Analgesia with Gabapentin and Pregabalin May Involve N-Methyl-d-Aspartate Receptors, Neurexins, and Thrombospondins.

The gabapentinoid drugs gabapentin and pregabalin (Neurontin and Lyrica) are mainstay treatments for neuropathic pain and preventing focal seizures. Both drugs have similar effects to each other in animal models and clinically. Studies have shown that a protein first identified as an auxiliary subunit of voltage-gated calcium channels (the α 2 δ-subunit type 1 [α 2 δ-1], or Ca V a2d1) is the high-affinity binding site for gabapentin and pregabalin and is required for the efficacy of these drugs. The α 2 δ-1 protein is required for the ability of gabapentin and pregabalin to reduce neurotransmitter release in neuronal tissue, consistent with a therapeutic mechanism of action via voltage-gated calcium channels. However, recent studies have revealed that α 2 δ-1 interacts with several proteins in addition to voltage-gated calcium channels, and these additional proteins could be involved in gabapentinoid pharmacology. Furthermore, gabapentin and pregabalin have been shown to modify the action of a subset of N-methyl-d-aspartate-sensitive glutamate receptors, neurexin-1α, and thrombospondin proteins by binding to α 2 δ-1. Thus, these effects may contribute substantially to gabapentinoid therapeutic mechanism of action. SIGNIFICANCE STATEMENT: It is widely believed that gabapentin and pregabalin act by modestly reducing the membrane localization and activation of voltage-gated calcium channels at synaptic endings in spinal cord and neocortex via binding to the α 2 δ-1 protein. However, recent findings show that the α 2 δ-1 protein also interacts with N-methyl-d-aspartate-sensitive glutamate receptors, neurexin-1α, thrombospondins (adhesion molecules), and other presynaptic proteins. These newly discovered interactions, in addition to actions at calcium channels, may be important mediators of gabapentin and pregabalin therapeutic effects.

Safety and efficacy of outpatient sleeve gastrectomy: 2534 cases performed in a single free-standing ambulatory surgical center.

BACKGROUND: Sleeve gastrectomy (SG) is currently the most widely performed operation for treatment of morbid obesity. SG leads to significant weight loss and reduction in weight related comorbidities. Procedures performed in ambulatory surgical centers (ASC) can provide several advantages over hospital-based surgery. We present results of 2,534 consecutive patients who underwent SG in an ASC. OBJECTIVE: Assess the safety and efficacy of outpatient SG in a freestanding ASC. SETTING: Free-standing ASC, Eviva Bariatrics, Seattle WA. METHODS: Data was collected retrospectively for all patients undergoing SG from January 2008 - January 2018, n = 2,534. Revisional procedures were not excluded from this study. Patients were excluded from the ASC if they weighed >450 pounds, if anticipated surgery time was > 2 hours, if the patient had impaired mobility limiting early ambulation, or if there were medical problems requiring postoperative monitoring beyond 23 hours. RESULTS: Mean age was 45.9 years. Mean preoperative body mass index (BMI) was 41.9. Mean operative time was 70 minutes. 30-day complications included 3 mortalities (0.12%), 60 (2.53%) re-admissions, 35 (1.42%), re-operations, and 31 (1.22%) direct transfers from the ASC to a nearby hospital. There were 25 staple line leaks (0.99%). There were no open conversions. At 6 months average excess body weight loss (EWL) was 56.3% and total weight loss (TWL) was 20.9% (n = 1,758/2,303). At 1 year, EWL was 70.1% and TWL was 26.4% (n = 1,199/2,125). CONCLUSION: With experienced surgeons, appropriate protocols, and a consistent operative team, SG can be performed safely in a free-standing ASC.

