Mark Corriveau

Genome annotation in the presence of insertional RNA editing

MOTIVATIONnInsertional RNA editing renders gene prediction very difficult compared to organisms without such RNA editing. A case in point is the mitochondrial genome of Physarum polycephalum in which only about one-third of the number of genes that are to be expected given its length are annotated. Thus, gene prediction methods that explicitly take into account insertional editing are needed for successful annotation of such genomes.nnnRESULTSnWe annotate the mitochondrial genome of P.polycephalum using several different approaches for gene prediction in organisms with insertional RNA editing. We computationally validate our annotations by comparing the results from different methods against each other and as proof of concept experimentally validate two of the newly predicted genes. We more than double the number of annotated putative genes in this organism and find several intriguing candidate genes that are not expected in a mitochondrial genome.nnnAVAILABILITYnThe C source code of the programs described here are available upon request from the corresponding author.

Extracranial ligation of ethmoidal arteries before resection of giant olfactory groove or planum sphenoidale meningiomas: 3 illustrative cases with a review of the literature on surgical techniques

OBJECTnThere are several surgical techniques for reducing blood loss-open surgical and endoscopic-prior to resection of giant anterior skull base meningiomas, especially when preoperative embolization is risky or not technically feasible. The authors present examples of an institutional experience using surgical ligation of the anterior and posterior ethmoidal arteries producing persistent tumor blush in partially embolized tumors.nnnMETHODSnThe authors identified 12 patients who underwent extracranial surgical ligation of ethmoidal arteries through either a transcaruncular or a Lynch approach. Of these, 3 patients had giant olfactory groove or planum sphenoidale meningiomas. After approval from the institution privacy officer, the authors studied the medical records and imaging data of these 3 patients, with special attention to surgical technique and outcome. The variations of ethmoidal artery foramina pertaining to this surgical approach were studied using preserved human skulls from the Hamann-Todd Osteological Collection at the Museum of Natural History, Cleveland, Ohio.nnnRESULTSnThe extracranial ligation was performed successfully for control of the ethmoidal arteries prior to resection of hypervascular giant anterior skull base meningiomas. The surgical anatomy and landmarks for ethmoidal arteries were reviewed in anthropology specimens and available literature with reference to described surgical techniques.nnnCONCLUSIONSnExtracranial surgical ligation of anterior, and often posterior, ethmoidal arteries prior to resection of large olfactory groove or planum sphenoidale meningiomas provides a safe and feasible option for control of these vessels prior to either open or endoscopic resection of nonembolized or partially embolized tumors.

Coordinated interactions of multiple POT1-TPP1 proteins with telomere DNA

Background: POT1 and TPP1 protect the ends of human telomeres. Results: The secondary structure of single-stranded DNA alters the coordinated binding of multiple POT1-TPP1 proteins. Conclusion: Single-stranded telomere DNA is more susceptible to DNase I digestion when coated with POT1-TPP1 proteins. Significance: By altering DNA properties, coating of telomere DNA by POT1-TPP1 proteins may have a functional role in telomere maintenance. Telomeres are macromolecular nucleoprotein complexes that protect the ends of eukaryotic chromosomes from degradation, end-to-end fusion events, and from engaging the DNA damage response. However, the assembly of this essential DNA-protein complex is poorly understood. Telomere DNA consists of the repeated double-stranded sequence 5′-TTAGGG-3′ in vertebrates, followed by a single-stranded DNA overhang with the same sequence. Both double- and single-stranded regions are coated with high specificity by telomere end-binding proteins, including POT1 and TPP1, that bind as a heterodimer to single-stranded telomeric DNA. Multiple POT1-TPP1 proteins must fully coat the single-stranded telomere DNA to form a functional telomere. To better understand the mechanism of multiple binding, we mutated or deleted the two guanosine nucleotides residing between adjacent POT1-TPP1 recognition sites in single-stranded telomere DNA that are not required for multiple POT1-TPP1 binding events. Circular dichroism demonstrated that spectra from the native telomere sequence are characteristic of a G-quadruplex secondary structure, whereas the altered telomere sequences were devoid of these signatures. The altered telomere strands, however, facilitated more cooperative loading of multiple POT1-TPP1 proteins compared with the wild-type telomere sequence. Finally, we show that a 48-nucleotide DNA with a telomere sequence is more susceptible to nuclease digestion when coated with POT1-TPP1 proteins than when it is left uncoated. Together, these data suggest that POT1-TPP1 binds telomeric DNA in a coordinated manner to facilitate assembly of the nucleoprotein complexes into a state that is more accessible to enzymatic activity.

