Intravascular ultrasound aids in the performance of endovascular repair of abdominal aortic aneurysm

AbstractPurpose: The purpose of this retrospective review was to assess the accuracy of aortic measurements with intravascular ultrasound scan (IVUS) compared with computed tomographic (CT) scan and to assess the role of IVUS in the performance of endovascular repair of abdominal aortic aneurysms (AAAs). Methods: Seventy-eight patients undergoing repair of AAA with the AneuRx stent graft (Medtronic AVE, Inc, Santa Rosa, Calif) underwent measurement with CT scan and IVUS. The initial selection of stent graft size was made on the basis of the CT scan measurements, but the final decision for size was made on the basis of the IVUS measurements. Standard measurements of a phantom tube obtained with IVUS, CT scan, and digital caliper were also compared. Results: IVUS measurements of the phantom standard agreed closely with CT scan measurements. However, stent graft size initially selected with CT measurement was altered in 28% of cases on the basis of intraoperative IVUS measurements. No type I endoleaks were encountered in our series, and no aortic cuffs were necessary for endoleak repair. Conclusion: IVUS accurately measures the aorta for selection of stent grafts for endovascular repair of AAA and may prevent type I endoleaks and remedial procedures for their repair. (J Vasc Surg 2003;37:615-8

A prospective observational study of on-treatment plasma homocysteine levels as a biomarker of toxicity, depression and vitamin supplementation lead-in time pre pemetrexed, in patients with non-small cell lung cancer and malignant mesothelioma

OBJECTIVES: Vitamin supplementation reduces pemetrexed toxicity. Raised plasma homocysteine reflects deficiency in vitamin B12 and folate, and is suppressed by supplementation. This observational study of 112 patients receiving pemetrexed-based chemotherapy assessed homocysteine levels after 3 weeks of vitamin supplementation, hypothesising high levels would correlate with ongoing deficiency, thus increased toxicity. MATERIAL AND METHODS: Primary endpoint was the composite of proportion of patients with treatment delay/ dose reduction/ drug change or hospitalisation during the first six weeks of chemotherapy, comparing those with normal plasma homocysteine (successfully supplemented, SS) and those with high homocysteine (unsuccessfully supplemented, USS). Secondary endpoints included toxicity and analyses for depression. Post-hoc analysis examined correlation between interval of vitamin and folate supplementation and pemetrexed on primary endpoint and grade 3-4 toxicities. RESULTS: Eighty-four patients (84%) were successfully supplemented (SS group). The proportion of patients undergoing a treatment delay/ dose reduction/ drug change or hospitalisation in SS group was 44.0% (95% confidence interval [CI] 33.2%-55.3%) and in USS group was 18.8% (95% CI 4.0%-45.6%) (p = 0.09). Twelve percent of patients gave a past history of depression however 66% of patients had an on study Hospital Anxiety and Depression (HAD) score of >7. Supplementation status was not associated with depression. The median overall survival (OS) was 11.8 months (95% CI 8.6-16.5) in the SS group and 8.8 months (95% CI 6.6-16.2) in the US group (p = 0.5). The number of days (<7 or ≥ 7 days) between vitamin B12 and folate initiation and pemetrexed administration, had no effect on the primary endpoint and grade 3-4 toxicities. CONCLUSION: On-treatment homocysteine levels were not a biomarker of toxicity or depression. Standard vitamin supplementation is adequate in the majority of patients receiving pemetrexed. High HAD score were noted in this population giving an opportunity for mental health intervention. The lead-in time for vitamin supplementation can be short

Comparative PCET Study of a Donor-Acceptor Pair Linked by Ionized and Nonionized Asymmetric Hydrogen-Bonded Interfaces

A Zn(II) porphyrin-amidinium is the excited state electron donor (D) to a naphthalene diimide acceptor (A) appended with either a carboxylate or sulfonate functionality. The two-point hydrogen bond (---[H+]---) formed between the amidinium and carboxylate or sulfonate establishes a proton-coupled electron transfer (PCET) pathway for charge transfer. The two D---[H+]---A assemblies differ only by the proton configuration within the hydrogen bonding interface. Specifically, the amidinium transfers a proton to the carboxylate to form a non-ionized amidine-carboxylic acid two-point hydrogen network whereas the amidinium maintains both protons when bound to the sulfonate functionality forming an ionized amidinium-sulfonate two-point hydrogen network. These two interface configurations within the dyads thus allow for a direct comparison of PCET kinetics for the same donor and acceptor juxtaposed by an ionized and non-ionized hydrogen-bonded interface. Analysis of PCET kinetics ascertained from transient absorption and transient emission spectroscopy reveal that the ionized interface is more strongly impacted by the local solvent environment, thus establishing that the initial static configuration of the proton interface is a critical determinant to the kinetics of PCET.Chemistry and Chemical Biolog

Targeting β-catenin in acute myeloid leukaemia: past, present, and future perspectives

Acute myeloid leukaemia (AML) is an aggressive disease of the bone marrow with a poor prognosis. Evidence suggests long established chemotherapeutic regimens used to treat AML are reaching the limits of their efficacy, necessitating the urgent development of novel targeted therapies. Canonical Wnt signalling is an evolutionary conserved cascade heavily implicated in normal developmental and disease processes in humans. For over 15 years it's been known that the central mediator of this pathway, β-catenin, is dysregulated in AML promoting the emergence, maintenance, and drug resistance of leukaemia stem cells (LSC). Yet, despite this knowledge, and subsequent studies demonstrating the therapeutic potential of targeting Wnt activity in haematological cancers, β-catenin inhibitors have not yet reached the clinic. The aim of this review is to summarise the current understanding regarding the role and mechanistic dysregulation of β-catenin in AML and assess the therapeutic merit of pharmacologically targeting this molecule, drawing on lessons from other disease contexts