Microscopic polyangiitis with alveolar hemorrhage. A study of 29 cases and review of the literature. Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P)

Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis primarily associated with necrotizing glomerulonephritis and pulmonary capillaritis. In this retrospective study of 29 patients with MPA and alveolar hemorrhage (AH), we characterized the pulmonary manifestations at presentation and assessed the short- and long-term outcome. AH was diagnosed when bronchoalveolar lavage was macroscopically bloody, or contained hemosiderin-laden macrophages, in the absence of lung infection or pulmonary edema. MPA was diagnosed when AH was associated with focal segmental necrotizing glomerulonephritis at kidney biopsy or pathologically proved small-vessel vasculitis. There were 17 women and 12 men, with a mean age of 55.8 +/- 16.7 years. The onset was rapidly progressive, but in 8 (28%) patients, symptoms preceded the diagnosis for more than 1 year. The most constant systemic findings associated with AH were glomerulonephritis in 28 (97%) patients; fever (62%); myalgia and arthralgia (52%); weight loss (45%); ear, nose, and throat symptoms (31%); and skin involvement (17%). Lung opacities were bilateral in 26 (90%) patients, most frequently involving the lower part of the lungs. Bronchoalveolar lavage, performed in 27 patients, was hemorrhagic in 25 (93%), and contained numerous siderophages in others. Most patients were severely anemic (mean hemoglobin, 8.1 +/- 1.8 g/dL). ANCA, present in 27 (93%) patients, gave a perinuclear (14), cytoplasmic (11), or mixed (1) pattern. Mean serum creatinine level was 407 +/- 415 mumol/L. Renal biopsy confirmed the presence of necrotizing glomerulonephritis in 27 patients. Patients were treated with corticosteroids (100%), cyclophosphamide (79%), plasmapheresis (24%), dialysis (28%), and mechanical ventilation (10%). The overall mortality rate was 31% (9 patients). Deaths were related to vasculitis (5 patients) or side effects of treatment (4). Deaths were more frequent in aged or mechanically ventilated patients. The 5-year survival rate was 68%. The recovery of respiratory function among survivors was clinically considered complete in 20 (69%) patients. However, 7 patients (24%) had persistent alterations on pulmonary function tests. Of the 11 patients who had relapses, 2 died from AH.     

VAD or VMBCP in severe multiple myeloma. The Groupe d'Etudes et de Recherche sur le Myélome (GERM).

A randomized trial has been performed in which 91 patients with stage III myeloma and additional severe criteria were randomly allocated to either VAD or VMBCP. No significant difference was noted between these two groups using the following criteria: response rate (VMBCP: 54%; VAD: 39%), impact on symptoms, median survival (VMBCP: 14 months, VAD: 17 months). However, toxic effects and refusal to pursue treatment were more frequent with VAD than with VMBCP (12 v 6). Therefore, in this trial, VMBCP appears to be more useful than VAD.     

Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C

From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed cryoglobulins, rheumatoid factor, antinuclear, anticardiolipin, and antithyroglobulin antibodies. Cryoglobulin positivity is associated with systemic vasculitis and rheumatoid factor and HIV positivity. HIV coinfection is associated with arthralgia or myalgia, anticardiolipin antibodies, and thrombocytopenia.     

Usefulness of somatostatin receptor scintigraphy in the management of patients with Zollinger-Ellison syndrome. Groupe de Recherche et d''Etude du Syndrome de Zollinger-Ellison (GRESZE).

BACKGROUND: Management of patients with Zollinger-Ellison syndrome (ZES) depends on the presence of multiple endocrine neoplasia type 1 (MEN 1) or liver metastases, or both. Somatostatin receptor scintigraphy (SRS) detects previously unknown endocrine tumours. AIM AND METHODS: To evaluate SRS findings susceptible to modifying the management of patients with ZES-that is, relevant findings, and the specificity of these findings. The latter were defined according to our current therapeutic strategy in three subgroups of patients (sporadic, MEN 1, and liver metastases). PATIENTS: 85 consecutive patients without known extra-abdominal metastases were studied between September 1991 and March 1996. RESULTS: Relevant findings were found in 41% of 49 patients with sporadic disease but without liver metastases, in 22% of 18 patients with MEN 1 but without liver metastases, and in 17% of 18 patients with liver metastases. Follow up was available for 20 (74%) of 27 patients who had 23 relevant findings. Nineteen relevant findings (83%) were confirmed at a median of three (range 0.25-45) months of follow up; four (17%) were not confirmed at 30 (range 12-52) months (p = 0.025). Findings located in the duodenopancreatic area (90%), chest (100%), bone (100%), and liver (60%) were confirmed. Most findings for patients with MEN 1 involved the chest. CONCLUSION: SRS detects many anomalies susceptible to modifying management of patients with ZES, especially in those with sporadic disease. The specificity of hot spots located outside the liver seems very high. By contrast, the specificity of hot spots located in the liver remains to be evaluated when conventional imaging is negative.     

