One-year longitudinal evaluation of neuropsychiatric symptoms in Alzheimer's disease. The REAL.FR Study

Behavioral and Psychological Symptoms are major and frequent manifestations of Alzheimer's Disease (AD). The aim of the present study was to evaluate neuropsychiatric symptoms in the PHRC REAL.FR cohort (for Réseau sur la maladie d'Alzheimer Fran?ais) after one year of evolution. Four hundred and eighty two patients with mild and moderate AD were assessed. A majority of them had significant symptoms at inclusion (85.3 % of subjects with mild AD, 89.7% of patients with a moderate AD). Patients with mild AD had a significant increase of the Neuropsychiatric Inventory (NPI) frequency x severity scores for apathy and aberrant motor behavior. Patients with moderate AD had a significant increase of NPI disinhibition, aberrant motor behavior and sleep disorders scores. The variation of NPI total score at one year correlated positively with change in Zarit's caregiver burden score, independently of global cognitive evolution. After one year, a group of 54 patients were institutionalized in nursing home or long term care unit. When compared to non institutionalized patients, the institutionalized group was characterized at base line by a lower MMSE score, a higher Zarit caregiver burden score, and a higher NPI agitation and disinhibition scores.     

Limb salvage from a multidisciplinary treatment approach for skeletal and soft tissue sarcomas of the extremity.

Multimodality management of extremity skeletal and soft tissue sarcomas with preoperative intra-arterial Adriamycin and radiation therapy, radical surgical resection and postoperative chemotherapy or chemo-immunotherapy has resulted in preservation of a functional extremity in 13 or 14 patients. Seven of 8 patients with Stage IIIA and IIIB soft tissue sarcomas, managed with preoperative intra-arterial Adriamycin and radiation therapy, followed by en bloc soft tissue resection and 6 patients with bone sarcomas managed by preoperative treatment, followed by bone resection and replacement with cadaver bone allografts, remained free of disease from 4 to 34 months. The results of the combined modality approach were significantly better than the results obtained in patients managed by surgical resection alone, or by combination of operation with another single modality, both in terms of short term-recurrence free survival and salvage of a functional extremity.     

High-grade extremity soft tissue sarcomas: factors predictive of local recurrence and its effect on morbidity and mortality

OBJECTIVE: To identify patient characteristics associated with the development of local recurrence and the effect of local recurrence on subsequent morbidity and mortality in patients with intermediate- to high-grade extremity soft tissue sarcomas. SUMMARY BACKGROUND DATA: Numerous studies on extremity soft tissue sarcomas have consistently shown that presentation with locally recurrent disease is associated with the development of subsequent local recurrences and that large tumor size and high histologic grade are significant factors associated with decreased survival. However, the effect of local recurrence on patient survival remains unclear. METHODS: From 1975 to 1997, 753 patients with intermediate- to high-grade extremity soft tissue sarcomas were treated at UCLA. Treatment outcomes and patient characteristics were analyzed to identify factors associated with both local recurrence and survival. RESULTS: Patients with locally recurrent disease were at a significantly increased risk of developing a subsequent local recurrence. Local recurrence was a morbid event requiring amputation in 38% of the cases. The development of a local recurrence was the most significant factor associated with decreased survival. Once a patient developed a local recurrence, he or she was about three times more likely to die of disease compared to similar patients who had not developed a local recurrence. CONCLUSIONS: Local recurrence in patients with intermediate- to high-grade extremity soft tissue sarcomas is associated with the development of subsequent local recurrences, a morbid event decreasing functional outcomes and the most significant factor associated with decreased survival. Although 85% to 90% of patients with high-grade extremity soft tissue sarcomas are treatable with a limb salvage approach, patients who develop a local recurrence need aggressive treatment and should be considered for trials of adjuvant systemic therapy.     

Role of behavioural disturbance in the loss of autonomy for activities of daily living in Alzheimer patients

BACKGROUND: Cognitive impairment is associated with functional impairment in patients with Alzheimer's disease (AD). Behavioural disturbance is very common in these patients. Nevertheless, there has been very little research into the relations between behavioural disturbance and functional status in AD. The purpose of this study is to investigate the relationship between behavioural disturbance and functional status after taking account of cognitive impairment. MATERIAL AND METHODS: 579 patients were prospectively evaluated at 16 French hospitals, all referents for AD, and were diagnosed with possible or probable AD. These patients were assessed with NeuroPsychiatric Inventory (NPI), cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), Clinical Dementia Rating scale (CDR) and Instrumental Activities of Daily Living scale (IADL). RESULTS: The number of men with available data for IADL total score was too small to make any analysis. 'Group A' gathered 256 women for whom the relation between autonomy for Activities of Daily Living (ADL) and the other variables were determined. 'Group B', pooled 85 women for whom relations found were verified. Linear regression was used for the analysis. With age, cognitive impairment allows us to explain best (38%) the loss of autonomy for ADL. CONCLUSION: The role of behavioural disturbances in the loss of autonomy for ADL was not determinant in our study, whereas cognitive impairment and age were better able to determine the loss of autonomy for ADL. Further study is needed to explain the decline of functional status in AD patients.     

