Long-term effects of intermittent interleukin-2 therapy in chronic HIV-infected patients (ANRS 048-079 Trials)

OBJECTIVE: Interleukin (IL)-2 therapy leads to significant CD4 cell increases in HIV-infected patients. Since phase III trials are ongoing, studies supporting the long-term feasibility of this strategy are needed. METHODS: We studied the long-term outcomes of 131 patients treated with IL-2 in two studies initiated either before (ANRS 048) or following (ANRS 079) the advent of HAART. RESULTS: At the last assessment (median follow-up 3.4 years), these patients experienced a gain of 428 cells/microl and a decrease in plasma HIV RNA to 1.70 log10 copies/ml. In both studies, high CD4 cell counts were maintained with a median of ten 5-day cycles of subcutaneous IL-2. Median time since the last cycle was 2 years. At last assessment, 59% of 048 patients maintained a non-HAART regimen. Detailed analysis at week 170 showed that median CD4 cell counts were 856 (048) and 964 (079) cells/microl. This corresponded to a gain from baseline of 515 (048) and 627 (079) cells/microl. The median viral load decreases from baseline and corresponded to 1.70 (048) and 1.88 (079) log10 copies/ml. Comparisons across the studies showed that CD4 gains and viral load changes were similar whether HAART or non-HAART was used. The frequency of cycling, but not CD4 cell counts, viral loads or antiviral regimen at baseline, was predictive of long-term CD4 gain (P = 0.03). CONCLUSION: Altogether, these observations support IL-2 as a long-term therapeutic strategy in HIV infection.     

Left ventricular response to exercise in aortic stenosis: an exercise echocardiographic study

BACKGROUND: While normal at rest, left ventricular (LV) systolic function may become abnormal during exercise in patients with aortic stenosis. Once contraindicated in patients with aortic stenosis, exercise testing is now recommended in asymptomatic patients with aortic stenosis to elicit symptoms and thereby ascertain the need for aortic valve replacement. However, the clinical significance of an abnormal LV response to exercise in asymptomatic patients with aortic stenosis remains unknown. OBJECTIVE: The aim of this study was to evaluate the clinical implications of an abnormal LV response during exercise in the setting of aortic stenosis. METHODS: We monitored the LV response to exercise by 2D-Doppler echocardiography during a symptom limited semirecumbent bicycle exercise in 50 patients with tight aortic stenosis (aortic valve area < or = 1.0 cm(2)) and a normal LV systolic function (LV ejection fraction, EF > or = 50%) and followed them for an average of 11 months. RESULTS: Twenty patients had an abnormal LV response to exercise with a mean decrease in LV EF from 64 +/- 10 to 53 +/- 12% while 30 patients had a normal LV response to exercise with a mean increase in LV EF from 62 +/- 7 to 70 +/- 8%. Patients with an abnormal LV response during exercise were more likely to develop symptoms during exercise than patients with a normal LV response: 80% versus 27% (P< 0.0001). The survival free of cardiac events was significantly lower in patients with abnormal LV response to exercise than in patients with a normal response (P = 0.03). CONCLUSION: Exercise echocardiography provides objective data that facilitate interpretation of exercise elicited symptoms in asymptomatic patients with severe aortic stenosis. In addition, an abnormal LV response to exercise may predict a poor outcome.     

Plasma cell growth fraction using Ki-67 antigen expression identifies a subgroup of multiple myeloma patients displaying short survival within the ISS stage I

The current most powerful prognostic model in Multiple Myeloma (MM) combines beta-2 microglobulin (b2m) with albumin, corresponding to the International Staging System (ISS). However, the prognosis of patients within the ISS stage I (high albumin and low b2m) may vary. Ki-67 is a nuclear protein associated with cell proliferation. We retrospectively evaluated the percentage of bone marrow plasma cells expressing Ki-67 antigen (Ki-67 index) in a series of 174 untreated MM patients at diagnosis. Median survival was 51, 41 and 20 months respectively, and median Ki-67 index was 3.0%, 6.1% and 6.5% in ISS stages I, II, and III respectively. Independently of ISS, Ki-67 index > or =4% was highly predictive of adverse prognosis. Ki-67 index correlated with markers of intrinsic malignancy and with markers of tumour burden. Within ISS stage I, median survival was of 31 months (RR of death 2.65) in patients with Ki-67 index > or =4%. Eventually, the combination of Ki-67 with b2m produced an efficient prognostic model, which appeared most effective in our series when compared with b2m and KI-67 with chromosome 13 deletion models. In this series, we demonstrated that a proliferation marker provides clear-cut additional survival prognostic information to b2m into the ISS model.     