Does the future of laparoscopic sleeve gastrectomy lie in the outpatient surgery center? A retrospective study of the safety of 3162 outpatient sleeve gastrectomies.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a safe and effective procedure that can be performed as an outpatient procedure. OBJECTIVES: The aim of the study was to determine whether same-day discharge LSG is safe when performed in an outpatient surgery center. SETTING: Outpatient surgery centers. METHODS: The medical records of 3162 patients who underwent primary LSG procedure by 21 surgeons at 9 outpatient surgery centers from January 2010 through February 2018 were retrospectively reviewed. RESULTS: Three thousand one hundred sixty-two patients were managed with enhanced recovery after surgery protocol and were included in this analysis. The mean age and preoperative body mass index were 43.1 ± 10.8 years and 42.1 ± 7.1 kg/m2, respectively. Sleep apnea, type 2 diabetes, gastroesophageal reflux disease, hypertension, and hyperlipidemia were seen in 14.4%, 13.5%, 24.7%, 30.4%, and 17.6% patients, respectively. The mean total operative time was 56.4 ± 16.9 minutes (skin to skin). One intraoperative complication (.03%) occurred. The hospital transfer rate was .2%. The 30-day follow-up rate was 85%. The postoperative outcomes were analyzed based on the available data. The 30-day readmission, reoperation, reintervention, and emergency room visit rates were .6%, .6%, .2%, and .1%, respectively. The 30-day mortality rate was 0%. The total short-term complication rate was 2.5%. CONCLUSIONS: Same-day discharge seems to be safe when performed in an outpatient surgery center in selected patients. It would appear that outpatient surgery centers are a viable option for patients with minimal surgical risks.

High acuity sleeve gastrectomy patients in a free-standing ambulatory surgical center.

BACKGROUND: Procedures performed in ambulatory surgical centers (ASC) can provide several advantages over hospital-based surgery. Understandably, concerns have been raised regarding "high acuity" cases in the ASC setting. Recently the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) presented protocols for ASCs to follow, requiring them to perform only "low acuity" cases to be compliant with accreditation. OBJECTIVE: Assess the safety and efficacy of outpatient sleeve gastrectomy (SG) on the "high acuity patient" in a free-standing ASC. SETTING: Free-standing ASC, Eviva Bariatrics, Seattle, Washington. METHODS: Data were collected retrospectively for all patients who underwent sleeve gastrectomy from January 1, 2013 to December 31, 2015, n = 1112. Of those patients, 120 were classified as "high acuity." RESULTS: Mean age was 51.7 years (24-73), mean body mass index was 42.4 (26.2-65.9). Mean operative time was 91 minutes. Five patients (4.2%) were readmitted within 30 days. Causes of re-admission were portal vein thrombosis (n = 2), intra-abdominal abscess (n = 1), infected hematoma (n = 1), and postoperative bleeding (n = 1). One patient (0.83%) was transferred from the ASC to a nearby hospital due to a postoperative bleed. One patient (0.83%) had a re-operation to evacuate a hematoma. One patient had a re-operation to wash out an infected hematoma. There were 0 confirmed staple line leaks. There were no open conversions and no deaths within 30 days or at 1 year. Follow-up was 83% (n = 100) at 6 months, and 65.0% at 1 year (n = 78). CONCLUSION: Criteria such as age, body mass index, or prior bariatric surgery did not reflect worse outcomes in a specialized ASC. With experienced surgeons, appropriate protocols, and a consistent operative team, SG can be performed safely in a free-standing ASC on select "high acuity" patients.

A matrix model for valuing anesthesia service with the resource-based relative value system.

BACKGROUND: The purpose of this study was to propose a new crosswalk using the resource-based relative value system (RBRVS) that preserves the time unit component of the anesthesia service and disaggregates anesthesia billing into component parts (preoperative evaluation, intraoperative management, and postoperative evaluation). The study was designed as an observational chart and billing data review of current and proposed payments, in the setting of a preoperative holing area, intraoperative suite, and post anesthesia care unit. In total, 1,195 charts of American Society of Anesthesiology (ASA) physical status 1 through 5 patients were reviewed. No direct patient interventions were undertaken. RESULTS: Spearman correlations between the proposed RBRVS billing matrix payments and the current ASA relative value guide methodology payments were strong (r=0.94-0.96, P<0.001 for training, test, and overall). The proposed RBRVS-based billing matrix yielded payments that were 3.0%±1.34% less than would have been expected from commercial insurers, using standard rates for commercial ASA relative value units and RBRVS relative value units. Compared with current Medicare reimbursement under the ASA relative value guide, reimbursement would almost double when converting to an RBRVS billing model. The greatest increases in Medicare reimbursement between the current system and proposed billing model occurred as anesthetic management complexity increased. CONCLUSION: The new crosswalk correlates with existing evaluation and management and intensive care medicine codes in an essentially revenue neutral manner when applied to the market-based rates of commercial insurers. The new system more highly values delivery of care to more complex patients undergoing more complex surgery and better represents the true value of anesthetic case management.