Oral calcium tolerance test in the early diagnosis of primary hyperparathyroidism and multiple endocrine neoplasia type 1 in patients with the Zollinger-Ellison syndrome. Groupe de Recherche et d'Etude du Syndrome de Zollinger-Ellison.

BACKGROUND: In patients with the Zollinger-Ellison syndrome, the exclusion of multiple endocrine neoplasia type 1 is of important clinical relevance. Its diagnosis often relies on the existence of primary hyperparathyroidism. AIM AND METHODS: To investigate the parathyroid function of patients with the Zollinger-Ellison syndrome by use of an oral calcium tolerance test to identify both hypercalcaemic and normocalcaemic primary hyperparathyroidism, and, accordingly, multiple endocrine neoplasia type 1. PATIENTS: Among 51 consecutive patients with the Zollinger-Ellison syndrome referred to us between 1988 and 1994, 28 had not been investigated for parathyroid function and were prospectively studied. RESULTS: The investigation of calcium metabolism was abnormal in nine patients. One displayed characteristic features of humoral hypercalcaemia of malignancy. The diagnosis of primary hyperparathyroidism was biologically established in eight patients (29%) and subsequently confirmed by the presence of hyperplasia of the parathyroid glands in the seven patients who underwent neck exploration. Three patients with primary hyperparathyroidism had fasting hyper-calcaemia but the other five had normal fasting serum total calcium concentration and the diagnosis of primary hyperparathyroidism was established by means of the oral calcium tolerance test. Primary hyperparathyroidism was demonstrated in the five patients in whom the diagnosis of multiple endocrine neoplasia type 1 had been previously established on other criteria than primary hyperparathyroidism. By contrast, in three patients, primary hyperparathyroidism, either hypercalcaemic (one patient) or normocalcaemic (two patients) was the sole criteria for the diagnosis of multiple endocrine neoplasia type 1. These results also suggest that primary hyperparathyroidism is present before or close to the time of Zollinger-Ellison syndrome diagnosis. CONCLUSION: Complete investigation of the parathyroid function with calcium calcium and parathyroid hormone concentrations.     

Tumour lysis syndrome and acute kidney injury in high‐risk haematology patients in the rasburicase era. A prospective multicentre study from the Groupe de Recherche en Réanimation Respiratoire et Onco‐Hématologique

In tumour lysis syndrome (TLS), metabolic alterations caused by the destruction of malignant cells manifest as laboratory abnormalities with (clinical TLS) or without (laboratory TLS) organ dysfunction. This prospective multicentre cohort study included 153 consecutive patients with malignancies at high risk for TLS (median age 54 years (interquartile range, 38–66). Underlying malignancies were acute leukaemia (58%), aggressive non‐Hodgkin lymphoma (29.5%), and Burkitt leukaemia/lymphoma (12.5%). Laboratory TLS developed in 17 (11.1%) patients and clinical TLS with acute kidney injury (AKI) in 30 (19.6%) patients. After adjustment for confounders, admission phosphates level (odds ratio [OR] per mmol/l, 5.3; 95% confidence interval [95% CI], 1.5–18.3), lactic dehydrogenase (OR per x normal, 1.1; 95%CI, 1.005–1.25), and disseminated intravascular coagulation (OR, 4.1; 95%CI, 1.4–12.3) were associated with clinical TLS; and TLS was associated with day‐90 mortality (OR, 2.45; 95%CI, 1.09–5.50; P = 0.03). In this study, TLS occurred in 30.7% of high‐risk patients. One third of all patients experienced AKI, for which TLS was an independent risk factor. TLS was associated with increased mortality, indicating a need for interventional studies aimed at decreasing early TLS‐related deaths in this setting.     

Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires du Tube Digestif (GETAID).

