Euvrard S.,Edouard Herriot Hospital Group |
Morelon E.,Edouard Herriot Hospital Group |
Morelon E.,University of Lyon |
Morelon E.,French Institute of Health and Medical Research |
And 19 more authors.
New England Journal of Medicine | Year: 2012
Background: Transplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed. Methods: In this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors (in 64 patients) or to maintain their initial treatment (in 56). The primary end point was survival free of squamous-cell carcinoma at 2 years. Secondary end points included the time until the onset of new squamous-cell carcinomas, occurrence of other skin tumors, graft function, and problems with sirolimus. Results: Survival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group. Overall, new squamous-cell carcinomas developed in 14 patients (22%) in the sirolimus group (6 after withdrawal of sirolimus) and in 22 (39%) in the calcineurin-inhibitor group (median time until onset, 15 vs. 7 months; P = 0.02), with a relative risk in the sirolimus group of 0.56 (95% confidence interval, 0.32 to 0.98). There were 60 serious adverse events in the sirolimus group, as compared with 14 such events in the calcineurininhibitor group (average, 0.938 vs. 0.250). There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocols as in those with progressive protocols. In the sirolimus group, 23% of patients discontinued the drug because of adverse events. Graft function remained stable in the two study groups. Conclusions: Switching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma. These observations may have implications concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas. Copyright © 2012 Massachusetts Medical Society.
Hull R.D.,University of Calgary |
Schellong S.M.,University Hospital Carl Gustav Carus |
Tapson V.F.,Duke University |
Monreal M.,Carretera de Canyet s n |
And 5 more authors.
Annals of Internal Medicine | Year: 2010
Background: Extended-duration low-molecular-weight heparin has been shown to prevent venous thromboembolism (VTE) in high-risk surgical patients. Objective: To evaluate the efficacy and safety of extended-duration enoxaparin thromboprophylaxis in acutely ill medical patients. Design: Randomized, parallel, placebo-controlled trial. Randomization was computer-generated. Allocation was centralized. Patients, caregivers, and outcome assessors were blinded to group assignment. (ClinicalTrials.gov registration number: NCT00077753) Setting: 370 sites in 20 countries across North and South America, Europe, and Asia. Patients: Acutely ill medical patients 40 years or older with recently reduced mobility (bed rest or sedentary without [level 1] or with [level 2] bathroom privileges). Eligibility criteria for patients with level 2 immobility were amended to include only those who had additional VTE risk factors (age >75 years, history of VTE, or active or previous cancer) after interim analyses suggested lower-than-expected VTE rates. Intervention: Enoxaparin, 40 mg/d subcutaneously (2975 patients), or placebo (2988 patients), for 28 ± 4 days after receiving open-label enoxaparin for an initial 10 ± 4 days. Measurements: Incidence of VTE up to day 28 and of major bleeding events up to 48 hours after the last study treatment dose. Results: Extended-duration enoxaparin reduced VTE incidence compared with placebo (2.5% vs. 4%; absolute risk difference favoring enoxaparin, -1.53% [95.8% CI, -2.54% to -0.52%]). Enoxaparin increased major bleeding events (0.8% vs. 0.3%; absolute risk difference favoring placebo, 0.51% [95% CI, 0.12% to 0.89%]). The benefits of extended-duration enoxaparin seemed to be restricted to women, patients older than 75 years, and those with level 1 immobility. Limitation: Estimates of efficacy and safety for the overall trial population are difficult to interpret because of the change in eligibility criteria during the trial. Conclusion: Use of extended-duration enoxaparin reduces VTE more than it increases major bleeding events in acutely ill medical patients with level 1 immobility, those older than 75 years, and women. Primary Funding Source: Sanofi-aventis. © 2010 American College of Physicians.
Bailly F.,Groupe Hospitalier Pitie Salpetriere |
Maigne J.-Y.,Hotel Dieu |
Genevay S.,University of Geneva |
Marty M.,Hopital Henri Mondor |
And 3 more authors.
European Spine Journal | Year: 2014
Purpose: To compare, in a case-control study, clinical characteristics of patients with low back pain (LBP) with and without Modic 1 signal changes on MRI. Methods: Patients with chronic non-specific LBP and a recent (<6 months) MRI were prospectively screened and included in Modic 1 group or control group. Patients in control group were age- and gender-matched with patients with Modic 1 group. Pain characteristics, including night pain and worse pain on waking and morning stiffness, were recorded. The presence of at least one of these three characteristics indicated an inflammatory pain pattern. Patients were evaluated by questionnaires and physical examination (including lumbar range of motion). Data were analyzed by univariate and multivariate analyses. Results: 120 patients were included (60 in each group). The groups did not differ in sedentary work (p = 0.25), morning stiffness for >60 min (p = 0.19), waking at night (p = 0.08), worse pain on waking (p = 0.09), back stiffness (p = 0.12), or pain with flexion (p = 0.87). Modic 1 patients more frequently exhibited an inflammatory pain pattern (p = 0.006), worse pain with lumbar extension (p < 0.005) and responded better to oral steroids (p = 0.004) than did controls. On multivariate analysis, Modic 1 changes were associated with sedentary work [odds ratio 0.22 (95 % confidence interval 0.05-0.93)], pain with lumbar extension [11.2 (3.1-40.4)] and an inflammatory pain pattern [4.5 (1.2-16.9)]. Conclusions: Characteristics of patients with LBP and Modic 1 changes on MRI consist of an inflammatory pain pattern and pain with lumbar extension. Level of evidence 3b. © 2013 Springer-Verlag.
