Treatment of cytomegalovirus infection or disease in solid organ transplant recipients with valganciclovir.

Valganciclovir (VGC) has proved efficacious and safe for the prophylaxis against cytomegalovirus (CMV) in high-risk transplant recipients and for the treatment of CMV retinitis in AIDS patients. We used VGC for the treatment of CMV infection (viremia without symptoms) or disease (CMV syndrome or tissue-invasive disease) in kidney, heart, and lung transplant recipients. Fourteen transplant recipients were treated: five for asymptomatic CMV infection and nine for CMV disease. VGC was administered in doses adjusted to renal function for 4 to 12 weeks (induction and maintenance therapy). Clinically, all nine patients with CMV disease responded to treatment. Microbiologically, treatment with VGC turned blood culture negative for CMV within 2 weeks in all patients and was associated with a > or =2 log decrease in blood CMV DNA within 3 weeks in 8 of 8 tested patients. With a follow-up of 6 months (n = 12 patients), asymptomatic recurrent CMV viremia was noted in five cases, and CMV syndrome noted in one case (all cases in the first 2 months after the end of treatment). VGC was clinically well tolerated in all patients; however, laboratory abnormalities occurred in three cases (mild increase in transaminases, thrombocytopenia, and pancytopenia). This preliminary experience strongly suggests that therapy with VGC is effective against CMV in organ transplant recipients; however, the exact duration of therapy remains to be determined: a longer course may be necessary to prevent early recurrence.

Renal tissue oxygenation in essential hypertension and chronic kidney disease.

Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD). In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system) or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.

Robotic Gait Training Is not Superior to Conventional Treadmill Training in Parkinson Disease: A Single-Blind Randomized Controlled Trial.

BACKGROUND: The use of robots for gait training in Parkinson disease (PD) is growing, but no evidence points to an advantage over the standard treadmill. METHODS: In this randomized, single-blind controlled trial, participants aged <75 years with early-stage PD (Hoehn-Yahr <3) were randomly allocated to 2 groups: either 30 minutes of gait training on a treadmill or in the Lokomat for 3 d/wk for 4 weeks. Patients were evaluated by a physical therapist blinded to allocation before and at the end of treatment and then at the 3- and 6-month follow-up. The primary outcome measure was the 6-minute walk test. RESULTS: Of 334 screened patients, the authors randomly allocated 30 to receive gait training with treadmill or the Lokomat. At baseline, the 2 groups did not differ. At the 6-month follow-up, both groups had improved significantly in the primary outcome measure (treadmill: mean = 490.95 m, 95% confidence interval [CI] = 448.56-533.34, P = .0006; Lokomat: 458.6 m, 95% CI = 417.23-499.96, P = .01), but no significant differences were found between the 2 groups (P = .53). DISCUSSION: Robotic gait training with the Lokomat is not superior to treadmill training in improving gait performance in patients with PD. Both approaches are safe, with results maintained for up to 6 months.

Effect of grade on disease-free survival and overall survival in FIGO stage I adenocarcinoma of the endometrium.

OBJECTIVE: To analyse the effect of differentiation on disease-free survival (DFS) and overall survival (OS) in patients with stage I adenocarcinoma of the endometrium. PATIENTS AND METHODS: From 1979 to 1995, 350 patients with FIGO stage IA-IC with well (G1), moderately (G2) or poorly (G3) differentiated tumors were treated with surgery and high dose-rate brachytherapy with or without external radiation. Median age was 65 years (39-86 years). RESULTS: The 5-year DFS was 88+/-3% for the G1 tumors, 77+/-4% for the G2 tumors, and 67+/-7% for the G3 tumors (P=0.0049). With regard to the events contributing to DFS, the 5-year cumulative percentage of local relapse was 4.6% for the G1 tumors, 9.0% for the G2 tumors, and 4.6% (P=0.027) for the G3 tumors. Cumulative percentage of metastasis was 1.4, 6.3 and 7.2% (P<0.001), respectively, whereas percentages of death were 6.0, 7.9 and 20.7% (P<0.001). The 5-year OS was 91+/-3, 83+/-4 and 76+/-7%, respectively (P=0.0018). In terms of multivariate hazard ratios (HR), the relative differences between the three differentiation groups correspond to an increase of 77% of the risk of occurrence of either of the three events considered for the DFS (HR=1.77, 95% CI [0.94-3.33]), (P=0.078) for the G2 tumors and of 163% (HR=2.63, 95% CI [1.27-5.43]), (P=0.009) for the G3 tumors with respect to the G1 tumors. The estimated relative hazards for OS are, respectively, in line with those for DFS: HR=1.51 (P=0.282) for the G2 tumors; and HR=3.37 (P=0.003) for the G3 tumors. CONCLUSION: Patients with grade 1 tumors are those least exposed to either local relapse, metastasis, or death. In contrast patients with grade 2 tumors seem to be at higher risk of metastasis, whereas patients with grade 3 tumors appear at higher risk of death. Since we have looked at the first of three competing events (local relapse, metastasis and death), this suggests that patients with grade 3 tumors probably progress to death so fast that local relapse, if any, cannot be observed.

