T Cells Promote Bronchial Epithelial Cell Secretion of Matrix Metalloproteinase-9 via a C-C Chemokine Receptor Type 2 Pathway: Implications for Chronic Lung Allograft Dysfunction.

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. CLAD manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity in epithelial cell differentiation. Primary human bronchial epithelial cells (BECs) were treated with activated T cells in the presence or absence of transforming growth factor (TGF)-ß. The expression of epithelial and mesenchymal markers was investigated. The secretion of inflammatory cytokines and matrix metalloproteinase (MMP)-9 was measured in culture supernatants and in plasma from lung transplant recipients (LTRs): 49 stable, 29 with BOS, and 16 with RAS. We demonstrated that C-C motif chemokine 2 secreted by T cells supports TGF-ß-induced MMP-9 production by BECs after binding to C-C chemokine receptor type 2. Longitudinal investigation in LTRs revealed a rise in plasma MMP-9 before CLAD onset. Multivariate analysis showed that plasma MMP-9 was independently associated with BOS (odds ratio [OR] = 6.19, p = 0.002) or RAS (OR = 3.9, p = 0.024) and predicted the occurrence of CLAD 12 months before the functional diagnosis. Thus, immune cells support airway remodeling through the production of MMP-9. Plasma MMP-9 is a potential predictive biomarker of CLAD.

Operational considerations for the management of non-communicable diseases in humanitarian emergencies.

Non-communicable diseases (NCD) represent an increasing global challenge with the majority of mortality occurring in low- and middle-income countries (LMICs). Concurrently, many humanitarian crises occur in these countries and the number of displaced persons, either refugees or internally displaced, has reached the highest level in history. Until recently NCDs in humanitarian contexts were a neglected issue, but this is changing. Humanitarian actors are now increasingly integrating NCD care in their activities and recognizing the need to harmonize and enhance NCD management in humanitarian crises. However, there is a lack of a standardized response during operations as well as a lack of evidence-based NCD management guidelines in humanitarian settings. An informal working group on NCDs in humanitarian settings, formed by members of the World Health Organization, Médecins Sans Frontières, the International Committee of the Red Cross, the International Federation of the Red Cross and others, and led by the United Nations High Commissioner for Refugees, teamed up with the University of Geneva and Geneva University Hospitals to develop operational considerations for NCDs in humanitarian settings. This paper presents these considerations, aiming at ensuring appropriate planning, management and care for NCD-affected persons during the different stages of humanitarian emergencies. Key components include access to treatment, continuity of care including referral pathways, therapeutic patient education/patient self-management, community engagement and health promotion. In order to implement these components, a standardized approach will support a consistent response, and should be based on an ethical foundation to ensure that the "do no harm" principle is upheld. Advocacy supported by evidence is important to generate visibility and resource allocation for NCDs. Only a collaborative approach of all actors involved in NCD management will allow the spectrum of needs and continuum of care for persons affected by NCDs to be properly addressed in humanitarian programmes.

[When should respiratory physicians consider lung transplantation for their patients? Inscription criteria for the national waiting list]. / Quand le pneumologue doit-il envisager la greffe pulmonaire pour un de ses patients?

INTRODUCTION: Placing a patient on the national lung transplant waiting list remains a difficult matter, and is more a question of timing than selection of the candidate according to disease-specific criteria. BACKGROUND: The listing criteria for cystic fibrosis are FEV1 less than 30% of the predicted value, hypoxaemia with a PaO2 less than 55 mm Hg and hypercapnia with a PaCO2 over 50 mm Hg. The rate of decline of FEV1, increasing antibiotic requirements and life threatening complications can all accelerate the listing procedure. For primary pulmonary hypertension the criteria are persistent dyspnoea, NYHA grade III or IVA, despite epoprostenol treatment and a 6 minute walk test of less than 250 metres. Sarcoidosis, lymphangioleiomyomatosis, histiocytosis X and connective tissue diseases are rare indications for which the listing criteria are similar to those for the more usual respiratory diseases. VIEWPOINTS: Further therapeutic advances, increased numbers of available organs and changes in the allocation rules will necessitate periodical updates of these selection and listing criteria. CONCLUSION: The optimal time for placing lung transplantation patients who have been referred early in the course of their disease on the waiting list will be determined by clinical experience and individual patient follow-up.

[Cyclosporine-induced follicular eruption]. / Toxidermie folliculaire à la ciclosporine.

