I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Preamble and Transition to ACC/AHA Guidelines to Reduce Cardiovascular Risk S50

The goals of the American College of Cardiology (ACC) and the American Heart Association (AHA) are to prevent cardiovascular diseases (CVD); improve the management of people who have these diseases through professional education and research; and develop guidelines, standards, and policies that promote optimal patient care and cardiovascular health. Toward these objectives, the ACC and AHA have collaborated with the National Heart, Lung, and Blood Institute (NHLBI) and stakeholder and professional organizations to develop …

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2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk

Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Nancy M. Albert, PhD, RN, FAHA

Biykem Bozkurt, MD, PhD, FACC, FAHA

Ralph G. Brindis, MD, MPH, MACC

Lesley H. Curtis, PhD, FAHA

David DeMets, PhD[¶¶][1]

Lee A. Fleisher, MD, FACC, FAHA

Samuel

/pdf/2014-acc-aha-guideline-on-perioperative-cardiovascular-3firuin78y.pdf

2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: A report of the American college of cardiology/American heart association task force on practice guidelines

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(04)16250-8.pdf

Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial

ContextIn patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone.ObjectiveTo determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death.Design, Setting, and PatientsRandomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003.InterventionsPatients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients).Main Outcome MeasuresThe primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death.ResultsThe median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation.ConclusionsCompared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used.Trial Registrationumin.ac.jp/ctr Identifier: C000000412

https://jamanetwork.com/journals/jama/articlepdf/202954/joc60064.pdf

Stereotactic Radiosurgery Plus Whole-Brain Radiation Therapy vs Stereotactic Radiosurgery Alone for Treatment of Brain Metastases: A Randomized Controlled Trial

Background: In patients with large dural defects of the anterior and ventral skull base after endonasal skull base surgery, there is a significant risk of a postoperative cerebrospinal fluid leak after reconstruction. Reconstruction with vascularized tissue is desirable to facilitate rapid healing, especially in irradiated patients.

Methods: We developed a neurovascular pedicled flap of the nasal septum mucoperiosteum and mucoperichondrium based on the nasoseptal artery, a branch of the posterior septal artery (Hadad-Bassagasteguy flap [HBF]). A retrospective review of patients undergoing endonasal skull base surgery at the University of Rosario, Argentina, and the University of Pittsburgh Medical Center was performed to identify patients who were reconstructed with a vascularized septal mucosal flap.

Results: Forty-three patients undergoing endonasal cranial base surgery were repaired with the septal mucosal flap. Two patients with postoperative cerebrospinal fluid leaks (5%) were successfully treated with focal fat grafts. We encountered no infectious or wound complications in this series of patients. One patient experienced a posterior nose bleed from the posterior nasal artery. This was controlled with electrocautery and the flap blood supply was preserved.

Conclusion: The HBF is a versatile and reliable reconstructive technique for defects of the anterior, middle, clival, and parasellar skull base. Its use has resulted in a sharp decrease in the incidence of postoperative cerebrospinal fluid leaks after endonasal skull base surgery and is recommended for the reconstruction of large dural defects and when postoperative radiation therapy is anticipated.

A novel reconstructive technique after endoscopic expanded endonasal approaches : Vascular pedicle nasoseptal flap

Purpose: Multiple brain metastases are a common health problem, frequently diagnosed in patients with cancer. The prognosis, even after treatment with whole brain radiation therapy (WBRT), is poor with average expected survivals less than 6 months. Retrospective series of stereotactic radiosurgery have shown local control and survival benefits in case series of patients with solitary brain metastases. We hypothesized that radiosurgery plus WBRT would provide improved local brain tumor control over WBRT alone in patients with two to four brain metastases. Methods: Patients with two to four brain metastases (all ≤25 mm diameter and known primary tumor type) were randomized to initial brain tumor management with WBRT alone (30 Gy in 12 fractions) or WBRT plus radiosurgery. Extent of extracranial cancer, tumor diameters on MRI scan, and functional status were recorded before and after initial care. Results: The study was stopped at an interim evaluation at 60% accrual. Twenty-seven patients were randomized (14 to WBRT alone and 13 to WBRT plus radiosurgery). The groups were well matched to age, sex, tumor type, number of tumors, and extent of extracranial disease. The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients who had boost radiosurgery. The median time to local failure was 6 months after WBRT alone (95% confidence interval [CI], 3.5–8.5) in comparison to 36 months (95% CI, 15.6–57) after WBRT plus radiosurgery ( p = 0.0005). The median time to any brain failure was improved in the radiosurgery group ( p = 0.002). Tumor control did not depend on histology ( p = 0.85), number of initial brain metastases ( p = 0.25), or extent of extracranial disease ( p = 0.26). Patients who received WBRT alone lived a median of 7.5 months, while those who received WBRT plus radiosurgery lived 11 months ( p = 0.22). Survival did not depend on histology or number of tumors, but was related to extent of extracranial disease ( p = 0.02). There was no neurologic or systemic morbidity related to stereotactic radiosurgery. Conclusions: Combined WBRT and radiosurgery for patients with two to four brain metastases significantly improves control of brain disease. WBRT alone does not provide lasting and effective care for most patients.

Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases.

