A simplified scoring system in de novo follicular lymphoma treated initially with immunochemotherapy.

In follicular lymphoma (FL), no prognostic index has been built based solely on a cohort of patients treated with initial immunochemotherapy. There is currently a need to define parsimonious clinical models for trial stratification and to add on biomolecular factors. Here, we confirmed the validity of both the follicular lymphoma international prognostic index (FLIPI) and the FLIPI2 in the large prospective PRIMA trial cohort of 1135 patients treated with initial R-chemotherapy ± R maintenance. Furthermore, we developed a new prognostic tool comprising only 2 simple parameters (bone marrow involvement and ß2-microglobulin [ß2m]) to predict progression-free survival (PFS). The final simplified score, called the PRIMA-PI (PRIMA-prognostic index), comprised 3 risk categories: high (ß2m > 3 mg/L), low (ß2m ≤ 3 mg/L without bone marrow involvement), and intermediate (ß2m ≤ 3 mg/L with bone marrow involvement). Five-year PFS rates were 69%, 55%, and 37% in the low-, intermediate-, and high-risk groups, respectively (P < .0001). In addition, achieving event-free survival (EFS) or not at 24 months (EFS24) was a strong posttreatment prognostic parameter for subsequent overall survival, and the PRIMA-PI was correlated with EFS24. The results were confirmed in a pooled external validation cohort of 479 patients from the FL2000 LYSA trial and the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource. Five-year EFS in the validation cohort was 77%, 57%, and 44% in the PRIMA-PI low-, intermediate-, and high-risk groups, respectively (P < .0001). The PRIMA-PI is a novel and easy-to-compute prognostic index for patients initially treated with immunochemotherapy. This could serve as a basis for building more sophisticated and integrated biomolecular scores.

Rituximab treatment circumvents the prognostic impact of tumor-infiltrating T-cells in follicular lymphoma patients.

Previous immunohistochemical (IHC) studies showed controversial data about the prognostic value of tumor-infiltrating lymphocytes (TILs) in follicular lymphoma (FL). To clarify this issue, a large series of FL samples from rituximab-treated patients enrolled in the randomized PRIMA trial was examined. IHC was quantified using automated image analysis in 417, 287, 418, 406, 379, and 369 patients for CD3, CD4, CD8, PD1, ICOS, and FOXP3, respectively. RNAseq analysis was used to quantify TIL-related mRNA transcripts from 148 patients. When each IHC marker was used as a continuous variable in the whole cohort, high CD3 counts were associated with better progression-free survival (PFS) (P = .025). When an optimal IHC cut point was applied to the whole patient population, high CD3 counts and high PD1 counts were associated with better PFS (P = .011 and P = .044, respectively), whereas none of the other TIL markers had any significant correlation with outcome. When a stringent analysis was performed by dividing the whole cohort into a training set and a validation set, none of the TIL markers showed a prognostic significance in both groups. RNAseq analysis showed a significant correlation between high levels of CD3 and CD8 transcripts and better PFS (P = .001 and P = .037, respectively). No prognostic correlation was found as to the level of other immune gene transcripts. These results suggest that the IHC prognostic value of TILs is circumvented by rituximab treatment, although there is a trend for high numbers of CD3+ TILs to correlate with better PFS.

Statin use is safe and does not impact prognosis in patient with de novo follicular lymphoma treated with immunochemotherapy: An exploratory analysis of the PRIMA cohort study.

An adverse prognostic impact of statin use in lymphoma was first suspected from in vitro data showing an impairment of anti-CD20 antibody binding. However, further clinical studies suggested an improved outcome associated with their use in hematological malignancies. In particular, a survival benefit was reported for patients with follicular lymphoma on statins. Our objective was to assess the outcome of follicular lymphoma patients treated in the PRIMA study with immunochemotherapy according to the use of statins. Among the 1,217 patients enrolled in the PRIMA study, 1,135 were included in the present study. Concomitant treatments at registration were available for all patients. Among those 1,135 patients, 119 were on statins (10.5%) at diagnosis. Adverse events frequencies, event-free survival (EFS), time to next lymphoma treatment (TTNLT), time to next chemotherapy (TTNCT), and overall survival (OS) were evaluated according to the use of statins. The rates of overall and specific cardiovascular adverse events between the two groups of patients were comparable both during induction and maintenance. Outcome in terms of response rates or EFS, TTNLT, TTNCT, and OS were similar regardless of the use of statins (P = 0.57, P = 0.85, P = 0.30, and P = 0.43, respectively) in univariate analysis and after further adjustments for potential confounding factors in multivariate analysis. In conclusion, statin use does not impact the prognosis of patients with follicular lymphoma treated with immunochemotherapy.