BACKGROUND: Cyclosporine is one of the immunosuppressant agents most widely used in the prevention and treatment of organ transplant rejection and also in autoimmune diseases. Many cutaneous side effects have been described with oral cyclosporine, mainly in transplant recipients, for example, hypertrichosis, gingival hyperplasia and viral skin infections. Here, we report an unusual follicular eruption induced by this drug. PATIENTS AND METHODS: A 22-year-old man presenting cystic fibrosis received a double-lung graft in January 2005. Six weeks later, he developed a subacute eruption of follicular papules, not highly pruritic, located mainly on the trunk, the extensor surfaces of the limbs and the face. Diagnosis of cyclosporine-induced follicular eruption was adopted on the basis of the histological and microbiological findings. Complete regression was obtained after switching to tacrolimus. DISCUSSION: Three similar cases were previously reported characterized by typical follicular changes different from those observed in hypertrichosis or pilar keratosis. This rare cutaneous side effect may be explained by the direct action of cyclosporine on the pilosebaceous unit: this drug is known to extend the anagen phase of the follicular cycle and to induce toxic follicular dystrophy at higher tissue concentrations. This particular toxicity is usually seen after many months of treatment. In our patient, the time to onset was shorter, probably due to occasionally excessive plasma concentrations.

[A rare familial form of idiopathic pulmonary fibrosis with Poly(A)-specific ribonuclease (PARN) mutation]. / Mutation poly(A)-specific ribonuclease (PARN) et fibrose pulmonaire idiopathique familiale : à propos d'un cas au centre hospitalier universitaire de Bordeaux.

New techniques of DNA sequences allow to discover genetics mutations involved in familial pulmonary fibrosis. Among them, the PARN (Poly[A]-specific ribonuclease) mutation. Herein, we report the case of one patient who has pulmonary fibrosis with PARN mutation and the experience of our patient care.

Intermediate-term results after en bloc double-lung transplantation with bronchial arterial revascularization. Bordeaux Lung and Heart-Lung Transplant Group.

OBJECTIVE: Between May 1990 and January 1994, 18 patients underwent en bloc double-lung transplantation with tracheal anastomosis and bronchial arterial revascularization. Because at that time it was already suggested that chronic ischemia could be a contributing factor in occurrence of obliterative bronchiolitis, the purpose of this study was to evaluate, with a follow-up ranging from 22 to 69 months, the midterm effects of bronchial arterial revascularization on development of obliterative bronchiolitis. RESULTS: Results were assessed according to tracheal healing, functional results, rejection, infection, and incidence of obliterative bronchiolitis. There were no intraoperative deaths or reexplorations for bleeding related to bronchial arterial revascularization, but there were three hospital deaths and five late deaths, two of them related to obliterative bronchiolitis. According to the criteria previously defined, tracheal healing was assessed as grade I, IIa, or IIb in 17 patients and grade IIIa in only one patient. Early angiography (postoperative days 20 to 40) demonstrated a patent graft in 11 of the 14 patients in whom follow-up information was obtained. Ten patients are currently alive with a 43-month mean follow-up. Among the 15 patients surviving more than 1 year, functional results have been excellent except in five in whom obliterative bronchiolitis has developed and who had an early or late graft thrombosis. Furthermore, those patients had a significantly higher incidence of late acute rejection (p < 0.02), cytomegalovirus disease (p < 0.006), and bronchitis episodes (p < 0.0008) than patients free from obliterative bronchiolitis. CONCLUSION: We conclude that besides its immediate beneficial effect on tracheal healing, long-lasting revascularization was, at least in this small series, associated with an absence of obliterative bronchiolitis, thus suggesting but not yet proving the possible role of chronic ischemia in this multifactorial disease.

Prognostic factors and long-term results after thymoma resection: a series of 307 patients.

Three hundred seven cases of patients who underwent operation for thymoma (196 of whom had myasthenia gravis) were analyzed to assess the prognostic values of Masaoka clinical staging, completeness of resection, histologic classification, history of myasthenia gravis, and postoperative radiotherapy. According to the Masaoka staging system, 135 thymomas were stage I, 70 were stage II, 83 were stage III, and 19 were stage IV. According to the Verley and Hollmann histologic classification system, 67 thymomas were type 1, 77 were type 2, 139 were type 3, and 24 were type 4. Two hundred sixty patients underwent complete resection, 30 underwent incomplete resection, and 17 underwent biopsy. Postoperative radiotherapy was performed mainly in cases of invasive or metastatic thymoma. Mean follow-up was 8 years; eight patients were unavailable for follow-up. The overall 10- and 15-year survivals were 67% and 57%, respectively. In univariate analysis, three prognostic factors were established: completeness of resection, Masaoka clinical staging, and histologic classification. Furthermore, among patients with stage III thymomas, survival was significantly higher for patients with complete resection than for patients with incomplete resection (p < 0.001). Completeness of resection should therefore be taken into account in clinical-pathologic staging. We did not find any significant difference with respect to disease-free survival between patients who had postoperative radiotherapy and those who did not. In multivariate analysis, the sole significant prognostic factor was completeness of resection. On the basis of these findings, a new clinical-pathologic staging system is proposed.