Primary Pulmonary Synovial Sarcoma during Pregnancy: A Diagnostic and Therapeutic Dilemma.

Synovial sarcoma is a rare soft tissue sarcoma that typically arises in the extremities of young adults. We report a case of a 26-year-old pregnant woman with biopsy-proven primary synovial sarcoma of the lung that was treated with chemotherapy with radiographic response. This is only the third documented case of primary pulmonary synovial sarcoma occurring during pregnancy and the first case where chemotherapy was given.

Does the site of anterior tracheal puncture affect the success rate of retrograde intubation? A prospective, manikin-based study.

Background. Retrograde intubation is useful for obtaining endotracheal access when direct laryngoscopy proves difficult. The technique is a practical option in the "cannot intubate / can ventilate" scenario. However, it is equally useful as an elective technique in awake patients with anticipated difficult airways. Many practitioners report difficulty successfully advancing the endotracheal tube due to anatomical obstructions and the acute angle of the anterograde guide. The purpose of this study was to test whether a more caudal tracheal puncture would increase the success rate. Methods. Twenty-four anesthesiology residents were randomly assigned to either a cricothyroid or a cricotracheal puncture group. Each was instructed how to perform the technique and then attempted it on a manikin at their assigned site. Data collection included whether the trachea was intubated, the number of attempts required, and the total time. Results. Both groups displayed a high degree of success. While the group assigned to the cricotracheal site required significantly more time to perform the procedure, they accomplished it in fewer attempts than the cricothyroid group. Conclusion. Retrograde intubation performed via a cricotracheal puncture site, while more time consuming, resulted in fewer attempts to advance the endotracheal tube and may reduce in vivo laryngeal trauma.

Selection for high oridonin yield in the Chinese medicinal plant Isodon (Lamiaceae) using a combined phylogenetics and population genetics approach.

Oridonin is a diterpenoid with anti-cancer activity that occurs in the Chinese medicinal plant Isodon rubescens and some related species. While the bioactivity of oridonin has been well studied, the extent of natural variation in the production of this compound is poorly known. This study characterizes natural variation in oridonin production in order to guide selection of populations of Isodon with highest oridonin yield. Different populations of I. rubescens and related species were collected in China, and their offspring were grown in a greenhouse. Samples were examined for oridonin content, genotyped using 11 microsatellites, and representatives were sequenced for three phylogenetic markers (ITS, rps16, trnL-trnF). Oridonin production was mapped on a molecular phylogeny of the genus Isodon using samples from each population as well as previously published Genbank sequences. Oridonin has been reported in 12 out of 74 species of Isodon examined for diterpenoids, and the phylogeny indicates that oridonin production has arisen at least three times in the genus. Oridonin production was surprisingly consistent between wild-collected parents and greenhouse-grown offspring, despite evidence of gene flow between oridonin-producing and non-producing populations of Isodon. Additionally, microsatellite genetic distance between individuals was significantly correlated with chemical distance in both parents and offspring. Neither heritability nor correlation with genetic distance were significant when the comparison was restricted to only populations of I. rubescens, but this result should be corroborated using additional samples. Based on these results, future screening of Isodon populations for oridonin yield should initially prioritize a broad survey of all species known to produce oridonin, rather than focusing on multiple populations of one species, such as I. rubescens. Of the samples examined here, I. rubescens or I. japonicus from Henan province would provide the best source of oridonin.

Development of microsatellite markers for the medicinal plant Isodon rubescens (Lamiaceae) and related species.

PREMISE OF THE STUDY: Microsatellite markers were developed for the medicinal plant Isodon rubescens to investigate genetic variability of the species and, in future studies, to assess its relation to the content of pharmacologically active chemicals produced by the plant. METHODS AND RESULTS: Eleven primer pairs were identified and tested in multiple populations of I. rubescens and related species (I. henryi, I. enanderianus, I. lophanthoides) from the People's Republic of China. The primers amplified dinucleotide repeats and had between two and 12 alleles per locus in a given population. CONCLUSIONS: These microsatellites will be useful for understanding patterns of phytochemical variation in I. rubescens and have the potential to be applied to research on evolutionary processes in other species of the genus Isodon.

