Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 340
Filter
1.
Cancer Radiother ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38866650

ABSTRACT

PURPOSE: MRI is essential in the management of brain tumours. However, long waiting times reduce patient accessibility. Reducing acquisition time could improve access but at the cost of spatial resolution and diagnostic quality. A commercially available artificial intelligence (AI) solution, SubtleMR™, can increase the resolution of acquired images. The objective of this prospective study was to evaluate the impact of this algorithm that halves the acquisition time on the detectability of brain lesions in radiology and radiotherapy. MATERIAL AND METHODS: The T1/T2 MRI of 33 patients with brain metastases or meningiomas were analysed. Images acquired quickly have a matrix divided by two which halves the acquisition time. The visual quality and lesion detectability of the AI images were evaluated by radiologists and radiation oncologist as well as pixel intensity and lesions size. RESULTS: The subjective quality of the image is lower for the AI images compared to the reference images. However, the analysis of lesion detectability shows a specificity of 1 and a sensitivity of 0.92 and 0.77 for radiology and radiotherapy respectively. Undetected lesions on the IA image are lesions with a diameter less than 4mm and statistically low average gadolinium-enhancement contrast. CONCLUSION: It is possible to reduce MRI acquisition times by half using the commercial algorithm to restore the characteristics of the image and obtain good specificity and sensitivity for lesions with a diameter greater than 4mm.

2.
Neurosci Res ; 170: 181-186, 2021 Sep.
Article in English | MEDLINE | ID: mdl-32768417

ABSTRACT

Visuospatial memory (VSM) performance depends on intrinsic (biopsychosocial parameters) and extrinsic (space) factors. We aimed at characterizing the determinants of VSM performance according to space. Young healthy adults, 20 males and 41 females (23 ±â€¯3 years old), were assessed for VSM performance through a pathway learning task, in reaching (eCorsi Block Tapping task) and walking space (Virtual Walking Corsi Task). We evaluated psychosocial factors through seven questionnaires - Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Fatigue Severity Scale, Profile of the Mood States, 2nd edition, short version, Coping Inventory for Stressful Situations, Measurement of Ambiguity Tolerance, Motives for Physical Activities Measure-Revised, mental rotation capabilities and locomotor characteristics (physical activity level through embedded trackers and the International Physical Activity Questionnaire, and gait parameters). The most explanatory biopsychosocial determinants of VSM performance were i) mental rotation capabilities and fatigue indicator in reaching space, and ii) mental rotation capabilities and physical activity level (tracked active energy expenditure only) in walking space. These results suggest that specific parameters should be preferred for the evaluation and strengthening of VSM capabilities in both reaching or walking spaces.


Subject(s)
Cognition , Walking , Adult , Fatigue , Female , Gait , Humans , Male , Young Adult
3.
Cancer Radiother ; 24(8): 851-859, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33129717

ABSTRACT

PURPOSE: Flaps are increasingly used during reconstructive surgery of head and neck cancers to improve functional outcomes. There are no guidelines as to whether the whole flap or its anastomotic border should be included in the primary tumour target volume of postoperative radiotherapy to prevent local relapses. Relapse and toxicity rates can increase substantially if the whole flap received full dose. Our aim was to determine whether flaps were included in the primary tumour target volume and to report the patterns of relapse and toxicity. MATERIALS AND METHODS: Consecutive patients in 2014 through 2016, with or without a flap, receiving postoperative radiotherapy were selected in a retrospective monocentric control study. Flaps were homogenously delineated blind to treating radiation oncologists using a flap-specific atlas. Tumour recurrence, acute and late toxicity were evaluated using univariate and propensity score analyses. RESULTS: A hundred patients were included; 54 with a flap. Median flap volume included in the tumour volume was 80.9%. Twelve patients experienced local recurrences: six with a flap, among whom two within their flap (3.7%). Patients with flaps had larger median tumour volumes to be irradiated (25cm3 versus 58cm3, p<0.001) and higher acute/late toxicity rates (p<0.001) even after adjustment on biases (more advanced T stage, oral cavity, active smoking in patients with flaps). Locoregional recurrence and survival rates were similar between patients with/without a flap. CONCLUSION: Recurrences within a flap were rare in this series when including the whole flap body in the 60Gy-clinical target volume but inclusion of the flap in the primary tumour target volume increased toxicity. Multicentric studies are warranted.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/surgery , Neoplasm Recurrence, Local , Surgical Flaps/transplantation , Adult , Aged , Aged, 80 and over , Analysis of Variance , Female , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/mortality , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Postoperative Care/methods , Propensity Score , Radiation Injuries/etiology , Plastic Surgery Procedures/methods , Retrospective Studies
4.
Cancer Radiother ; 24(4): 340-344, 2020 Jul.
Article in French | MEDLINE | ID: mdl-32444285

