Hybrid supervised and reinforcement learning for the design and optimization of nanophotonic structures.

From higher computational efficiency to enabling the discovery of novel and complex structures, deep learning has emerged as a powerful framework for the design and optimization of nanophotonic circuits and components. However, both data-driven and exploration-based machine learning strategies have limitations in their effectiveness for nanophotonic inverse design. Supervised machine learning approaches require large quantities of training data to produce high-performance models and have difficulty generalizing beyond training data given the complexity of the design space. Unsupervised and reinforcement learning-based approaches on the other hand can have very lengthy training or optimization times associated with them. Here we demonstrate a hybrid supervised learning and reinforcement learning approach to the inverse design of nanophotonic structures and show this approach can reduce training data dependence, improve the generalizability of model predictions, and significantly shorten exploratory training times. The presented strategy thus addresses several contemporary deep learning-based challenges, while opening the door for new design methodologies that leverage multiple classes of machine learning algorithms to produce more effective and practical solutions for photonic design.

Noninvasive wearable electroactive pharmaceutical monitoring for personalized therapeutics.

To achieve the mission of personalized medicine, centering on delivering the right drug to the right patient at the right dose, therapeutic drug monitoring solutions are necessary. In that regard, wearable biosensing technologies, capable of tracking drug pharmacokinetics in noninvasively retrievable biofluids (e.g., sweat), play a critical role, because they can be deployed at a large scale to monitor the individuals' drug transcourse profiles (semi)continuously and longitudinally. To this end, voltammetry-based sensing modalities are suitable, as in principle they can detect and quantify electroactive drugs on the basis of the target's redox signature. However, the target's redox signature in complex biofluid matrices can be confounded by the immediate biofouling effects and distorted/buried by the interfering voltammetric responses of endogenous electroactive species. Here, we devise a wearable voltammetric sensor development strategy-centering on engineering the molecule-surface interactions-to simultaneously mitigate biofouling and create an "undistorted potential window" within which the target drug's voltammetric response is dominant and interference is eliminated. To inform its clinical utility, our strategy was adopted to track the temporal profile of circulating acetaminophen (a widely used analgesic and antipyretic) in saliva and sweat, using a surface-modified boron-doped diamond sensing interface (cross-validated with laboratory-based assays, R2 ∼ 0.94). Through integration of the engineered sensing interface within a custom-developed smartwatch, and augmentation with a dedicated analytical framework (for redox peak extraction), we realized a wearable solution to seamlessly render drug readouts with minute-level temporal resolution. Leveraging this solution, we demonstrated the pharmacokinetic correlation and significance of sweat readings.

The Impact of Sex, Body Mass Index, Age, Exercise Type and Exercise Duration on Interstitial Glucose Levels during Exercise.

The impact of age, sex and body mass index on interstitial glucose levels as measured via continuous glucose monitoring (CGM) during exercise in the healthy population is largely unexplored. We conducted a multivariable generalized estimating equation (GEE) analysis on CGM data (Dexcom G6, 10 days) collected from 119 healthy exercising individuals using CGM with the following specified covariates: age; sex; BMI; exercise type and duration. Females had lower postexercise glycemia as compared with males (92 ± 18 vs. 100 ± 20 mg/dL, p = 0.04) and a greater change in glycemia during exercise from pre- to postexercise (p = 0.001) or from pre-exercise to glucose nadir during exercise (p = 0.009). Younger individuals (i.e., <20 yrs) had higher glucose during exercise as compared with all other age groups (all p < 0.05) and less CGM data in the hypoglycemic range (<70 mg/dL) as compared with those aged 20-39 yrs (p < 0.05). Those who were underweight, based on body mass index (BMI: <18.5 kg/m2), had higher pre-exercise glycemia than the healthy BMI group (104 ± 20 vs. 97 ± 17 mg/dL, p = 0.02) but similar glucose levels after exercise. Resistance exercise was associated with less of a drop in glycemia as compared with aerobic or mixed forms of exercise (p = 0.008) and resulted in a lower percent of time in the hypoglycemic (p = 0.04) or hyperglycemic (glucose > 140 mg/dL) (p = 0.03) ranges. In summary, various factors such as age, sex and exercise type appear to have subtle but potentially important influence on CGM measurements during exercise in healthy individuals.