Heavy metal and pesticide content in commonly prescribed individual raw Chinese Herbal Medicines.

Heavy metal and pesticide contamination has previously been reported in Chinese Herbal Medicines (CHMs), in some cases at potentially toxic levels. This study was conducted to determine general patterns and toxicological significance of heavy metal and pesticide contamination in a broad sample of raw CHMs. Three-hundred-thirty-four samples representing 126 species of CHMs were collected throughout China and examined for arsenic, cadmium, chromium, lead, and mercury. Of the total, 294 samples representing 112 species were also tested for 162 pesticides. At least 1 metal was detected in all 334 samples (100%) and 115 samples (34%) had detectable levels of all metals. Forty-two different pesticides were detected in 108 samples (36.7%), with 1 to 9 pesticides per sample. Contaminant levels were compared to toxicological reference values in the context of different exposure scenarios. According to a likely scenario of CHM consumption, only 3 samples (1%) with heavy metals and 14 samples (5%) with pesticides were found with concentrations that could contribute to elevated background levels of contaminant exposure. According to the most conservative scenario of CHM consumption, 231 samples (69%) with heavy metals and 81 samples (28%) with pesticides had contaminants that could contribute to elevated levels of exposure. Wild collected plants had higher contaminant levels than cultivated samples. Cadmium, chromium, lead, and chlorpyrifos contamination showed weak correlations with geographic location. Based on our assumptions of the likely mode of consumption of raw CHMs, the vast majority (95%) of the 334 samples in this study contained levels of heavy metals or pesticides that would be of negligible concern. However, given the number of samples with detectable contaminants and the range between the more likely and more conservative scenarios of contaminant exposure, more research and monitoring of heavy metals (especially cadmium and chromium) and pesticide residues (especially chlorpyrifos) in raw CHMs are advised.

Traditional Medicine Collection Tracking System (TM-CTS): a database for ethnobotanically driven drug-discovery programs.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanically driven drug-discovery programs include data related to many aspects of the preparation of botanical medicines, from initial plant collection to chemical extraction and fractionation. The Traditional Medicine Collection Tracking System (TM-CTS) was created to organize and store data of this type for an international collaborative project involving the systematic evaluation of commonly used Traditional Chinese Medicinal plants. MATERIALS AND METHODS: The system was developed using domain-driven design techniques, and is implemented using Java, Hibernate, PostgreSQL, Business Intelligence and Reporting Tools (BIRT), and Apache Tomcat. RESULTS: The TM-CTS relational database schema contains over 70 data types, comprising over 500 data fields. The system incorporates a number of unique features that are useful in the context of ethnobotanical projects such as support for information about botanical collection, method of processing, quality tests for plants with existing pharmacopoeia standards, chemical extraction and fractionation, and historical uses of the plants. The database also accommodates data provided in multiple languages and integration with a database system built to support high throughput screening based drug discovery efforts. It is accessed via a web-based application that provides extensive, multi-format reporting capabilities. CONCLUSIONS: This new database system was designed to support a project evaluating the bioactivity of Chinese medicinal plants. The software used to create the database is open source, freely available, and could potentially be applied to other ethnobotanically driven natural product collection and drug-discovery programs.

Developing a library of authenticated Traditional Chinese Medicinal (TCM) plants for systematic biological evaluation--rationale, methods and preliminary results from a Sino-American collaboration.