The Prognostic Impact of CD163-Positive Macrophages in Follicular Lymphoma: A Study from the BC Cancer Agency and the Lymphoma Study Association.

PURPOSE: We aimed to assess the prognostic significance of follicular lymphoma-associated macrophages in the era of rituximab treatment and maintenance. EXPERIMENTAL DESIGN: We applied immunohistochemistry for CD68 and CD163 to two large tissue microarrays (TMA). The first TMA included samples from 186 patients from the BC Cancer Agency (BCCA) who had been treated with first-line systemic treatment including rituximab, cyclophosphamide, vincristine, and prednisone. The second contained 395 samples from PRIMA trial patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and randomized to rituximab maintenance or observation. Macrophage infiltration was assessed using Aperio image analysis. Each of the two cohorts was randomly split into training/validation sets. RESULTS: An increased CD163-positive pixel count was predictive of adverse outcome in the BCCA dataset [5-year progression-free survival (PFS) 38% vs. 72%, respectively, P = 0.004 in the training cohort and 5-year PFS 29% vs. 61%, respectively, P = 0.004 in the validation cohort]. In the PRIMA trial, an increased CD163 pixel count was associated with favorable outcome (5-year PFS 60% vs. 44%, respectively, P = 0.011 in the training cohort and 5-year PFS 55% vs. 37%, respectively, P = 0.030 in the validation cohort). CONCLUSIONS: CD163-positive macrophages predict outcome in follicular lymphoma, but their prognostic impact is highly dependent on treatment received.

Low skeletal muscle mass and risk of functional decline in elderly community-dwelling women: the prospective EPIDOS study.

OBJECTIVES: To assess relationships between low skeletal muscle mass (SMM) and functional decline in community-dwelling elderly women. DESIGN: Secondary analysis of data from EPIDOS, a French prospective observational multicenter cohort study of osteoporosis epidemiology. SETTING: One center in France between 1992 and 1994. PARTICIPANTS: Women aged 75 years or older without disability and with available baseline SMM measurements. MEASUREMENTS: SMM was assessed using dual-energy X-ray absorptiometry and functional decline was defined as loss of at least one Instrumental Activity of Daily Living component. Associations linking low SMM to functional decline were estimated using the Cox proportional hazards model. RESULTS: Of 975 women followed for 4 years, 452 (46.4%) experienced functional decline. Factors independently associated with functional decline were decreased SMM (adjusted hazard ratio [aHR] per SD decrease, 1.12; 95% confidence interval [95% CI], 1.01-1.24), older age (aHR per SD increase, 1.28; 95% CI, 1.17-1.39), one or more comorbidities (aHR, 1.65; 95%CI, 1.05-2.59), and impaired chair-stand test (aHR, 1.35; 95% CI, 1.01-1.82). The second SMM quartile was associated with functional decline (aHR, 1.39; 95% CI, 1.06-1.84) and the lowest quartile showed a nearly significant association (aHR, 1.29; 95% CI, 0.98-1.72). Factors negatively associated with functional decline were living alone (aHR, 0.76; 95% CI, 0.59-0.96), higher handgrip strength (aHR per SD increase, 0.88; 95% CI, 0.78-0.88), and walking speed (aHR per SD increase, 0.86; 95% CI, 0.77-0.96). CONCLUSION: Low SMM was independently associated with functional decline within 4 years after adjustment for age, muscle strength, physical performance, and comorbidities in community-dwelling elderly women.

[Is retention justified after interceptive treatment of Class II malocclusion?]. / La contention est-elle justifiée après traitement interceptif de classe II ?

