Ranibizumab for retinal angiomatous proliferation

Graefe's Archive for Clinical and Experimental Ophthalmology -     

Developments in surgical revascularization to achieve improved morbidity and mortality

Coronary artery bypass graft surgery remains the main treatment modality for multivessel coronary artery disease and has consistently been demonstrated to have significantly lower rates of major adverse cardiac and cerebrovascular events in comparison to percutaneous coronary intervention. In this article we will explore the advances over time and the recent refinements in the techniques of surgical revascularization and how these contribute to the superior outcome profile associated with coronary artery bypass graft surgery. These include the current outcome status of coronary artery bypass grafting; the major landmark trials, registries and meta-analyses comparing coronary artery bypass grafting and percutaneous coronary intervention; the developments in coronary artery disease lesion classification; the techniques for the physiological assessment of coronary artery lesions; bypass grafting using arterial conduits; the role of off-pump coronary artery surgery; the outcomes of reoperative surgery; hybrid techniques for coronary revascularization; minimally invasive coronary artery surgery and finally robotic surgery.     

Variations in the Application of Various Perfusion Technologies in Great Britain and Ireland—A National Survey

In an attempt to reduce the negative sequelae of cardiopulmonary bypass (CPB), a variety of new technologies have been created. This study investigates variations in the application of these technologies throughout Great Britain and Ireland (GB & I). All perfusion departments within GB & I were surveyed about equipment and technologies used in CPB. Eighty‐five percent of units use a standard arterial line filter in all cases. Forty percent of units occasionally use leukocyte‐depleting filters in various sites within the circuit. Sixteen percent always use some element of heparin‐bonded circuit, but 62% never use them. Twenty‐five percent use solely rotary pumps, 18% use solely centrifugal pumps, and 56% use both. Finally, 20% are now using minimal extracorporeal circulation in certain clinical scenarios. These decisions are most frequently affected by clinician preference and cost. This survey has highlighted significant variation in the utilization of various technologies used in CPB. While some variation between centers is to be expected, as innovative technologies are adopted at varying rates, surveys such as this are useful for alerting clinicians to gaps between evidence‐based knowledge and clinical practice.     

The neurocognitive enhancement of surgeons: an ethical perspective

Neurocognitive enhancement is a rapidly expanding scientific field. The vast ethical implications of this developing field for surgical practice have yet to be considered within the literature. This article outlines the reasons surgeons may, in the near future, consider using neurocognitive enhancement and addresses the resulting significant ethical implications of this. We do not seek to support or denounce the potential role of neurocognitive enhancement in surgeons, but to stimulate a debate, which, with ever-increasing levels of stimulant use in schools and colleges, and with a pharmaceutical industry driving the creation of new neuroactive products, has now become a necessity.     

Does Re-operation have an Effect on Outcome Following Heart Transplantation?

OBJECTIVE: Previous cardiac operation has traditionally been considered as a potential risk factor for patients undergoing heart transplantation. This study aimed to evaluate the outcome of patients undergoing heart transplantation as a second cardiac procedure and compare it with primary heart transplantation, using meta-analytical methodology. METHODS: A literature search was undertaken to identify relevant comparative studies. Outcomes of interest were classified into four categories: (a) intra-operative times; (b) post-operative outcomes; (c) resources; (d) actuarial outcomes. RESULTS: Seven studies matched the selection criteria, reporting on 1004 patients. Six hundred and twenty-three had transplantation as primary operation and 381 as re-operation. The 1-year, 2-year, and 5-year mortality were similar for the two groups (HR=0.85, p=0.54; HR=0.97, p=0.88; and HR=1.04, p=0.92, respectively). Total operative, cold-ischaemic, by-pass, and cross-clamp times were significantly longer for the re-operation group by 59.44 (p<0.001), 14.62 (p=0.05), 25.24 (p<0.001), and 7.93 (p<0.001)min, respectively. Both ICU and hospital stay were longer for the re-operation group but only the former was statistically significant (WMD=1.37; p=0.02). Post-operative complications were similar, except re-exploration rate and blood transfusion requirement, which were higher in the re-operation group (OR=3.51; p<0.001 and WMD=2.21; p<0.001, respectively). CONCLUSIONS: Heart transplantation following previous cardiac operation is technically demanding requiring longer operative times compared to primary heart transplantation. It does not, however, add a significant risk to the survival of the patient, and associated morbidity is not significantly compromised.     

Multi-detector computed tomography in coronary artery bypass graft assessment: a meta-analysis

Multi-detector computed tomography (MDCT) has become an alternative to coronary angiography in diagnosis of graft occlusion and stenosis after coronary artery bypass. A literature search was performed for studies comparing angiography to 8-slice, 16-slice, and 64-slice MDCT in the assessment of coronary grafts. In assessing occlusion, 14 studies produced pooled sensitivity of 97.6%, specificity of 98.5%, diagnostic odds ratio of 934.2, area under the curve of 0.996, and Q* of 0.977. Ninety-six percent of all grafts were visualized for occlusion assessment. Beta blockers, symptomatic status, and postoperative period did not significantly affect diagnostic performance. Stenosis assessment produced sensitivity of 88.7% and specificity of 97.4%. Eighty-eight percent of patent grafts could be assessed for stenosis. The diagnostic accuracy of MDCT approaches angiography for diagnosing graft occlusion and stenosis in patients with venous and arterial coronary bypass grafts. Our findings show that cardiac surgeons will need to interpret MDCT images of both native and grafted vessels soon in preparation for primary or re-do coronary bypass grafting procedures.     

Studies of genomic copy number changes in human cancers reveal signatures of DNA replication stress

Human cancers are characterized by the presence of genomic instability. Recently, two studies have catalogued the presence of a specific class of genomic aberrations, large deletions and insertions, in a few thousand human cancers and reported that most of the prevalent recurrent focal deletions targeted common fragile sites and large genes. In various experimental systems, deletions in common fragile sites and large genes have been linked to the presence of DNA replication stress. Thus, taken together, these results suggest the presence of DNA replication stress in human cancers, consistent with the recently proposed oncogene-induced DNA damage model for cancer development.     

Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis

Apoptosis has been shown to be a significant form of cell loss in many diseases. Detachment of photoreceptors from the retinal pigment epithelium, as seen in various retinal disorders, causes photoreceptor loss and subsequent vision decline. Although caspase-dependent apoptotic pathways are activated after retinal detachment, caspase inhibition by the pan-caspase inhibitor Z-VAD fails to prevent photoreceptor death; thus, we investigated other pathways leading to cell loss. Here, we show that receptor interacting protein (RIP) kinase-mediated necrosis is a significant mode of photoreceptor cell loss in an experimental model of retinal detachment and when caspases are inhibited, RIP-mediated necrosis becomes the predominant form of death. RIP3 expression, a key activator of RIP1 kinase, increased more than 10-fold after retinal detachment. Morphological assessment of detached retinas treated with Z-VAD showed decreased apoptosis but significantly increased necrotic photoreceptor death. RIP1 kinase inhibitor necrostatin-1 or Rip3 deficiency substantially prevented those necrotic changes and reduced oxidative stress and mitochondrial release of apoptosis-inducing factor. Thus, RIP kinase-mediated programmed necrosis is a redundant mechanism of photoreceptor death in addition to apoptosis, and simultaneous inhibition of RIP kinases and caspases is essential for effective neuroprotection and may be a novel therapeutic strategy for treatment of retinal disorders.