Hepatic ischemia reperfusion injury: Contemporary perspectives on pathogenic mechanisms and basis for hepatoprotection-the good, bad and deadly

Hepatic ischemia reperfusion (IR) injury is an important clinical problem complicating liver surgery and transplantation. The pathogenesis underlying reperfusion injury after warm ischemia is complex, encompassing a multitude of different cell types and signalling mechanisms innate and/or mobilized to the liver. Since the author's 2003 review in the Journal, considerable progress has been achieved in enhancing our understanding of some of the pathogenic pathways and crucial mediators of hepatic inflammation such as the heme oxygenase system, CXC chemokines, Toll-like receptors as well as the mode of parenchymal cell death in IR injury. A better appreciation of these mechanisms will accelerate efforts in designing optimal interventions to prevent hepatic IR injury and improve outcomes after liver transplantation.     

Use of a treatment optimization algorithm involving statin-ezetimibe combination aids in achievement of guideline-based low-density lipoprotein targets in patients with dyslipidemia at high vascular risk Guideline-based Undertaking to Improve Dyslipidemia Management in Canada (GUIDANC)

Background

Despite the well-established benefits of strategies to reduce low-density lipoprotein cholesterol (LDL-C), many patients fail to achieve the guideline recommended targets. The objective of this study was to evaluate the impact of an enhanced 26-week algorithm-based treatment optimization strategy, involving titration of statin monotherapy and/or combination therapy with statin and ezetimibe, on achievement of guideline-based LDL-C targets in patients at high risk for atherosclerotic disease.

Methods and Results

In this national (172-physician) quality enhancement research initiative involving 2334 Canadian men and women (median age, 65 years) at high vascular risk who were not at the guideline-recommended LDL-C target despite statin therapy, 36.6% and 45.5% of patients achieved an LDL-C <2.0 mmol/L at visit 2 and visit 3, respectively, using the treatment optimization algorithm. The percentage of patients achieving the 2009 Canadian Cardiovascular Society (CCS)-recommended target of either LDL-C <2.0 mmol/L or a 50% or greater reduction from baseline increased from 6.8% at visit 1 to 43.3% at visit 2 and to 52.1% at visit 3. Attainment of LDL-C targets increased significantly with consecutive visits (P < .001). Use of ezetimibe in combination with statin therapy was associated with greater target achievement.

Conclusions

Use of a structured treatment optimization algorithm, based on titration of statin dosages and incorporation of ezetimibe therapy when required, enabled the majority of high-risk patients to achieve guideline-recommended targets, thereby narrowing the care gap that exists in dyslipidemia management.     

The clinico-radiological spectrum of isolated cortical vein thrombosis

Isolated cortical vein thrombosis (ICVT) in the absence of sinus or great venous involvement is rare. Various MRI sequences have been proposed for diagnostic accuracy, although follow-up data are limited. The optimal management strategy remains uncertain. Patients with ICVT treated between 2006 and 2008 were retrospectively studied. Diagnostic and follow-up neuroimaging were reviewed independently, and we evaluated their treatment and outcomes. Five patients (mean age 41 years; range, 25–54 years) were included. All presented with seizures. Focal neurological deficits were noted in one patient only. T2^∗ susceptibility-weighted MRI abnormalities were observed in all patients. T2-weighted parenchymal hyperintensities involving the cortical–subcortical regions around the ICVT had completely resolved on follow-up scans. Clinical outcomes were uniformly good, despite variable treatment strategies. We observed significant, yet reversible, parenchymal T2-weighted MRI lesions in our patients with ICVT. Follow-up clinical and radiological studies demonstrate recovery independent of treatment regimes. T2^∗-weighted MRI was found to be a useful diagnostic tool and might improve diagnostic accuracy in carefully selected patients with new-onset seizures.     