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

Study Design: A multicenter, retrospective review of C5 palsy after cervical spine surgery. Objective: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. Methods: We conducted a multicenter, retrospective review of 13u2009946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ2 tests or Fisher exact tests for categorical variables. Results: Of the 13u2009946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). Conclusion: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date.

Epidemiology and Outcomes of Vertebral Artery Injury in 16 582 Cervical Spine Surgery Patients: An AOSpine North America Multicenter Study.

Study Design: A multicenter retrospective case series was compiled involving 21 medical institutions. Inclusion criteria included patients who underwent cervical spine surgery between 2005 and 2011 and who sustained a vertebral artery injury (VAI). Objective: To report the frequency, risk factors, outcomes, and management goals of VAI in patients who have undergone cervical spine surgery. Methods: Patients were evaluated on the basis of condition-specific functional status using the Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA) score, the Nurick scale, and the 36-Item Short-Form Health Survey (SF-36). Results: VAIs were identified in a total of 14 of 16u2009582 patients screened (8.4 per 10u2009000). The mean age of patients with VAI was 59 years (±10) with a female predominance (78.6%). Patient diagnoses included myelopathy, radiculopathy, cervical instability, and metastatic disease. VAI was associated with substantial blood loss (770 mL), although only 3 cases required transfusion. Of the 14 cases, 7 occurred with an anterior-only approach, 3 cases with posterior-only approach, and 4 during circumferential approach. Fifty percent of cases of VAI with available preoperative imaging revealed anomalous vessel anatomy during postoperative review. Average length of hospital stay was 10 days (±8). Notably, 13 of the 14 (92.86%) cases resolved without residual deficits. Compared to preoperative baseline NDI, Nurick, mJOA, and SF-36 scores for these patients, there were no observed changes after surgery (P = .20-.94). Conclusions: Vertebral artery injuries are potentially catastrophic complications that can be sustained from anterior or posterior cervical spine approaches. The data from this study suggest that with proper steps to ensure hemostasis, patients recover function at a high rate and do not exhibit residual deficits.

Vancomycin-resistant enterococci infection: not just for the transplanted

Abstract Vancomycin-resistant enterococcal (VRE) blood stream infections (BSIs) pose significant hazards to patients with hematologic malignancy. We compared and examined VRE BSI rates, patient characteristics and clinical outcomes for two cohorts of patients: those who did and did not undergo hematopoietic cell transplant (HCT). In this single institution study, we retrospectively analyzed records of consecutive patients from 1998 through 2011. Over this 14-year period, VRE was identified in 14% of all BSIs in patients with HCT with a cumulative rate of 1.9% (48/2581 BSIs/patients). VRE was identified in 10% of all BSIs in non-HCT patients with a cumulative rate of 1.1% (35/3154 BSIs/patients). Transplant patients who developed VRE BSI tended to be younger, hospitalized more frequently, were exposed to vancomycin therapy frequently, and were more likely to have had a central venous catheter removed. VRE remains a significant cause of morbidity and mortality, as 22 deaths were directly or indirectly attributed to this infection. Both HCT and non-HCT patients are susceptible to VRE infection and are equally at risk for adverse outcomes related to VRE BSI.