ABSTRACT

PURPOSE: MRI is sometimes critical to optimal radiotherapy planning but may be contraindicated in increasing numbers of patients who carry an implantable cardiac device (ICD, pacemaker or defibrillator). MATERIAL AND METHODS: This literature search reviews studies of MRI in DCI patients, morbidity and procedures for the different types of ICD. RESULTS: Several retrospective studies and two recent large prospective studies have shown that the use of an ICD is not an absolute contraindication to MRI, given that specific DCI monitoring is performed under the tridisciplinary supervision of the oncologist, radiologist and cardiologist for MRI≤1.5T. The rate of major complications is less than 5% unless probe replacement is performed. When it can be anticipated, new MRI-compatible ICD can be implanted rather than conventional ICD, but probe replacement is not currently recommended. Data for MRI beyond 1.5T and in case of MRI repeatability in the context of MRI-Linac treatments are lacking. CONCLUSIONS: MRI may be performed in ICD patients, as the risk of morbidity is very low; provided that tridisciplinary evaluation is performed.


Subject(s)
Defibrillators, Implantable , Magnetic Resonance Imaging , Pacemaker, Artificial , Radiotherapy Planning, Computer-Assisted , Age Factors , Contraindications, Procedure , Defibrillators, Implantable/adverse effects , Humans , Magnetic Resonance Imaging/adverse effects , Pacemaker, Artificial/adverse effects , Prospective Studies , Retrospective Studies , Time Factors
5.
Cancer Radiother ; 23(8): 860-866, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31677901

ABSTRACT

PURPOSE: Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3cm in diameter) and limited in number, in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15cm3) or brain metastases located next to critical structures. MATERIAL AND METHODS: Patients with brain metastases treated with the 6×6Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated. RESULTS: Sixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N=5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity. CONCLUSION: The 6×6Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way.


Subject(s)
Brain Neoplasms/radiotherapy , Cerebral Hemorrhage/radiotherapy , Radiation Dose Hypofractionation , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Brain Neoplasms/secondary , Cerebral Hemorrhage/etiology , Female , Humans , Male , Middle Aged , Radiosurgery/adverse effects , Radiosurgery/mortality , Retrospective Studies , Time Factors , Tumor Burden
6.
Bone Joint J ; 101-B(2): 207-212, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30700116