Object. Transsphenoidal approaches have been used for a century for the resection of pituitary and other sellar tumors. More recently, the standard endonasal approach has been expanded to provide access to other, parasellar lesions. With the addition of the endoscope, this expansion carries significant potential for the resection of skull base lesions. Methods. The anatomical landmarks and surgical techniques used in expanded (extended) endoscopic approaches to the rostral, anterior skull base are reviewed and presented, accompanied by case illustrations of each segment (or module) of approach. The rostral half of the anterior skull base is divided into modules of approach: sellar/parasellar, transplanum/transtuberculum, and transcribriform. Case illustrations of successful resections of lesions with each module are presented and discussed. Conclusions. Endoscopic, expanded endonasal approaches to rostral anterior skull base lesions are feasible and hold great potential for decreased morbidity. The effectiveness and appropriate use of these techniques must be evaluated by close examination of outcomes as case series expand.

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Expanded endonasal approach: the rostrocaudal axis. Part I. Crista galli to the sella turcica

Hypoxia contributes to the progression of a variety of cancers by activating adaptive transcriptional programs that promote cell survival, motility and tumor angiogenesis. Although the importance of hypoxia and subsequent hypoxia-inducible factor-1alpha (HIF-1alpha) activation in tumor angiogenesis is well known, their role in the regulation of glioma-derived stem cells is unclear. In this study, we show that hypoxia (1% oxygen) promotes the self-renewal capacity of CD133-positive human glioma-derived cancer stem cells (CSCs). Propagation of the glioma-derived CSCs in a hypoxic environment also led to the expansion of cells bearing CXCR4 (CD184), CD44(low) and A2B5 surface markers. The enhanced self-renewal activity of the CD133-positive CSCs in hypoxia was preceded by upregulation of HIF-1alpha. Knockdown of HIF-1alpha abrogated the hypoxia-mediated CD133-positive CSC expansion. Inhibition of the phosphatidylinositol 3-kinase(PI3K)-Akt or ERK1/2 pathway reduced the hypoxia-driven CD133 expansion, suggesting that these signaling cascades may modulate the hypoxic response. Finally, CSCs propagated at hypoxia robustly retained the undifferentiated phenotype, whereas CSCs cultured at normoxia did not. These results suggest that response to hypoxia by CSCs involves the activation of HIF-1alpha to enhance the self-renewal activity of CD133-positive cells and to inhibit the induction of CSC differentiation. This study illustrates the importance of the tumor microenvironment in determining cellular behavior.

Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha.

Objective Reconstruction of the cranial base using vascularized tissue promotes rapid and complete healing, thus avoiding complications caused by persistent communication between the cranial cavity and the sinonasal tract. The Hadad-Bassagasteguy flap (HBF), a neurovascular pedicled flap of the nasal septum mucoperiosteum and mucoperichondrium based on the nasoseptal artery, seems to be advantageous for the reconstruction of the cranial base after endonasal cranial base surgery. Methods We performed a retrospective review of patients who underwent endonasal cranial base surgery at the University of Pittsburgh Medical Center from January 30, 2006 to January 30, 2007, identifying patients who experienced reconstruction with a vascularized septal mucosal flap (HBF). We analyzed the demographic data, pathological characteristics, site and extent of resection, use of cerebrospinal fluid (CSF) diversion techniques, and outcome. Results Seventy-five patients who underwent endonasal cranial base endoscopic surgery received repair with the HBF. In this population, we encountered eight postoperative CSF leaks (10.66%), all in patients who required intra-arachnoidal dissection. When we correct the statistical analysis to include only patients with intra- arachnoidal lesions, the postoperative CSF leak rate is 14.5% (eight of 55 patients). It is notable that six CSF (33%) leaks occurred in our first 25 repairs, whereas we encountered only two postoperative leaks (4%) in the last 50 patients. The corrected CSF leak rate, considering only intra-arachnoidal lesions, was two (5.4%) of 37 patients. This improvement in the CSF leak rate reflects our growing experience and comfort with this reconstructive technique. All of our failures could be matched to a specific technical mistake. In addition, we modified the flap-harvesting technique to allow for staged procedures and the removal of caudal lesions. These special circumstances require storage of the flap in the antrum during the removal of caudal lesions, and suturing of the flap in its original position for staged procedures. One patient experienced a posterior nose bleed from the posterior nasal artery. This was controlled with bipolar electrocautery, thereby preserving the flap blood supply. We encountered no infectious or wound complications in this series of patients. The donor site accumulates crusting, which requires debridement until mucosalization is complete; this usually occurs 6 to 12 weeks after surgery. Conclusion The HBF is a versatile and reliable reconstructive technique for repairing defects of the anterior, middle, clival, and parasellar cranial base. Its use has resulted in a significant decrease in our incidence of CSF leaks after endonasal cranial base surgery. Attention to technical details is of paramount importance to achieve the best outcomes.

Amin B. Kassam

Papers

A novel reconstructive technique after endoscopic expanded endonasal approaches : Vascular pedicle nasoseptal flap

Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases.

Expanded endonasal approach: the rostrocaudal axis. Part I. Crista galli to the sella turcica

Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha.

Endoscopic reconstruction of the cranial base using a pedicled nasoseptal flap.