Put on Your Para-spectacles: The Development of Optimized CRISPR-Cas13-Based Approaches to Image RNA Dynamics in Real Time.

Live-cell RNA imaging is a powerful approach to observe the real-time dynamics of RNA metabolism. Two recent papers describe an optimized fluorescence-based CRISPR-Cas13 approach to image colocalized or repeat-containing RNAs in real time, as well as demonstrate simultaneous RNA-DNA labeling by using Cas13 and Cas9 in tandem.

Cost-utility analysis of minimally invasive versus open multilevel hemilaminectomy for lumbar stenosis.

STUDY DESIGN: Two-year cost-utility study comparing minimally invasive (MIS) versus open multilevel hemilaminectomy in patients with degenerative lumbar spinal stenosis. OBJECTIVE: The objective of the study was to determine whether MIS versus open multilevel hemilaminectomy for degenerative lumbar spinal stenosis is a cost-effective advancement in lumbar decompression surgery. SUMMARY OF BACKGROUND DATA: MIS-multilevel hemilaminectomy for degenerative lumbar spinal stenosis allows for effective treatment of back and leg pain while theoretically minimizing blood loss, tissue injury, and postoperative recovery. No studies have evaluated comprehensive healthcare costs associated with multilevel hemilaminectomy procedures, nor assessed cost-effectiveness of MIS versus open multilevel hemilaminectomy. METHODS: Fifty-four consecutive patients with lumbar stenosis undergoing multilevel hemilaminectomy through an MIS paramedian tubular approach (n=27) versus midline open approach (n=27) were included. Total back-related medical resource utilization, missed work, and health state values [quality adjusted life years (QALYs), calculated from EuroQuol-5D with US valuation] were assessed after 2-year follow-up. Two-year resource use was multiplied by unit costs based on Medicare national allowable payment amounts (direct cost) and work-day losses were multiplied by the self-reported gross-of-tax wage rate (indirect cost). Difference in mean total cost per QALY gained for MIS versus open hemilaminectomy was assessed as incremental cost-effectiveness ratio (ICER: COST(MIS)-COST(OPEN)/QALY(MIS)-QALY(OPEN)). RESULTS: MIS versus open cohorts were similar at baseline. MIS and open hemilaminectomy were associated with an equivalent cumulative gain of 0.72 QALYs 2 years after surgery. Mean direct medical costs, indirect societal costs, and total 2-year cost ($23,109 vs. $25,420; P=0.21) were similar between MIS and open hemilaminectomy. MIS versus open approach was associated with similar total costs and utility, making it a cost equivalent technology compared with the traditional open approach. CONCLUSIONS: MIS versus open multilevel hemilaminectomy was associated with similar cost over 2 years while providing equivalent improvement in QALYs. In our experience, MIS versus open multilevel hemilaminectomy is a cost equivalent technology for patients with lumbar stenosis-associated radicular pain.

Effect of host factors and COVID-19 infection on the humoral immune repertoire in treated HIV.

People with HIV (PWH) appear to be at higher risk for suboptimal pathogen responses and for worse COVID-19 outcomes, but the effects of host factors and COVID-19 on the humoral repertoire remain unclear. We assessed the antibody isotype/subclass and Fc-receptor binding Luminex arrays of non-SARS-CoV-2 and SARS-CoV-2 humoral responses among antiretroviral therapy-treated (ART-treated) PWH. Among the entire cohort, COVID-19 infection was associated with higher cytomegalovirus (CMV) responses (vs. the COVID- cohort ), potentially signifying increased susceptibility or a consequence of persistent inflammation. Among the COVID+ participants, (a) higher BMI was associated with a striking amplification of SARS-CoV-2 responses, suggesting exaggerated inflammatory responses, and (b) lower nadir CD4 was associated with higher SARS-CoV-2 IgM and FcγRIIB binding capacity, indicating poorly functioning extrafollicular and inhibitory responses. Among the COVID-19- participants, female sex, older age, and lower nadir CD4 were associated with unique repertoire shifts. In this first comprehensive assessment of the humoral repertoire in a global cohort of PWH, we identify distinct SARS-CoV-2-specific humoral immune profiles among PWH with obesity or lower nadir CD4+ T cell count, underlining plausible mechanisms associated with worse COVID-19-related outcomes in this setting. Host factors associated with the humoral repertoire in the COVID-19- cohort enhance our understanding of these important shifts among PWH.