ABSTRACT

AIMS: Cementless primary total hip arthroplasty (THA) is associated with risks of bleeding and thromboembolism. Anticoagulants are effective as venous thromboprophylaxis, but with an increased risk of bleeding. Tranexamic acid (TXA) is an efficient antifibrinolytic agent, but the mode and timing of its administration remain controversial. This study aimed to determine whether two intravenous (IV) TXA regimens (a three-hour two-dose (short-TXA) and 11-hour four-dose (long-TXA)) were more effective than placebo in reducing perioperative real blood loss (RBL, between baseline and day 3 postoperatively) in patients undergoing THA who receive rivaroxaban as thromboprophylaxis. The secondary aim was to assess the non-inferiority of the reduction of blood loss of the short protocol versus the long protocol. PATIENTS AND METHODS: A multicentre, prospective, randomized, double-blind, placebo-controlled trial was undertaken involving 229 patients undergoing primary cementless THA using a posterior approach, whose extended rivaroxaban thromboprophylaxis started on the day of surgery. There were 98 male and 131 female patients, with a mean age of 65.5 years (32 to 91). The primary outcome, perioperative RBL, was evaluated at 72 hours postoperatively. The efficacy of short- and long-TXA protocols in the reduction of perioperative RBL was compared with a placebo group. RESULTS: TXA significantly reduced perioperative blood loss compared with placebo (p < 0.001); the mean differences were 525.3 ml (short-TXA vs placebo) and 550.1 ml (long-TXA vs placebo). No venous or arterial thromboembolic complications were reported. The upper boundary of the 95% confidence interval, when comparing short and long protocols, was below the pre-specified margin of non-inferiority (p = 0.027). CONCLUSION: In patients undergoing primary cementless THA, using a posterior approach, who are treated with rivaroxaban for thromboembolic prophylaxis, short- and long-TXA IV protocols are significantly more effective than placebo in reducing perioperative RBL, without any thromboembolic complications. Non-inferiority of a short- versus a long-TXA protocol in reducing perioperative RBL was supported in a secondary analysis.


Subject(s)
Arthroplasty, Replacement, Hip , Blood Loss, Surgical/prevention & control , Hematologic Agents/therapeutic use , Joint Diseases/surgery , Rivaroxaban/therapeutic use , Tranexamic Acid/therapeutic use , Adult , Aged , Aged, 80 and over , Antifibrinolytic Agents/therapeutic use , Bone Cements , Cementation , Chemoprevention , Double-Blind Method , Factor Xa Inhibitors/therapeutic use , Female , Hip Joint/surgery , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome
7.
Rhinology ; 55(2): 106-112, 2017 Jun 01.
Article in English | MEDLINE | ID: mdl-28501886

ABSTRACT

BACKGROUND: This study evaluated the efficacy of rhinophototherapy in patients with chronic rhinosinusitis (CRS) without nasal polyps. METHOD: In this randomized double-blind, placebo-controlled trial, CRS patients (n=50) received either mixed visible and ultraviolet (UVA and UVB) light source application (mUV/VIS) or visible light alone that served as placebo. Both groups were treated for 3 weeks. RESULTS: Results in the rhinophototherapy and placebo group were not significantly different and failed to reduce patient-reported outcomes measures (Rhinosinusits Disability Index, Visual Analogic Scale of symptom severity) and objective scores (rhinomanometry, olfactory thresholds, nasal Nitic Oxide concentrations), immediately and one month after treatment. CONCLUSIONS: The present data suggest that rhinophototherapy is not an efficient treatment for chronic rhinosinusitis without nasal polyps.


Subject(s)
Phototherapy/methods , Rhinitis/therapy , Sinusitis/therapy , Administration, Intranasal , Adolescent , Adult , Aged , Chronic Disease , Double-Blind Method , Endoscopy , Female , Humans , Male , Middle Aged , Patient Reported Outcome Measures , Prospective Studies
8.
Ned Tijdschr Geneeskd ; 160: D758, 2016.
Article in Dutch | MEDLINE | ID: mdl-27879183

