors of Epstein-Barr Virus (EBV) reactivation and EBV-related lymphoproliferative diseases (LPDs) in 175 consecutive patients who received a reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cumulative incidence of EBV reactivation at 6 months after allo-HSCT defined as an EBV PCR load above 1000 copies of EBV DNA/10(5) cells was 15%, and none of these patients experienced any sign or symptom of LPD. A total of 17 patients, who had EBV DNA levels exceeding 1000 copies/10(5) cells on two or more occasions, were pre-emptively treated with rituximab. With a median follow-up of 655 (range, 92-1542) days post allo-HSCT, there was no statistically significant difference in term of outcome between those patients who experienced an EBV reactivation and those who did not. In multivariate analysis, the use of antithymocyte globulin as part of the RIC regimen was the only independent risk factor associated with EBV reactivation (relative risk=4.9; 95% confidence interval, 1.1-21.0; P=0.03). We conclude that patients undergoing RIC allo-HSCT using anti-thymocyte globulin as part of the preparative regimen are at higher risk for EBV reactivation. However, this did not impact on outcome, as quantitative monitoring of EBV viral load by PCR and preemptive rituximab therapy allowed for significantly reducing the risk of EBV-related LPD.

Is there a role for all-trans retinoic acid in combination with recombinant erythropoetin in myelodysplastic syndromes? A report on 59 cases.

Erythropoiesis-stimulating agents (ESAs) remain the first-line treatment of anemia in lower risk myelodysplastic syndromes (MDS) without 5q deletion. A preliminary report suggested that adding all-trans retinoic acid (ATRA) to ESAs may improve their erythroid response, particularly in patients with high endogenous erythropoietin (EPO) level, and may improve other cytopenias. We conducted a prospective multicenter study of EPO-beta and ATRA in anemic MDS patients with marrow blasts <10% and either previous ESA failure or relapse, endogenous EPO >500 U/l or other cytopenia(s) (absolute neutrophilic count <1.0 G/l or platelets <50 G/l). A total of 59 patients were evaluable after 12 weeks of treatment. The erythroid response rates according to IWG 2000 and 2006 criteria, respectively, were as follows: overall: 49 and 36%; patients with previous ESA failure (n=28): 43 and 32%; patients with endogenous EPO >500 U/l (n=18): 11 and 19%; patients transfused >2 red blood cells units/month (n=28) 43 and 39%. Only one neutrophil, but no platelet response, and no major side effect were observed. EPO-beta-ATRA combination appears a possible therapeutic option in anemia of MDS having failed an ESA alone, but not in patients with high endogenous EPO level, and does not improve neutropenia and thrombocytopenia.