Successful relief of central poststroke pain with BurstDR spinal cord stimulation: A case series.

Background: Central poststroke pain (CPSP) is a commonly undertreated condition that can negatively impact a patient's quality of life. The efficacy of spinal cord stimulation (SCS) for the treatment of CPSP is not established due to limited studies. Case Description: Here, two patients, ages 42 and 75, sustained strokes resulting in CPSP. After failed medical management, both underwent placement of paddle-lead SCS systems utilizing BurstDR stimulation that successfully resulted in pain resolution. Conclusion: Two patients with CPSP were successfully treated with paddle lead SCS with BurstDR programming.

Movement disorder Deep brain stimulation Hybridization: Patient and caregiver outcomes.

Background and Objectives: Deep brain stimulation (DBS) is a well-established surgical treatment for certain movement disorders and involves the implantation of brain electrodes connected to implantable pulse generators (IPGs). As more device manufacturers have entered the market, some IPG technology has been designed to be compatible with brain electrodes from other manufacturers, which has facilitated the hybridization of implant technology. The aim of this study was to assess the benefits of hybridization of non-rechargeable, constant voltage IPGs to rechargeable, constant current IPGs. Methods: A list of DBS movement disorder patients who had their non-rechargeable, constant voltage IPGs replaced with rechargeable, constant current IPGs from a different manufacturer was compiled. Structured surveys of these patients, and their caregivers when applicable, were undertaken to determine both patient and caregiver satisfaction in this DBS hybridization strategy. Results: Eighteen patients met inclusion criteria and twelve patients or their caregivers completed the structured survey (67% response rate). Nine patients had Parkinson's disease (75%), three had essential tremor (25%). Nine (75%) were converted from bilateral single-channel IPGs, and three (25%) were converted from a unilateral dual-channel IPGs. Overall, 92% of patients and caregivers surveyed reported improvement or no change in their symptoms, 92% reported a decrease or no change in their medication requirements, and 92% report they are satisfied or very satisfied with their IPG hybridization and would recommend the surgery to similar patients. There were no immediate surgical complications. Conclusion: In this series of movement disorder DBS patients, surgery was safe and patient and caregiver satisfaction were high with a hybridization of non-rechargeable, constant voltage IPGs to rechargeable, constant current IPGs.

Inactivation of spinal cord stimulator implanted pulse generators after elective surgery: an under-recognized problem.

STUDY DESIGN: We retrospectively analyzed a database of implanted pulse generators (IPGs) for spinal cord stimulation (SCS) implanted by a single surgeon (NDT). We additionally report a series of five illustrative patient cases. OBJECTIVES: The electronics of SCS IPGs are susceptible to damage when implanted patients undergo surgery. Some SCSs have a dedicated surgery mode, while others recommend turning the SCS off to protect it from damage. IPG inactivation may require resetting or replacement surgery. We aimed to explore the prevalence of this real-world problem which has not been studied. SETTING: Pittsburgh, Pennsylvania. METHODS: Using a single surgeon SCS database, we identified cases of IPG inactivation after a non-SCS surgery and analyzed the management. We then reviewed the charts of five illustrative cases. RESULTS: Among 490 SCS IPG implantations between 2016-2022, 15 (3%) of the 490 patients' IPGs became inactivated after another non-SCS surgery. 12 (80%) required surgical IPG replacement, while 3 (20%) were able to have their IPG function restored non-operatively. In cases analyzed thus far, surgery mode was often not activated prior to surgery. CONCLUSION: SCS IPG inactivation by surgery is not a rare problem and is presumably engendered by monopolar electrocautery. Premature IPG replacement surgery carries risks and reduces the cost-effectiveness of SCS. Awareness of this problem may prompt more preventative measures to be taken by surgeons, patients, and caretakers, and encourage technological advances to render IPGs less vulnerable to surgical tools. Further research is needed to determine what quality improvement measures could prevent electrical damage to IPGs.

Paddle Lead Spinal Cord Stimulation in the Morbidly Obese Patient Population: Outcomes and Complications in a Single-Surgeon Cohort.