Long-term outcomes following intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: 5-year treatment arm results from a prospective randomized double-blind sham-controlled multi-center study.

BACKGROUND: Damaged or degenerated vertebral endplates are a significant cause of vertebrogenic chronic low back pain (CLBP). Modic changes are one objective MRI biomarker for these patients. Prior data from the treatment arm of a sham-controlled, RCT showed maintenance of clinical improvements at 2 years following ablation of the basivertebral nerve (BVN). This study reports 5-year clinical outcomes. METHODS: In total, 117 US patients were treated successfully with BVN ablation. Patient-reported outcomes of ODI, VAS, postablation treatments, and patient satisfaction were collected at a minimum of 5-years following BVN ablation. Primary outcome was mean change in ODI. Comparisons between the postablation and baseline values were made using an analysis of covariance with alpha 0.05. RESULTS: Of the 117 US treated patients 100 (85%) were available for review with a mean follow-up of 6.4 years (5.4-7.8 years). Mean ODI score improved from 42.81 to 16.86 at 5-year follow-up, a reduction of 25.95 points (p < 0.001). Mean reduction in VAS pain score was 4.38 points (baseline of 6.74, p < 0.001). In total, 66% of patients reported a > 50% reduction in pain, 47% reported a > 75% reduction in pain, and 34% of patients reported complete pain resolution. Composite responder rate using thresholds of ≥ 15-point ODI and ≥ 2-point VAS for function and pain at 5 years was 75%. CONCLUSION: CLBP patients treated with BVN ablation exhibit sustained clinical improvements in function and pain with high responder rates at a mean of 6.4 years following treatment. BVN ablation is a durable, minimally invasive treatment for vertebrogenic CLBP.

Polytomous Rasch Analyses of Surgeons' Decision-Making on Choice of Procedure in Endoscopic Lumbar Spinal Stenosis Decompression Surgeries.

BACKGROUND: With the growing prevalence of lumbar spinal stenosis, endoscopic surgery, which incorporates techniques such as transforaminal, interlaminar, and unilateral biportal (UBE) endoscopy, is increasingly considered. However, the patient selection criteria are debated among spine surgeons. OBJECTIVE: This study used a polytomous Rasch analysis to evaluate the factors influencing surgeon decision-making in selecting patients for endoscopic surgical treatment of lumbar spinal stenosis. METHODS: A comprehensive survey was distributed to a representative sample of 296 spine surgeons. Questions encompassed various patient-related and clinical factors, and responses were captured on a logit scale graphically displaying person-item maps and category probability curves for each test item. Using a Rasch analysis, the data were subsequently analyzed to determine the latent traits influencing decision-making. RESULTS: The Rasch analysis revealed that surgeons' preferences for transforaminal, interlaminar, and UBE techniques were easily influenced by comfort level and experience with the endoscopic procedure and patient-related factors. Harder-to-agree items included technological aspects, favorable clinical outcomes, and postoperative functional recovery and rehabilitation. Descriptive statistics suggested interlaminar as the best endoscopic spinal stenosis decompression technique. However, logit person-item analysis integral to the Rasch methodology showed highest intensity for transforaminal followed by interlaminar endoscopic lumbar stenosis decompression. The UBE technique was the hardest to agree on with a disordered person-item analysis and thresholds in category probability curve plots. CONCLUSION: Surgeon decision-making in selecting patients for endoscopic surgery for lumbar spinal stenosis is multifaceted. While the framework of clinical guidelines remains paramount, on-the-ground experience-based factors significantly influence surgeons' selection of patients for endoscopic lumbar spinal stenosis surgeries. The Rasch methodology allows for a more granular psychometric evaluation of surgeon decision-making and accounts better for years-long experience that may be lost in standardized clinical guideline development. This new approach to assessing spine surgeons' thought processes may improve the implementation of evidence-based protocol change dictated by technological advances was endorsed by the Interamerican Society for Minimally Invasive Spine Surgery (SICCMI), the International Society for Minimal Intervention in Spinal Surgery (ISMISS), the Mexican Spine Society (AMCICO), the Brazilian Spine Society (SBC), the Society for Minimally Invasive Spine Surgery (SMISS), the Korean Minimally Invasive Spine Society (KOMISS), and the International Society for the Advancement of Spine Surgery (ISASS).