Indication of intermediate retention after early treatment of class II malocclusion has not been yet assessed by comparative studies. Therefore, it is up to the practitioner to analyse the need for retention in the time period between the two phases. Does wearing a retainer indeed decrease the chance of relapse between phase one and phase two? We performed a retrospective comparative study consisting of 90 subjects in mixed dentition with class II molar relationships with an increased overjet (> or = 5 mm) treated in the J.-J. Aknin office with DAC appliance. The sample was divided into two groups: 31 patients wearing retention represented by a removable Hawley plate and 59 children in supervision without retention. Three lateral head-films were made at the beginning and the end of early treatment and before the resumption of the second phase treatment. Studied cephalometrics parameters were assessed according to superimposing Pancherz's analysis. A statistical analysis was performed. Results showed a significantly lower relapse of incisor's protrusion in the group wearing an upper retainer. Results' interpretation was in accordance with the assessment of confusion's factors and selection's criteria. Besides, this study was carried out in intention-to-treat and retention's effectiveness in proportion with patient's compliance. Nevertheless, the study was performed in real conditions. In conclusion, and without randomised trial, results show that retention seems to decrease maxillary incisor movements. It is therefore justified in cases presenting with important class II especially with procumbent incisors.

[Is hyperdivergence a contraindication in the early treatment of Class II malocclusion?]. / L'hyperdivergence est-elle une contre-indication dans le traitement précoce des classes II?

Vertical growth pattern is supposed to have adverse effects on sagittal growth and is considered as a contra-indication for early treatment. The aim of this retrospective cohort study was to analyse whether early treatment of children with Class II malocclusion was able to achieve as an important sagittal correction on subjects with growth vertical pattern as on subjects without vertical pattern without modification of vertical growth. The study was composed of 123 children (110 months old in average), with Class II division 1 malocclusion : 34 children with excessive vertical growth pattern and 74 children without excessive vertical growth pattern, both treated with DAC appliance, and 15 not treated subjects with excessive vertical growth pattern. Data were collected at the start of the study (t(1)), after the active treatment (t(1')) and 29 months after t(1) (t(2)). A Pancherz cephalometric analysis was applied on the lateral roentgenograms. Differences were evaluated with t-test. Results show that DAC appliance may be an orthopedic appliance indicated to achieve correction in class II skeletal pattern by mandibular growth without augmentation of vertical dimension.

Evaluation of previously nonscreened hereditary hemorrhagic telangiectasia patients shows frequent liver involvement and early cardiac consequences.

UNLABELLED: Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by cutaneous, mucosal, and sometimes visceral arteriovenous malformations. Severe hepatic manifestations have been characterized in a subgroup of patients, but few data are available in previously nonscreened patients. We prospectively evaluated liver involvement and its cardiac consequences in such patients. Between 2000 and 2005, we prospectively evaluated the clinical, biological, and hepatic Doppler sonography (DS) characteristics of 102 consecutive HHT patients (mean age, 52.5 years; range, 19-88; 80.4%) with an identified genetic mutation. Patients were segregated into three different severity groups according to DS values. Factors predictive of an abnormal DS, according to predetermined criteria, and of a high cardiac index were identified by logistic and linear regression analysis, respectively. Abnormal liver biology and clinical signs of hepatic involvement were present in 35.3% and 27.5% of cases, respectively. Abnormal DS (defined as at least enlargement of the main hepatic artery) was observed in 56 (54.9%) cases, and direct or indirect signs of significant fistulas were present in 26 (25.5%) cases. Abnormal liver biology and a mutation involving the ACVRL1 gene were predictive of hepatic ultrasound (US) abnormalities. The diameter of the main hepatic artery and the presence of focal nodular hyperplasia (FNH) were predictive of a higher cardiac index. CONCLUSION: This large prospective series of previously nonscreened HHT patients identified a subgroup at risk of liver involvement (patients with abnormal liver biology and ACVRL1 mutations) and a subgroup with a higher cardiac index: future studies will show whether such patients would benefit from systematic DS screening and long-term cardiac surveillance.

Are patients with self-inflicted injuries more likely to die?