Initial experience with dual-lumen balloon catheter injection for preoperative Onyx embolization of skull base paragangliomas.

OBJECT Paragangliomas are highly vascular head and neck tumors for which preoperative embolization is often considered to facilitate resection. The authors evaluated their initial experience using a dual-lumen balloon to facilitate preoperative embolization in 5 consecutive patients who underwent preoperative transarterial Onyx embolization assisted by the Scepter dual-lumen balloon catheter between 2012 and 2014. OBJECT The authors reviewed the demographic and clinical records of 5 patients who underwent Scepter-assisted Onyx embolization of a paraganglioma followed by resection between 2012 and 2014. Descriptive statistics of clinical outcomes were assessed. RESULTS Five patients (4 with a jugular and 1 with a vagal paraganglioma) were identified. Three paragangliomas were embolized in a single session, and each of the other 2 were completed in 3 staged sessions. The mean volume of Onyx used was 14.3 ml (range 6-30 ml). Twenty-seven vessels were selectively catheterized for embolization. All patients required selective embolization via multiple vessels. Two patients required sacrifice of parent vessels (1 petrocavernous internal carotid artery and 1 vertebral artery) after successful balloon test occlusion. One patient underwent embolization with Onyx-18 alone, 2 with Onyx-34 alone, and 1 with Onyx-18 and -34. In each case, migration of Onyx was achieved within the tumor parenchyma. The mean time between embolization and resection was 3.8 days (range 1-8 days). Gross-total resection was achieved in 3 (60%) patients, and the other 2 patients had minimal residual tumor. The mean estimated blood loss during the resections was 556 ml (range 200-850 ml). The mean postoperative hematocrit level change was -17.3%. Two patients required blood transfusions. One patient, who underwent extensive tumor penetration with Onyx, developed a temporary partial cranial nerve VII palsy that resolved to House-Brackmann Grade I (out of VI) at the 6-month follow-up. One patient experienced improvement in existing facial nerve weakness after embolization. CONCLUSIONS Scepter catheter-based Onyx embolization seems to be safe and effective. It was associated with excellent distal tumor vasculature penetration and holds promise as an adjunct to conventional transarterial Onyx embolization of paragangliomas. However, the ease of tumor penetration should encourage caution in practitioners who may be able to effect comparable improvement in blood loss with more conservative proximal Onyx penetration.

Simultaneous stent expansion/balloon deflation technique to salvage failed balloon remodeling.

Herniation, with possible embolization, of coils into the parent vessel following aneurysm coiling remains a frequent challenge. For this reason, balloon or stent assisted embolization remains an important technique. Despite the use of balloon remodeling, there are occasions where, on deflation of the balloon, some coils, or even the entire coil mass, may migrate. We report the successful use of a simultaneous adjacent stent deployment bailout technique in order to salvage coil prolapse during balloon remodeling in three patients. Case No 1 was a wide neck left internal carotid artery bifurcation aneurysm, measuring 9 mm×7.9 mm×6 mm with a 5 mm neck. Case No 2 was a complex left superior hypophyseal artery aneurysm, measuring 5.3 mm×4 mm×5 mm with a 2.9 mm neck. Case No 3 was a ruptured right posterior communicating artery aneurysm, measuring 4 mm×4 mm×4.5 mm with a 4 mm neck. This technique successfully returned the prolapsed coil mass into the aneurysm sac in all cases without procedural complications. The closed cell design of the Enterprise VRD (Codman and Shurtleff Inc, Raynham, Massachusetts, USA) makes it ideal for this bailout technique, by allowing the use of an 0.021 inch delivery catheter (necessary for simultaneous access) and by avoiding the possibility of an open cell strut getting caught on the deflated balloon. We hope this technique will prove useful to readers who may find themselves in a similar predicament.

Minimizing bleeding complications in spinal tumor surgery with preoperative Onyx embolization via dual-lumen balloon catheter.