Early stage primary bone lymphoma - a retrospective, multicenter rare cancer network (rcn) study

Purpose: Primary bone lymphoma (PBL) accounts for less than 1% of all malignant lymphomas, and 4-5% of all extra-nodal lymphomas. In this study, the disease profile, outcome, and prognostic factors were assessed in patients with stage I and II PBL.Patients and Methods: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Inclusion criteria were age > 16 years, stage I and II, minimum 6 months follow-up and a biopsy-proven confirmation of non-Hodgkin's lymphoma (NHL). Eighty-seven patients underwent chemoradiotherapy (CXRT), 15 radiotherapy (RT) without (13) or with (2) surgery, 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range: 4-60). The median number of CXT cycles was 6 (range: 2-8). Median follow-up was 41 months (range: 6-242).Results: The overall response rate at the end of treatment was 91% (CR 74%, PR 17%). Local recurrence or progression was observed in 12 (10%) patients, and systemic recurrence in 17 (15%). Causes of death included disease progression in 21, unrelated in 5, CXT-related toxicity in 1, and second primary cancer in 2 patients. The 5-yr overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78% and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS were age <50 years (P=0.008), international prognostic index (IPI) score ≤1 (P=0.009), high grade histology (P=0.04), CXRT (P=0.05), CXT (P=0,0004), complete response (CR) (P<0.0001), number of CXT cycles ( ≥6 ) (P=0.01), and RT dose > 40 Gy (P=0.005). All above-mentioned parameters were also significant for LSS except for age and number of chemotherapy cycles. For LC, only CR and stage I were favorable factors. In multivariate analysis, IPI score, RT dose, complete response, and chemotherapy were independently influencing the outcome (OS and LSS). Complete response at the end of treatment was the only predicting factor for LC. Six patients developed grade 3 or more toxicities, according to Common Terminology Criteria for Adverse Events (CTCAE) V3.0.Conclusion: This large multicenter study confirms the relatively good prognosis of early stage PBL treated with combined CXRT. Local control was excellent, while systemic failures were rare. An adequate dose of RT (40 Gy or more) and complete CXT regime (≥ 6 cycles) were associated with better outcome.

Management of transitional-cell carcinoma of the renal pelvis and ureter.

Transitional-cell carcinoma of the renal pelvis or ureter is a relatively rare disease. Several risk factors are smoking, occupational carcinogens, analgesic abuse or Balkan nephropathy. The grade and stage of the disease have the most significant impact on the outcome. The treatment of renal pelvis and ureter tumours is open or laparoscopic surgery varying from conservative to more extensive surgical procedures, i.e. radical nephroureterectomy including removal of the contents of Gerota's fascia with ipsilateral ureter and a cuff of bladder at its distal extent. Most available data are from retrospective studies and surgery is the mainstay of treatment. Chemotherapy and/or radiation therapy are possible adjuvant or primary treatment for selected patients; however, prospective studies are needed to confirm their use.

Mortality of patients with COPD participating in chronic disease management programmes: a happy end?