BACKGROUND: Paddle lead spinal cord stimulation (SCS) is used to treat refractory chronic pain. Morbidly obese patients seek SCS to reduce chronic pain. However, these patients face worse surgical outcomes, and the SCS literature has not evaluated safety and efficacy in this patient population. This study is the largest single-surgeon case series to date on morbidly obese patients with paddle lead SCS implantations. The primary objective is to report postoperative complication rates in morbidly obese patients receiving SCS implants. The secondary objective is to report patient-reported pain scores and Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and physical function scores in these patients. METHODS: A retrospective chart review was conducted. The patient charts were reviewed from the day of procedure consent to 6 months postop. Demographic information, pain scores, PROMIS scores, neurological complications, infections, and wound complications were documented. RESULTS: Sixty-seven patients were included. The mean preoperative BMI was 44.47 ± 4.02 kg/m2. The mean age was 58.9 ± 11.4 years old. There were no neurological complications. 3/67 (4%) developed culture-positive infections. Nine out of sixty-seven (13%) patients developed superficial wound dehiscence without underlying infection. The mean postop PROMIS physical function score was 31.6 ± 6.2 (n = 16) and the mean post-op PROMIS pain interference score was 64.0 ± 6.4 (n = 16). There was a reduction in pain scores, from 7.9 ± 1.7 preop to 5.7 ± 2.5 postop (n = 22, P = 0.004). CONCLUSIONS: Paddle lead SCS implantation is safe for morbidly obese patients. The only minimal-risk complications present were postoperative infections and wound dehiscence. Surgical care can be modified to further reduce the rates of infection and dehiscence.

Spinal cord stimulation: A novel approach to pain management in Dercum's disease.

Background: Dercum's Disease (DD) is a rare chronic pain syndrome in which patients experience extreme burning pain associated with subcutaneous lipomatous tissue deposits. These patients may also present with; weakness, psychiatric symptoms, metabolic derangements, sleep disturbance, impaired memory, and easy bruising. Common risk factors for DD include: obesity, Caucasian race, and female sex. The etiology of DD remains under debate while it has proven highly resistant to treatment (i.e., requiring high doses of opioids for adequate pain management). Case Description: A 48-year-old female with DD and a prior spinal cord stimulator (SCS) placed for chronic back pain, presented with recurrent back pain, and increased falling. Surgery to replace her SCS resulted in improvement in her back pain and a decreased incidence of falls. Furthermore, she noticed significant improvement in the burning pain attributed to her subcutaneous nodules; this most markedly occurred at and below the level of stimulator placement. Conclusion: A 48-year-old female with the extremely rare condition, DD experienced dramatic reduction in her pain following the successful revision of her SCS.

The American Society of Pain and Neuroscience (ASPN) Evidence-Based Clinical Guideline of Interventional Treatments for Low Back Pain.

Introduction: Painful lumbar spinal disorders represent a leading cause of disability in the US and worldwide. Interventional treatments for lumbar disorders are an effective treatment for the pain and disability from low back pain. Although many established and emerging interventional procedures are currently available, there exists a need for a defined guideline for their appropriateness, effectiveness, and safety. Objective: The ASPN Back Guideline was developed to provide clinicians the most comprehensive review of interventional treatments for lower back disorders. Clinicians should utilize the ASPN Back Guideline to evaluate the quality of the literature, safety, and efficacy of interventional treatments for lower back disorders. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations. Experts from the fields of Anesthesiology, Physiatry, Neurology, Neurosurgery, Radiology, and Pain Psychology developed the ASPN Back Guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Scopus, and meeting abstracts to identify and compile the evidence (per section) for back-related pain. Search words were selected based upon the section represented. Identified peer-reviewed literature was critiqued using United States Preventive Services Task Force (USPSTF) criteria and consensus points are presented. Results: After a comprehensive review and analysis of the available evidence, the ASPN Back Guideline group was able to rate the literature and provide therapy grades to each of the most commonly available interventional treatments for low back pain. Conclusion: The ASPN Back Guideline represents the first comprehensive analysis and grading of the existing and emerging interventional treatments available for low back pain. This will be a living document which will be periodically updated to the current standard of care based on the available evidence within peer-reviewed literature.

Best Practices for Minimally Invasive Lumbar Spinal Stenosis Treatment 2.0 (MIST): Consensus Guidance from the American Society of Pain and Neuroscience (ASPN).

