Comparative effectiveness and safety of image guidance systems in surgery: a preclinical randomised study.

BACKGROUND: Over the past decade image guidance systems have been widely adopted in specialties such as neurosurgery and otorhinolaryngology. Nonetheless, the evidence supporting the use of image guidance systems in surgery remains limited. New augmented reality systems offer the possibility of enhanced operating room workflow compared with existing triplanar image displays, but recent studies have highlighted several concerns, particularly the risk of inattentional blindness and impaired depth perception. The aim of this study was to compare simultaneously the effectiveness and safety of various image guidance systems against standard surgery. METHODS: In this preclinical randomised study design 50 novice surgeons were allocated to no image guidance, triplanar display, always-on solid overlay, always-on wire mesh overlay, or on-demand inverse realism overlay. Each participant was asked to identify a basilar tip aneurysm in a validated model head. The primary outcomes were time to task completion, and tool path length. The secondary outcomes were recognition of an unexpected finding (a surgical clip) and subjective depth perception (using a Likert scale). FINDINGS: Surgeons' time to task completion and tool path length were significantly lower in groups using any form of image guidance than in groups with no image guidance (p<0·001 and p=0·003, respectively). The tool path distance was also lower in groups using augmented reality than in those using triplanar display (p=0·010). Always-on solid overlay resulted in the greatest inattentional blindness (20% recognition of unexpected finding by all surgeons). Wire mesh and on-demand overlays mitigated but did not negate inattentional blindness, and were comparable with triplanar display (40% recognition of unexpected finding in all groups). Wire mesh and inverse realism overlays also resulted in better subjective depth perception than always-on solid overlay (p=0·031 and p=0·008, respectively). INTERPRETATION: This study suggests that new augmented reality platforms incorporating always-on wire mesh and on-demand inverse realism might improve surgical performance, at least in novice surgeons. All image display modalities, including existing triplanar display, carry a risk of inattentional blindness. FUNDING: Wellcome Trust.

Improved prediction of postoperative pediatric cerebellar mutism syndrome using an artificial neural network.

BACKGROUND: Postoperative pediatric cerebellar mutism syndrome (pCMS) is a common but severe complication that may arise following the resection of posterior fossa tumors in children. Two previous studies have aimed to preoperatively predict pCMS, with varying results. In this work, we examine the generalization of these models and determine if pCMS can be predicted more accurately using an artificial neural network (ANN). METHODS: An overview of reviews was performed to identify risk factors for pCMS, and a retrospective dataset was collected as per these defined risk factors from children undergoing resection of primary posterior fossa tumors. The ANN was trained on this dataset and its performance was evaluated in comparison to logistic regression and other predictive indices via analysis of receiver operator characteristic curves. The area under the curve (AUC) and accuracy were calculated and compared using a Wilcoxon signed-rank test, with P < .05 considered statistically significant. RESULTS: Two hundred and four children were included, of whom 80 developed pCMS. The performance of the ANN (AUC 0.949; accuracy 90.9%) exceeded that of logistic regression (P < .05) and both external models (P < .001). CONCLUSION: Using an ANN, we show improved prediction of pCMS in comparison to previous models and conventional methods.

REV1 restrains DNA polymerase zeta to ensure frame fidelity during translesion synthesis of UV photoproducts in vivo.

Exposure to ultraviolet light induces a number of forms of damage in DNA, of which (6-4) photoproducts present the most formidable challenge to DNA replication. No single DNA polymerase has been shown to bypass these lesions efficiently in vitro suggesting that the coordinate use of a number of different enzymes is required in vivo. To further understand the mechanisms and control of lesion bypass in vivo, we have devised a plasmid-based system to study the replication of site-specific T-T(6-4) photoproducts in chicken DT40 cells. We show that DNA polymerase zeta is absolutely required for translesion synthesis (TLS) of this lesion, while loss of DNA polymerase eta has no detectable effect. We also show that either the polymerase-binding domain of REV1 or ubiquitinated PCNA is required for the recruitment of Polzeta as the catalytic TLS polymerase. Finally, we demonstrate a previously unappreciated role for REV1 in ensuring bypass synthesis remains in frame with the template. Our data therefore suggest that REV1 not only helps to coordinate the delivery of DNA polymerase zeta to a stalled primer terminus but also restrains its activity to ensure that nucleotides are incorporated in register with the template strand.

Improved Prediction of Surgical Resectability in Patients with Glioblastoma using an Artificial Neural Network.

In managing a patient with glioblastoma (GBM), a surgeon must carefully consider whether sufficient tumour can be removed so that the patient can enjoy the benefits of decompression and cytoreduction, without impacting on the patient's neurological status. In a previous study we identified the five most important anatomical features on a pre-operative MRI that are predictive of surgical resectability and used them to develop a simple, objective, and reproducible grading system. The objective of this study was to apply an artificial neural network (ANN) to improve the prediction of surgical resectability in patients with GBM. Prospectively maintained databases were searched to identify adult patients with supratentorial GBM that underwent craniotomy and resection. Performance of the ANN was evaluated against logistic regression and the standard grading system by analysing their Receiver Operator Characteristic (ROC) curves; Area Under Curve (AUC) and accuracy were calculated and compared using Wilcoxon signed rank test with a value of p < 0.05 considered statistically significant. In all, 135 patients were included, of which 33 (24.4%) were found to have complete excision of all contrast-enhancing tumour. The AUC and accuracy were significantly greater using the ANN compared to the standard grading system (0.87 vs. 0.79 and 83% vs. 80% respectively; p < 0.01 in both cases). In conclusion, an ANN allows for the improved prediction of surgical resectability in patients with GBM.

Spontaneous pregnancies following discontinuation of IVF/ICSI treatment: an internet-based survey.

