Rapid generation of potent antibodies by autonomous hypermutation in yeast

The predominant approach for antibody generation remains animal immunization, which can yield exceptionally selective and potent antibody clones owing to the powerful evolutionary process of somatic hypermutation. However, animal immunization is inherently slow, has poor compatibility with certain antigens (e.g., integral membrane proteins), and suffers from self-tolerance and immunodominance, which limit the functional spectrum of antibodies that can be obtained. Here, we describe Autonomous Hypermutation yEast surfAce Display (AHEAD), a synthetic recombinant antibody generation technology that imitates somatic hypermutation inside engineered yeast. In AHEAD, antibody fragments are encoded on an error-prone orthogonal DNA replication system, resulting in Saccharomyces cerevisiae populations that continuously mutate surface-displayed antibody repertoires. Simple cycles of yeast culturing and enrichment for antigen binding drive the evolution of high-affinity antibody clones in a readily parallelizable process that takes as little as 2 weeks. We applied AHEAD to generate nanobodies against the SARS-CoV-2 S glycoprotein, a GPCR, and other targets. The SARS-CoV-2 nanobodies, concurrently evolved from an open-source naive nanobody library in 8 independent experiments, reached subnanomolar affinities through the sequential fixation of multiple mutations over 3-8 AHEAD cycles that saw [~]580-fold and [~]925-fold improvements in binding affinities and pseudovirus neutralization potencies, respectively. These experiments highlight the defining speed, parallelizability, and effectiveness of AHEAD and provide a template for streamlined antibody generation at large with salient utility in rapid response to current and future viral outbreaks.

Antibody reactivity to SARS-CoV-2 in adults from the Vancouver metropolitan area, Canada

BackgroundQuantifying antibody reactivity against multiple SARS-CoV-2 antigens at the population level may help understand individual differences in COVID-19 severity. Pre-existing low antibody cross-reactivity may be particularly prevalent among childcare providers, including pediatric health care workers (HCW) who may be more exposed to circulating coronaviruses. MethodsCross-sectional study that included adults in the Vancouver area in British Columbia (BC), Canada, between May 17 and June 19, 2020. SARS-CoV-2 seroprevalence was ascertained by measuring total SARS-CoV-2 IgG/M/A antibodies against a recombinant spike (S1) protein and adjusted for bias due to false-positive and false-negative test results. A novel, high sensitivity multiplex assay was also used to profile IgG against four SARS-CoV-2 antigens, SARS-CoV and four circulating coronaviruses. FindingsAmong 276 participants (71% HCW), three showed evidence of direct viral exposure, yielding an adjusted seroprevalence of 0.60% [95%CI 0% - 2.71%], with no difference between HCW and non-HCW, or between paediatric and adult HCW. Among the 273 unexposed individuals, 7.3% [95%CI 4.5% - 11.1%], 48.7 [95%CI 42.7% - 54.8%] and 82.4% [95%CI 77.4% - 86.7%] showed antibody reactivity against SARS-CoV-2 RBD, N or Spike proteins, respectively. SARS-CoV-2 reactivity did not significantly correlate with age, sex, did not significantly differ between HCW and non-HCW (prevalence 1.0% vs 1.0%; P=1.00) and between pediatric and adult HCW (0.7% vs 1.6%; P=0.54), and modestly correlated with reactivity to circulating coronaviruses (Spearman rho range: 0.130 to 0.224 for 7 significant (FDR 5%), out of 16 correlations, from 36 correlations tested). InterpretationA substantial proportion of individuals showed low, but detectable antibody reactivity against SARS-CoV-2 antigens in this population despite low evidence of direct SARS-CoV-2 exposure. FundingNIAID/NIH

Microvascular decompression of the posterior cerebral artery for treatment of oculomotor nerve palsy

Oculomotor nerve palsy resulting from non-aneurysmal vascular compression is extremely rare. Microvascular decompression (MVD) has been previously shown to improve oculomotor nerve palsy (ONP) secondary to arterial compression. A 71-year-old female, with a history of Cushing’s disease previously treated with two transsphenoidal resections and Gamma Knife radiosurgery, presented with one year of progressive left eye diplopia and was diagnosed with a partial left oculomotor nerve palsy. We performed an orbitozygomatic craniotomy for MVD of the left posterior cerebral artery, which was found to be compressing the oculomotor nerve against the tentorium. Unfortunately, the patient’s partial ONP remained unchanged at one year follow-up. The present case suggests inconsistent outcomes of MVD for ONP. Patients with prior sellar or parasellar irradiation may be less likely to benefit from this treatment approach.