Comparative Analysis of Learning Curve, Complexity, Psychological Stress, and Work Relative Value Units for CPT 62380 Endoscopic Lumbar Spinal Decompression vs Traditional Lumbar Spine Surgeries: A Paired Rasch Survey Study.

BACKGROUND: Effective 1 January 2017, single-level endoscopic lumbar discectomy received a Category I Current Procedural Terminology (CPT) code 62380. However, no work relative value units (RVUs) are currently assigned to the procedure. An international team of endoscopic spine surgeons conducted a study, endorsed by several spine societies, analyzing the learning curve, difficulty, psychological intensity, and estimated work RVUs of endoscopic lumbar spinal decompression compared with other common lumbar spine surgeries. METHODS: A survey comparing CPT 62380 to 10 other comparator CPT codes reflective of common spine surgeries was developed to assess the work RVUs in terms of learning curve, difficulty, psychological intensity, and work effort using a paired Rasch method. RESULTS: The survey was sent to 542 spine specialists. Of 322 respondents, 150 completed the survey for a 43.1% completion rate. Rasch analysis of the submitted responses statistically corroborated common knowledge that the learning curve with lumbar endoscopic spinal surgery is steeper and more complex than with traditional translaminar lumbar decompression surgeries. It also showed that the psychological stress and mental and work effort with the lumbar endoscopic decompression surgery were perceived to be higher by responding spine surgeons compared with posterior comparator decompression and fusion surgeries and even posterior interbody and posterolateral fusion surgeries. The regression analysis of work effort vs procedural difficulty showed the real-world evaluation of the lumbar endoscopic decompression surgery described in CPT code 62380 with a calculated work RVU of 18.2464. CONCLUSION: The Rasch analysis suggested the valuation for the endoscopic lumbar decompression surgery should be higher than for standard lumbar surgeries: 111.1% of the laminectomy with exploration and/or decompression of spinal cord and/or cauda equina (CPT 63005), 118.71% of the laminectomy code (CPT 63047), which includes foraminotomy and facetectomy, 152.1% of the hemilaminectomy code (CPT 63030), and 259.55% of the interlaminar or interspinous process stabilization/distraction without decompression code (CPT 22869). This research methodology was endorsed by the Interamerican Society for Minimally Invasive Spine Surgery (SICCMI), the Mexican Society of Spinal Surgeons (AMCICO), the International Society For Minimally Invasive Spine Surgery (ISMISS), the Brazilian Spine Society (SBC), the Society for Minimally Invasive Spine Surgery (SMISS), the Korean Minimally Invasive Spine Surgery (KOMISS), and the International Society for the Advancement of Spine Surgery (ISASS). CLINICAL RELEVANCE: This study provides an updated reimbursement recommendation for endoscopic spine surgery. LEVEL OF EVIDENCE: Level 3.

Autonomous wearable sweat rate monitoring based on digitized microbubble detection.

Advancements in wearable bioanalytical microsystems have enabled diurnal and (semi)continuous monitoring of physiologically-relevant indices that are accessible through probing sweat. To deliver an undistorted and physiologically-meaningful interpretation of these readings, tracking the sweat secretion rate is essential, because it allows for calibrating the biomarker readings against variations in sweat secretion and inferring the body's hydration/electrolyte homeostasis status. To realize an autonomous wearable solution with intrinsically high signal-to-noise ratio sweat rate sensing capabilities, here, we devise a digitized microbubble detection mechanism-delivered by a hybrid microfluidic/electronic system with a compact footprint. This mechanism is based on the intermittent generation of microliter-scale bubbles via electrolysis and the instantaneous measurement of their time-of-flight (and thus, velocity) via impedimetric sensing. In this way, we overcome the limitations of previously proposed sweat rate sensing modalities that are inherently susceptible to non-targeted secretion characteristics (pH, conductivity, and temperature), constrained by volume, or lack system integration for autonomous on-body operation. By deploying our solution in human subject trials, we validate the utility of our solution for seamless monitoring of exercise- and iontophoretically-induced sweat secretion profiles.

Differential Agnostic Effect Size Analysis of Lumbar Stenosis Surgeries.