Introduction: Lumbar spinal stenosis (LSS) is a common spinal disease of aging with a growing patient population, paralleling population growth. Minimally invasive treatments are evolving, and the use of these techniques needs guidance to provide the optimal patient safety and efficacy outcomes. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for guidance on the prudent use of the innovative minimally invasive surgical therapies for the treatment of symptomatic LSS. The executive board nominated experts spanning anesthesiology, physiatry, orthopedic surgery, and neurosurgery based on expertise, publications, research, diversity and field of practice. Evidence was reviewed, graded using the United States Preventive Services Task Force (USPSTF) criteria for evidence and recommendation strength and grade, and expert opinion was added to make consensus points for best practice. Results: The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Scopus, and meeting abstracts to identify and compile the evidence (per section) for LSS-related pain. Search words were selected based upon the section represented. Identified peer-reviewed literature was critiqued using USPSTF criteria and consensus points are presented. Discussion: The algorithm for patient selection in the management of symptomatic spinal stenosis is evolving. Careful consideration of patient selection and anatomic architecture variance is critical for improved outcomes and patient safety. Conclusion: ASPN created a guidance for best practice for minimally invasive surgical treatment of symptomatic spinal stenosis.

Design, synthesis, and biological evaluation of C6-difluoromethylenated epoxymorphinan Mu opioid receptor antagonists.

The recent widespread abuse of high potency synthetic opioids, such as fentanyl, presents a serious threat to individuals affected by substance use disorder. Synthetic opioids generally exhibit prolonged in vivo circulatory half-lives that can outlast the reversal effects of conventional naloxone-based overdose antidotes leading to a life-threatening relapse of opioid toxicity known as renarcotization. In this manuscript, we present our efforts to combat the threat of renarcotization by attempting to extend the half-life of traditional MOR antagonists through the design of novel, fluorinated 4,5-epoxymorphinans possessing increased lipophilicity. Analogues were prepared via a concise synthetic strategy highlighted by decarboxylative Wittig olefination of the C6 ketone to install a bioisosteric 1,1-difluoromethylene unit. C6-difluoromethylenated compounds successfully maintained in vitro potency against an EC90 challenge of fentanyl and were predicted to have enhanced circulatory half-life compared to the current standard of care, naloxone. Subsequent in vivo studies demonstrated the effective blockade of fentanyl-induced anti-nociception in mice.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations on Best Practices for Cervical Neurostimulation.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on the use of neurostimulation in the cervical region to improve outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for an often-overlooked area of neurostimulation practice. MATERIALS AND METHODS: Authors were chosen based upon their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to the present. Identified studies were graded using the US Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant. RESULTS: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The NACC recommends best practices regarding the use of cervical neuromodulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be utilized as a guide to assist decision making when clinically appropriate.

Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized, Double-Blind Primary Endpoint.

OBJECTIVE: Published reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease. MATERIALS AND METHODS: Participants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life. RESULTS: The study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period. CONCLUSION: Directional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians.

Development and Characterization of Novel Conductive Sensing Fibers for In Vivo Nerve Stimulation.

Advancements in electrode technologies to both stimulate and record the central nervous system's electrical activities are enabling significant improvements in both the understanding and treatment of different neurological diseases. However, the current neural recording and stimulating electrodes are metallic, requiring invasive and damaging methods to interface with neural tissue. These electrodes may also degrade, resulting in additional invasive procedures. Furthermore, metal electrodes may cause nerve damage due to their inherent rigidity. This paper demonstrates that novel electrically conductive organic fibers (ECFs) can be used for direct nerve stimulation. The ECFs were prepared using a standard polyester material as the structural base, with a carbon nanotube ink applied to the surface as the electrical conductor. We report on three experiments: the first one to characterize the conductive properties of the ECFs; the second one to investigate the fiber cytotoxic properties in vitro; and the third one to demonstrate the utility of the ECF for direct nerve stimulation in an in vivo rodent model.

Covalently Loaded Naloxone Nanoparticles as a Long-Acting Medical Countermeasure to Opioid Poisoning.