ABSTRACT

OBJECTIVE: The aim of this research was to assess the effect of providing personalised self-management support on patient activation (knowledge, skills, self-efficacy) and self-management behaviour. DESIGN: Cluster randomised trial in 15 general practices (Dutch Trial Register No.: NTR 3960). METHOD: Patients aged 18 years or older with a chronic condition were invited to participate in the study. The Self-Management Screening (SeMaS) questionnaire - which illustrates barriers to self-management - was used as a tool for personalised self-management support. Nurse practitioners in the intervention practices were trained for 2 hours in using SeMaS and personalising self-management support on the basis of the SeMaS profile. At baseline and after 6 months, patients filled in questionnaires on patient activation (PAM-13) and lifestyle. Using data from the questionnaires and medical records, the use of individual care plans, referrals to self-management interventions, self-monitoring and healthcare use were assessed. We used a multiple multilevel regression model for data analysis. RESULTS: After 6 months, no difference was found in patient activation between the control group (n = 348) and the intervention group (n = 296). 29.4% of the patients in the intervention group performed self-monitoring, versus 15.2% in the control group (regression coefficient r = 0.9, p = 0.01). In the per-protocol analysis (control n = 348; intervention n = 136), the number of individual care plans (r = 1.3, p = 0.04) and the number of patients performing self-monitoring (r = 1.0; p = 0.01) were higher in the intervention group. CONCLUSION: Personalised self-management support with the use of the SeMaS method stimulates self-monitoring and the use of individual care plans. The intervention had no effect on patient activation or lifestyle. Given the positive secondary outcomes, the further potential of the tool should be researched.


Subject(s)
Chronic Disease/therapy , Disease Management , Precision Medicine/methods , Self Care/methods , Self Efficacy , Female , Humans , Male , Middle Aged , Surveys and Questionnaires
9.
Ann Oncol ; 27(10): 1922-8, 2016 10.
Article in English | MEDLINE | ID: mdl-27502701

ABSTRACT

BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS: The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.


Subject(s)
Bevacizumab/administration & dosage , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Ultrasonography/methods , Adult , Aged , Aged, 80 and over , Angiogenesis Inhibitors/administration & dosage , Biomarkers, Tumor , Contrast Media/administration & dosage , Female , France , Humans , Male , Middle Aged , Neoplasms/pathology
10.
Sci Rep ; 6: 20899, 2016 Feb 11.
Article in English | MEDLINE | ID: mdl-26864735

ABSTRACT

Electron-phonon coupling is a fundamental inelastic interaction in condensed matter and in molecules. Here we probe phonon excitations using quantum interference in electron transport occurring in short chains of anthraquinone based molecular junctions. By studying the dependence of molecular junction's conductance as a function of bias voltage and temperature, we show that inelastic scattering of electrons by phonons can be detected as features in conductance resulting from quenching of quantum interference. Our results are in agreement with density functional theory calculations and are well described by a generic two-site model in the framework of non-equilibrium Green's functions formalism. The importance of the observed inelastic contribution to the current opens up new ways for exploring coherent electron transport through molecular devices.

11.
Vox Sang ; 110(2): 199-201, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26383177

ABSTRACT

This study examined the prevalence of three human herpesviruses (HHV), namely HHV-4 (Epstein-Barr virus/EBV), HHV-6b and HHV-7 in leucoreduced blood products obtained from the Sainte-Justine Hospital blood bank. A total of 100 specimens, including 34 red blood cell concentrates, 33 platelet bags and 33 plasma units, were collected and screened by a sensitive PCR assay using virus-specific primers. Positive units were then retested by quantitative PCR. Of the 100 specimens, one platelet unit tested positive for EBV.


Subject(s)
Blood Banks/statistics & numerical data , Herpesvirus 4, Human/isolation & purification , Plasma/virology , Blood Banks/standards , Blood Cells/virology , Humans
12.
Vox Sang ; 110(2): 150-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26389829