Genial tubercle position and genioglossus advancement in obstructive sleep apnea (OSA) treatment: a systematic review / 대한악안면성형재건외과학회지

BACKGROUND@#To systematically review the literature for methods to localize the genial tubercle as a means for performing an advancement of the genioglossus muscle.@*METHODS@#PubMed, Google Scholar, CRISP, EMBASE, CINAHL, and Scopus were searched from inception through June 16, 2015.@*RESULTS@#One hundred fifty-two articles were screened, and the full text versions of 12 articles were reviewed in their entirety and 7 publications reporting their methodology for localizing the genial tubercle. Based upon these measurements and the results published from radiographic imaging and cadaveric dissections of all the papers included in this study, we identified the genial tubercle as being positioned within the mandible at a point 10 mm from the incisor apex and 10 mm from the lower mandibular border.@*CONCLUSION@#Based upon the results of this review, the genial tubercles were positioned within the mandible at a point 10 mm from the incisor apex and 10 mm from the lower mandible border. It may serve as an additional reference for localizing the genial tubercle and the attachment of the genioglossus muscle to the mandible, although the preoperative radiological evaluation and the palpation of the GT are recommended to accurately isolate.

Application of the new American Thyroid Association guidelines leads to a substantial rate of completion total thyroidectomy to enable adjuvant radioactive iodine.

BACKGROUND: The recently published 2015 American Thyroid Association guidelines recognize lobectomy as a viable alternative for low-risk cancers and advise more conservative use of radioactive iodine. Some factors indicating adjuvant treatment with radioactive iodine (and therefore completion total thyroidectomy), however, only can be found upon pathologic investigation. METHODS: We performed a retrospective analysis including patients with American Thyroid Association low- and low-to-intermediate risk well-differentiated thyroid cancer 1-4 cm. We evaluated how often radioactive iodine would be indicated and compared this with our historic rate. A subanalysis was performed to determine the rate of completion total thyroidectomy necessary, based on the indications for adjuvant radioactive iodine therapy. RESULTS: A total of 394/1,000 (39.4%) patients were included for final analysis. Adjuvant radioactive iodine would have been favored in 101/394 (25.6%) of patients, which is 2.5 times less than was given in our historic cohort. Completion total thyroidectomy to enable adjuvant radioactive iodine would have been recommended in 29/149 (19.5%) patients preoperatively eligible for lobectomy. CONCLUSION: Despite the tightened regulations for radioactive iodine, about 20% of patients with apparently "low-risk" well-differentiated thyroid cancer who are eligible for lobectomy may need completion total thyroidectomy because of pathologic findings for which radioactive iodine use is listed as considered or favored by the current guidelines.

Surgical Approaches for Symptomatic Cerebral Cavernous Malformations of the Thalamus and Brainstem

OBJECTIVE: Surgical resection of thalamic and brainstem cerebral cavernous malformations (CCMs) is associated with significant operative morbidity, but it may be outweighed, in some cases, by the neurological damage from recurrent hemorrhage in these eloquent areas. The goals of this retrospective cohort study are to describe the technical nuances of surgical approaches and determine the postoperative outcomes for CCMs of the thalamus and brainstem. MATERIALS AND METHODS: We reviewed an institutional database of patients harboring thalamic or brainstem CCMs, who underwent surgical resection from 2010 to 2014. The baseline and follow-up neuroimaging and clinical findings of each patient and the operative details of each case were evaluated. RESULTS: A total of eight patients, including two with thalamic and six with brainstem CCMs, were included in the study cohort. All patients had progressive neurological deterioration from recurrent CCM hemorrhage, and the median modified Rankin Scale (mRS) at presentation was 3. The median CCM maximum diameter and volume were 1.7 cm and 1.8 cm³, respectively. The thalamic CCMs were resected using the anterior transcallosal transchoroidal and supracerebellar infratentorial approaches each in one case (13%). The brainstem CCMs were resected using the retrosigmoid and suboccipital trans-cerebellomedullary fissure approaches each in three cases (38%). After a median follow-up of 11.5 months, all patients were neurologically stable or improved, with a median mRS of 2. The rate of functional independence (mRS 0-2) was 63%. CONCLUSION: Microneurosurgical techniques and approaches can be safely and effectively employed for the management of thalamic and brainstem CCMs in appropriately selected patients.