Tuberculosis in transplanted lungs.

Over a 4-year period in four of 61 patients (6.5%) who survived lung transplantation, pulmonary tuberculosis developed at a mean of 7.5 months (range 3 to 13 months) after operation. Clinical and radiologic features were atypical. Definitive bacteriologic diagnosis, which was established on bronchial, sputum, and pleural fluid samples, may be delayed by the concomitant presence of other infective organisms and the necessity for repeated sampling. All patients were treated successfully with antituberculous chemotherapy, but one patient also required lobectomy. At a mean follow-up of 2.25 years (range, 1 to 3 years), three patients are free of active disease, and one patient had a recurrence at 2 years. Tuberculosis in transplanted lungs is an uncommon but serious infection that may elude diagnosis but respond well to treatment.

Posterior dislocation of the sternoclavicular joint leading to mediastinal compression.

Dislocations of the sternoclavicular joint are uncommon, and the posterior variety have a potential for considerable morbidity. We report a case with compression of the vital structures within the superior mediastinum. It was a rugby player getting run over by the scrum. The mechanism was an indirect force exerted forward and laterally against the shoulder. The patient complained of pain and dysphagia. A systolic right cervical murmur was heard. Angiography was normal and esophagography showed extrinsic esophageal compression. Surgical reduction was performed because there was a slight pneumomediastinum on the computed tomography. This case report demonstrates the mechanism, complications, and treatment of such a lesion.

Long-term functional results after bilateral lung transplantation. Bordeaux Lung and Heart-Lung Transplant Group.

Between February 1988 and January 1992, 61 patients have undergone bilateral lung transplantations (42 heart-lung and 19 double-lung) in Bordeaux. The underlying diseases were primary or secondary hypertension (20), emphysema (22), or other diseases including cystic fibrosis, pulmonary fibrosis, silicosis, and sarcoidosis (19). Actuarial survival for double-lung and heart-lung transplant recipients was 66% and 72% at 1 year and 57% and 53% at 3 years, respectively. Forty-two patients were still alive 6 months after operation, and we studied their pulmonary function at the short and long term. All parameters except arterial carbon dioxide tension had improved dramatically at 6 months (p < 0.0001). Vital capacity, forced expiratory volume in 1 second, and forced expiratory flow rate between 25% and 75% of vital capacity were at 79% +/- 3%, 92% +/- 5%, and 105% +/- 8% of the predicted values, respectively. Arterial oxygen tension was 88 +/- 3 mm Hg. Nine months after operation, a slight decrease in forced expiratory volume in 1 second and forced expiratory flow rate between 25% and 75% of vital capacity appeared but values remained more than 75% predicted. This was related to the occurrence of obliterative bronchiolitis in 6 patients (14%). At 9 months, flow rates and oxygen tension of these 6 patients were highly different from those of patients free of obliterative bronchiolitis (p < 0.0002 for flow rates and p < 0.01 for oxygen tension). Only 1 patient required retransplantation. The others are living an almost normal life. Our results are discussed in view of the published reports on single-lung transplantation. Short-term results of bilateral lung transplantation are thus excellent and maintained on a long-term basis. Therefore, in our opinion, bilateral lung transplantation is the therapy of choice for pulmonary hypertension and emphysema.

Expanding wire stents in benign tracheobronchial disease: indications and complications.

Prosthetic tracheobronchial stents provide palliative treatment for narrowed airways where surgical resection is inadvisable. Over a 1-year period, 28 Gianturco expanding wire stents were used in 15 patients for nonneoplastic indications: pure fibrous airway stenosis (6), fibroinflammatory stenosis (4), and tracheobronchial malacia (5). Insertion was technically straightforward. A satisfactory airway lumen with immediate improvement in ventilatory function was obtained in all patients. After insertion all patients had an irritation-type cough that either subsided spontaneously (10 patients) or was successfully suppressed with inhaled corticosteroid therapy (5 patients). The most common complication (12 patients) was granuloma formation leading to stent removal in 3 patients with fibroinflammatory stenosis. Other complications were dysphagia (1), suction catheter entrapment (1), and fatal massive hemoptysis (1). At a mean follow-up of 13 months (range, 3 to 19 months) all remaining stents are functioning well with no displacement or infection. Overall results were satisfactory in pure fibrous stenoses and tracheobronchial malacia but poor in the presence of inflammation. Tracheobronchial wire stents can be successfully used in selected patients.