The mu opioid receptor antagonist naloxone has been a vital, long-standing countermeasure in the ongoing battle against opioid use disorders (OUD) and toxicity. However, due to its distinctive short elimination half-life, naloxone has shown diminished efficacy in cases of synthetic opioid poisoning as larger or repeated doses of the antidote have been required to achieve adequate reversal of severe respiratory depression and prevent episodes of renarcotization. This report describes the synthesis, characterization, and in vivo evaluation of a novel, nanoparticle-based naloxone formulation that provides extended protection against the toxic effects of the powerful synthetic opioid fentanyl. The strategy was predicated on a modified two-step protocol involving the synthesis and subsequent nanoprecipitation of a poly(lactic-co-glycolic acid) polymer scaffold bearing a covalently linked naloxone chain end (drug loading ∼7% w/w). Pharmacokinetic evaluation of the resulting covalently loaded naloxone nanoparticles (cNLX-NP) revealed an elimination half-life that was 34 times longer than high dose free naloxone (10 mg/kg) in male Sprague-Dawley rats. This enhancement was further demonstrated by cNLX-NP in subsequent in vivo studies affording protection against fentanyl-induced respiratory depression and antinociception for up to 48 h following a single intramuscular injection. These discoveries support further investigation of cNLX-NP as a potential therapeutic to reverse overdose and prevent renarcotization from fentanyl and its potent analogs.

Countermeasures for Preventing and Treating Opioid Overdose.

The only medication available currently to prevent and treat opioid overdose (naloxone) was approved by the US Food and Drug Administration (FDA) nearly 50 years ago. Because of its pharmacokinetic and pharmacodynamic properties, naloxone has limited utility under some conditions and would not be effective to counteract mass casualties involving large-scale deployment of weaponized synthetic opioids. To address shortcomings of current medical countermeasures for opioid toxicity, a trans-agency scientific meeting was convened by the US National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) on August 6 and 7, 2019, to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. The meeting was initiated by the Chemical Countermeasures Research Program (CCRP), was organized by NIAID, and was a collaboration with the National Institute on Drug Abuse/NIH (NIDA/NIH), the FDA, the Defense Threat Reduction Agency (DTRA), and the Biomedical Advanced Research and Development Authority (BARDA). This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: (1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; (2) methocinnamox, a novel opioid receptor antagonist; (3) covalent naloxone nanoparticles; (4) serotonin (5-HT)1A receptor agonists; (5) fentanyl-binding cyclodextrin scaffolds; (6) detoxifying biomimetic "nanosponge" decoy receptors; and (7) antibody-based strategies. These approaches could also be applied to treat opioid use disorder.

Parametric evaluation of deep brain stimulation parameter configurations for Parkinson's disease using a conformal wearable and wireless inertial sensor system and machine learning.

Deep brain stimulation enables highly specified patient-unique therapeutic intervention ameliorating the symptoms of Parkinson's disease. Inherent to the efficacy of deep brain stimulation is the acquisition of an optimal parameter configuration. Using conventional methods, the optimization process for tuning the deep brain stimulation system parameters can intrinsically induce strain on clinical resources. An advanced means of quantifying Parkinson's hand tremor and distinguishing between parameter settings would be highly beneficial. The conformal wearable and wireless inertial sensor system, such as the BioStamp nPoint, has a volumetric profile on the order of a bandage that readily enables convenient quantification of Parkinson's disease hand tremor. Furthermore, the BioStamp nPoint has been certified by the FDA as a 510(k) medical device for acquisition of medical grade data. Parametric variation of the amplitude parameter for deep brain stimulation can be quantified through the BioStamp nPoint conformal wearable and wireless inertial sensor system mounted to the dorsum of the hand. The acquired inertial sensor signal data can be wirelessly transmitted to a secure Cloud computing environment for post-processing. The quantified inertial sensor data for the parametric study of the effects of varying amplitude can be distinguished through machine learning classification. Software automation through Python can consolidate the inertial sensor data into a suitable feature set format. Using the multilayer perceptron neural network considerable machine learning classification accuracy is attained to distinguish multiple parametric settings of amplitude for deep brain stimulation, such as 4.0 mA, 2.5 mA, 1.0 mA, and 'Off' status representing a baseline. These findings constitute an advance toward the pathway of attaining real-time closed loop automated parameter configuration tuning for treatment of Parkinson's disease using deep brain stimulation.

Peripheral subcutaneous field stimulation for the treatment of spinal cord injury at-level pain: case report, literature review, and 5-year follow-up.