The aim of this study was to develop and validate an endoscopic index for assessing the severity of Crohn's disease. Endoscopic findings were prospectively collected by a multicentre group in 75 patients with Crohn's colitis according to a previously validated procedure. The presence of nine preselected lesions was recorded in the following segments (1) rectum, (2) sigmoid and left colon, (3) transverse colon, (4) right colon, and (5) ileum. In addition the extent of the diseased and ulcerated areas were estimated in each segment. These segmental data were recorded on a standard form, together with the endoscopist's global estimate of lesion severity. A stepwise multiple regression was used to derive an index which was correlated with the endoscopist's global evaluation of lesion severity. Four mucosal lesions: deep and superficial ulcerations, ulcerated and non-ulcerated stenosis, and both estimates of extent involved were selected and weighted to obtain a Crohn's Disease Endoscopic Index of Severity which correlated with the endoscopist's global appraisal of lesion severity (r = 0.83). This index was then prospectively shown to be valid in a further series of 113 colonoscopies (r = 0.81). The index was calculated in 54 patients with active Crohn's disease, before and at the end of a course of corticosteroids: index variations correctly reflected changes in colitis severity as evaluated by the endoscopists (r = 0.72). For endoscopists familiar with the data collection procedure, this Crohn's Disease Endoscopic Index of Severity should be of value in the follow up of patients, especially in clinical trials.     

Evaluation of the PSAMAO "Roulez Protégé" mass media campaign in Burkina Faso. Prévention du SIDA sur les Axes Migratoires de l'Afrique de l'Ouest.

This study assesses the impact of the Prevention du SIDA sur les Axes Migratoires de l'Afrique de l'Ouest Roulez Protege mass media campaign in Burkina Faso on truckers' likelihood of talking with colleagues about HIV/AIDS, using condoms with an occasional sexual partner, and intending to use a condom in the future. A total of 764 and 1,032 truckers were interviewed in 1997 and 2000 along the Ouagadougou-Niangoloko trucking route. Truckers' exposure to the program has been high and the main message promoted has been greatly understood among those exposed. Logistic regression analyses suggest that the campaign did not have direct behavioral impacts. Exposure to radio spots and participation in group discussions were found to be significantly associated with truckers discussing AIDS with peers or reporting intentions to use a condom in the future. Exposure to Roulez Protege messages through television or billboards was not found to be significantly associated with interpersonal discussion or condom use intentions. Programs should seek to sustain and expand the indirect effects of these types of programs in West Africa. Reinforcing interpersonal counseling interventions should, down the road, lead to overall knowledge and behavior changes among the high-risk trucker population.     

Quality of life-adjusted survival analysis of high-dose therapy with autologous bone marrow transplantation versus sequential chemotherapy for patients with aggressive lymphoma in first complete remission. Groupe d'Etude les Lymphomes de l'Adulte (GELA)

Evaluating high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in term of both duration and quality of life (QOL) presents major interests for patients with non-Hodgkin lymphoma. The quality-adjusted time without symptom and toxicity (Q-TWiST) methodology was applied to the LNH87-2 trial comparing HDT with ASCT versus sequential chemotherapy in 541 patients in first complete remission (CR). Overall survival (OS) and disease-free survival (DFS) curves were used to estimate duration of 4 health states: acute short-term toxicity (Tox1), secondary toxicity (Tox2), time without symptom and toxicity (TWiST), and relapse (Rel). Areas under survival curves (AUC) were retrospectively weighted according to QOL coefficients. HDT increased, but not significantly, TWiST (+2. 4 months in AUC, P =.17) and decreased Rel (-3 months, P <.01). Survival estimates did not differ between the 2 treatments (AUC 47.7 months for OS, 39.7 months for DFS). High-risk patients treated by HDT versus chemotherapy had a significant benefit in DFS (AUC 28.8 versus 24.9 months, P <.01) but not in OS (AUC 37.3 versus 36 months, P =.27). Sensitivity analysis, performed by varying QOL coefficients, demonstrated significant quality-adjusted survival gain in high-risk patients treated by HDT. In low-risk patients, a diagram provided an aid to clinical decision-making. This analysis supports the use of HDT in these patients with adverse prognostic factors in the first CR, even after adjusting for QOL using the Q-TWiST method. (Blood. 2000;95:3687-3692)     

Indicators of "Healthy Aging" in older women (65-69 years of age). A data-mining approach based on prediction of long-term survival

Background

Prediction of long-term survival in healthy adults requires recognition of features that serve as early indicators of successful aging. The aims of this study were to identify predictors of long-term survival in older women and to develop a multivariable model based upon longitudinal data from the Study of Osteoporotic Fractures (SOF).