Total vertebrectomy for en bloc resection of lung cancer invading the spine.

We describe a technique of total vertebrectomy for en bloc resection of a non-small cell lung cancer with vertebral invasion through a combination of thoracic and enlarged posterior approaches, and present our entire experience of total and partial vertebrectomy for tumors invading vertebral bodies or the costovertebral angle.

Bronchial revascularization in double-lung transplantation: a series of 8 patients. Bordeaux Lung and Heart-Lung Transplant Group.

Donor airway ischemia is the main cause for defective tracheal or bronchial healing after double-lung transplantation. Anatomical studies and bronchial arteriograms have shown that the right intercostal bronchial artery is constant (95% of instances) and provides an important blood supply to the distal trachea, the carina, and the right bronchial tree as well as to the left side through a subcarinal and periadventitial anastomostic network. To maintain this important bilateral bronchial circulation, it is of capital importance not to mobilize the arteries individually and to avoid large dissections around the carina. Both bronchi can thus be revascularized by indirect aortic reimplantation using a bypass graft to a single aortic patch that includes the origin of the right intercostal bronchial artery. Furthermore, the origin of other vessels (a common trunk and left arteries) can be found within a short distance of the right intercostal bronchial artery and possibly be contained within the same aortic patch. From a series of 56 lung transplantations, 8 patients underwent restoration of the bronchial vascularization using a recipient saphenous vein graft between the donor bronchial arteries and the anterior aspect of the recipient's ascending aorta. A lower tracheal anastomosis was performed. Bronchial arterial blood supply was evaluated both by endoscopy and by arteriography at about the 15th postoperative day. The bronchial circulation was visualized at this time in five of seven arteriographies, and this was associated with excellent tracheal healing in all 8 patients.

Bone remodelling in monoclonal gammopathies of uncertain significance, symptomatic and nonsymptomatic myeloma.

In order to characterize the abnormalities of bone remodelling in the various stages of plasma cell disorders, we studied 60 patients (29 monoclonal gammopathies of uncertain significance (MGUS), 13 stage I myeloma, 18 stage III myeloma). We carried out histomorphometric study of bone biopsies in 34 patients and measurement of osteocalcin and the calciuria/creatinine ratio. Bone remodelling was approximately normal (BV/TV:21.2 +/- 7, ES:4.1 +/- 2, OS:16.5 +/- 10) in MGUS. Stage I myeloma was characterised by parallel increases in resorption surfaces and osteoid surfaces (BV/TV:18 +/- 5, ES/BS:7.4 +/- 3.5, OS/BS:24.8 +/- 11.5), of the ca/cr ratio and osteocalcin. In stage III myeloma, resorption surfaces and the ca/cr ratio showed an even greater increase while osteoid surfaces, osteocalcin and trabecular bone volume decreased (BV/TV 13.6 +/- 6, ES/BS:12.1 +/- 6, OS/BS:13.6 +/- 8.3). Osteocalcin and osteoid surfaces were correlated (r = 0.5). There was a positive correlation between osteocalcin and the number of plasmocytes in stage 1 myeloma (r = 0.64) and a negative correlation in stage III myeloma (r = 0.9). Bone remodeling was normal in MGUS; bone remodelling grew with a parallel increase of formation and resorption in stage I; bone resorption increased while bone formation decreased in stage III myeloma.

Histological appearance of the intra-osseous vessels of the femoral head in aseptic osteonecrosis of the hip, with or without antiphospholipid antibodies.

UNLABELLED: It has been suggested that in some patients non-traumatic aseptic osteonecrosis of the hip (AOH) could be the result of the intra-osseous thrombosis. Antiphospholipid antibodies (APL) have been associated with venous and arterial occlusive events and the association between AOH and APL syndrome has been reported. OBJECTIVES: To compare bone vessels of the femoral head in patients operated on for AOH with or without APL. PATIENTS: Twenty patients (mean age 47 yrs) with AOH were included: in eight patients APL (IgG-ELISA) were negative (< 8 GPL units), in nine patients APL were doubtful (8-15 GPL units), and in three patients APL were positive (> 15 GPL units). METHODS: Bone vessels were examined: arteriosclerotic lesions, i.e. fibrosis or thickening of the media and rupture of the internal elastic lamina, thrombosis or vasculitis were sought in the femoral heads after total hip replacement or core decompression. RESULTS: Bone vessel lesions were the same in the three groups.