ABSTRACT

BACKGROUND AND OBJECTIVES: Platelet concentrates (PCs) are associated with transfusion reactions involving hypotension, particularly bradykinin-mediated acute hypotensive transfusion reactions. This study aims to determine the incidence of hypotensive events and more specifically acute hypotensive transfusion reaction associated with PC transfusions. We also sought to ascertain whether these reactions are associated with elevated bradykinin levels. MATERIALS AND METHODS: This is a prospective descriptive study of PCs administered at Sainte-Justine Hospital over 28 months. All PCs administered during this period were screened for hypotension through review of all transfusion-associated reaction reports (TARRs) sent to the blood bank. All residual PC bags were returned to the blood bank. TARRs associated with hypotension were reviewed by adjudicators that established the imputability of the PC transfusion to the reaction. Bradykinin levels were sampled in the first 168 PC bags returned to the blood bank. Levels were compared between PCs associated with hypotension and control PCs not associated with hypotension. RESULTS: A total of 3672 PC bags were returned to the blood bank; 25 PCs were associated with hypotension. Adjudicators ascertained that five hypotensive events were imputable to PCs of which one was an acute hypotensive transfusion reaction (incidence: 0·03%). Bradykinin level in the latter PC was 10 pg/ml, whereas levels were 226·2 ± 1252 pg/ml in the 143 control PCs. CONCLUSION: Our results show a low incidence of hypotension after PC transfusion. We identified only one acute hypotensive transfusion reaction. No correlation between bradykinin level and the occurrence of acute hypotensive reactions could be observed given that only one event was identified.


Subject(s)
Hypotension/etiology , Platelet Transfusion/adverse effects , Transfusion Reaction/etiology , Blood Banks/standards , Humans
14.
Transfus Clin Biol ; 22(3): 107-11, 2015 Aug.
Article in French | MEDLINE | ID: mdl-26049675

ABSTRACT

Red blood cell units are stored up to 42 days post-collection. The standard policy of blood banks is to deliver the oldest units in order to limit blood wastage. Many caregivers believe that giving fresh rather than old units can improve the outcome of their transfused patients. The ABLE study aims to check if the transfusion of red blood cell units stored seven days or less (fresh arm) improve the outcome of transfused critically ill adults compared to patients who received units delivered according to the standard delivery policy (control arm). From March 2009 to May 2014, 1211 patients were allocated to the fresh arm, 1219 to the control arm (length of storage: 6.1 ± 4.9 and 22.0 ± 8.4 days respectively, P<0.001). The primary outcome measure was 90-day all-cause mortality post-randomisation: there were 448 deaths (37.0%) in the fresh arm and 430 (35.3%) in the control arm (absolute risk difference: 1.7%; 95% confidence interval: -2.1% to 5.5%). In a survival analysis, the risk of death was higher in the fresh arm (hazard ratio: 1.1; 95%CI: 0.9 to 1.2), but the difference was not statistically significant (P=0.38). The same trend against the fresh arm was observed with all but one secondary outcome measures. The conclusion is that the transfusion of red blood cell units stored seven days or less does not improve the outcome of critically ill adults compared to the transfusion of units stored about three weeks (22.0 ± 8.4 days).


Subject(s)
Blood Preservation/methods , Critical Illness/therapy , Erythrocyte Aging , Erythrocyte Transfusion , Adult , Canada/epidemiology , Critical Care/methods , Critical Illness/mortality , Diagnosis-Related Groups , Europe/epidemiology , Female , Hospital Mortality , Humans , Male , Time Factors , Treatment Outcome
15.
J Biomed Inform ; 53: 100-12, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25239261

ABSTRACT

PURPOSE: Although tailoring health education messages to individual characteristics of patients has shown promising results, most patient education materials still take a one-size-fits-all approach. The aim of this study was to develop a method for tailoring health education messages to patients' preferences for various message features, using the concept of personas. This is a preliminary study focused on education for coronary heart disease (CHD) patients. METHODS: This study used a three-step approach. First, we created personas by (i) performing k-means cluster analysis on data from an online survey that assessed the preferences of 213 CHD patients for various message features and, (ii) creating a vivid description of the preferences per patient cluster in an iterative process with the research team. Second, we developed adaptation rules to tailor existing educational messages to the resulting personas. Third, we conducted a pilot validation by adapting nine existing educational messages to each of the personas. These messages and the resulting personas were then presented to a separate group of 38 CHD patients who visited the cardiology outpatient clinic. They were first asked to choose their most preferred, second most preferred, and least preferred persona. Subsequently, they were asked to rate three of the adapted messages; one for every of the persona choices. RESULTS: We created five personas that pertained to five patient clusters. Personas varied mainly on preferences for medical or lay language, current or future temporal perspective, and including or excluding explicit health risks. Fifty-five different adaptation rules were developed, primarily describing adaptations to the message's perspective, level of detail, sentence structure, and terminology. Most participants in the validation study could identify with one of the five personas, although some of them found it hard to choose. On average, 68.5% of all participants rated the messages that matched their most preferred persona more positively than, or in the same way as, the messages that matched their least preferred persona. CONCLUSIONS: The persona-based method developed in this study can be used to create a manageable set of patient-centered tailored messages, while additionally using the developed personas to assess patients' preferences.