Treatment monitoring by 18F-FDG PET/CT in patients with sarcomas: interobserver variability of quantitative parameters in treatment-induced changes in histopathologically responding and nonresponding tumors

Measurements of tumor glucose use by (18)F-FDG PET need to be standardized within and across institutions. Various parameters are used for measuring changes in tumor glucose metabolic activity with (18)F-FDG PET in response to cancer treatments. However, it is unknown which of these provide the lowest variability between observers. Knowledge of the interobserver variability of quantitative parameters is important in sarcomas as these tumors are frequently large and demonstrate heterogeneous (18)F-FDG uptake. METHODS: A total of 33 patients (16 men, 17 women; mean age, 47 +/- 18 y) with high-grade sarcomas underwent (18)F-FDG PET/CT scans before and after neoadjuvant chemotherapy. Two independent investigators measured the following parameters on the pretreatment and posttreatment scans: maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), SUVmean in an automatically defined volume (SUVauto), and tumor-to-background ratio (TBR). The variability of the different parameters was compared by concordance correlation coefficient (CCC), variability effect coefficient, and Bland-Altman plots. RESULTS: Baseline SUVmax, SUVpeak, SUVmean, SUVauto, and TBR averaged 10.36, 7.78, 4.13, and 6.22 g/mL and 14.67, respectively. They decreased to 5.36, 3.80, 1.79, and 3.25 g/mL and 6.62, respectively, after treatment. SUVmax, SUVpeak, and SUVauto measurements and their changes were reproducible (CCC > or = 0.98). However, SUVauto poorly differentiated between responding and nonresponding tumors. The high intratumoral heterogeneity of (18)F-FDG resulted in frequent failure of the thresholding algorithm, which necessitated manual corrections that in turn resulted in a higher interobserver variability of SUVmean (CCCs for follow-up and change were 0.96 and 0.91, respectively; P < 0.005). TBRs also showed a significantly higher variability than did SUVpeak (CCCs for follow-up and change were 0.94 and 0.86, respectively; P < 0.005). CONCLUSION: SUVmax and SUVpeak provided the most robust measurements of tumor glucose metabolism in sarcomas. Delineation of the whole-tumor volume by semiautomatic thresholding did not decrease the variability of SUV measurements. TBRs were significantly more observer-dependent than were absolute SUVs. These findings should be considered for standardization of clinical (18)F-FDG PET/CT trials.     

Management of carcinoma of the rectum and anus without abdominoperineal resection

Since 1979, 16 patients with cancer of the rectum and anus have been treated without abdominoperineal resection. All have received radiotherapy. Nine of these had local excision before receiving radiotherapy. There has been no evidence of recurrent cancer in 15 of the 16 patients with a median follow-up period of 24 months (range 14 to 52 months) for a recurrence rate of 6 percent. We conclude that limited excision, radiotherapy, or both are viable alternatives to abdominoperineal resection of small, early cancers of the rectum and anus.     

Ultraviolet irradiation of blood prevents transfusion-induced sensitization and marrow graft rejection in dogs

In a canine model using DLA-identical littermate pairs, we have shown that a regimen of three transfusions of donor blood given 24, 17, and 10 days before transplant uniformly leads to marrow graft rejection, presumably due to sensitization to minor (non-DLA) histocompatibility antigens. Untransfused dogs uniformly achieve sustained engraftment. In the present study, we investigated whether the exposure of blood to ultraviolet (UV) light (220-300 nm) prior to transfusion prevented sensitization of the recipient and allowed for successful marrow engraftment. Ten dogs were each given three pretransplant transfusions from the marrow donor. Each transfusion consisted of 50 mL of whole blood exposed in vitro to UV light for a total of 1.35 J/cm2. All ten dogs achieved engraftment. In contrast, all four dogs that had received sham-exposed transfusions rejected their grafts. In vitro studies revealed that although cell viability was not affected, leukocytes contained in UV-exposed blood were unable to function as stimulator cells in mixed leukocyte cultures or as accessory cells in mitogen- stimulated cultures. These data are consistent with the hypothesis that accessory cells are involved in transfusion-induced sensitization. We conclude that in vitro exposure of blood to UV light before transfusion prevents sensitization and allows for subsequent marrow engraftment.