Bisphosphonate's and Intermittent Parathyroid Hormone's Effect on Human Spinal Fusion: A Systematic Review of the Literature

There has been a conscious effort to address osteoporosis in the aging population. As bisphosphonate and intermittent parathyroid hormone (PTH) therapy become more widely prescribed to treat osteoporosis, it is important to understand their effects on other physiologic processes, particularly the impact on spinal fusion. Despite early animal model studies and more recent clinical studies, the impact of these medications on spinal fusion is not fully understood. Previous animal studies suggest that bisphosphonate therapy resulted in inhibition of fusion mass with impeded maturity and an unknown effect on biomechanical strength. Prior animal studies demonstrate an improved fusion rate and fusion mass microstructure with the use of intermittent PTH. The purpose of this study was to determine if bisphosphonates and intermittent PTH treatment have impact on human spinal fusion. A systematic review of the literature published between 1980 and 2015 was conducted using major electronic databases. Studies reporting outcomes of human subjects undergoing 1, 2, or 3-level spinal fusion while receiving bisphosphonates and/or intermittent PTH treatment were included. The results of relevant human studies were analyzed for consensus on the effects of these medications in regards to spinal fusion. There were nine human studies evaluating the impact of these medications on spinal fusion. Improved fusion rates were noted in patients receiving bisphosphonates compared to control groups, and greater fusion rates in patients receiving PTH compared to control groups. Prior studies involving animal models found an improved fusion rate and fusion mass microstructure with the use of intermittent PTH. No significant complications were demonstrated in any study included in the analysis. Bisphosphonate use in humans may not be a deterrent to spinal fusion. Intermittent parathyroid use has shown early promise to increase fusion mass in both animal and human studies but further studies are needed to support routine use.

The Clinical Correlations between Diabetes, Cigarette Smoking and Obesity on Intervertebral Degenerative Disc Disease of the Lumbar Spine

STUDY DESIGN: Retrospective analysis of a nationwide private insurance database. Chi-square analysis and linear regression models were utilized for outcome measures. PURPOSE: The purpose of this study was to investigate any relationship between lumbar degenerative disc disease, diabetes, obesity and smoking tobacco. OVERVIEW OF LITERATURE: Diabetes, obesity, and smoking tobacco are comorbid conditions known to individually have effect on degenerative disc disease. Most studies have only been on a small populous scale. No study has yet to investigate the combination of these conditions within a large patient cohort nor have they reviewed the combination of these conditions on degenerative disc disease. METHODS: A retrospective analysis of insurance billing codes within the nationwide Humana insurance database was performed, using PearlDiver software (PearlDiver, Inc., Fort Wayne, IN, USA), to identify trends among patients diagnosed with lumbar disc degenerative disease with and without the associated comorbidities of obesity, diabetes, and/or smoking tobacco. Patients billed for a comorbidity diagnosis on the same patient record as the lumbar disc degenerative disease diagnosis were compared over time to patients billed for lumbar disc degenerative disease without a comorbidity. There were no sources of funding for this manuscript and no conflicts of interest. RESULTS: The total number and prevalence of patients (per 10,000) within the database diagnosed with lumbar disc degenerative disease increased by 241.4% and 130.3%, respectively. The subsets of patients within this population who were concurrently diagnosed with either obesity, diabetes, tobacco use, or a combination thereof, was significantly higher than patients diagnosed with lumbar disc degenerative disease alone (p <0.05 for all). The number of patients diagnosed with lumbar disc degenerative disease and smoking rose significantly more than patients diagnosed with lumbar disc degenerative disease and either diabetes or obesity (p <0.05). The number of patients diagnosed with lumbar disc degenerative disease, smoking and obesity rose significantly more than the number of patients diagnosed with lumbar disc degenerative disease and any other comorbidity alone or combination of comorbidities (p <0.05). CONCLUSIONS: Diabetes, obesity and cigarette smoking each are significantly associated with an increased diagnosis of lumbar degenerative disc disease. The combination of smoking and obesity had a synergistic effect on increased rates of lumbar degenerative disc disease. Patient education and preventative care is a vital goal in prevention of degenerative disc disease within the general population.