Subject(s)
Cardiology/methods , Coronary Disease/diagnosis , Coronary Disease/therapy , Patient Education as Topic/methods , Aged , Cluster Analysis , Communication , Female , Health Education , Heart Diseases/therapy , Humans , Language , Male , Middle Aged , Patient Satisfaction , Patient-Centered Care , Physician-Patient Relations , Pilot Projects , Research Design , Self Care
16.
Ann Oncol ; 25(12): 2351-2356, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25274615

ABSTRACT

BACKGROUND: Brain metastases (BMs) are associated with a poor prognosis. Standard treatment comprises whole-brain radiation therapy (WBRT). As neo-angiogenesis is crucial in BM growth, combining angiogenesis inhibitors such as bevacizumab with radiotherapy is of interest. We aimed to identify the optimal regimen of bevacizumab combined with WBRT for BM for phase II evaluation and provide preliminary efficacy data. PATIENTS AND METHODS: In this multicentre single-arm phase I study with a 3 + 3 dose-escalation design, patients with unresectable BM from solid tumours received three cycles of bevacizumab at escalating doses [5, 10 and 15 mg/kg every 2 weeks at dose levels (DL) 0, 1 and 2, respectively] and WBRT (30 Gy/15 fractions/3 weeks) administered from day 15. DL3 consisted of bevacizumab 15 mg/kg with WBRT from day 15 in 30 Gy/10 fractions/2 weeks. Safety was evaluated using NCI-CTCAE version 3. BM response (RECIST 1.1) was assessed by magnetic resonance imaging at 6 weeks and 3 months after WBRT. RESULTS: Nineteen patients were treated, of whom 13 had breast cancer. There were no DLTs. Grade 1-2 in-field and out-field toxicities occurred for five and nine patients across all DLs, respectively, including three and six patients (including one patient with both, so eight patients overall) of nine patients in DL3. One patient experienced BM progression during treatment (DL0). At the 3-month post-treatment assessment, 10 patients showed a BM response: one of three treated at DL0, one of three at DL1, two of three at DL2 and six of seven at DL3, including one complete response. BM progression occurred in five patients, resulting in two deaths. The remaining patient died from extracranial disease progression. CONCLUSION: Bevacizumab combined with WBRT appears to be a tolerable treatment of BM. DL3 warrants further efficacy evaluation based on the favourable safety/efficacy balance. ClinicalTrials.gov Identifier: NCT01332929.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Brain Neoplasms/secondary , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Brain/radiation effects , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Combined Modality Therapy , Dose-Response Relationship, Drug , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged
17.
Int J Biochem Cell Biol ; 52: 152-60, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24569117

ABSTRACT

The recovery of an intact epithelium following injury is critical for restoration of lung homeostasis, a process that may be altered in cystic fibrosis (CF). In response to injury, progenitor cells in the undamaged areas migrate, proliferate and re-differentiate to regenerate an intact airway epithelium. The mechanisms regulating this regenerative response are, however, not well understood. In a model of circular wound injury of well-differentiated human airway epithelial cell (HAEC) cultures, we identified the gap junction protein Cx26 as an important regulator of cell proliferation. We report that induction of Cx26 in repairing HAECs is associated with cell proliferation. We also show that Cx26 is expressed in a population of CK14-positive basal-like cells. Cx26 silencing in immortalized cell lines using siRNA and in primary HAECs using lentiviral-transduced shRNA enhanced Ki67-labeling index and Ki67 mRNA, indicating that Cx26 acts a negative regulator of HAEC proliferation. Cx26 silencing also markedly decreased the transcription of KLF4 in immortalized HAECs. We further show that CF HAECs exhibited deregulated expression of KLF4, Ki67 and Cx26 as well enhanced rate of wound closure in the early response to injury. These results point to an altered repair process of CF HAECs characterized by rapid but desynchronized initiation of HAEC activation and proliferation.


