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.

[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.

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.

Impact of donor-to-recipient weight ratio on survival after bilateral lung transplantation.

BACKGROUND: The aim of this study was to investigate the relationship between donor-to-recipient weight ratio and post-transplantation survival. METHODS: From February 1988 to November 2006, 255 adult bilateral lung transplantation patients from 2 different centers were retrospectively analyzed. The cohort was divided into 4 groups depending on the quartile ranges of the donor-to-recipient weight ratio. A time-to-event analysis was performed for risk of death after transplantation conditional on 5-year survival using Kaplan-Meier and Cox proportional hazards models. RESULTS: The mean weight ratio for the study cohort was 1.23 ± 0.39. For all lung transplant recipients during the study period, survival rate at 5 years was 58%. Median survival was 6.3 years in the cohort subgroup with weight ratio <1.23, whereas the median survival was 7.7 years for the cohort subgroup with weight ratio >1.23. Weight ratio >1.23 recipients had a significant survival advantage out to 5 years compared with weight ratio <1.23 recipients (66.1% vs 51.1%, P = .0126). With the aim to assess underweight and overweight donors vs recipients, we have divided all patients into 4 groups, from quartile 1 to 4, based on donor-to-recipient weight ratio. Weight ratio strata affected overall survival, with quartile 1 (lower weight ratio recipients) experiencing the lowest 5-year survival (39.1%), followed by quartile 2 (57.8%), quartile 4 (68.2%), and quartile 3 (70.3%) recipients. The effect of weight ratio strata on survival was statistically significant for the quartile 1 recipients (lower quartile) as compared with the 3 other quartiles. CONCLUSIONS: Our findings show a statistically significant effect of donor-to-recipient weight ratios on bilateral lung transplantation survival. A higher donor-to-recipient weight ratio was associated with improved survival after bilateral lung transplantation and likely reflects a mismatch between a relatively overweight donor vs recipient. In contrast, a lower donor-to-recipient ratio was associated with increased mortality after bilateral lung transplantation.

Influence of gender donor-recipient combinations on survival after human lung transplantation.

BACKGROUND: In the current practice of lung transplantation, donor and recipient genders are neither directly considered nor matched. However, some data have suggested a possible effect of gender combinations on survival following lung transplantation. METHODS: A total of 249 adult lung transplant recipients at a single center between February 1988 and December 2008, were analyzed retrospectively for donor-recipient gender matching. We compared the mortality by calculating one-term survival rates after transplantation using the Kaplan-Meier method with comparisons using the log-rank (Mantel-Cox) test. Statistical significance of the mean effects of size matching was assessed by paired Student t tests and Wilcoxon signed rank tests. RESULTS: Kaplan-Meier survival analysis shown that male compared to female recipients did not have an effect on outcomes after lung transplantation at 5 years (P=.5379), 10 years (P=.107), 15 years (P=.0841), 20 years (P=.0711). No effect of gender on lung transplantation outcomes was observed with donor-recipient gender mismatches at 5 years (P=.1804), 10 years (P=.1457), 15 years (P=.0731), or 20 years (P=.0629). Similarly, no differences were observed for each gender combination. The degree of size matching was defined as the ratio of donor-to-recipient predicted total lung capacity. The ratios were similar for the donor-recipient gender match and significantly different for the donor-recipient gender mismatch. CONCLUSIONS: These analyses suggested that gender was not a significant independent risk factor affecting survival after lung transplantation. Size mismatch caused by gender mismatch did not increase mortality.

[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.

[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.

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.

Determinants of the difference between expired and core temperatures: effect of a breath-hold.

After a 30-s breath-hold (BH), expired temperature (TE) does not reach core temperature. One explanation is that the gas in the airways is not in thermal equilibrium with the airway walls. This possibility was eliminated by comparing TE in six subjects breathing either helium-oxygen or air after a BH. Another possibility is that the airway walls and surrounding tissues have sufficient thermal inertia to slow down thermal equilibrium during BH. This was checked by measuring oral and upper esophageal temperatures after cooling or heating the airways. It took more than 2 min for these temperatures to recover their steady-state value. Six subjects were requested to perform a long apnea after hyperventilating for 1 min and then taking a single breath of 100% oxygen. TE was still lower than core temperature after a 1-min BH, and there was no difference after a 2-min BH. The difference between expired and core temperatures during BH thus appears to be due to the thermal inertia of the airways and their surrounding tissues.