Spinal cord injury (SCI) frequently engenders chronic pain which may be classified as occurring above, at, or below the level of injury. Since patients with SCI may have a complex combination of nociceptive and neuropathic pain, pharmacological interventions often fail. Peripheral subcutaneous field stimulation (PSFS) is a novel neuromodulation surgery for pain in which subcutaneous electrodes designed for spinal cord stimulation are placed subcutaneously in a region of pain. We report the case of a 26-year-old man who was an unrestrained driver in a motor vehicle accident and suffered a complete ASIA A spinal cord injury with paraplegia due to a T4 three-column burst fracture. He underwent successful surgical fixation of the fracture (7/27/12) and developed severe at-level SCI-associated pain which failed all conservative measures. After a successful trial, two octrode leads (Abbott Medical, Plano, TX, USA) were placed for PSFS under general anesthesia and were connected to a right flank rechargeable pulse generator (11/6/13). At 60 months postoperative, the patient continues to use the peripheral field stimulation system on a daily basis and reports near complete relief of his at-level spinal cord injury pain. He noted instantaneous relief of his pain once ideal stimulation programming was achieved and has tolerated complete cessation of all narcotic use. His current programming settings are: Frequency of 50 Hz (Hz), Pulse Width of 350 µs (µsec), Amplitude of 0.00 miliamps (mA), Comf of 7.70 mA, and Perc of 4.50 mA. Chronic pain is a challenging and expensive sequela to manage in SCI patients and newer therapies are needed. Our case suggests that SCI at-level pain may respond durably to PSFS and provides the longest published follow-up on a case of PSFS. Peripheral subcutaneous field stimulation remains an investigational treatment for chronic pain syndrome and larger, long-term follow up studies are needed for the FDA and payers to approve this modality.

The Efficacy of BurstDR Spinal Cord Stimulation for Chronic Abdominal Pain: A Clinical Series.

BACKGROUND: Chronic abdominal pain is a debilitating condition known for its multifactorial nature. Outcomes with spinal cord stimulation (SCS) for abdominal pain syndromes are noticeably absent in the literature. To date, there have been no published reports of novel waveforms of SCS for management of chronic abdominal pain. We assessed the efficacy and durability of BurstDR SCS in reducing abdominal pain and analgesic consumption. CASE DESCRIPTION: We performed a retrospective review of medical records from 3 patients with different etiologies of abdominal pain (postherniorrhaphy pain syndrome, Crohn disease, abdominal neuropathy). All patients underwent thoracic laminectomy for BurstDR SCS paddle lead and pulse generator placement after a successful trial stimulation period. Data were collected with a telephone survey after a minimum duration of >24 months following implantation. Pain scores were measured using a numeric rating scale. Two of 3 patients were entirely pain-free and reported Patient Global Impression of Change scores of 7 after a minimum follow-up of >24 months. While the third patient continued to have chronic as well as episodic abdominal pain, he was able to discontinue all narcotic pain medications and experienced a 33% decrease in frequency and 60% decrease in severity of monthly pain exacerbations. He reported satisfaction and a Patient Global Impression of Change of 6. CONCLUSIONS: BurstDR SCS is a new programming modality, and long-term follow-up is necessary to determine its durability. Despite varying etiologies of abdominal pain, this series suggests BurstDR SCS sustained for >2 years might be effective as a treatment for abdominal pain syndromes. Future studies of SCS would benefit from standardized abdominal pain scores and high-powered studies using global patient registries.

Prevention of Implant-Associated Infection in Neuromodulation: Review of the Literature and Prototype of a Novel Protective Implant Coating.

Background: Implanting hardware into surgical sites increases the rate of infection associated with these sites. Without novel efforts to reduce this rate of infection, we can expect to see an increase in the number of hardware-associated infections as more patients are implanted with these devices. These infections often necessitate the removal of these devices resulting in a significant financial and clinical burden to patients. We developed a prototype antibiotic coating using products that are both low cost and that can be sourced easily. Our study aims to test the effectiveness of this coating against bacteria commonly observed in hospital-associated infections. Methods: The antibiotic coating was prepared by combining one gram of vancomycin and 500 mg of ciprofloxacin in 50 mL of glycerol. The coating was examined for inhibition of growth of Pseudomonas aeruginosa PA14 and Staphylococcus aureus AH2486 and compared with the bacterial growth of the above bacteria in glycerol alone. The growth curves were plotted measuring the bacterial growth at 5 h intervals. Results: The results of the growth curves clearly demonstrate a lack of bacterial growth when these bacteria are combined with glycerol combined with our selected antibiotic agents. Conclusion: There appears to be a limited interest from device companies in developing new strategies for infection prevention associated with neurosurgical hardware, and we propose that this prototype will be an effective and low-cost solution to a large problem.