Does vascular endothelial growth factor in the rheumatoid synovium predict joint destruction? A clinical, radiological, and pathological study in 12 patients monitored for 10 years.

OBJECTIVE: Synovial angiogenesis is at the epicenter of rheumatoid pannus development and is largely dependent on vascular endothelial growth factor (VEGF). We sought to determine whether the VEGF level in rheumatoid synovial tissue is a marker for disease severity. PATIENTS AND METHODS: Twelve patients with rheumatoid arthritis (RA) underwent a clinical and radiological evaluation at the time of a synovial biopsy done during joint surgery required by RA progression (T1) and, on average, 10 years later (T2). Immunohistochemistry was used to detect and quantitate VEGF in the synovial biopsy taken at T1. RESULTS: VEGF labeling was seen on endothelial cells and macrophages in all 12 synovial biopsies. The amount of endothelial-cell VEGF labeling (assessed semi-quantitatively) was significantly correlated with Larsen score progression during the 10-year follow-up. The amounts of endothelial cell or macrophage VEGF labeling was not correlated with the joint count, radiological stage of the biopsied joint or progression of this stage, Larsen scores at T1 or T2, presence of rheumatoid factor, or presence of extra-articular manifestations. CONCLUSION: Our results suggest that the amount of VEGF in the rheumatoid synovium may be a marker for joint destruction in patients with RA.

[Tracheobronchial healing in lung or heart-lung transplantation. An anatomical study of forty anastomoses in men]. / La cicatrisation trachéo-bronchique chez le transplanté pulmonaire ou cardio-pulmonaire. Etude anatomique de quarante anastomoses chez l'homme.

The post operative evaluation and endoscopic follow-up of 34 tracheal or bronchial anastomoses after lung or heart-lung transplantation show some aspects of the tracheobronchial healing and difficulties in the healing process: primary type I mucomucosal healing in only 6 cases, secondary type II mucosal healing in 15, delayed type III healing after mucosal or deep parietal necrosis in 13, type IV distant ulcerations of mucosa and spur lesions in 12. Type III difficulties of healing mainly occur after double-lung transplantations which always suffer from ischemia. Autologous tracheal or bronchial sutures in 3 transplanted patients submitted to standard immunosuppressive therapy including corticosteroids were uneventful and type I. This experience suggests that among all factors having an influence on bronchial healing, ischemia of the donor tracheobronchial tree is predominant, justifying all attempts of bronchial revascularization after double-lung transplantation. The efficacy of the arterial revascularization is verified in 3 cases of tracheal anastomosis after double-lung transplantation with type I or II tracheal healing.

[Capsular retraction of shoulder: prospective study of imaging benefits in 20 patients]. / Capsulites rétractiles de l'épaule: étude prospective de l'apport de l'imagerie chez 20 patients.

PURPOSE: To evaluate the contribution of principal imaging techniques in diagnosis and treatment in adhesive capsulitis of the shoulder. MATERIALS AND METHODS: In 20 patients presenting adhesive capsulitis of shoulder since mean of 6,7 months, the following examinations were performed: radiographies, angioscintigraphy, MRI as well as an opaque arthrography and a bursography associated with corticosteroid injection. Patients were followed during one year. RESULTS: The opaque arthrography was to affirm the adhesive capsulitis for the inclusion of the patients. Radiographies (patchy demineralization) and scintigraphy (hyperfixation) were often pathological. In MRI, T1 fat-saturated sequences after contrast injection almost always showed enhancement of the articular capsula, the synovia, the miscellaneous bone or the sub-acromial bursa. The latter was often modified and retracted at bursography. In 19 of 20 cases, a functional improvement was observed after the opacifications. CONCLUSION: Therapeutic effect of both arthrography and bursography is almost proved. Post contrast MRI confirms presence of vascular troubles in all the shoulder structures even at this advanced stage.

[Pulmonary fibroma]. / Fibrome pulmonaire.

The authors report the case of a pulmonary fibroma in a 66 year-old smoker. Intrapulmonary localization of solitary fibrous tumors is rare; these tumors are more frequently described in pleura. Histologically, the presence of spindle cells without nuclear atypy on a collagen background must evoke the diagnosis made difficult by the unusual localization.

[Solitary fibrous thoracic tumor: a rare tumor with unpredictable course]. / Tumeur fibreuse solitaire de la plèvre.

A 68-year-old woman presented chest pain and exercise-induced dypnea for one year. Diagnosis was a thoracic solitary fibrous tumor. These tumors are very rare. Clinical outcome is generally good except in 13% of the cases with a malignant component. Complete surgical resection is required.