Eyebrow Incision for Surgical Evacuation of a Lobar Intracerebral Hematoma with a Novel Endoport System

Large lobar intracerebral hemorrhages (ICHs) can cause rapid neurological deterioration, and affected patients have low rates of survival and functional independence. Currently, the role of surgical intervention in the management patients with lobar ICHs is controversial. Minimally invasive technologies have been developed which may potentially decrease the operative morbidity of ICH surgery. The aim of this case report is to describe the technical aspects of the use of a novel minimally invasive endoport system, the BrainPath (NICO, Indianapolis, IN, USA), through an eyebrow incision for evacuation of a large lobar hematoma. An 84-year-old female presented with a left frontal ICH, measuring 7.5 cm in maximal diameter and 81 cm³ in volume, secondary to cerebral amyloid angiopathy. Through a left eyebrow incision, a miniature modified orbitozygomatic craniotomy was performed, which allowed endoport cannulation of the hematoma from a lateral subfrontal cortical entry point. Endoport-assisted hematoma evacuation resulted in nearly 90% volume reduction and improvement of the patient's functional status at clinical follow-up. We found that minimally invasive endoport technology can be employed in conjunction with conventional neurosurgical skull base principles to achieve safe and effective evacuation of large lobar hematomas in carefully selected patients.

Adverse Effects of Aggressive Blood Pressure Control in Patients with Intracerebral Hemorrhage

BACKGROUND: Medical management of patients presenting with spontaneous intracerebral hemorrhage (ICH) is focused on blood pressure (BP) management. However, the BP goal to prevent ICH expansion remains controversial. Recent clinical trials have suggested that aggressive BP control is safe but may not have the previously thought benefits. CASE REPORT: We present an example of aggressive BP control in the setting of hypertensive ICH, in accordance to previously established protocols. This resulted in adverse effects in the form of acute kidney injury and watershed infarcts, which impeded the patients' recovery and prolonged his hospitalization. CONCLUSIONS: Hypertensive individuals have altered cerebral autoregulation curves shifted to the right and require higher arterial pressures to maintain adequate cerebral blood flow. Hence, aggressive BP reduction may result in cerebral hypoperfusion as well as other forms of end-organ damage.

Preoperative Embolization of Cerebral Arteriovenous Malformations with Silk Suture and Particles: Technical Considerations and Outcomes

OBJECTIVE: Embolization of cerebral arteriovenous malformations (AVMs) is commonly performed prior to surgical resection in order to reduce intraoperative bleeding and improve the safety of resection. Although most modern embolization procedures utilize permanent embolic agents, silk suture and polyvinyl alcohol (PVA) particles may offer unique advantages for preoperative devascularization. The aims of this retrospective cohort study are to describe the technical considerations and determine the outcomes for preoperative silk suture and PVA particle embolization (SPE) of AVMs. MATERIALS AND METHODS: We performed a retrospective review of our AVM embolization database. AVM patients who underwent preoperative SPE and subsequent surgical resection were included for analysis. Baseline patient demographics, AVM characteristics, embolization and operative records, and post-treatment outcomes were reviewed. RESULTS: A total of 11 patients who underwent 12 preoperative SPE procedures were included for analysis. Five AVMs were ruptured (45%), and the median nidus volume was 3.0 cm3 (range: 1.3-42.9 cm³). The Spetzler-Martin grade was I-II in seven patients (64%) and III-IV in four patients (36%). The degree of nidal obliteration was less than 25% in two procedures (17%), 25-50% in one procedure (8%), 50-75% in eight procedures (67%), and greater than 75% in one procedure (8%). The rates of post-embolization AVM hemorrhage and mortality were 8% and 0%, respectively. The postoperative angiographic obliteration rate was 100%, and the modified Rankin Scale score improved or stable in 91% of patients (median follow-up duration 2 months). CONCLUSION: Preoperative AVM SPE affords a reasonable risk to benefit profile for appropriately selected patients.

Preoperative Embolization of Cerebral Arteriovenous Malformations with Silk Suture and Particles: Technical Considerations and Outcomes

OBJECTIVE: Embolization of cerebral arteriovenous malformations (AVMs) is commonly performed prior to surgical resection in order to reduce intraoperative bleeding and improve the safety of resection. Although most modern embolization procedures utilize permanent embolic agents, silk suture and polyvinyl alcohol (PVA) particles may offer unique advantages for preoperative devascularization. The aims of this retrospective cohort study are to describe the technical considerations and determine the outcomes for preoperative silk suture and PVA particle embolization (SPE) of AVMs. MATERIALS AND METHODS: We performed a retrospective review of our AVM embolization database. AVM patients who underwent preoperative SPE and subsequent surgical resection were included for analysis. Baseline patient demographics, AVM characteristics, embolization and operative records, and post-treatment outcomes were reviewed. RESULTS: A total of 11 patients who underwent 12 preoperative SPE procedures were included for analysis. Five AVMs were ruptured (45%), and the median nidus volume was 3.0 cm3 (range: 1.3-42.9 cm³). The Spetzler-Martin grade was I-II in seven patients (64%) and III-IV in four patients (36%). The degree of nidal obliteration was less than 25% in two procedures (17%), 25-50% in one procedure (8%), 50-75% in eight procedures (67%), and greater than 75% in one procedure (8%). The rates of post-embolization AVM hemorrhage and mortality were 8% and 0%, respectively. The postoperative angiographic obliteration rate was 100%, and the modified Rankin Scale score improved or stable in 91% of patients (median follow-up duration 2 months). CONCLUSION: Preoperative AVM SPE affords a reasonable risk to benefit profile for appropriately selected patients.

Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate in Asian Subjects with Human Immunodeficiency Virus 1 Infection: A Sub-Analysis of Phase 3 Clinical Trials / 감염과화학요법

The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) were analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naïve and ART-experienced Asian subjects infected with human immunodeficiency virus (HIV)-1. Studies GS-US-236-102 and GS-US-236-103 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naïve subjects, comparing E/C/F/TDF versus efavirenz (EFV)/F/TDF or ritonavir-boosted atazanavir (ATV+RTV) plus emtricitabine/tenofovir DF (F/TDF), respectively. Studies GS-US-236-115 and GS-US-236-121 were randomized, open-label, 96-week long conducted in ART-experienced subjects, who switched to E/C/F/TDF from ritonavir-boosted protease inhibitors (PI+RTV)+F/TDF, or non-nucleoside reverse transcriptase inhibitors (NNRTI)+F/TDF regimens. The E/C/F/TDF appeared to have sustained efficacy and safety and was well tolerated in the small number of ART-naïve and ART-experienced Asian subjects.

Simultaneous determination of 3-chlorotyrosine and 3-nitrotyrosine in human plasma by direct analysis in real time-tandem mass spectrometry

A novel method for the simultaneous determination of 3-nitrotyrosine (NT) and 3-chlorotyrosine (CT) in human plasma has been developed based on direct analysis in real time-tandem mass spectrometry (DART-MS/MS). Analysis was performed in the positive ionization mode using multiple reaction monitoring (MRM) of the ion transitions at m/z 216.2/170.1 for CT, m/z 227.2/181.1 for NT and m/z 230.2/184.2 for the internal standard, d (3)-NT. The assay was linear in the ranges 0.5-100 μg/mL for CT and 4-100 μg/mL for NT with corresponding limits of detection of 0.2 and 2 μg/mL. Intra- and inter-day precisions and accuracies were respectively <15% and ±15%. Matrix effects were also evaluated. The method is potentially useful for high throughput analysis although sensitivity needs to be improved before it can be applied in clinical research.

Balloon Anchor Technique for Pipeline Embolization Device Deployment Across the Neck of a Giant Intracranial Aneurysm

Treatment of giant intracranial aneurysms, via either surgical or endovascular approaches, is associated with a high level of technical difficulty as well as a high rate of treatment-related morbidity and mortality. Flow-diverting stents, such as the Pipeline embolization device (PED), have drastically altered the therapeutic strategies for the treatment of giant aneurysms. Gaining endovascular access using a microcatheter to the portion of the parent artery distal to the aneurysm neck is requisite for safe and effective stent deployment. Giant aneurysms are often associated with vascular tortuosity, which necessitates significant catheter support systems to enable maneuvering of PEDs across the aneurysm neck. This is also required in order to reduce the probability of stent herniation within giant aneurysms. We report on a case of a giant supraclinoid internal carotid artery (ICA) aneurysm which was treated successfully with a PED utilizing a balloon anchor technique to facilitate direct microcatheter access across the aneurysm neck.

Microsurgical Strategies Following Failed Endovascular Treatment with the Pipeline Embolization Device: Case of a Giant Posterior Cerebral Artery Aneurysm

Treatment of giant posterior circulation aneurysms, via endovascular or microsurgical approaches, carries a high risk of morbidity and mortality. While flow-diverting stents (FDSs) represent a potent therapy for endovascular reconstruction of complex aneurysms, they are also associated with novel complications for which effective salvage techniques are lacking. We present a unique complication from failed treatment with a FDS. A 51 year-old male presented with increasing headaches secondary to a giant, fusiform aneurysm of the left posterior cerebral artery, which was largely thrombosed. Due to progressive enlargement of the aneurysm corresponding to worsening clinical symptoms, the lesion was treated with two Pipeline embolization devices (ev3, Plymouth, MN, United States). Three months after Pipeline embolization device treatment, complete posterior cerebral artery occlusion was observed at the origin of the proximal stent. Despite the lack of arterial inflow, the aneurysm dome continued to grow, resulting in obstructive hydrocephalus. Therefore microsurgical intervention was undertaken to trap and excise the aneurysm. The patient's postoperative course was complicated by multiple venous infarcts, ultimately resulting in death. Successful microsurgical obliteration of aneurysms previously treated with FDSs is extremely difficult. A combination of judicious preoperative planning and meticulous intraoperative surgical technique are requisite for effective management of these complicated cases.

