Coronary collaterals and risk for restenosis after percutaneous coronary interventions: a meta-analysis

The benefit of the coronary collateral circulation (natural bypass network) on survival is well established. However, data derived from smaller studies indicates that coronary collaterals may increase the risk for restenosis after percutaneous coronary interventions. The purpose of this systematic review and meta-analysis of observational studies was to explore the impact of the collateral circulation on the risk for restenosis.

The role of adjuvant hormonal treatment after surgery for localized high-risk prostate cancer: results of a matched multiinstitutional analysis

Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n = 86) or no adjuvant ADT (group 2, n = 86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5-10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.

Does surgery improve outcomes for esophageal squamous cell carcinoma? An analysis using the surveillance epidemiology and end results registry from 1998 to 2008

We examined survival associated with locally advanced esophageal squamous cell cancer (SCC) to evaluate if treatment without surgery could be considered adequate.

The role of radiation therapy in resected T2 N0 esophageal cancer: a population-based analysis

The prognosis of even early-stage esophageal cancer is poor. Because there is not a consensus on how to manage T2 N0 disease, we examined survival after resection of T2 N0 esophageal cancer, with or without radiation therapy.

Anthracyclines during induction therapy in acute myeloid leukaemia: a systematic review and meta-analysis

This systematic review and meta-analysis compared the efficacy of different anthracyclines and anthracycline dosing schedules for induction therapy in acute myeloid leukaemia in children and adults younger than 60 years of age. Twenty-nine randomized controlled trials were eligible for inclusion in the review. Idarubicin (IDA), in comparison to daunorubicin (DNR), reduced remission failure rates (risk ratio (RR) 0·81; 95% confidence interval (CI), 0·66-0·99; P = 0·04), but did not alter rates of early death or overall mortality. Superiority of IDA for remission induction was limited to studies with a DNR/IDA dose ratio <5 (ratio <5: RR 0·65; 95% CI, 0·51-0·81; P < 0·001; ratio ≥5: RR 1·03; 95% CI, 0·91-1·16; P = 0·63). Higher-dose DNR, compared to lower-dose DNR, was associated with reduced rates for remission failure (RR 0·75; 95% CI, 0·60-0·94; P = 0·003) and overall mortality (RR 0·83; 95% CI, 0·75-0·93; P < 0·001), but not for early death. Comparisons of several other anthracycline derivates did not reveal significant differences in outcomes. Survival estimates in adults suggest that both high-dose DNR (90 mg/m(2) daily × 3 or 50 mg/m(2) daily × 5) and IDA (12 mg/m(2) daily × 3) can achieve 5-year survival rates of between 40 and 50 percent.

Analysis of pedigree and conformation data to explain genetic variability of the horse breed Franches-Montagnes

Franches-Montagnes is the only native horse breed in Switzerland, therefore special efforts should be made for ensuring its survival. The objectives of this study were to characterize the structure of this population as well as genetic variability with pedigree data, conformation traits and molecular markers. Studies were focused to clarify if this population is composed of a heavy- and a light-type subpopulation. Extended pedigree records of 3-year-old stallions (n = 68) and mares (n = 108) were available. Evaluations of body conformation traits as well as pedigree data and molecular markers did not support the two-subpopulation hypothesis. The generation interval ranged from 7.8 to 9.3 years. The complete generation equivalent was high (>12). The number of effective ancestors varied between 18.9 and 20.1, whereof 50% of the genetic variability was attributed to seven of them. Genetic contribution of Warmblood horses ranged from 36% to 42% and that of Coldblood horses from 4% to 6%. The average inbreeding coefficient reached 6%. Inbreeding effective population size was 114.5 when the average increase of the inbreeding coefficient per year since 1910 was taken. Our results suggest that bottleneck situations occurred because of selection of a small number of sire lines. Promotion of planned matings between parents that are less related is recommended in order to avoid a reduction of the genetic diversity.