While the popularity of and expenditures for herbal therapies (aka "ethnomedicines") have increased globally in recent years, their efficacy, safety, mechanisms of action, potential as novel therapeutic agents, cost-effectiveness, or lack thereof, remain poorly defined and controversial. Moreover, published clinical trials evaluating the efficacy of herbal therapies have rightfully been criticized, post hoc, for their lack of quality assurance and reproducibility of study materials, as well as a lack of demonstration of plausible mechanisms and dosing effects. In short, clinical botanical investigations have suffered from the lack of a cohesive research strategy which draws on the expertise of all relevant specialties. With this as background, US and Chinese co-investigators with expertise in Traditional Chinese Medicine (TCM), botany, chemistry and drug discovery, have jointly established a prototype library consisting of 202 authenticated medicinal plant and fungal species that collectively represent the therapeutic content of the majority of all commonly prescribed TCM herbal prescriptions. Currently housed at Harvard University, the library consists of duplicate or triplicate kilogram quantities of each authenticated and processed species, as well as "detanninized" extracts and sub-fractions of each mother extract. Each species has been collected at 2-3 sites, each separated geographically by hundreds of miles, with precise GPS documentation, and authenticated visually and chemically prior to testing for heavy metals and/or pesticides contamination. An explicit decision process has been developed whereby samples with the least contamination were selected to undergo ethanol extraction and HPLC sub-fractionation in preparation for high throughput screening across a broad array of biological targets including cancer biology targets. As envisioned, the subfractions in this artisan collection of authenticated medicinal plants will be tested for biological activity individually and in combinations (i.e., "complex mixtures") consistent with traditional ethnomedical practice. This manuscript summarizes the rationale, methods and preliminary "proof of principle" for the establishment of this prototype, authenticated medicinal plant library. It is hoped that these methods will foster scientific discoveries with therapeutic potential and enhance efforts to systematically evaluate commonly used herbal therapies worldwide.

Mini-open versus open decompression and fusion for lumbar degenerative spondylolisthesis with stenosis.

The outcome of less invasive surgical techniques in comparison to traditional surgical techniques has been the source of debate. In this retrospective study, 51 patients who had undergone posterior lumbar fusion along with bilateral decompression were enrolled. Twenty-one patients underwent fusion using a standard, midline open technique (open group) and 30 patients underwent fusion using a mini-open technique, with a small, central incision for the decompression and bilateral paramedian incisions for the posterolateral fusion and placement of cannulated pedicle screws (mini-open group). Surgical variables were compared between the 2 groups. Patients in both groups experienced significant improvements in leg pain at 12 months, with a reduction in visual analog scale scores from 7.6 to 2.4 in the open group, and 7.8 to 2.3 in the mini-open group. There were no statistical differences between the groups in the magnitude of improvement of either the visual analog scale or Oswestry Disability Index scores. Operative times, blood loss, and length of hospitalization failed to show statistically significant differences between the groups, although there was a trend toward less blood loss and shorter hospitalization in the mini-open group. Fusion results and complications were similar between the 2 groups. Both techniques resulted in similarly statistically significant improvements in pain and clinical function.

Trends in epidemiology and management of type II odontoid fractures: 20-year experience at a model system spine injury tertiary referral center.

STUDY DESIGN: A retrospective cohort study of consecutive type II Odontoid fractures presenting to a Level 1 Regional Model Systems Spinal Cord Injury Center between June 1985 and July 2006. OBJECTIVE: To assess trends in management of type II Odontoid fractures presenting to a Level 1 Model Systems Regional Spinal Cord Injury Center over a 20-year period. SUMMARY OF BACKGROUND DATA: Type II Odontoid fracture management is controversial, and a majority of studies have had relatively small cohorts. There is no consensus regarding definitive treatment, particularly in older patients. METHODS: Medical records of 263 consecutive type II Odontoid fractures from June 1985 to July 2006 were retrospectively reviewed. Patients were excluded if they had neurologic deficits, nonacute fracture, or ambiguous fracture classification. A cohort of 192 neurologically intact, acute type II odontoid fractures were identified. Admission records were reviewed for age, date of injury, date of admission, date of discharge, mechanism of injury, associated injuries, medical comorbidities, and radiologic findings. RESULTS: There was a statistically significant increase in the rate of presentation of type II odontoid fractures with time. The average age and medical comorbidities of the patient did not change over time. The probability of operative management markedly increased over time, corresponding to a statistically significant increase in length of hospital stay for patients undergoing surgery. The discharge disposition correlated significantly to both age of the patient and associated injuries. CONCLUSIONS: The number and frequency of type II odontoid fractures compared with other spine injuries seems to be increasing over the last 2 decades, which may be correlated with the increasing number of elderly persons in the population, given that referral patterns have been unchanged at our institution. Prospective outcomes data are needed to better elucidate optimal treatment algorithms from both, an outcomes and cost-efficacy perspective.