Subject(s)
Bronchi/metabolism , Bronchi/pathology , Connexins/metabolism , Cystic Fibrosis/metabolism , Cystic Fibrosis/pathology , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Cell Differentiation/physiology , Cell Proliferation/physiology , Cells, Cultured , Connexin 26 , Epithelial Cells/metabolism , Epithelial Cells/pathology , Humans , Kruppel-Like Factor 4 , Kruppel-Like Transcription Factors/metabolism
18.
Vox Sang ; 104(4): 342-9, 2013 May.
Article in English | MEDLINE | ID: mdl-23294337

ABSTRACT

BACKGROUND AND OBJECTIVES: Plasma transfusions are commonly used in adult and paediatric intensive care units. Recent data suggest an association between plasma transfusions and worse clinical outcome in adult trauma patients. To date, no prospective paediatric study has addressed this issue. Our objective was to prospectively analyse the association between plasma transfusions and clinical outcome of critically ill children. MATERIALS AND METHODS: Prospective, observational and single centre study that includes all consecutive admissions to a tertiary level multidisciplinary paediatric critical care unit over a 1-year period. The primary outcome measure was the incidence after transfusion of new or progressive multiple organ dysfunction syndrome. Secondary outcome measures included nosocomial infections, intensive care unit length of stay and 28-day mortality. Odds ratios were adjusted for weight, severity of illness, coagulopathy, plasma transfusions prior to admission, need for extracorporeal life support and transfusion of other labile blood products. RESULTS: A total of 831 patients were enrolled, among which 94 (11%) received at least one plasma transfusion. In the latter group of patients, the adjusted odds ratio for an increased incidence of new or progressive multiple organ dysfunction syndrome was 3.2 (P = 0.002). There was also a significant difference in the occurrence of nosocomial infections and intensive care unit length of stay, but no significant difference in the 28-day mortality. CONCLUSIONS: In critically ill children, plasma transfusions seem to be independently associated with an increased occurrence of new or progressive multiple organ dysfunction syndrome, nosocomial infections and prolonged length of stay.


Subject(s)
Blood Component Transfusion/methods , Critical Illness/therapy , Plasma , Adolescent , Adult , Aged , Child , Child, Preschool , Humans , Incidence , Middle Aged , Prospective Studies , Treatment Outcome , Young Adult
19.
Orthop Traumatol Surg Res ; 98(6): 696-705, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22951052

