A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ...ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.
Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress.
The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Objectives Adequate hepatic arterial (HA) flow to the bile duct is essential in liver transplantation. This study was conducted to determine if the ratio of directly measured HA flow to ...weight is related to the occurrence of biliary complications after deceased donor liver transplantation. Methods A retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. Rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with HA flow by body weight of, respectively, <5 ml/min/kg ( n = 884) and ≥5 ml/min/kg ( n = 1800). Results Patients with a lower ratio of HA flow to weight had higher body weight (92 kg versus 76 kg; P < 0.001) and lower HA flow (350 ml/min versus 550 ml/min; P < 0.001). A lower ratio of HA flow to weight was associated with higher rates of biliary complications at 2 months, 6 months and 12 months (19.8%, 28.2% and 31.9% versus 14.8%, 22.4% and 25.8%, respectively; P < 0.001). Conclusions A ratio of HA flow to weight of < 5 ml/min/kg is associated with higher rates of biliary complications. This ratio may be a useful parameter for application in the prevention and early detection of biliary complications.
Efficient production of definitive endoderm from embryonic stem (ES) cells opens doors to the possibilities of differentiation of endoderm-derived tissues such as the intestines, pancreas, and liver ...that could address the needs of people with chronic diseases involving these organs. The lessons learned from developmental biology have contributed significantly to in vitro differentiation of definitive endoderm. Gastrulation, a process that results in the production of all three embryonic germ cell layers, definitive endoderm, mesoderm, and ectoderm, is an important step in embryonic development. Gastrulation occurs as a result of the events that are orchestrated by the signaling pathways involving Nodal, FGF, Wnt, and BMP. Understanding these signaling pathways has led to the introduction of key ingredients such as Activin A, FGF, Wnt, and BMP to the differentiation protocols that have been able to produce definitive endoderm from ES cells. Efficient production of definitive endoderm needs to meet the specific criteria that include (a) increase in the production of markers of definitive endoderm such as Sox 17, FOXA2, GSC, and Mixl1; (b) decrease in the production of markers of primitive/visceral/parietal endoderm, Sox 7 and OCT4; and (c) decrease in the mesoderm markers (Brachyury, MEOX) and ectoderm markers (Sox1 and ZIC1).
Colorectal cancer is genetically heterogeneous. Tumors in some patients have defects in mismatch DNA repair. These tumors have a high level of mutations that can lead to immune recognition. In a ...group of patients with microsatellite-unstable tumors, pembrolizumab led to longer progression-free survival and was less toxic than standard chemotherapy.
When implemented in several common surgical procedures, clinical pathways have been reported to reduce costs and resource utilization, while maintaining or improving patient care. However, there is ...little data to support their use in more complex surgery. The objective of this study was to determine the effects of clinical pathway implementation in patients undergoing elective pancreaticoduodenectomy (PD) on cost and resource utilization.
Outcome data from before and after the development of a clinical pathway were analyzed. The clinical pathway standardized the preoperative outpatient care, critical care, and postoperative floor care of patients who underwent PD. An independent department determined total costs for each patient, which included all hospital and physician costs, in a blinded review. Outcomes that were examined included perioperative mortality, postoperative morbidity, length of stay, readmissions, and postoperative clinic visits.
From January, 1996 to December, 1998, 148 consecutive patients underwent PD or total pancreatectomy; 68 before pathway development (PrePath) and 80 after pathway implementation (PostPath). There were no significant differences in patient demographics, comorbid conditions, underlying diagnosis, or use of neoadjuvant therapy between the two groups. Mean total costs were significantly reduced in PostPath patients compared with PrePath patients ($36,627 vs. $47,515; P = .003). Similarly, mean length of hospital stay was also significantly reduced in PostPath patients (13.5 vs. 16.4 days; P = .001). The total cost differences could not be attributed solely to differences in room and board costs. Cost and length-of-stay differences remained when outliers were excluded from the analysis. Despite these findings, there were no significant differences between PrePath and PostPath patients in terms of perioperative mortality (3% vs. 1%), readmissions within 1 month of discharge (15% vs. 11%), or mean number of clinic visits within 90 days of discharge (3.3 vs. 3.4 visits).
The establishment of a clinical pathway for PD patients dramatically reduced costs and resource utilization without any apparent detrimental effect on quality of patient care. These findings support the implementation of clinical pathways for PD patients, as well as investigation into pathway care for other complex surgical procedures.
Summary Background Pazopanib, a multitargeted tyrosine kinase inhibitor, has single-agent activity in patients with advanced non-adipocytic soft-tissue sarcoma. We investigated the effect of ...pazopanib on progression-free survival in patients with metastatic non-adipocytic soft-tissue sarcoma after failure of standard chemotherapy. Methods This phase 3 study was done in 72 institutions, across 13 countries. Patients with angiogenesis inhibitor-naive, metastatic soft-tissue sarcoma, progressing despite previous standard chemotherapy, were randomly assigned by an interactive voice randomisation system in a 2:1 ratio in permuted blocks (with block sizes of six) to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over. Patients, investigators who gave the treatment, those assessing outcomes, and those who did the analysis were masked to the allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat. The trial is registered with ClinicalTrials.gov , number NCT00753688. Findings 372 patients were registered and 369 were randomly assigned to receive pazopanib (n=246) or placebo (n=123). Median progression-free survival was 4·6 months (95% CI 3·7–4·8) for pazopanib compared with 1·6 months (0·9–1·8) for placebo (hazard ratio HR 0·31, 95% CI 0·24–0·40; p<0·0001). Overall survival was 12·5 months (10·6–14·8) with pazopanib versus 10·7 months (8·7–12·8) with placebo (HR 0·86, 0·67–1·11; p=0·25). The most common adverse events were fatigue (60 in the placebo group 49% vs 155 in the pazopanib group 65%), diarrhoea (20 16% vs 138 58%), nausea (34 28% vs 129 54%), weight loss (25 20% vs 115 48%), and hypertension (8 7% vs 99 41%). The median relative dose intensity was 100% for placebo and 96% for pazopanib. Interpretation Pazopanib is a new treatment option for patients with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy. Funding GlaxoSmithKline.
Introduction: Adrenal cortical carcinoma (ACC) is rare, and presenting symptoms vary widely depending on functional or non-functional endocrine status. These tumors are most commonly treated with ...surgical resection and postoperative mitotane administration. Case Report: This is an unusual presentation of a 23- year-old female with no significant past medical history, admitted to the hospital with syncope and dyspnea. Computed tomography angiography (CTA) demonstrated extensive bilateral pulmonary embolisms, with an associated 16-cm assumed right lobe hepatic mass with suprahepatic vena cava tumor thrombus extension beyond the level of the hepatic veins. The patient underwent a complete resection of the right adrenal mass, with inferior vena cava resection, thrombectomy, and placement of caval interposition graft without the use of bypass. Pathology was consistent with adrenal cortical carcinoma. Conclusion: This case of an adrenal cortical carcinoma, with a rare presentation of bilateral pulmonary embolisms, was treated with a surgical R0 resection. This included a right adrenalectomy with IVC resection and interposition graft. Tumors with IVC involvement and tumor thrombus can be treated with surgical resection and IVC grafting, without the use of bypass.
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