A Multicenter Study of the Presentation, Treatment, and Outcomes of Cervical Dural Tears

Study Design: Retrospective multicenter case series study. Objective: Because cervical dural tears are rare, most surgeons have limited experience with this complication. A multicenter study was performed to better understand the presentation, treatment, and outcomes following cervical dural tears. Methods: Multiple surgeons from 23 institutions retrospectively identified 21 rare complications that occurred between 2005 and 2011, including unintentional cervical dural tears. Demographic data and surgical history were obtained. Clinical outcomes following surgery were assessed, and any reoperations were recorded. Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA), Nurick classification (NuC), and Short-Form 36 (SF36) scores were recorded at baseline and final follow-up at certain centers. All data were collected, collated, and analyzed by a private research organization. Results: There were 109 cases of cervical dural tears among 18u2009463 surgeries performed. In 101 cases (93%) there was no clinical sequelae following successful dural tear repair. There were statistical improvements (P < .05) in mJOA and NuC scores, but not NDI or SF36 scores. No specific baseline or operative factors were found to be associated with the occurrence of dural tears. In most cases, no further postoperative treatments of the dural tear were required, while there were 13 patients (12%) that required subsequent treatment of cerebrospinal fluid drainage. Analysis of those requiring further treatments did not identify an optimum treatment strategy for cervical dural tears. Conclusions: In this multicenter study, we report our findings on the largest reported series (n = 109) of cervical dural tears. In a vast majority of cases, no subsequent interventions were required and no clinical sequelae were observed.

Cervical dural arteriovenous malformation and large epidural venous varices in a rare adult presentation of congenital vascular bone syndrome

61-year-old male presented with shortness of breath and chest pain. Workup for acute myocardial infarction was negative; however, computed tomography angiography visualized what a vascular malformation within the cervical spinal canal. Given the patients history of Servelle-Martorell syndrome, neurovascular imaging was performed. We present the unique vascular findings of a right thyrocervical trunk-based dural arteriovenous malformation (dAVM) and a large epidural venous varix. The cervical dAVM induced intervertebral foraminal widening and polyradiculopathy, representing a rare adult case of congenital vascular bone syndrome.

Peroneal nerve decompression

Peroneal neuropathy is a common pathology encountered by neurosurgeons. Symptoms include pain, numbness, and foot drop. When secondary to compression of the nerve at the fibular head, peroneal (fibular) nerve release is a low-risk procedure that can provide excellent results with pain relief and return of function. In this video, the authors highlight key operative techniques to ensure adequate decompression of the nerve while protecting the 3 major branches, including the superficial peroneal nerve, deep peroneal nerve, and recurrent genicular (articular) branches. Key steps include positioning, circumferential nerve dissection, fascial opening, isolation of the major branches, and closure. The video can be found here: https://youtu.be/0y9oE8w1FIU .

Differences in Pressure Within the Sac of Human Ruptured and Nonruptured Cerebral Aneurysms

BACKGROUNDnHemodynamics plays a critical role in the development, growth, and rupture of intracranial aneurysms. This data could be vital in determining individual aneurysm rupture risk and could facilitate our understanding of aneurysms.nnnOBJECTIVEnTo present the largest prospective cross-sectional cohort study of intrasaccular pressure recordings of ruptured and nonruptured intracranial aneurysms and describe the hemodynamic differences that exist between ruptured and nonruptured aneurysms.nnnMETHODSnDuring endovascular treatment, a standard 1.8-Fr 200 m length microcatheter was navigated into the dome of the aneurysm prior to coil embolization. With the microcatheter centralized within the dome of the aneurysm, an arterial pressure transducer was attached to the proximal end of the microcatheter to measure the stump pressure inside the aneurysm dome.nnnRESULTSnIn 68 aneurysms (28 ruptured, 40 nonruptured), we observed that ruptured cerebral aneurysms had a lower systolic and mean arterial pressure compared to nonruptured cohort (Pxa0=xa0.0008). Additionally, the pulse pressures within the dome of ruptured aneurysms were significantly more narrow than that of unruptured aneurysms (Pxa0=xa0.0001). These findings suggest that there may be an inherent difference between ruptured and nonruptured aneurysms and such recordings obtained during routine digital subtraction angiography could potentially become a widely applied technique to augment risk stratification of aneurysms.nnnCONCLUSIONnOur preliminary data present new evidence distinguishing ruptured from unruptured aneurysms that may have a critical role as a predictive parameter to stratify the natural history of nonruptured intracranial aneurysms and as a new avenue for future investigation.