BACKGROUND: Intraoperative bleeding is a significant risk in surgery for highly vascular spinal tumors, but preoperative embolization can safely decrease intraoperative blood loss in extrinsic spine tumors. Onyx, widely used for cerebrovascular embolization, has been increasingly used as an embolic agent for preoperative spinal tumor embolization. The Scepter catheter, a dual-lumen balloon catheter, may improve tumor parenchymal penetration without the danger and limitations of significant embolic reflux. This may reduce bleeding risk during spinal surgery. METHODS: Eleven consecutive cases of preoperative Onyx embolization of extrinsic spinal tumors were identified, all of whom had subsequent spinal surgery. Demographic data and clinical variables were collected. Patients were divided into Scepter (n=6) and non-Scepter (n=5) groups. The Mann-Whitney U test was used to compare continuous outcome variables and the Fisher exact test was used to compare categorical variables. RESULTS: Estimated blood loss in the Scepter group was significantly lower than in the non-Scepter group (584±124 vs 2400±738 mL, p=0.004). The volume of intraoperative transfusion was also significantly lower (1.2±0.4 vs 5.8±1.7 units, p=0.004). There was no significant difference in the number of vessels embolized, vials of Onyx used, use of coiling adjunct, contrast load, radiation dose, or fluoroscopy time per pedicle (p>0.05). CONCLUSIONS: The addition of the Scepter catheter to preoperative Onyx embolization is safe and feasible. In this small series, the Scepter catheter was associated with a reduction of intraoperative bleeding by 76% and a 79% lower transfusion volume. This was not accompanied by any unwanted increase in vials of Onyx used, contrast load, radiation dose, or fluoroscopy time.

Transorbital superior ophthalmic vein sacrifice to preserve vision in ocular hypertension from aseptic cavernous sinus thrombosis.

Aseptic cavernous sinus thrombosis (CST) is rare and may clinically masquerade as a carotid cavernous fistula. Conventional management includes oral anticoagulation, but cases of ocular hypertension affecting vision may require more aggressive intervention. We report a case of a woman with spontaneous bilaterally occluded cavernous sinuses with elevated intraocular pressure (IOP), which resolved immediately following unilateral superior ophthalmic vein (SOV) sacrifice. She was subsequently placed on oral anticoagulants. By 4 months postoperatively her IOP was normalized and her vision had improved. Repeat angiography demonstrated stable venous filling, with some mild improvement of flow through the cavernous sinus. Coil-mediated sacrifice of the SOV might be an effective means to relieve ocular hypertension and preserve vision in the setting of aseptic CST.

Complex decision-making in stroke: preoperative mechanical thrombectomy of septic embolus for emergency cardiac valve surgery.

Stroke is a common and devastating embolic manifestation of infective endocarditis. We report a case of cardioembolic stroke in a patient with enterococcal endocarditis, with National Institutes of Health Stroke Scale score of 3. A middle-aged patient with bacterial endocarditis exhibited mild intermittent left hemiparesis and dysarthria in the setting of severe aortic insufficiency requiring urgent aortic valve replacement. Cerebrovascular imaging revealed a partially occlusive thrombus in the M1 segment of the right middle cerebral artery, which became symptomatic during relative hypotension. Given the expected hypotension during the urgently needed aortic valve replacement, there was a significant risk of infarction of most of the right hemisphere. Thus, mechanical thrombectomy was performed immediately prior to thoracotomy, and the patient awoke neurologically intact. This case demonstrates avoidance of a large stroke due to a subocclusive thrombus and anticipated intraoperative hypotension with preoperative mechanical thrombectomy.

Simultaneous stent expansion/balloon deflation technique to salvage failed balloon remodeling.

Herniation, with possible embolization, of coils into the parent vessel following aneurysm coiling remains a frequent challenge. For this reason, balloon or stent assisted embolization remains an important technique. Despite the use of balloon remodeling, there are occasions where, on deflation of the balloon, some coils, or even the entire coil mass, may migrate. We report the successful use of a simultaneous adjacent stent deployment bailout technique in order to salvage coil prolapse during balloon remodeling in three patients. Case No 1 was a wide neck left internal carotid artery bifurcation aneurysm, measuring 9 mm×7.9 mm×6 mm with a 5 mm neck. Case No 2 was a complex left superior hypophyseal artery aneurysm, measuring 5.3 mm×4 mm×5 mm with a 2.9 mm neck. Case No 3 was a ruptured right posterior communicating artery aneurysm, measuring 4 mm×4 mm×4.5 mm with a 4 mm neck. This technique successfully returned the prolapsed coil mass into the aneurysm sac in all cases without procedural complications. The closed cell design of the Enterprise VRD (Codman and Shurtleff Inc, Raynham, Massachusetts, USA) makes it ideal for this bailout technique, by allowing the use of an 0.021 inch delivery catheter (necessary for simultaneous access) and by avoiding the possibility of an open cell strut getting caught on the deflated balloon. We hope this technique will prove useful to readers who may find themselves in a similar predicament.