The objective was to determine the likelihood of conceiving spontaneously following cessation of IVF/ICSI; how long does it take and what factors are associated with conception? The design was an internet-based survey. All registered users of www.ivf-infertility.com received an electronic questionnaire addressing issues relating to the duration and cause of infertility, number of IVF/ICSI cycles and outcome, whether they conceived following cessation of IVF/ICSI and the time taken to conceive and outcome. Four hundred and eighty four patients responded of whom 403 met the study criteria. The overall cumulative live birth rate over a 6-year period following cessation of IVF/ICSI was 29%. Eighty-two percent of conceptions occurred within 2 years. Positive factors associated with spontaneous conception were unexplained infertility (p = 0.02), ovulation dysfunction (p = 0.01), infertility less than four years prior to IVF/ICSI (p = 0.045) and 2 years or less since discontinuation of IVF/ICSI (p < 0.001) and up to four attempts at IVF/ICSI (p = 0.02). In conclusion, 29% of couples conceived spontaneously over a 6-year period following the cessation of IVF/ICSI. The findings of this study can be used to counsel and reassure women following IVF/ICSI.

Regulatory approval of new medical devices: cross sectional study.

OBJECTIVE:  To investigate the regulatory approval of new medical devices. DESIGN:  Cross sectional study of new medical devices reported in the biomedical literature. DATA SOURCES:  PubMed was searched between 1 January 2000 and 31 December 2004 to identify clinical studies of new medical devices. The search was carried out during this period to allow time for regulatory approval. ELIGIBILITY CRITERIA FOR STUDY SELECTION:  Articles were included if they reported a clinical study of a new medical device and there was no evidence of a previous clinical study in the literature. We defined a medical device according to the US Food and Drug Administration as an "instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article." MAIN OUTCOME MEASURES:  Type of device, target specialty, and involvement of academia or of industry for each clinical study. The FDA medical databases were then searched for clearance or approval relevant to the device. RESULTS:  5574 titles and abstracts were screened, 493 full text articles assessed for eligibility, and 218 clinical studies of new medical devices included. In all, 99/218 (45%) of the devices described in clinical studies ultimately received regulatory clearance or approval. These included 510(k) clearance for devices determined to be "substantially equivalent" to another legally marketed device (78/99; 79%), premarket approval for high risk devices (17/99; 17%), and others (4/99; 4%). Of these, 43 devices (43/99; 43%) were actually cleared or approved before a clinical study was published. CONCLUSIONS:  We identified a multitude of new medical devices in clinical studies, almost half of which received regulatory clearance or approval. The 510(k) pathway was most commonly used, and clearance often preceded the first published clinical study.

Comparative effectiveness and safety of image guidance systems in neurosurgery: a preclinical randomized study.

OBJECT: Over the last decade, image guidance systems have been widely adopted in neurosurgery. Nonetheless, the evidence supporting the use of these systems in surgery remains limited. The aim of this study was to compare simultaneously the effectiveness and safety of various image guidance systems against that of standard surgery. METHODS: In this preclinical, randomized study, 50 novice surgeons were allocated to one of the following groups: 1) no image guidance, 2) triplanar display, 3) always-on solid overlay, 4) always-on wire mesh overlay, and 5) on-demand inverse realism overlay. Each participant was asked to identify a basilar tip aneurysm in a validated model head. The primary outcomes were time to task completion (in seconds) and tool path length (in mm). The secondary outcomes were recognition of an unexpected finding (i.e., a surgical clip) and subjective depth perception using a Likert scale. RESULTS: The time to task completion and tool path length were significantly lower when using any form of image guidance compared with no image guidance (p < 0.001 and p = 0.003, respectively). The tool path distance was also lower in groups using augmented reality compared with triplanar display (p = 0.010). Always-on solid overlay resulted in the greatest inattentional blindness (20% recognition of unexpected finding). Wire mesh and on-demand overlays mitigated, but did not negate, inattentional blindness and were comparable to triplanar display (40% recognition of unexpected finding in all groups). Wire mesh and inverse realism overlays also resulted in better subjective depth perception than always-on solid overlay (p = 0.031 and p = 0.008, respectively). CONCLUSIONS: New augmented reality platforms may improve performance in less-experienced surgeons. However, all image display modalities, including existing triplanar displays, carry a risk of inattentional blindness.

Analysis of CPD ultraviolet lesion bypass in chicken DT40 cells: polymerase η and PCNA ubiquitylation play identical roles.

Translesion synthesis (TLS) provides a mechanism of copying damaged templates during DNA replication. This potentially mutagenic process may operate either at the replication fork or at post-replicative gaps. We used the example of T-T cyclobutane pyrimidine dimer (CPD) bypass to determine the influence of polymerase recruitment via PCNA ubiquitylation versus the REV1 protein on the efficiency and mutagenic outcome of TLS. Using mutant chicken DT40 cell lines we show that, on this numerically most important UV lesion, defects in polymerase η or in PCNA ubiquitylation similarly result in the long-term failure of lesion bypass with persistent strand gaps opposite the lesion, and the elevation of mutations amongst successful TLS events. Our data suggest that PCNA ubiquitylation promotes CPD bypass mainly by recruiting polymerase η, resulting in the majority of CPD lesions bypassed in an error-free manner. In contrast, we find that polymerase ζ is responsible for the majority of CPD-dependent mutations, but has no essential function in the completion of bypass. These findings point to a hierarchy of access of the different TLS polymerases to the lesion, suggesting a temporal order of their recruitment. The similarity of REV1 and REV3 mutant phenotypes confirms that the involvement of polymerase ζ in TLS is largely determined by its recruitment to DNA by REV1. Our data demonstrate the influence of the TLS polymerase recruitment mechanism on the success and accuracy of bypass.