BACKGROUND: Concerns about increased mortality could question the role of COPD chronic disease management (CDM) programmes. We aimed at extending a recent Cochrane review to assess the effects of CDM on mortality in patients with COPD. METHODS: Mortality data were available for 25 out of 29 trials identified in a COPD integrated care systematic review. Meta-analysis using random-effects models was performed, followed by subgroup analyses according to study length (3-12 months vs >12 months), main intervention component (exercise, self-management, structured follow-up) and use of an action plan. RESULTS: The meta-analysis showed no impact of CDM on mortality (pooled OR: 1.00, 95% CI 0.79 to 1.28). CONCLUSIONS: These results do not suggest that CDM programmes expose patients with COPD to excessive mortality risk.

Early-Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network (RCN) Study.

PURPOSE: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL.¦PATIENTS AND METHODS: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242).¦RESULTS: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score ≤1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC.¦CONCLUSION: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome.

Reemergence of dormant Coats disease after 30 years.

Purpose. We describe an atypical case of a patient with Coats disease that re-emerged after 30 years, illustrating a previously poorly understood long-term evolution of the disease. Methods. A 20-year-old man consulted for visual acuity (VA) decrease in the left eye (LE) to 0.3. Fundus examination revealed an exudative lesion with telangiectasias in the superior peripheral retina compatible with the diagnosis of Coats disease. Results. The patient was treated with cryotherapy and argon laser. Visual acuity improved to 0.5 and remained stable during a 1-year follow-up. The patient did not seek further clinical follow-up. Thirty years later, he returned complaining of a progressive VA decrease in the LE. Snellen VA was measured to counting fingers. Fundus examination revealed stage 3A Coats disease with macular exudation and a serous retinal detachment in the inferior quadrants requiring the placement of an encircling band, external drainage, and cryotherapy of the vascular lesions. After 10 additional sessions of argon laser on the vascular malformations, exudation regressed further and best-corrected VA increased to 0.1 at the end of the follow-up period. Conclusions. Coats disease must be considered as a chronic disease, which necessitates a very long-term follow-up even in the absence of subjective visual loss. The disease can reawaken and recur with force in previously unaffected areas of the retina several decades later. The gold standard treatment consists of cryotherapy and argon laser. However, in cases of very important retinal exudation, surgical management with subretinal drainage may be necessary.

A new technique with high reproducibility to estimate renal oxygenation using BOLD-MRI in chronic kidney disease.

OBJECTIVES: To assess inter-observer variability of renal blood oxygenation level-dependent MRI (BOLD-MRI) using a new method of analysis, called the concentric objects (CO) technique, in comparison with the classical ROI (region of interest)-based technique. METHODS: MR imaging (3T) was performed before and after furosemide in 10 chronic kidney disease (CKD) patients (mean eGFR 43±24ml/min/1.73m(2)) and 10 healthy volunteers (eGFR 101±28ml/min1.73m(2)), and R2* maps were determined on four coronal slices. In the CO-technique, R2* values were based on a semi-automatic procedure that divided each kidney in six equal layers, whereas in the ROI-technique, all circles (ROIs) were placed manually in the cortex and medulla. The mean R2*values as assessed by two independent investigators were compared. RESULTS: With the CO-technique, inter-observer variability was 0.7%-1.9% across all layers in non-CKD, versus 1.6%-3.8% in CKD. With the ROI-technique, median variability for cortical and medullary R2* values was 3.6 and 6.8% in non-CKD, versus 4.7 and 12.5% in CKD; similar results were observed after furosemide. CONCLUSION: The CO-technique offers a new, investigator-independent, highly reproducible alternative to the ROI-based technique to estimate renal tissue oxygenation in CKD.

Maximising the duration of disease control in metastatic renal cell carcinoma with targeted agents: an expert agreement.