Microsurgical Extraction of a Malfunctioned Pipeline Embolization Device Following Complete Deployment

The Pipeline Embolization Device (PED) is an effective treatment approach for complex intracranial aneurysms. Intraprocedural complications during PED deployment are seldom reported. We report a rare complication of a PED malfunction identified immediately following complete deployment during endovascular treatment of a giant middle cerebral artery (MCA) bifurcation aneurysm. After multiple failed attempts at endovascular retrieval of the malfunctioned PED, the patient was taken for microsurgical extraction due to accumulation of thrombus on the proximal unopened portion of the stent and widespread distal dissemination of emboli. After removing the PED from the vessel lumen and resecting the giant aneurysm, we could not reanastamose the proximal MCA to the distal segment. The management of PED malfunction is poorly understood. While removal of an incompletely deployed PED may be undertaken with limited adverse effects, retrieval of a fully deployed PED is associated with a much higher risk of morbidity. Until larger case series of such complications better define the risks and benefits of endovascular or microsurgical retrieval of malfunctioned PEDs, the management of these rare intraprocedural complications will be based on the unique aspects of each individual case and the expertise of the treating neurointerventionalist.

Predictive Capability of the Spetzler-Martin versus Supplementary Grading Scale for Microsurgical Outcomes of Cerebellar Arteriovenous Malformations

The recently described supplementary grading scale may be superior to the widely used Spetzler-Martin grading scale in the prediction of microsurgical outcomes for cerebellar arteriovenous malformations (AVM). We report two cases of ruptured cerebellar AVMs with the same Spetzler-Martin grade but different supplementary grades treated with microsurgical resection. Both patients had symptomatic brainstem compression from cerebellar hematomas and subsequently underwent uncomplicated surgeries; however, their outcomes were significantly different. It has previously been proposed that AVMs distort cerebellar anatomy in a different manner than supratentorial cerebral anatomy thereby potentially resulting in misrepresentation when utilizing the Spetzler-Martin grading scale. However, the components of the supplementary grading scale are independent of cerebellar anatomy, which may explain why it has been shown to be better than the Spetzler-Martin grading scale for prediction of surgical outcomes. In addition, due to the smaller volume of the posterior fossa compared to the supratentorial compartment, rupture of cerebellar AVMs may result in rapid and catastrophic neurological compromise. Therefore, the role of microsurgery may be more critical for AVMs of the cerebellar than for those located elsewhere. Simple and effective grading systems are invaluable tools for clinical and surgical decision-making, although the decisions rendered should always be made in conjunction with the patient's presentation and the physician's experience.

Influences of configuration changes of the patella on the knee extensor mechanism.

Biomechanical analysis of the configuration changes of the patella was studied. Normal patellar tracking in the sagittal plane was obtained by recording and digitizing knee extension of six healthy adults with fluoroscopy. Based on the digitized data, the changes of patellar thickness were simulated by translating its axis and its forward and backward tilting by rotation in the sagittal plane. We assumed that the extensor moment remained constant before and after the patellar configuration was changed. Therefore, using a balance beam, model equilibrium was reached, after each simulated change of patellar configuration, of the forces involved in the extensor mechanism: the quadriceps muscle force, tension of patella tendon and patellofemoral joint reaction force. The results revealed that when the patellar thickness decreased, quadriceps force increased but patellofemoral joint reaction force decreased and the reverse was seen when the patella thickened. Backward tilting of the patella decreased quadriceps force and patellofemoral joint reaction force and increased the patella tendon/quadriceps force ratio, which produced a better mechanical advantage of force transmission of patella. The reverse was seen in forward tilting. These results suggest that the patella could be tilted backward for the older patient undergoing total knee replacement. For younger patients with relatively strong quadriceps musculature, we suggest that the patellar thickness could be decreased to reduce the patellofemoral joint reaction force so as to reduce the chance of failure of the patella prosthesis.