Therapy of basilar artery occlusion: a systematic analysis comparing intra-arterial and intravenous thrombolysis

BACKGROUND AND PURPOSE: Basilar artery occlusion (BAO) is an infrequent form of acute stroke, which invariably leads to death or long-term disability if not recanalized. A traditional recanalization approach based on historical controls and pathophysiological consideration is local intra-arterial thrombolysis (IAT) in eligible patients. This necessitates diagnostic evaluation and treatment in stroke centers equipped with an interventional neuroradiological service on a 24-hour basis, but its superiority to the technically simple intravenous thrombolysis (IVT) remains unproven. METHODS: We analyzed systematically published case series of substantial size reporting the outcome of BAO after IAT or IVT. RESULTS: In 420 BAO patients treated with IVT (76) and IAT (344), death or dependency were equally common: 78% (59 of 76) and 76% (260 of 344), respectively (P=0.82). Recanalization was achieved more frequently with IAT (225 of 344; 65%) than with IVT (40 of 76; 53%; P=0.05), but survival rates after IVT (38 of 76; 50%) and IAT (154 of 344; 45%) were equal (P=0.48). A total of 24% of patients treated with IAT and 22% treated with IVT reached good outcomes (P=0.82). Without recanalization, the likelihood of good outcome was close to nil (2%). CONCLUSIONS: Recanalization occurs in more than half of BAO patients treated with IAT or IVT, and 45% to 55% of survivors regain functional independence. Although improved therapy forms for BAO are necessary, hospitals not equipped for IAT may set up IVT protocols. The effect of IVT is probably not much different from the effect of IAT. IVT represents probably the best treatment that can be offered to victims of acute BAO in such hospitals.

Molecular survival strategies of Echinococcus multilocularis in the murine host

Larval infection with Echinococcus multilocularis starts with the intrahepatic postoncospheral development of a metacestode that-at its mature stage-consists of an inner germinal and an outer laminated layer (GL ; LL). In certain cases, an appropriate host immune response may inhibit parasite proliferation. Several lines of evidence obtained in vivo and in vitro indicate the important bio-protective role of the LL. For instance, the LL has been proposed to protect the GL from nitric oxide produced by periparasitic macrophages and dendritic cells, and also to prevent immune recognition by surrounding T cells. On the other hand, the high periparasitic NO production by peritoneal exsudate cells contributes to periparasitic immunosuppression, explaining why iNOS deficienct mice exhibit a significantly lower susceptibility towards experimental infection. The intense periparasitic granulomatous infiltration indicates a strong host-parasite interaction, and the involvement of cellular immunity in control of the metacestode growth kinetics is strongly suggested by experiments carried out in T cell deficient mouse strains. Carbohydrate components of the LL, such as Em2(G11) and Em492, as well as other parasite metabolites yield immunomodulatory effects that allow the parasite to survive in the host. I.e., the IgG response to the Em2(G11)-antigen takes place independently of alpha-beta+CD4+T cells, and in the absence of interactions between CD40 and CD40 ligand. Such parasite molecules also interfere with antigen presentation and cell activation, leading to a mixed Th1/Th2-type response at the later stage of infection. Furthermore, Em492 and other (not yet published) purified parasite metabolites suppress ConA and antigen-stimulated splenocyte proliferation. Infected mouse macrophages (AE-MØ) as antigen presenting cells (APC) exhibited a reduced ability to present a conventional antigen (chicken ovalbumin, C-Ova) to specific responder lymph node T cells when compared to normal MØ. As AE-MØ fully maintain their capacity to appropriately process antigens, a failure in T cell receptor occupancy by antigen-Ia complex or/and altered co-stimulatory signals can be excluded. Studying the status of accessory molecules implicated in T cell stimulation by MØ, it could be shown that B7-1 (CD80) and B7-2 (CD86) remained unchanged, whereas CD40 was down-regulated and CD54 (=ICAM-1) slightly up-regulated. FACS analysis of peritoneal cells revealed a decrease in the percentage of CD4+ and CD8+T cells in AE-infected mice. Taken together the obstructed presenting-activity of AE-MØ appeared to trigger an unresponsiveness of T cells leading to the suppression of their clonal expansion during the chronic phase of AE infection. Interesting information on the parasite survival strategy and potential can be obtained upon in vitro and in vivo treatment. Hence, we provided very innovative results by showing that nitazoxanide, and now also, respectively, new modified compounds may represent a useful alternative to albendazole. In the context of chemotherapeutical repression of parasite growth, we searched also for parasite molecules, whose expression levels correlate with the viability and growth activity of E. multilocularis metacestode. Expression levels of 14-3-3 and II/3-10, relatively quantified by realtime reverse transcription-PCR using a housekeeping gene beta-actin, were studied in permissive nu/nu and in low-permissive wild type BALB/c mice. At 2 months p.i., the transcription level of 14-3-3 was significantly higher in parasites actively proliferating in nu/nu mice compared to parasites moderately growing in wild type mice. Immunoblotting experiments confirmed at the protein level that 14-3-3 was over-expressed in parasites derived from nu/nu mice at 2 months p.i. In vitro-treatment of E. multilocularis with an anti-echinococcal drug nitazoxanide for a period of 8 days resulted in a significant decrease of both 14-3-3 and II/3-10 transcription levels,

Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial

PURPOSE: The European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada trial on temozolomide (TMZ) and radiotherapy (RT) in glioblastoma (GBM) has demonstrated that the combination of TMZ and RT conferred a significant and meaningful survival advantage compared with RT alone. We evaluated in this trial whether the recursive partitioning analysis (RPA) retains its overall prognostic value and what the benefit of the combined modality is in each RPA class. PATIENTS AND METHODS: Five hundred seventy-three patients with newly diagnosed GBM were randomly assigned to standard postoperative RT or to the same RT with concomitant TMZ followed by adjuvant TMZ. The primary end point was overall survival. The European Organisation for Research and Treatment of Cancer RPA used accounts for age, WHO performance status, extent of surgery, and the Mini-Mental Status Examination. RESULTS: Overall survival was statistically different among RPA classes III, IV, and V, with median survival times of 17, 15, and 10 months, respectively, and 2-year survival rates of 32%, 19%, and 11%, respectively (P < .0001). Survival with combined TMZ/RT was higher in RPA class III, with 21 months median survival time and a 43% 2-year survival rate, versus 15 months and 20% for RT alone (P = .006). In RPA class IV, the survival advantage remained significant, with median survival times of 16 v 13 months, respectively, and 2-year survival rates of 28% v 11%, respectively (P = .0001). In RPA class V, however, the survival advantage of RT/TMZ was of borderline significance (P = .054). CONCLUSION: RPA retains its prognostic significance overall as well as in patients receiving RT with or without TMZ for newly diagnosed GBM, particularly in classes III and IV.

The influence of the surgeon's and the hospital's caseload on survival and local recurrence after colorectal cancer surgery

BACKGROUND: Past studies have identified surgeon- and institution- related characteristics as prognostic factors in colorectal cancer surgery. The present work assesses the influence of the surgeon's and the hospital's caseload on long-term results of colorectal cancer surgery. METHODS: The data on 2706 patients from 2, randomized, colorectal cancer trials (Swiss Group for Clinical Cancer Research [SAKK] 40/81, SAKK 40/87) investigating adjuvant intraportal and systemic chemotherapy and 1 concurrent registration study (SAKK 40/88) were reviewed. A first analysis included 1809 eligible, nonmetastatic patients from all 3 studies. A subsequent subgroup analysis included 915 eligible patients from both randomized trials. Overall survival (OS), disease-free survival (DFS), and local recurrence (LR) were analyzed in multivariate models taking into account the possible effect of clustering. The main potential covariates were surgeon's annual caseload (>5 operations/year vs < or =5 operations/year), hospital's annual caseload (>26 operations/year vs < or =26 operations/year), tumor site, T stage, and nodal status. RESULTS: Primary analysis of all 3 studies combined found a high surgeon's caseload to be positively associated with OS (P = .025) and marginally with DFS (P = .058). Separate analysis for each trial, however, showed that a high surgeon's caseload was beneficial for outcome in both randomized trials but not in the registration study. A subgroup analysis of 915 patients with 376 rectal and 539 colonic primaries from both randomized trials, therefore, was performed. Neither age, gender, year of operation, adjuvant chemotherapy (intraportal vs systemic vs operation alone), hospital academic status (university vs non-university), training status of the surgeon (certified surgeon vs surgeon-in-training), nor inclusion in 1 of the 2 randomized trials (SAKK 40/81 vs SAKK 40/87) was a significant predictor of outcome. However, both high surgeon's and high hospital's annual caseloads were independent, beneficial prognostic factors for OS (P = .0003, P = .044) and DFS (P = .0008, P = .020), and marginally significant factors for LR (P = .057, P = .055). CONCLUSIONS: High surgeon's and hospital's annual caseloads are strong, independent prognostic factors for extending overall and disease-free survival and reducing the rate of local recurrence in 2 randomized colorectal cancer trials.