Methods

We considered only the youngest subjects (n = 4,097) enrolled in the SOF cohort (65 to 69 years of age) and excluded older SOF subjects more likely to exhibit a "frail" phenotype. A total of 377 phenotypic measures were screened to determine which were of most value for prediction of long-term (19-year) survival. Prognostic capacity of individual predictors, and combinations of predictors, was evaluated using a cross-validation criterion with prediction accuracy assessed according to time-specific AUC statistics.

Results

Visual contrast sensitivity score was among the top 5 individual predictors relative to all 377 variables evaluated (mean AUC = 0.570). A 13-variable model with strong predictive performance was generated using a forward search strategy (mean AUC = 0.673). Variables within this model included a measure of physical function, smoking and diabetes status, self-reported health, contrast sensitivity, and functional status indices reflecting cumulative number of daily living impairments (HR ≥ 0.879 or RH ≤ 1.131; P < 0.001). We evaluated this model and show that it predicts long-term survival among subjects assigned differing causes of death (e.g., cancer, cardiovascular disease; P < 0.01). For an average follow-up time of 20 years, output from the model was associated with multiple outcomes among survivors, such as tests of cognitive function, geriatric depression, number of daily living impairments and grip strength (P < 0.03).

Conclusions

The multivariate model we developed characterizes a "healthy aging" phenotype based upon an integration of measures that together reflect multiple dimensions of an aging adult (65-69 years of age). Age-sensitive components of this model may be of value as biomarkers in human studies that evaluate anti-aging interventions. Our methodology could be applied to data from other longitudinal cohorts to generalize these findings, identify additional predictors of long-term survival, and to further develop the "healthy aging" concept.     

Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives.

The relationships between clinical activity, endoscopic severity, and biological parameters in Crohn's disease have not been thoroughly investigated and a link was therefore sought between these three elements. The following parameters were determined simultaneously in 121 consecutive patients with colonic or ileocolonic Crohn's disease: Crohn's disease activity index, Crohn's disease endoscopic index of severity, and serum albumin, alpha 2-globulin, alpha 1-antitrypsin, orosomucoid, C reactive protein, erythrocyte sedimentation rate, platelets, lymphocyte and polymorphonuclear cell counts, haematocrit, and faecal alpha 1-antitrypsin concentration. The distribution of these parameters was studied and transformation was used so that data matched the normal distribution closely. A weak but significant correlation (r = 0.32; p < 0.001) was found between clinical and endoscopic indices in the whole group of patients and this correlation seemed to be homogenous in various patient subgroups (clinically quiescent or active disease, pure colonic disease, untreated patients). Endoscopic or clinical indices were also found to be weakly linked with biological parameters (r < 0.50). Stepwise linear regression identified C reactive protein as predictive of the clinical index, and, successively, alpha 2-globulin, erythrocyte sedimentation rate, faecal alpha 1-antitrypsin, serum orosomucoid, and alpha 1-antitrypsin as predictive of the endoscopic index. Both predictions were poor--the biological variables accounting for only 22 and 44% respectively of the clinical and endoscopic index variations. In conclusion, Crohn's disease clinical activity seems to be virtually independent of the severity of the mucosal lesions and biological activity.     

Impaired cell-mediated immunity in systemic lupus erythematosus (SLE). A controlled study of 23 untreated patients.

Cell-mediated immunity was evaluated in 23 patients with systemic lupus erythematosus (SLE) prior to therapy and in 23 control subjects. The patients with SLE who had moderate to severe disease activity had significantly fewer positive delayed skin tests to streptokinase-streptodornase (SK-SD) and Candida than the control subjects, and a higher frequency of anergy than either the control subjects or the patients with mild SLE. Significant impairment of lymphocyte transformation to all common antigens tested was found in patients with SLE as compared to both normal subjects and control subjects with disease. Phytohemagglutinin response was reduced in patients with SLE as compared to normal subjects but not to the control subjects with disease. Lymphocyte transformation responses to SK-SD and Candida were also significantly lower in patients with moderate to severe SLE as compared to patients with mildly active SLE. Primary immune response to keyhole limpet hemocyanin (KLH) was impaired in patients with SLE as measured by lymphocyte transformation and total KLH antibody, but not 2-mercaptoethanol resistant antibody. The data indicate defective T-cell function in SLE, and suggest that the impairment relates in part to disease activity.