With six targeted agents approved (sorafenib, sunitinib, temsirolimus, bevacizumab [+interferon], everolimus and pazopanib), many patients with metastatic renal cell carcinoma (mRCC) will receive multiple therapies. However, the optimum sequencing approach has not been defined. A group of European experts reviewed available data and shared their clinical experience to compile an expert agreement on the sequential use of targeted agents in mRCC. To date, there are few prospective studies of sequential therapy. The mammalian target of rapamycin (mTOR) inhibitor everolimus was approved for use in patients who failed treatment with inhibitors of vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) based on the results from a Phase III placebo-controlled study; however, until then, the only licensed agents across the spectrum of mRCC were VEGF(R) inhibitors (sorafenib, sunitinib and bevacizumab + interferon), and as such, a large body of evidence has accumulated regarding their use in sequence. Data show that sequential use of VEGF(R) inhibitors may be an effective treatment strategy to achieve prolonged clinical benefit. The optimal place of each targeted agent in the treatment sequence is still unclear, and data from large prospective studies are needed. The Phase III AXIS study of second-line sorafenib vs. axitinib (including post-VEGF(R) inhibitors) has completed, but the data are not yet published; other ongoing studies include the Phase III SWITCH study of sorafenib-sunitinib vs. sunitinib-sorafenib (NCT00732914); the Phase III 404 study of temsirolimus vs. sorafenib post-sunitinib (NCT00474786) and the Phase II RECORD 3 study of sunitinib-everolimus vs. everolimus-sunitinib (NCT00903175). Until additional data are available, consideration of patient response and tolerability to treatment may facilitate current decision-making regarding when to switch and which treatment to switch to in real-life clinical practice.

La néphropathie ischémique par athérosclérose aortorénale : acquisitions thérapeutiques [Atherosclerotic renal artery disease management update]

In the case of atherosclerotic renal artery disease, the best conclusive results lie principally not in the degree of the stenosis but rather in the degree the renal parenchymal disease beyond the stenosis itself. These determining factors involve the controlling of the patients blood pressure, the improvement in the renal function and the beneficial results to the cardiovascular system. Besides the indispensable medical treatment, a revascularisation by angioplasty may be indicated. This procedure with or without vascular stent often allows satisfactory angiographic results. A treatment by surgical revascularisation is only recommended in the case of extensive atherosclerotic lesions of the aorta, complex lesions of the latter or an abdominal aortic aneurism. Although the frequency of restenosis of angioplasty with stent remains extremely low, the risk of cholesterol emboli due to the diffuse atherosclerotic lesions of the abdominal aorta, must be considered at the time of each aortic catheterization. The therapeutic approach of atherosclerotic renal artery disease must be dictated by the whole cardiovascular risk factors and by the threat of target organs. The control of the blood pressure and the maintenance of the renal function must be integrated in the decisional algorithm as well as the possible risks in carrying out an eventual revascularisation procedure. Finally, the renal angioplasty should in numerous situations be integrated in the overall assumption of responsibility of the atherosclerotic vascular diseases, and should be part of the medical treatment. Several questions still do exist; at what moment an atherosclerotic renal artery stenosis should and e considered critical, and which procedure should be considered for which patient? The purpose of this review is to propose a decisional tool for individualized treatments in the light of results from randomized and controlled studies.

Personality traits, behavioral and psychological symptoms and cognitive decline in patients at an early stage of Alzheimer's disease

The aim of this doctoral thesis was to study personality characteristics of patients at an early stage of Alzheimer's disease (AD), and more specifically to describe personality and its changes over time, and to explore its possible links with psychological and symptoms (BPS) and cognitive level. The results were compared to those of a group of participants without cognitive disorder through three empirical studies. In the first study, the findings showed significant personality changes that follow a specific trend in the clinical group. The profil of personality changes showed an increase in Neuroticism and a decrease in Extraversion, Openess to experiences, and Conscientiousness over time. The second study highlighted that personality and BPS occur early in the cours of AD. Recognizing them as possible precoce signs of neurodegeneration may prove to be a key factor for early detection and intervention. In the third study, a significant association between personality changes and cognitive status was observed in the patients with incipient AD. Thus, changes in Neuroticism and Conscientiousness were linked with cognitive deterioration, whereas decreased Openness to experiences and Conscientiousness over time predicted loss of independence in daily functioning. Other well-known factors such as age, education level or civil status were taken into account to predict cognitive decline. The three studies suggested five important implications: (1) cost-effective screening should take into account premorbid and specific personality changes; (2) psycho-educative interventions should provide information on the possible personality changes and BPS that may occur at the beginning of the disease; (3) using personality traits alongside other variables in the future studies on prevention might help to better understand AD's etiology; (4) individual treatment plans (psychotherapeutic, social, and pharmacological) might be adapted to the specific changes in personality profiles; (5) more researches are needed to study the impact of social-cultural and lifestyle variables on the development of AD.