Capeau J.,French Institute of Health and Medical Research |
Bouteloup V.,University of Bordeaux Segalen |
Katlama C.,University Pierre and Marie Curie |
Bastard J.-P.,French Institute of Health and Medical Research |
And 6 more authors.
AIDS | Year: 2012
Objective: To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009. Design: Prospective study of 1046 patients at 47 French clinical sites. Methods: Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure. Results: Among the cohort, representing 7846 person-years of follow-up (PYFU), 54% received indinavir, 75% stavudine and 52% didanosine. Overall, 111 patients developed diabetes, with an incidence of 14.1/1000 PYFU (14.6 in men, 12.6 in women). Incidence peaked in 1999-2000 (23.2/1000 PYFU) and decreased thereafter. The incidence of diabetes was associated [adjusted hazard ratio (aHR), all P<0.02] with older age (hazard ratio=2.13 when 40-49 years, hazard ratio=3.63 when ≥50 years), overweight (hazard ratio=1.91 for a BMI 25-29kg/m, hazard ratio=2.85 >30kg/m), waist-to-hip ratio (hazard ratio=3.87 for ≥0.97male/0.92 female), time-updated lipoatrophy (hazard ratio=2.14) and short-term exposure to indinavir (0-1year: hazard ratio=2.53), stavudine (0-1year: hazard ratio=2.56, 1-2years: hazard ratio=2.65) or didanosine (2-3years: hazard ratio=3.16). Occurrence of diabetes was not associated with HIV-related markers, hepatitis C, hypertension or family history of diabetes. Insulin resistance was predictive for incident diabetes. Conclusions: In this nationwide cohort, followed for 10 years after cART initiation, diabetes incidence peaked in 1990-2000, was markedly higher than that reported for European uninfected or other HIV-infected populations (4-6/1000 PYFU) and linked with age and adiposity. Adiposity and glycemic markers should be monitored in aging HIV-infected patients. © 2012 Wolters Kluwer Health Lippincott Williams & Wilkins.
Attal M.,Hopital Purpan |
Lauwers-Cances V.,Hopital Purpan |
Marit G.,Hopital Haut Leveque |
Caillot D.,Center Hospitalier Le Bocage |
And 19 more authors.
New England Journal of Medicine | Year: 2012
BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebocontrolled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation. METHODS:We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival. RESULTS:Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P<0.001). This benefit was observed across all patient subgroups, including those based on the β 2- microglobulin level, cytogenetic profile, and response after transplantation. With a median follow-up period of 45 months, more than 70% of patients in both groups were alive at 4 years. The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups. The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group (P = 0.002). Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001). CONCLUSIONS:Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.) Copyright © 2012 Massachusetts Medical Society.
Leccia M.-T.,Grenoble University Hospital Center |
Del Giudice P.,CH Intercommunal de Frejus St Raphael Dermatologie Infectiologie |
Dreno B.,Hotel Dieu
Journal of the European Academy of Dermatology and Venereology | Year: 2014
In recent years, significant progress has been made in the understanding of the pathophysiological mechanisms of acne and the role of Propionibacterium acnes. With this review, the authors aim to provide an update on the current understanding of the role of P. acnes in the development of acne lesions and analysing the potential implications for future treatments. A total of 188 articles published between January 1980 and March 2013 were searched using key words such as acne, P. acnes, microbiology, Corynebacterium acnes, acne vulgaris, pathogenesis, antibiotic, vaccination and a combination of those key words. From those articles, 77 were analysed in depth. Recent data confirm that P. acnes has a strong proinflammatory activity and targets molecules involved in the innate cutaneous immunity, keratinocytes and sebaceous glands of the pilosebaceous follicle and leads to the development of comedones. Furthermore, the profile of its different strains may differ between healthy subjects and acne patients. The better understanding of the role of P. acnes may allow for new perspectives in the treatment of acne. Novel therapies should target molecules implicated in the activation of innate immunity, including toll-like receptors, protease-activated receptors and topical antimicrobial peptides; the latter may be an alternative to topical antibiotics and thus a solution for limiting bacterial resistance induced by topical macrolides. Vaccines may also be promising. However, the most appropriate candidate remains to be selected. © 2013 European Academy of Dermatology and Venereology.