Covalent Poly(lactic acid) Nanoparticles for the Sustained Delivery of Naloxone.

The opioid epidemic currently plaguing the United States has been exacerbated by an alarming rise in fatal overdoses as a result of the proliferated abuse of synthetic mu opioid receptor (MOR) agonists, such as fentanyl and its related analogues. Attempts to manage this crisis have focused primarily on widespread distribution of the clinically approved opioid reversal agent naloxone (Narcan); however, due to the intrinsic metabolic lability of naloxone, these measures have demonstrated limited effectiveness against synthetic opioid toxicity. This work reports a novel polymer-based strategy to create a long-acting formulation of naloxone with the potential to address this critical issue by utilizing covalent nanoparticle (cNP) drug delivery technology. Covalently loaded naloxone nanoparticles (Nal-cNPs) were prepared via the naloxone-initiated, ring-opening polymerization (ROP) of l-lactide in the presence of a bifunctional thiourea organocatalyst with subsequent precipitation of the resulting naloxone-poly(l-lactic acid) polymer. This protocol afforded well-defined nanoparticles possessing a drug loading of approximately 7% w/w. The resulting Nal-cNPs demonstrated excellent biocompatibility, while exhibiting sustained linear release kinetics in vitro and blocking the effects of high dose (10 mg/kg) acute morphine for up to 98 h in an in vivo rodent model of neuropathic pain.

Clinical Outcomes After Spine Surgery for Traumatic Injury in the Octogenarian Population.

OBJECTIVE: To review the surgical outcomes of the octogenarian population at a single institution after spinal traumatic injury. METHODS: Patients with both radiographic and clinical evidence of acute traumatic spine injury were reviewed using an institutional trauma survey to determine patient demographics and outcome data in a population of patients aged 80 years and older. RESULTS: Thirty-nine patients aged 80 years and older underwent surgical intervention for acute spinal trauma. There were 25 cases of cervical spine and 14 cases of thoracolumbar spine surgical intervention. Falls were the number one cause of acute spinal injury (31/39, 71%). Major respiratory disorders were the most common postoperative adverse event (12/39, 31%). Five patients experienced superficial wound dehiscence, fascial dehiscence, superficial infection, or delayed wound erosion. Patients were either discharged to home (10.5%), inpatient rehabilitation, (38.5%), skilled nursing facilities (17.9%), or long-term care facilities (17.9%). The postoperative mortality was 10.3%. CONCLUSIONS: Although the octogenarian population has increased risk for postoperative events after acute spinal injuries, surgical intervention may be worthwhile in the elderly population. Although direct surgical complication rates are not higher, medical risks are significantly higher after surgery.

Deep Brain Stimulation of the Hypothalamus Leads to Increased Metabolic Rate in Refractory Obesity.

OBJECTIVE: Obesity has become a worldwide epidemic, with very few long-term successful treatment options for refractory disease. Deep brain stimulation (DBS) of the bilateral lateral hypothalamus (LH) in refractory obesity has been performed safely. However, questions remain regarding the optimal settings and its effects on metabolic rate. The goals of our experiment were to determine the optimal DBS settings and the actual effect of optimal stimulation on energy expenditure. METHODS: After bilateral LH DBS implantation, 2 subjects with treatment refractory obesity underwent 4 days of metabolic testing. The subjects slept overnight in a respiratory chamber to measure their baseline sleep energy expenditure, followed by 4 consecutive days of resting metabolic rate (RMR) testing at different stimulation settings. On day 4, the optimized DBS settings were used, and sleep energy expenditure was measured again overnight in the room calorimeter. RESULTS: During daily testing, the RMR fluctuated acutely with changes in stimulation settings and returned to baseline immediately after turning off the stimulation. Optimal stimulation settings selected for participants showed a 20% and 16% increase in RMR for the 2 participants. Overnight sleep energy expenditure measurements at these optimized settings on day 4 yielded a 10.4% and 4.8% increase over the baseline measurements for the 2 participants. CONCLUSIONS: These findings have demonstrated the efficacy of optimized DBS of the LH on increasing the RMR acutely and maintaining this increase during overnight sleep. These promising preliminary findings have laid the groundwork for the possible treatment of refractory obesity with DBS.