ABSTRACT

BACKGROUND: Clostridium spp. are saprophytic Gram-positive bacteria found in soil and capable of generating endospores. Spore germination occurs when environmental conditions are favorable. Clostridium spp. can cause infections of compound fractures and deep wounds contaminated from soil micro-organisms. HYPOTHESIS: Clostridium spp. infections of traffic-related injuries are particularly severe events whose outcome is uncertain even with aggressive medical and surgical treatment. MATERIALS AND METHODS: We retrospectively reviewed 12 patients (median age, 45 years) with Clostridium spp. bone and/or joint infections complicating compound limb fractures with soil contamination and extensive soft-tissue damage. Prophylactic amoxicillin-clavulanic acid therapy was administred, followed by emergency surgical wound debridment and lavage. Fracture fixation was performed immediately in nine patients (external in four and internal in five) or at a later time on three patients. The immediate outcome was unfavourable in all 12 cases, requiring early reoperation after a median of 10 days (range, 5-25 days). RESULTS: Median time to Clostridium strain identification was 14.5 days (range, 5-160). All infections were polymicrobial. Surgical wound excision, hardware removal (in four cases), and antibiotic therapy produced a favourable outcome in one patient, with no recurrence after 2 years of follow-up; the outcome was unfavourable in 11 cases, with delayed fracture union, septic non-union, impaired healing, and/or chronic sinus tract drainage. Several second-line treatments were used in these 11 patients: intramedullary nailing without bone grafting in four patients, with three failures; decortication and grafting in two patients, with failure in both; nailing with decortication in one patient, who had a good outcome; and the induced membrane procedure described by Masquelet in four patients, all of whom had good outcomes. After a median follow-up of 24 months (range, 18-53 months), the bone infection had subsided in eight patients. The remaining four patients had septic non-union. DISCUSSION: Clostridium spp. infections are particularly severe. The diagnosis is delayed and identification of the organism is challenging. The treatment is difficult and results in unfavorable outcomes in one-third of cases. The identification of Clostridium in specimens from an osteoarticular infection indicates a need for extremely extensive and aggressive surgical resection, as spore resistance may impair the in vivo efficacy of antimicrobial agents. LEVEL OF EVIDENCE: IV (retrospective cohort study).


Subject(s)
Arm Injuries/surgery , Clostridium Infections/epidemiology , Clostridium/isolation & purification , Fracture Fixation/adverse effects , Fractures, Bone/surgery , Leg Injuries/surgery , Wound Healing , Adolescent , Adult , Aged , Clostridium Infections/microbiology , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Young Adult
20.
Orthop Traumatol Surg Res ; 98(5): 484-90, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22542983

ABSTRACT

INTRODUCTION: Perioperative blood loss is a frequent cause of complications in total hip replacement (THR). The present prospective study assessed the efficacy of tranexamic acid (Exacyl(®)) in reducing blood loss in primary THR associated to rivaroxaban (Xarelto(®)) thromboprophylaxis. HYPOTHESIS: Tranexamic acid associated to rivaroxaban reduces blood loss. MATERIAL AND METHOD: A prospective case-control study included 70 primary cementless THRs performed by a single surgeon on a standardized technique, between September 2009 and September 2010. Thirty-seven patients received perioperative tranexamic acid; all patients received rivaroxaban thromboprophylaxis. RESULTS: There was no significant difference between the two groups in terms of peroperative blood-loss volume or rates of thromboembolic or ischemic events or hematoma. Postoperative blood loss, D0-5 differential hemoglobinemia and real blood loss (in mL 100% hematocrit) were significantly lower in the tranexamic acid group. No transfusions were required in the tranexamic acid group, versus four in the control group. DISCUSSION: Tranexamic acid associated to direct anti-Xa (antithrombin-independent) oral anticoagulants was effective in reducing postoperative blood loss, improving hemoglobinemia at 5 days and reducing transfusion rates. The results also confirmed the efficacy of and tolerance for rivaroxaban thromboprophylaxis in primary THR, with no clinical thrombotic events induced by the association of tranexamic acid with rivaroxaban. CONCLUSIONS: Tranexamic acid is a simple means of reducing postoperative blood loss in THR, without increased risk of thromboembolism when associated to rivaroxaban thromboprophylaxis. LEVEL OF EVIDENCE: Level III prospective case-control study.


Subject(s)
Arthroplasty, Replacement, Hip/methods , Morpholines/administration & dosage , Postoperative Hemorrhage/prevention & control , Prostheses and Implants , Thiophenes/administration & dosage , Thrombosis/prevention & control , Tranexamic Acid/administration & dosage , Aged , Anticoagulants/administration & dosage , Antifibrinolytic Agents/administration & dosage , Arthroplasty, Replacement, Hip/adverse effects , Bone Cements , Case-Control Studies , Dose-Response Relationship, Drug , Factor Xa Inhibitors , Female , Follow-Up Studies , Humans , Male , Postoperative Hemorrhage/etiology , Prospective Studies , Rivaroxaban , Single-Blind Method , Thrombosis/etiology , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...