Dupouy S.,French Institute of Health and Medical Research |
Mourra N.,Service dAnatomopathologie |
Doan V.K.,French Institute of Health and Medical Research |
Gompel A.,UF de Gynecologie Hotel Dieu |
And 2 more authors.
Biochimie | Year: 2011
A growing challenge in medicine today, is the need to improve the suitability of drug treatments for cancer patients. In this field, biomarkers have become the "flags" to provide additional information in tumor biology. They are a relay between the patient and practitioner and consequently, aid in the diagnosis, providing information for prognosis, or in some cases predicting the response to specific therapies. In addition to being markers, these tumor "flags" can also be major participants in the process of carcinogenesis. Neurotensin receptor 1 (NTSR1) was recently identified as a prognosis marker in breast, lung, and head and neck squamous carcinomas. Neurotensin (NTS) was also shown to exert numerous oncogenic effects involved in tumor growth and metastatic spread. These effects were mostly mediated by NTSR1, making the NTS/NTSR1 complex an actor in cancer progression. In this review, we gather information on the oncogenic effects of the NTS/NTSR1 complex and its associated signaling pathways in order to illuminate its significant role in tumor progression and its potential as a biomarker and a therapeutic target in some tumors. © 2011 Elsevier Masson SAS. All rights reserved.
Laurini J.A.,University of Nebraska Medical Center |
Perry A.M.,University of Nebraska Medical Center |
Boilesen E.,University of Nebraska Medical Center |
Diebold J.,Hotel Dieu |
And 5 more authors.
Blood | Year: 2012
The distribution of non-Hodgkin lymphoma (NHL) subtypes differs around the world but a systematic study of Latin America has not been done. Therefore, we evaluated the relative frequencies of NHL subtypes in Central and South America (CSA). Five expert hematopathologists classified consecutive cases of NHL from 5 CSA countries using the WHO classification and compared them to 400 cases from North America (NA). Among the 1028 CSA cases, the proportions of B- and T-cell NHL and the sex distribution were similar to NA. However, the median age of B-cell NHL in CSA (59 years) was significantly lower than in NA (66 years; P < .0001). The distribution of high-grade (52.9%) and low-grade (47.1%) mature B-cell NHL in CSA was also significantly different from NA (37.5% and 62.5%; P < .0001). Diffuse large B-cell lymphoma was more common in CSA (40%) than in NA (29.2%; P < .0001), whereas the frequency of follicular lymphoma was similar in Argentina (34.1%) and NA (33.8%), and higher than the rest of CSA (17%; P < .001). Extranodal NK/T-cell NHL was also more common in CSA (P < .0001). Our study provides new objective evidence that the distribution of NHL subtypes varies significantly by geographic region and should prompt epidemiologic studies to explain these differences. © 2012 by The American Society of Hematology.
Vincent M.,Medical Diabetes |
Nobecourt E.,Hotel Dieu
Diabetes and Metabolism | Year: 2013
Aim: Low-dose intravenous infusions of regular insulin, usually initiated in the emergency department and continued in the intensive care unit (ICU), are the standard care for patients with diabetic ketoacidosis (DKA) to ensure rapid resolution of hyperglycaemia and ketoacidosis. Several studies have evaluated whether subcutaneous injections of the rapid-acting analogue insulin lispro may be an alternative to intravenous insulin infusion for avoiding ICU admissions of uncomplicated DKA cases. Methods: This review summarizes the current clinical evidence for the effectiveness and safety of subcutaneous insulin lispro injections in non-severe DKA patients. Relevant studies were identified by a systematic literature search through the PubMed database. Results: To date, four small randomized studies (156 patients overall; three studies in adults and one in paediatric patients with diabetes) have directly compared subcutaneous insulin lispro injections every 1-2. h vs continuous intravenous infusions of regular insulin. Patients with severe complications were excluded. In all studies, the mean time to resolution of DKA was similar in both treatment groups [range (three studies): lispro 10-14.8. h; regular insulin 11-13.2. h]. The mean time to resolution of hyperglycaemia, total insulin doses required, number of hospitalization days and number of hypoglycaemic episodes were similar in both treatment groups; no severe complications or DKA recurrences were reported, and one study showed a 39% cost reduction for the insulin lispro group. Conclusion: In patients with mild-to-moderate DKA, subcutaneous injections of insulin lispro every 1-2. h offer a feasible alternative to continuous intravenous infusions of regular insulin, and should now be evaluated in larger, more appropriately powered studies. © 2013.
Frija-Orvoen E.,Hotel Dieu
Medecine du Sommeil | Year: 2015
Pulse oximetry is currently used in many clinical applications. Usually reliable and accurate, a good knowledge of the limitations in measurement is necessary before use. This paper describes technical principles and limitations of pulse oximetry.