Are beta-blockers needed in patients receiving spironolactone for severe chronic heart failure? An analysis of the COPERNICUS study

BACKGROUND: The beneficial effects of beta-blockers and aldosterone receptor antagonists are now well established in patients with severe systolic chronic heart failure (CHF). However, it is unclear whether beta-blockers are able to provide additional benefit in patients already receiving aldosterone antagonists. We therefore examined this question in the COPERNICUS study of 2289 patients with severe CHF receiving the beta1-beta2/alpha1 blocker carvedilol compared with placebo. METHODS: Patients were divided post hoc into subgroups according to whether they were receiving spironolactone (n = 445) or not (n = 1844) at baseline. Consistency of the effect of carvedilol versus placebo was examined for these subgroups with respect to the predefined end points of all-cause mortality, death or CHF-related hospitalizations, death or cardiovascular hospitalizations, and death or all-cause hospitalizations. RESULTS: The beneficial effect of carvedilol was similar among patients who were or were not receiving spironolactone for each of the 4 efficacy measures. For all-cause mortality, the Cox model hazard ratio for carvedilol compared with placebo was 0.65 (95% CI 0.36-1.15) in patients receiving spironolactone and 0.65 (0.51-0.83) in patients not receiving spironolactone. Hazard ratios for death or all-cause hospitalization were 0.76 (0.55-1.05) versus 0.76 (0.66-0.88); for death or cardiovascular hospitalization, 0.61 (0.42-0.89) versus 0.75 (0.64-0.88); and for death or CHF hospitalization, 0.63 (0.43-0.94) versus 0.70 (0.59-0.84), in patients receiving and not receiving spironolactone, respectively. The safety and tolerability of treatment with carvedilol were also similar, regardless of background spironolactone. CONCLUSION: Carvedilol remained clinically efficacious in the COPERNICUS study of patients with severe CHF when added to background spironolactone in patients who were practically all receiving angiotensin-converting enzyme inhibitor (or angiotensin II antagonist) therapy. Therefore, the use of spironolactone in patients with severe CHF does not obviate the necessity of additional treatment that interferes with the adverse effects of sympathetic activation, specifically beta-blockade.

Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies

OBJECTIVE: To estimate the prognosis over 5 years of HIV-1-infected, treatment-naive patients starting HAART, taking into account the immunological and virological response to therapy. DESIGN: A collaborative analysis of data from 12 cohorts in Europe and North America on 20,379 adults who started HAART between 1995 and 2003. METHODS: Parametric survival models were used to predict the cumulative incidence at 5 years of a new AIDS-defining event or death, and death alone, first from the start of HAART and second from 6 months after the start of HAART. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. RESULTS: During 61 798 person-years of follow-up, 1005 patients died and an additional 1303 developed AIDS. A total of 10 046 (49%) patients started HAART either with a CD4 cell count of less than 200 cells/microl or with a diagnosis of AIDS. The 5-year risk of AIDS or death (death alone) from the start of HAART ranged from 5.6 to 77% (1.8-65%), depending on age, CD4 cell count, HIV-1-RNA level, clinical stage, and history of injection drug use. From 6 months the corresponding figures were 4.1-99% for AIDS or death and 1.3-96% for death alone. CONCLUSION: On the basis of data collected routinely in HIV care, prognostic models with high discriminatory power over 5 years were developed for patients starting HAART in industrialized countries. A risk calculator that produces estimates for progression rates at years 1 to 5 after starting HAART is available from www.art-cohort-collaboration.org.

CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials

BACKGROUND: We evaluated the ability of CA15-3 and alkaline phosphatase (ALP) to predict breast cancer recurrence. PATIENTS AND METHODS: Data from seven International Breast Cancer Study Group trials were combined. The primary end point was relapse-free survival (RFS) (time from randomization to first breast cancer recurrence), and analyses included 3953 patients with one or more CA15-3 and ALP measurement during their RFS period. CA15-3 was considered abnormal if >30 U/ml or >50% higher than the first value recorded; ALP was recorded as normal, abnormal, or equivocal. Cox proportional hazards models with a time-varying indicator for abnormal CA15-3 and/or ALP were utilized. RESULTS: Overall, 784 patients (20%) had a recurrence, before which 274 (35%) had one or more abnormal CA15-3 and 35 (4%) had one or more abnormal ALP. Risk of recurrence increased by 30% for patients with abnormal CA15-3 [hazard ratio (HR) = 1.30; P = 0.0005], and by 4% for those with abnormal ALP (HR = 1.04; P = 0.82). Recurrence risk was greatest for patients with either (HR = 2.40; P < 0.0001) and with both (HR = 4.69; P < 0.0001) biomarkers abnormal. ALP better predicted liver recurrence. CONCLUSIONS: CA15-3 was better able to predict breast cancer recurrence than ALP, but use of both biomarkers together provided a better early indicator of recurrence. Whether routine use of these biomarkers improves overall survival remains an open question.

A systematic review of the survival and complication rates of resin-bonded bridges after an observation period of at least 5 years

OBJECTIVES: The objectives of this systematic review were to assess the 5-year survival of resin-bonded bridges (RBBs) and to describe the incidence of technical and biological complications. METHODS: An electronic Medline search complemented by manual searching was conducted to identify prospective and retrospective cohort studies on RBBs with a mean follow-up time of at least 5 years. Patients had to have been examined clinically at the follow-up visit. Assessment of the identified studies and data extraction were performed independently by two reviewers. Failure and complication rates were analyzed using random-effects Poissons regression models to obtain summary estimates of 5-year proportions. RESULTS: The search provided 6110 titles and 214 abstracts. Full-text analysis was performed for 93 articles, resulting in 17 studies that met the inclusion criteria. Meta-analysis of these studies indicated an estimated survival of RBBs of 87.7% (95% confidence interval (CI): 81.6-91.9%) after 5 years. The most frequent complication was debonding (loss of retention), which occurred in 19.2% (95% CI: 13.8-26.3%) of RBBs over an observation period of 5 years. The annual debonding rate for RBBs placed on posterior teeth (5.03%) tended to be higher than that for anterior-placed RBBs (3.05%). This difference, however, did not reach statistical significance (P=0.157). Biological complications, like caries on abutments and RBBs lost due to periodontitis, occurred in 1.5% of abutments and 2.1% of RBBs, respectively. CONCLUSION: Despite the high survival rate of RBBs, technical complications like debonding are frequent. This in turn means that a substantial amount of extra chair time may be needed following the incorporation of RBBs. There is thus an urgent need for studies with a follow-up time of 10 years or more, to evaluate the long-term outcomes.

A systematic review of the 5-year survival and complication rates of implant-supported single crowns

OBJECTIVES: The objective of this systematic review was to assess the 5-year survival of implant-supported single crowns (SCs) and to describe the incidence of biological and technical complications. METHODS: An electronic MEDLINE search complemented by manual searching was conducted to identify prospective and retrospective cohort studies on SCs with a mean follow-up time of at least 5 years. Failure and complication rates were analyzed using random-effects Poisson's regression models to obtain summary estimates of 5-year proportions. RESULTS: Twenty-six studies from an initial yield of 3601 titles were finally selected and data were extracted. In a meta-analysis of these studies, survival of implants supporting SCs was 96.8% [95% confidence interval (CI): 95.9-97.6%] after 5 years. The survival rate of SCs supported by implants was 94.5% (95% CI: 92.5-95.9%) after 5 years of function. The survival rate of metal-ceramic crowns, 95.4% (95% CI: 93.6-96.7%), was significantly (P=0.005) higher than the survival rate, 91.2% (95% CI: 86.8-94.2%), of all-ceramic crowns. Peri-implantitis and soft tissue complications occurred adjacent to 9.7% of the SCs and 6.3% of the implants had bone loss exceeding 2 mm over the 5-year observation period. The cumulative incidence of implant fractures after 5 years was 0.14%. After 5 years, the cumulative incidence of screw or abutment loosening was 12.7% and 0.35% for screw or abutment fracture. For supra-structure-related complications, the cumulative incidence of ceramic or veneer fractures was 4.5%. CONCLUSION: It can be concluded that after an observation period of 5 years, high survival rates for implants and implant-supported SCs can be expected. However, biological and particularly technical complications are frequent.