STUDY DESIGN: A meta-analysis of 89 randomized prospective, prospective, and retrospective studies on spinal endoscopic surgery outcomes. OBJECTIVE: The study aimed to provide familiar Oswestry Disability Index (ODI), visual analog scale (VAS) back, and VAS leg effect size (ES) data following endoscopic decompression for sciatica-type back and leg pain due to lumbar herniated disc, foraminal, or lateral recess spinal stenosis. BACKGROUND: Higher-grade objective clinical outcome ES data are more suitable than lower-grade clinical evidence, including cross-sectional retrospective study outcomes or expert opinion to underpin the ongoing debate on whether or not to replace some of the traditional open and with other forms of minimally invasive spinal decompression surgeries such as the endoscopic technique. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 31 December 2019 identified 89 eligible studies on lumbar endoscopic decompression surgery enrolling 23,290 patient samples using the ODI and VAS for back and leg pain used for the ES calculation. RESULTS: There was an overall mean overall reduction of ODI of 46.25 (SD 6.10), VAS back decrease of 3.29 (SD 0.65), and VAS leg reduction of 5.77 (SD 0.66), respectively. Reference tables of familiar ODI, VAS back, and VAS leg show no significant impact of study design, follow-up, or patients' age on ES observed with these outcome instruments. There was no correlation of ES with long-term follow-up (P = 0.091). Spinal endoscopy produced an overall ODI ES of 0.92 extrapolated from 81 studies totaling 12,710 patient samples. Provided study comparisons to tubular retractor microdiscectomy and open laminectomy showed an ODI ES of 0.9 (2895 patients pooled from 16 studies) and 0.93 (1188 patients pooled from 5 studies). The corresponding VAS leg ES were 0.92 (12,631 endoscopy patients pooled from 81 studies), 0.92 (2348 microdiscectomy patients pooled from 15 studies), and 0.89 (1188 open laminectomy patients pooled from 5 studies). CONCLUSION: Successful clinical outcomes can be achieved with various lumbar surgeries. ESs with endoscopic spinal surgery are on par with those found with open laminectomy and microsurgical decompression. CLINICAL RELEVANCE: This article is a meta-analysis on the benefit overlap between lumbar endoscopy, microsurgical decompression, laminectomy, and lumbar decompression fusion.

Estimating the impact of expanded access to antiretroviral therapy on maternal, paternal and double orphans in sub-Saharan Africa, 2009-2020.

BACKGROUND: HIV/AIDS has orphaned 11.6 million children in sub-Saharan Africa. Expanded antiretroviral therapy (ART) use may reduce AIDS orphanhood by decreasing adult mortality and population-level HIV transmission. METHODS: We modeled two scenarios to measure the impact of adult ART use on the incidence of orphanhood in 10 sub-Saharan African countries, from 2009 to 2020. Demographic model data inputs were obtained from cohort studies, UNAIDS, UN Population Division, WHO and the US Census Bureau. RESULTS: Compared to current rates of ART uptake, universal ART access averted 4.37 million more AIDS orphans by year 2020, including 3.15 million maternal, 1.89 million paternal and 0.75 million double orphans. The number of AIDS orphans averted was highest in South Africa (901.71 thousand) and Nigeria (839.01 thousand), and lowest in Zimbabwe (86.96 thousand) and Côte d'Ivoire (109.12 thousand). CONCLUSION: Universal ART use may significantly reduce orphanhood in sub-Saharan Africa.

Physician's manual reporting underestimates mortality: evidence from a population-based HIV/AIDS treatment program.

BACKGROUND: In clinical and cohort research, mortality estimates are often derived from manual reports generated by physicians or electronic reports from vital event registries. We examined the rate of underreporting of deaths by manual methods as compared with electronic reports from a vital event registry. METHODS: The retrospective analyses included deaths among participants registered in an observational cohort who initiated highly-active antiretroviral therapy (HAART) between August 1, 1996 and June 30, 2006. Deaths were routinely reported manually by physicians and through annual electronic record linkages with a population-based vital event registry. Multivariate logistic regression was carried out to assess independent predictors of death reporting by manual methods. RESULTS: Of the 3,116 individuals included in the analyses, 622 (20.0%) died during follow-up. Manual reporting by physicians only identified 377 (60.6%), while electronic linkages captured 598 (96.1%) of all deaths. Multivariate analysis indicated that deaths among individuals with lower CD4 cell count, higher HIV plasma viral load, a history of injection drug use, and under the care of an HIV-experienced physicians were more likely to be reported manually. Furthermore, non-accidental deaths were more likely to be reported manually, and manual reporting of deaths increased over time. CONCLUSIONS: Relying only on manual reports to ascertain deaths significantly underestimates the total number of deaths in the population. This can generate important biases when evaluating the impact of therapeutic interventions in the populational setting.