BACKGROUND: Suicide represents one of the leading causes of trauma in industrialized countries. However, when compared with unintentional injury and assault, the outcome of self-inflicted injury has not been well described. METHODS: All patients admitted to a French academic trauma center from January 2002 to December 2004 and listed in a trauma data bank were included in a prospective analysis. Variables including mortality, circumstances (unintentional vs. assault vs. self-inflicted), and mechanism of injury were recorded. RESULTS: About 1,004 continuous trauma patients were analyzed: 151 (15%) with self-inflicted injuries, 761 (76%) with unintentional injuries, and 91 (9%) with injuries from assault. When compared with patients suffering from unintentional injuries and assault, self-inflicted injury patients presented more frequently after a fall from height (94 of 151 vs. 133 of 759 and 0 of 91, p < 0.05) and with a severe head injury (47 of 151 vs. 172 of 752 and 10 of 91, p < 0.05). They also had a more severe injury (Injury Severity Score, 28 +/- 21 vs. 22 +/- 16 and 12 +/- 10; p < 0.05), a lower probability of survival (Trauma Related Injury Severity Score, 0.71 +/- 0.37 vs. 0.83 +/- 0.28 and 0.92 +/- 0.19; p < 0.05), and survival rate (70% vs. 85% and 93%, p < 0.05). In multivariate analysis, Trauma Related Injury Severity Score (odds ratio, 0.54; 95% confidence interval, 0.45-0.59; p < 0.001), age (odds ratio, 1.17; confidence interval, 1.02-1.34; p < 0.05), and mechanism of trauma (p = 0.01) were independently correlated with the final mortality rate. CONCLUSIONS: Self-inflicted injury patients presented with a higher mortality rate that was related to increased injury severity. The circumstances surrounding the trauma were not independently associated with an increased odds ratio of death after major trauma.

Prometheus: the implementation of clinical coding schemes in French routine general practice.

BACKGROUND: Clinical data are most useful, both at the individual level and collectively, if they are coded according to a standard classification system. However, clinicians often have little motivation to routinely code their consultation data. The main classification systems available in French primary care are the International Classification of Primary Care (ICPC) and the Dictionary of Consultation Results (DCR). OBJECTIVE: To assess the feasibility of using the ICPC-2 and the DCR for coding health problems managed in routine general practice in France. METHODS: Between December 2001 and June 2003, 61 volunteer general practitioners (GPs) from the Paris area prospectively recorded the health problems they managed at consultations, using either the ICPC (36 GPs) or the DCR (25 GPs), for a period of six months. They were equipped with one of three proprietary medical software applications specifically adapted for the study, or one open source utility, interfacing with five other, non-adapted, proprietary software programs. They had a two-day training session, were financially compensated, and were provided with electronic feedback. RESULTS: The mean reported coding time per consultation was 2.5 minutes, but 28 physicians (46%) judged the coding time excessive and reported a maximum acceptable time of 1.2 minutes. Coding consultation data was considered more useful at the collective level (by 95% of physicians) than at the individual practice level (by 69%). Only 34 physicians (56%) expressed willingness to carry on routine coding after the end of the study. Some results differed depending on the classification system used, especially due to confounding factors, as some physicians could have previously used the given system. CONCLUSIONS: Coding health problems on a routine basis proved to be feasible. However, this process can be used on a more widespread basis and linked to other management data only if physicians are specially trained and rewarded, and the software incorporates large terminologies mapped with classifications.

[Analysis of the medical activity related to cancer in a network of multidisciplinary hospitals using claims databases, the reseau Concorde Oncology Network]. / Estimation et analyse de l'activité cancérologique d'un ensemble d'établissements participant à un réseau régional à partir des données du PMSI, le réseau Concorde.

Recently, to answer patients, caregivers and professionals needs, the "Plan Cancer" has been presented by the French Government. This plan is intended to improve quality of care in cancer patients and finally, patients' survival and quality of life. This planned strategy stresses the importance of organized interactions between hospitals and between the various health professionals. Measuring the number of patients with cancer and the activity related to cancer in large networks of multidisciplinary hospitals has became a real challenge in France for organizational, quality of care and economic reasons. Many University Hospitals in France have chosen to face this question by using the French DRG based information system called PMSI. It allows estimating the proportion of hospital stays concerned by cancers that are identified with algorithms based on ICD 10. However, French databases of hospital discharges do not allow patients identification. We collected data on hospital stays and patients in a subset of an organized network focused on cancer care and composed of 55 public or private hospitals in the Rhone-Alpes area. We used these data to estimate the number of patients who had been hospitalized within the network in 2000. Approximately 110,000 hospital stays were related with a diagnostic of cancer, corresponding to a number of patients within a range of 30345 to 35700. In absence of communicating files between hospitals, claims databases are an interesting source of information for cancer burden. The recent implementation of a procedure allowing the linkage of data concerning each patient should permit better estimates in the future. The main limitation will remain the possibility of a hospital to participate to more than one network.