Transorbital superior ophthalmic vein sacrifice to preserve vision in ocular hypertension from aseptic cavernous sinus thrombosis.

Aseptic cavernous sinus thrombosis (CST) is rare and may clinically masquerade as a carotid cavernous fistula. Conventional management includes oral anticoagulation, but cases of ocular hypertension affecting vision may require more aggressive intervention. We report a case of a woman with spontaneous bilaterally occluded cavernous sinuses with elevated intraocular pressure (IOP), which resolved immediately following unilateral superior ophthalmic vein (SOV) sacrifice. She was subsequently placed on oral anticoagulants. By 4 months postoperatively her IOP was normalized and her vision had improved. Repeat angiography demonstrated stable venous filling, with some mild improvement of flow through the cavernous sinus. Coil-mediated sacrifice of the SOV might be an effective means to relieve ocular hypertension and preserve vision in the setting of aseptic CST.

Complex decision-making in stroke: preoperative mechanical thrombectomy of septic embolus for emergency cardiac valve surgery.

Stroke is a common and devastating embolic manifestation of infective endocarditis. We report a case of cardioembolic stroke in a patient with enterococcal endocarditis, with National Institutes of Health Stroke Scale score of 3. A middle-aged patient with bacterial endocarditis exhibited mild intermittent left hemiparesis and dysarthria in the setting of severe aortic insufficiency requiring urgent aortic valve replacement. Cerebrovascular imaging revealed a partially occlusive thrombus in the M1 segment of the right middle cerebral artery, which became symptomatic during relative hypotension. Given the expected hypotension during the urgently needed aortic valve replacement, there was a significant risk of infarction of most of the right hemisphere. Thus, mechanical thrombectomy was performed immediately prior to thoracotomy, and the patient awoke neurologically intact. This case demonstrates avoidance of a large stroke due to a subocclusive thrombus and anticipated intraoperative hypotension with preoperative mechanical thrombectomy.

Resolution of trigeminal neuralgia by coil embolization of a persistent primitive trigeminal artery aneurysm.

The persistent primitive trigeminal artery (PTA) is a rare anastomosis between the carotid artery and basilar artery. While most PTAs are asymptomatic, lateral variants can occasionally compress the trigeminal nerve and precipitate trigeminal neuralgia. Aneurysms of the PTA are exceptionally rare in the literature and have not previously been associated with trigeminal neuralgia. We present the first case of an aneurysm of the PTA causing trigeminal neuralgia. The patient underwent coil embolization of the aneurysm which relieved her symptoms. We propose embolization as a viable therapeutic option for the resolution of trigeminal neuralgia when the condition is secondary to irritation by the high velocity pulsatile flow of an aneurysm.

Resolution of trigeminal neuralgia by coil embolization of a persistent primitive trigeminal artery aneurysm.

The persistent primitive trigeminal artery (PTA) is a rare anastomosis between the carotid artery and basilar artery. While most PTAs are asymptomatic, lateral variants can occasionally compress the trigeminal nerve and precipitate trigeminal neuralgia. Aneurysms of the PTA are exceptionally rare in the literature and have not previously been associated with trigeminal neuralgia. We present the first case of an aneurysm of the PTA causing trigeminal neuralgia. The patient underwent coil embolization of the aneurysm which relieved her symptoms. We propose embolization as a viable therapeutic option for the resolution of trigeminal neuralgia when the condition is secondary to irritation by the high velocity pulsatile flow of an aneurysm.

Cost-effectiveness of transforaminal lumbar interbody fusion for Grade I degenerative spondylolisthesis.