Coping strategies as determinants of quality of life in stroke patients: a longitudinal study

BACKGROUND: Quality of life (QoL) is reduced for stroke patients and coping strategies have been suggested as determinants of QoL. Thus far the relationship between coping and QoL has only been examined in small-scale cross-sectional designs. Therefore, the current study set out to examine this relationship in a longitudinal setting. METHODS: Stroke patients who were discharged home were interviewed at 4 different time points; just before discharge (T1), and 2 months (T2), 5 months (T3) and 9-12 months after discharge (T4). QoL was measured by the EQ-5D index score and the SF-36 utility score and coping expressed in terms of tenacious goal pursuit and flexible goal adjustment. Modified Rankin scale was assessed as a measure of general functioning. RESULTS: Eighty stroke patients were included. Coping was not predictive of QoL at T1 and T2 but rather at T3 and T4. At T4 both coping strategies determined the levels of QoL as measured with the EQ-5D index score; higher levels of tenacious goal pursuit as well as flexible goal adjustment were associated with higher levels of QoL. This regression model explained 44% of the variance. CONCLUSIONS: Coping is a powerful determinant of QoL, but only more than 5 months after discharge; before this time QoL is mainly determined by general functioning. Both coping strategies were important determinants of QoL.     

Pancreatoblastoma: a report from the European cooperative study group for paediatric rare tumours (EXPeRT)

Background

Pancreatoblastoma is a very rare malignant tumour typically occurring in the early years of life. Due to its rarity, standardised diagnostic and therapeutic guidelines are not available for pancreatoblastoma.

Methods

The newborn cooperative group denominated EXPeRT – European cooperative study group for paediatric rare tumours – combined in a joint analysis of all cases registered between 2000 and 2009 by the national groups of Italy, France, United Kingdom, Poland and Germany.

Results

Twenty patients <18 years old (median age 4 years) were analysed: nine had distant metastases at diagnosis. Seventeen patients had tumour resection, at initial or delayed surgery. Eighteen received chemotherapy (response rate 73%), seven received radiotherapy. For the whole series, 5-year event-free survival and overall survival were 58.8% and 79.4%, respectively. Outcome did not correlate with tumour site and size, but was strongly influenced by the feasibility of tumour complete resection.

Conclusions

This international study confirms the rarity of the disease, the critical role of surgical resection both as therapy and as a prognostic variable, and the potential efficacy of chemotherapy. The adoption of an intensive multidisciplinary approach is required, as well as the referral to highly experienced centres. Further international cooperation is needed to collect larger series and stimulate biological studies to improve our understanding of the biology and the natural history of PBL.     

Limits of Day-Before Lymphoscintigraphy to Localize Sentinel Nodes in Women with Cervical Cancer

Background  Lymph node status in cervical cancer is a major prognostic factor. Sentinel lymph node (SN) biopsy using radiocolloid and blue dye labeling and preoperative lymphoscintigraphy has emerged as a potential alternative to systematic lymphadenectomy. The aim of this study was to evaluate the contribution of preoperative lymphoscintigraphy to SN biopsy. Methods  Between April 2001 and December 2005, 71 of 77 patients with cervical cancer (38 patients with stages IA or IB1, and 39 patients with stage IB2, IIA or IIB) underwent laparoscopic SN procedure using radiocolloid and blue dye with day-before lymphoscintigraphy. The SN identification rates and false-negative rates were studied. Results  Seventy patients underwent a combined technique and the last patient a radiocolloid technique alone due to blue dye allergic reaction. Detection rate of lymphoscintigraphy was 84.5% (60/71), with 1.4 sentinel nodes per patient. Three of 11 patients (27.3%) with no SN on lymphoscintigraphy had at least one SN during surgery. Sixteen of 27 patients (59.3%) with solitary SN on lymphoscintigraphy had multiple SNs. Nine of 35 patients (25.7%) with unilateral SNs on lymphoscintigraphy had bilateral SNs at surgery (kappa = 0.44 [0.19–0.64]). When categorized into <2 and ≥2 sentinel nodes, the correlation between lymphoscintigraphic and surgical detection was poor (kappa = 0.05 [0.0–0.18]). Conclusions  SN biopsy is a feasible and accurate method to stage early cervical cancer. However, day-before lymphoscintigraphy is poorly correlated to surgical SN mapping.     

Disease status, costs and quality of life of patients with rheumatoid arthritis in France: the ECO-PR Study

ObjectiveTo investigate resource consumption and quality of life (utility) in a sample of patients covering the full spectrum of the disease, modalities of patient management and geographic areas.MethodsInformation on demographics, disease parameters, work capacity and resource consumption (in the past 1, 3 or 12 months depending on the resource) was collected in an anonymous mail survey from all members of a national patient association (ANDAR). Results are presented for the sample and by level of functional capacity, in €2005.Results1487 patients were included in the analysis (response rate 49%). Mean age was 62.7 years and 83.5% of respondents were female. Mean disease duration was 18 years; mean HAQ was 1.42; fatigue and pain ranked 5.6 and 4.8 on a scale between 0 and 10, respectively. Of patients below 60 years, 34% had taken early retirement due to RA, and only 15% of patients with a HAQ of 2 or higher were working. Productivity losses were estimated at €5076, of which indemnity payments covered €1944. Direct health care costs were €11,757 in the societal perspective and €9216 in the perspective of the national health insurance. Direct non-medical costs (including informal care) were €4857 and €136 respectively. Costs to society increased from €9400 in mild disease to €40,700 in severe disease, and to public payers from €6000 to €19,000. Utility decreased simultaneously from 0.80 to 0.06.ConclusionThe study confirms overall findings in other studies in other countries, and provides the first estimate of all costs by disease severity in France.