A ferrobotic system for automated microfluidic logistics.

Automated technologies that can perform massively parallelized and sequential fluidic operations at small length scales can resolve major bottlenecks encountered in various fields, including medical diagnostics, -omics, drug development, and chemical/material synthesis. Inspired by the transformational impact of automated guided vehicle systems on manufacturing, warehousing, and distribution industries, we devised a ferrobotic system that uses a network of individually addressable robots, each performing designated micro-/nanofluid manipulation-based tasks in cooperation with other robots toward a shared objective. The underlying robotic mechanism facilitating fluidic operations was realized by addressable electromagnetic actuation of miniature mobile magnets that exert localized magnetic body forces on aqueous droplets filled with biocompatible magnetic nanoparticles. The contactless and high-strength nature of the actuation mechanism inherently renders it rapid (~10 centimeters/second), repeatable (>10,000 cycles), and robust (>24 hours). The robustness and individual addressability of ferrobots provide a foundation for the deployment of a network of ferrobots to carry out cross-collaborative logistics efficiently. These traits, together with the reconfigurability of the system, were exploited to devise and integrate passive/active advanced functional components (e.g., droplet dispensing, generation, filtering, and merging), enabling versatile system-level functionalities. By applying this ferrobotic system within the framework of a microfluidic architecture, the ferrobots were tasked to work cross-collaboratively toward the quantification of active matrix metallopeptidases (a biomarker for cancer malignancy and inflammation) in human plasma, where various functionalities converged to achieve a fully automated assay.

A wearable freestanding electrochemical sensing system.

To render high-fidelity wearable biomarker data, understanding and engineering the information delivery pathway from epidermally retrieved biofluid to a readout unit are critical. By examining the biomarker information delivery pathway and recognizing near-zero strained regions within a microfluidic device, a strain-isolated pathway to preserve biomarker data fidelity is engineered. Accordingly, a generalizable and disposable freestanding electrochemical sensing system (FESS) is devised, which simultaneously facilitates sensing and out-of-plane signal interconnection with the aid of double-sided adhesion. The FESS serves as a foundation to realize a system-level design strategy, addressing the challenges of wearable biosensing, in the presence of motion, and integration with consumer electronics. To this end, a FESS-enabled smartwatch was developed, featuring sweat sampling, electrochemical sensing, and data display/transmission, all within a self-contained wearable platform. The FESS-enabled smartwatch was used to monitor the sweat metabolite profiles of individuals in sedentary and high-intensity exercise settings.

A programmable epidermal microfluidic valving system for wearable biofluid management and contextual biomarker analysis.

Active biofluid management is central to the realization of wearable bioanalytical platforms that are poised to autonomously provide frequent, real-time, and accurate measures of biomarkers in epidermally-retrievable biofluids (e.g., sweat). Accordingly, here, a programmable epidermal microfluidic valving system is devised, which is capable of biofluid sampling, routing, and compartmentalization for biomarker analysis. At its core, the system is a network of individually-addressable microheater-controlled thermo-responsive hydrogel valves, augmented with a pressure regulation mechanism to accommodate pressure built-up, when interfacing sweat glands. The active biofluid control achieved by this system is harnessed to create unprecedented wearable bioanalytical capabilities at both the sensor level (decoupling the confounding influence of flow rate variability on sensor response) and the system level (facilitating context-based sensor selection/protection). Through integration with a wireless flexible printed circuit board and seamless bilateral communication with consumer electronics (e.g., smartwatch), contextually-relevant (scheduled/on-demand) on-body biomarker data acquisition/display was achieved.

A 3D-printed microfluidic-enabled hollow microneedle architecture for transdermal drug delivery.