Obesity in pregnancy: a major healthcare issue

The prevalence of maternal obesity is rising, up to 20% in some antenatal clinics, in line with the prevalence of obesity in the general population. Maternal obesity poses significant risks for all aspects of pregnancy. There are risks to the mother with increased maternal mortality, pre-eclampsia, diabetes and thromboembolic disorders. There is increased perinatal mortality, macrosomia and congenital malformation. The obstetric management, with increased operative delivery rate, and increased difficulty of anaesthesia, carry risk for the obese mother. Long term complications associated with maternal obesity include increased likelihood of maternal weight retention and exacerbation of obesity. This review aims to discuss these risks with a view to suggesting management to ensure the best outcome for both the mother and the offspring.     

Cytopathological analysis of vitreous in intraocular lymphoma

OBJECTIVE: To describe the cytopathological method used in the analysis of vitreous samples in the diagnosis of primary intraocular lymphoma (PIOL). PARTICIPANTS: Seven patients with refractory posterior uveitis referred to a regional ocular inflammatory service were diagnosed as having PIOL between 1999 and 2006. METHODS: Clinical features of the uveitis and cytopathological preparation of the samples were described. All patients underwent vitrectomy and samples were placed in formal saline or prepared fresh. Following paraffin embedding generating a cell block, immunostaining, and polymerase chain reactions were performed. RESULTS: Five women (71.4%) and two men (28.6%) (mean age 67.7 years) were included. Five patients had diagnostic vitrectomy performed within 6 months of presentation, but in two patients diagnosis was delayed up to 2 years. Uveitis was bilateral in two patients. Cytologic and immunohistochemical staining prepared from the vitreous specimens showed PIOL in all patients, and PCR displayed single band of immunoglobulin heavy chain rearrangement in five out of six samples tested. CONCLUSIONS: Diagnosis of PIOL is difficult due to small volume of sample with low number of malignant cells and inadequate preparation of samples. Our method of analysis with fresh samples together with immunohistochemistry and PCR analysis demonstrates a high yield of diagnosis reducing diagnostic delay.     

A polycaprolactone-β-tricalcium phosphate–heparan sulphate device for cranioplasty

Background

Cranioplasty is a surgical procedure used to treat a bone defect or deformity in the skull. To date, there is little consensus on the standard-of-care for graft materials used in such a procedure. Graft materials must have sufficient mechanical strength to protect the underlying brain as well as the ability to integrate and support new bone growth. Also, the ideal graft material should be individually customized to the contours of the defect to ensure a suitable aesthetic outcome for the patient.

Prosthetic intervention in the era of microvascular reconstruction of the mandible--a retrospective analysis of functional outcome

PURPOSE: The purpose of this retrospective study was to compare the functional outcomes of patients who had mandibular resection and reconstruction with and without prosthetic intervention, and to identify predictive factors that may have an impact on functional outcomes. MATERIALS AND METHODS: Two hundred twenty head and neck cancer patients who had undergone mandibular resection and reconstruction with at least 6 months of postoperative convalescence formed the basis of this retrospective review. Patients who did not receive prosthetic intervention formed group I (n = 142); those who received prosthetic intervention formed group II (n = 78). Functional outcomes were measured using four individual assessments (nutritional status, swallowing, masticatory performance, and speech) and one that combined the information from these assessments, the global measure of functional outcome (GMFO). Statistical analyses were used to compare the baseline characteristics and functional outcome between groups I and II and to analyze independent predictors for GMFO. RESULTS: Of the 220 patients reviewed, 78 (35%) had prosthetic intervention; group II patients had better individual functional outcome measures and GMFO. Use of a prosthesis remained associated with GMFO after controlling for other significant predictors; other independent predictors were xerostomia, number of remaining mandibular teeth, number of tooth-to-tooth contacts, type of reconstruction, flap interference, and tongue defect. Patients who had fewer mandibular teeth and received a smaller prosthesis had better overall outcome than patients who received a larger prosthesis. CONCLUSION: Patients who had prosthetic intervention after mandibular reconstruction had significantly better functional outcomes than patients who did not receive prosthetic intervention, even after adjusting for confounding variables.