Sedation and anesthesia options for pediatric patients in the radiation oncology suite.

External beam radiation therapy (XRT) has become one of the cornerstones in the management of pediatric oncology cases. While the procedure itself is painless, the anxiety it causes may necessitate the provision of sedation or anesthesia for the patient. This review paper will briefly review the XRT procedure itself so that the anesthesia provider has an understanding of what is occurring during the simulation and treatment phases. We will then examine several currently used regimens for the provision of pediatric sedation in the XRT suite as well as a discussion of when and how general anesthesia should be performed if deemed necessary. Standards of care with respect to patient monitoring will be addressed. We will conclude with a survey of the developing field of radiation-based therapy administered outside of the XRT suite.

Total synthesis and absolute configuration of (-)-berkeleyamide A.

A chiral-pool approach to (-)-berkeleyamide A 1 based on a diastereoselective nitrile oxide [3 + 2]-cycloaddition completes the first total synthesis establishing the absolute stereochemistry of the natural product.

Adjacent segment disease after cervical spine fusion.

Anterior cervical diskectomy and fusion is one of the most common cervical spine procedures. Although it is usually successful in relieving the symptoms of radiculopathy and myelopathy, the subsequent development of clinically significant disk disease at levels adjacent to the fusion is a matter of concern. Adjacent segment cervical disease occurs in approximately 3% of patients; the incidence is expected to increase to more than 25% of patients within the first 10 years after the index fusion procedure. The disease is well described in the literature, and significant basic science and clinical research has been conducted. Nonetheless, the cause of the disease is a matter of debate. A combination of factors probably contributes to its development, including the increased biomechanical stress placed on the disk space adjacent to a fusion and the natural history of cervical spondylosis in patients known to have such pathology. Clinical and biomechanical data are available to support each of these claims. Symptomatic disk disease adjacent to a cervical fusion is a significant clinical problem, and, therefore, motion-sparing technology has been developed to reduce its incidence. Two cervical disk replacement systems are currently approved by the US Food and Drug Administration for the treatment of symptomatic cervical spondylosis.

Monitored anesthesia care (MAC) sedation: clinical utility of fospropofol.

Fospropofol, a phosphorylated prodrug version of the popular induction agent propofol, is hydrolyzed in vivo to release active propofol, formaldehyde, and phosphate. Pharmacodynamic studies show fospropofol provides clinically useful sedation and EEG/bispectral index suppression while causing significantly less respiratory depression than propofol. Pain at the injection site, a common complaint with propofol, was not reported with fospropofol; the major patient complaint was transitory perianal itching during the drug's administration. Although many clinicians believe fospropofol can safely be given by a registered nurse, the FDA mandated that fospropofol, like propofol, must be used only in the presence of a trained anesthesia provider.

Endotracheal tube malposition within the pediatric population: a common event despite clinical evidence of correct placement.

PURPOSE: To ensure that the endotracheal tube (ETT) is ideally placed for proper ventilation, radiographic confirmation of ETT placement is frequently used to supplement clinical examination in the intensive care unit setting. However, fluoroscopy rarely serves the same role during surgery, despite the fact that portable units are often present in the operating room. The purpose of this study was to ascertain the value of fluoroscopy in determining ETT malposition among the pediatric surgical population. METHODS: Chest radiographs from 257 children (age 12 days-12 yr), who presented for a total of 446 individual procedures in the fluoroscopy suite, were studied to determine the incidence of ETTs placed too shallow (above the inferior clavicular border) or too deep (at or below the carina). A logistic regression with outcomes of correct and incorrect was used to analyze the data points. RESULTS: Eighteen percent of all the radiographs showed initial improper ETT placement, despite clinical evidence suggesting the contrary. The peak incidence of malposition, which occurred in patients under one year old, reached 35%. Incidence decreased with advancing age, but remained over 10% until the age of ten. A second attempt at positioning the tube, based on information from the chest radiograph, was successful in 95% of the cases. The remaining 5% required placement of the ETT under continuous fluoroscopic guidance. CONCLUSION: Fluoroscopy, when readily available in the operating room, is a safe and useful technique to ensure proper ETT placement among the pediatric population.