Embedding microfluidic architectures with microneedles enables fluid management capabilities that present new degrees of freedom for transdermal drug delivery. To this end, fabrication schemes that can simultaneously create and integrate complex millimeter/centimeter-long microfluidic structures and micrometer-scale microneedle features are necessary. Accordingly, three-dimensional (3D) printing techniques are suitable candidates because they allow the rapid realization of customizable yet intricate microfluidic and microneedle features. However, previously reported 3D-printing approaches utilized costly instrumentation that lacked the desired versatility to print both features in a single step and the throughput to render components within distinct length-scales. Here, for the first time in literature, we devise a fabrication scheme to create hollow microneedles interfaced with microfluidic structures in a single step. Our method utilizes stereolithography 3D-printing and pushes its boundaries (achieving print resolutions below the full width half maximum laser spot size resolution) to create complex architectures with lower cost and higher print speed and throughput than previously reported methods. To demonstrate a potential application, a microfluidic-enabled microneedle architecture was printed to render hydrodynamic mixing and transdermal drug delivery within a single device. The presented architectures can be adopted in future biomedical devices to facilitate new modes of operations for transdermal drug delivery applications such as combinational therapy for preclinical testing of biologic treatments.

A wearable electrofluidic actuation system.

We report a wearable electrofluidic actuation system, which exploits the alternating current electrothermal (ACET) effects to engineer biofluid flow profiles on the body. The wearable ACET flow is induced with the aid of corrosion-resistant electrode configurations (fabricated on a flexible substrate) and custom-developed, wirelessly programmable high frequency (MHz) excitation circuitry. Various tunable flow profiles are demonstrated with the aid of the devised flexible ACET electrode configurations, where the induced profiles are in agreement with the ACET theory and simulation. The demonstrated capabilities rendered by the presented system create new degrees of freedom for implementing advanced bioanalytical operations for future lab-on-the-body platforms.

A rapid and low-cost fabrication and integration scheme to render 3D microfluidic architectures for wearable biofluid sampling, manipulation, and sensing.

The large-scale deployment of wearable bioanalytical devices for general population longitudinal monitoring necessitates rapid and high throughput manufacturing-amenable fabrication schemes that render disposable, low-cost, and mechanically flexible microfluidic modules capable of performing a variety of bioanalytical operations within a compact footprint. The spatial constraints of previously reported wearable bioanalytical devices (with microfluidic operations confined to 2D), their lack of biofluid manipulation capability, and the complex and low-throughput nature of their fabrication process inherently limit the diversity and frequency of end-point assessments and prevent their deployment at large scale. Here, we devise a simple, scalable, and low-cost "CAD-to-3D Device" fabrication and integration scheme, which renders 3D and complex microfluidic architectures capable of performing biofluid sampling, manipulation, and sensing. The devised scheme is based on laser-cutting of tape-based substrates, which can be programmed at the software-level to rapidly define microfluidic features such as a biofluid collection interface, microchannels, and VIAs (vertical interconnect access), followed by the vertical assembly of pre-patterned layers to realize the final device. To inform the utility of our fabrication scheme, we demonstrated three representative devices to perform sweat collection (with visualizable secretion profile), sample filtration, and simultaneous biofluid actuation and sensing (using a sandwiched-interface). Our devised scheme can be adapted for the fabrication and manufacturing of current and future wearable bioanalytical devices, which in turn will catalyze the large-scale production and deployment of such devices for general population health monitoring.

Intraosseous Basivertebral Nerve Ablation for the Treatment of Chronic Low Back Pain: 2-Year Results From a Prospective Randomized Double-Blind Sham-Controlled Multicenter Study.

BACKGROUND: The purpose of the present study is to report the 2-year clinical outcomes for chronic low back pain (CLBP) patients treated with radiofrequency (RF) ablation of the basivertebral nerve (BVN) in a randomized controlled trial that previously reported 1-year follow up. METHODS: A total of 147 patients were treated with RF ablation of the BVN in a randomized controlled trial designed to demonstrate safety and efficacy as part of a Food and Drug Administration-Investigational Device Exemption trial. Evaluations, including patient self-assessments, physical and neurological examinations, and safety assessments, were performed at 2 and 6 weeks, and 3, 6, 12, 18, and 24 months postoperatively. Participants randomized to the sham control arm were allowed to cross to RF ablation at 12 months. Due to a high rate of crossover, RF ablation treated participants acted as their own control in a comparison to baseline for the 24-month outcomes. RESULTS: Clinical improvements in the Oswestry Disability Index (ODI), Visual Analog Scale (VAS), and the Medical Outcomes Trust Short-Form Health Survey Physical Component Summary were statistically significant compared to baseline at all follow-up time points through 2 years. The mean percent improvements in ODI and VAS compared to baseline at 2 years were 53.7 and 52.9%, respectively. Responder rates for ODI and VAS were also maintained through 2 years with patients showing clinically meaningful improvements in both: ODI ≥ 10-point improvement in 76.4% of patients and ODI ≥ 20-point improvement in 57.5%; VAS ≥ 1.5 cm improvement in 70.2% of patients. CONCLUSIONS: Patients treated with RF ablation of the BVN for CLBP exhibited sustained clinical benefits in ODI and VAS and maintained high responder rates at 2 years following treatment. Basivertebral nerve ablation appears to be a durable, minimally invasive treatment for the relief of CLBP.