OBJECT: Transforaminal lumbar interbody fusion (TLIF) for spondylolisthesis-associated back and leg pain is associated with improvement in pain, disability, and quality of life. However, given the rising health care costs associated with spinal fusion procedures and varying results of recent cost-utility studies, the cost-effectiveness of TLIF remains unclear. The authors set out to assess the comprehensive costs of TLIF at their institution and to determine its cost-effectiveness in the treatment of degenerative spondylolisthesis. METHODS: Forty-five patients undergoing TLIF for Grade I degenerative spondylolisthesis-associated back and leg pain after 6-12 months of conservative therapy were included. The authors assessed the 2-year back pain visual analog scale (VAS) score, leg pain VAS score, Oswestry Disability Index, and total back-related medical resource utilization, missed work, and health-state values (quality-adjusted life years [QALYs], calculated from EQ-5D with US valuation). Two-year resource use was multiplied by unit costs based on Medicare national allowable payment amounts (direct cost), and patient and caregiver workday losses were multiplied by the self-reported gross-of-tax wage rate (indirect cost). The mean total 2-year cost per QALY gained after TLIF was assessed. RESULTS: Compared with preoperative health states reported after at least 6 months of medical management, a significant improvement in back pain VAS score, leg pain VAS score, and Oswestry Disability Index was observed 2 years after TLIF, with a mean 2-year gain of 0.86 QALYs. The mean ± SD total 2-year cost of TLIF was $36,836 ± $11,800 (surgery cost, $21,311 ± $2800; outpatient resource utilization cost, $3940 ± $2720; indirect cost, $11,584 ± $11,363). Transforaminal lumbar interbody fusion was associated with a mean 2-year cost per QALY gained of $42,854. CONCLUSIONS: Transforaminal lumbar interbody fusion improved pain, disability, and quality of life in patients with degenerative spondylolisthesis-associated back and leg pain. The total cost per QALY gained for TLIF was $42,854 when evaluated 2 years after surgery with Medicare fees, suggesting that TLIF is a cost-effective treatment of lumbar spondylolisthesis.

Cost-effectiveness of multilevel hemilaminectomy for lumbar stenosis-associated radiculopathy.

BACKGROUND CONTEXT: Laminectomy for lumbar stenosis-associated radiculopathy is associated with improvement in pain, disability, and quality of life. However, given rising health-care costs, attention has been turned to question the cost-effectiveness of lumbar decompressive procedures. The cost-effectiveness of multilevel hemilaminectomy for radiculopathy remains unclear. PURPOSE: To assess the comprehensive medical and societal costs of multilevel hemilaminectomy at our institution and determine its cost-effectiveness in the treatment of degenerative lumbar stenosis. STUDY DESIGN: Prospective single cohort study. PATIENT SAMPLE: Fifty-four consecutive patients undergoing multilevel hemilaminectomy for lumbar stenosis-associated radiculopathy after at least 6 months of failed conservative therapy were included. OUTCOME MEASURES: Self-reported measures were assessed using an outcomes questionnaire that incorporated total back-related medical resource utilization, missed work, and improvement in leg pain (visual analog scale for leg pain [VAS-LP]), disability (Oswestry Disability Index [ODI]), quality of life (Short Form-12 [SF-12]), and health state values (quality-adjusted life years [QALYs], calculated from EuroQuol 5D [EQ-5D] with US valuation). METHODS: Over a 2-year period, total back-related medical resource utilization, missed work, and improvement in leg pain (VAS-LP), disability (ODI), quality of life (SF-12), and health state values (QALYs, calculated from EQ-5D with US valuation) were assessed. Two-year resource use was multiplied by unit costs based on Medicare national allowable payment amounts (direct cost), and patient and caregiver workday losses were multiplied by the self-reported gross-of-tax wage rate (indirect cost). Mean total 2-year cost per QALY gained after multilevel hemilaminectomy was assessed. RESULTS: Compared with preoperative health states reported after at least 6 months of medical management, a significant improvement in VAS-LP, ODI, and SF-12 (physical and mental components) was observed 2 years after multilevel hemilaminectomy, with a mean 2-year gain of 0.72 QALYs. Mean±standard deviation total 2-year cost of multilevel hemilaminectomy was $24,264±10,319 (surgery cost, $10,220±80.57; outpatient resource utilization cost, $3,592±3,243; and indirect cost, $10,452±9,364). Multilevel hemilaminectomy was associated with a mean 2-year cost per QALY gained of $33,700. CONCLUSIONS: Multilevel hemilaminectomy improved pain, disability, and quality of life in patients with lumbar stenosis-associated radiculopathy. Total cost per QALY gained for multilevel hemilaminectomy was $33,700 when evaluated 2 years after surgery with Medicare fees, suggesting that multilevel hemilaminectomy is a cost-effective treatment of lumbar radiculopathy.