Minimally invasive techniques for the management of lumbar disc herniation.

Traditionally, minimally invasive techniques for surgical discectomy have been defined as smaller incisions, tubular retractors, microscopically assisted tissue dissection, and conservative removal of only extruded or sequestered nucleus pulposus with preservation of the annulus. The first truly minimally invasive technique was chymopapain dissolution of the nucleus pulposus. Other percutaneous techniques followed; however, none were as efficacious as the gold standard of microlumbar discectomy until endoscopically visualized methods evolved to allow visualized mechanical discectomy through the foramen. In experienced hands, such a technique is as effective as microlumbar discectomy and results in less surgical morbidity for herniations that are appropriate for this minimally invasive endoscopic surgical portal that completely avoids traumatizing the normal anatomy of the dorsal musculature and ligamentous structures.

In-vivo endoscopic visualization of patho-anatomy in painful degenerative conditions of the lumbar spine.

The degenerative processes in an aging spine have been defined traditionally only by our knowledge of the biology of disc and facet degeneration, as well as interpretation of post-mortem cryosections by forensic anatomist Wolfgang Rauschning, M.D. In this chapter, visualization of in-vivo patho-anatomy in a degenerating disc and spinal segment is demonstrated at surgery using the Yeung Endoscopic Spine System (Y.E.S.S.), (Richard Wolf Surgical Instrument Company, Vernon Hills, IL, USA). An Institutional Review Board (IRB)-approved study of endoscopic treatment for degenerative conditions of the lumbar spine incorporated intraoperative probing under local anesthesia and endoscopic treatment of the visualized patho-anatomy. An intraoperative evocative chromo-discogram, using indigocarmine, was used to elicit discogenic pain and label the fissured and degenerative nucleus pulposus for surgical removal and thermal modulation. Painful patho-anatomy was probed in a conscious patient. The most common endoscopic finding was Inflammatory tissue in the disc and annulus. Inflammation was correlated with the presence of annular tears. Patho-physiologic changes that affect the exiting nerve, which contains the Dorsal Root Ganglion (DRG), was associated with stenotic and chemical irritation. Unavoidable postoperative dysesthesia was associated with the presence of an inflammatory membrane, and removal or thermal coagulation of "anomalous" furcal nerves in the foramen that branched off of the exiting spinal nerve. Neo-angiogenesis and neurogenesis in the inflammatory membrane present in the foraminal triangle was a new finding not reported in traditional clinical studies. Visualization and treatment of pathologic findings inside (annular tears) and outside the disc in Herniated Nucleus Pulposus (HNP), synovial cysts, foraminal stenosis, central stenosis, spondylolisthesis, is demonstrated. The endoscopic foraminal approach to the spine and disc is a technique that provides access to patho-anatomy in the lumbar spine not usually feasible with traditional surgical methods. Favorable surgical results allow for continued evolution of the endoscopic method, concomitant with the continued evolution of endoscopic spinal surgery.

HAART slows progression to anal cancer in HIV-infected MSM.

OBJECTIVE: Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM. DESIGN: A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008. METHODS: Time from first CD4 cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (<1996) were compared with those treated later (1996-2008). RESULTS: Anal cancer cases (n = 37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4 cell count nadir was 70 cells/µl (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [adjusted hazard ratio (AHR) 3.04, 95% confidence interval (95% CI) 1.48-6.24, P = 0.002], with a CD4 cell count nadir less than 100 cells/µl (AHR 2.21, 95% CI 1.06-4.62, P = 0.035) and longer duration of CD4 cell count less than 100 cells/µl (AHR 1.33, 95% CI 1.11-1.58, P = 0.002). CONCLUSION: Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART. Our results suggest that early use of HAART may delay progression to anal cancer.