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OBJECTIVE: Repaglinide is an oral anti-diabetic agent that has a short duration of action, and is suitable for preventing post-prandial rises in glucose levels. Targeting post-prandial glucose levels may lead to lower HbA(1c) levels and rates of hypoglycaemia than targeting pre-prandial glucose levels. RESEARCH DESIGN AND METHODS: In 42 centres, 193 drug-naive (n = 122) or metformin-treated (n = 71) individuals with Type 2 diabetes were randomly allocated to a 40-day period of repaglinide dose-titration (starting at 0.5 mg three times daily) based on either self-measured pre-prandial or post-prandial glucose levels. They were followed for a further 12 weeks and HbA(1c) and hypoglycaemia rates were recorded. RESULTS: Repaglinide reduced HbA(1c) by 1.25 and 1.07% in the post-prandial and pre-prandial groups, respectively (P for difference = 0.6), and achieved target glucose levels in 80.7 and 66.7%, respectively (P = 0.16). The effect of titration strategy differed by baseline drug therapy, and was more effective in the metformin-treated individuals who experienced a HbA(1c) fall of 0.6 vs. 1.10% with pre-prandial vs. post-prandial titration (P for metformin-allocated group interaction = 0.043). The rate of hypoglycaemia did not differ by group. CONCLUSIONS: In drug-naive individuals with Type 2 diabetes, similar HbA(1c) levels are achieved with repaglinide when dosing is adjusted according to either post-prandial or pre-prandial levels. Conversely, in metformin-treated individuals, repaglinide dosing according to post-prandial levels may lead to better glycaemic control than dosing according to pre-prandial levels. [ABSTRACT FROM AUTHOR]

Objective: Physical stress associated with the static posture of neurosurgeons over prolonged periods can result in fatigue and musculoskeletal disorders. Objective assessment of surgical ergonomics may contribute to postural awareness and prevent further complications. This pilot study examined the feasibility of using wearable technology as a biofeedback tool to address this gap., Methods: Ten neurosurgeons, including 5 attendings (all faculty) and 5 trainees (1 fellow, 4 residents), were recruited and equipped with two wearable sensors attached to the back of their head and their upper back. The sensors collected the average time spent in extended (≤ -10°), neutral (> -10° and < 10°), and flexed (≥ 10°) static postures (undetected activity for more than 10 seconds) during spine and cranial procedures. Feasibility outcomes aimed for more than 70% of accurate data collection. Exploratory outcomes included the comparison of postural variability within and between participants adjusted to their demographics excluding nonrelated surgical activities, and postoperative self-assessment surveys., Results: Sixteen (80%) of 20 possible recordings were successfully collected and analyzed from 11 procedures (8 spine, 3 cranial). Surgeons maintained a static posture during 52.7% of the active surgical time (mean 1.58 hrs). During spine procedures, all surgeons used an exoscope while standing, leading to a significantly longer time spent in a neutral static posture (p < 0.001, partial η2 = 0.14): attendings remained longer in a neutral static posture (36.4% ± 15.3%) than in the extended (9% ± 6.3%) and flexed (5.7% ± 3.4%) static postures; trainees also remained longer in a neutral static posture (30.2% ± 13.8%) than in the extended (11.1% ± 6.3%) and flexed (11.9% ± 6.6%) static postures. During cranial procedures, surgeons intermittently transitioned between standing/exoscope use and sitting/microscope use, with trainees spending a shorter time in a neutral static posture (16.3% vs 48.5%, p < 0.001) and a longer time in a flexed static posture (18.5% vs 2.7%, p < 0.001) compared with attendings. Additionally, longer cranial procedures correlated with surgeons spending a longer time (r = 0.94) in any static posture (extended, flexed, and neutral), with taller surgeons exhibiting longer periods in flexed and extended static postures (r = 0.86). Postoperative self-assessment revealed that attendings perceived spine procedures as more difficult than trainees (p = 0.029), while trainees found cranial procedures to be of greater difficulty than spine procedures (p = 0.012). Attendings felt more stressed (p = 0.048), less calmed (p = 0.024), less relaxed (p = 0.048), and experienced greater stiffness in their upper body (p = 0.048) and more shoulder pain (p = 0.024) during cranial versus spine procedures., Conclusions: Wearable technology is feasible to assess postural ergonomics and provide objective biofeedback to neurosurgeons during spine and cranial procedures. This study showed reproducibility for future comparative protocols focused on correcting posture and surgical ergonomic education.

Introduction: There are no optimal postoperative analgesia regimens for Nuss procedures. We compared the effectiveness of thoracic epidurals (EPI) and novel ambulatory erector spinae plane (ESP) catheters as part of multimodal pain protocols after Nuss surgery., Methods: Data on demographics, comorbidities, perioperative details, length of stay (LOS), in hospital and post discharge pain/opioid use, side effects, and emergency department (ED) visits were collected retrospectively in children who underwent Nuss repair with EPI (N = 114) and ESP protocols (N = 97). Association of the group with length of stay (LOS), in hospital opioid use (intravenous morphine equivalents (MEq)/kg over postoperative day (POD) 0-2), and oral opioid use beyond POD7 was analyzed using inverse probability of treatment weighting (IPTW) with propensity scores, followed by multivariable regression., Results: Groups had similar demographics. Compared to EPI, ESP had longer block time and higher rate of ketamine and dexmedetomidine use. LOS for ESP was 2 days IQR (2, 2) compared to 3 days IQR (3, 4) for EPI (p < 0.01). Compared to EPI, ESP group had higher opioid use (in MEq/kg) intraoperatively (0.32 (IQR 0.27, 0.36) vs. 0.28 (0.24, 0.32); p < 0.01) but lower opioid use on POD 0 (0.09 (IQR 0.04, 0.17) vs. 0.11 (0.08, 0.17); p = 0.03) and POD2 (0.00 (IQR 0.00, 0.00) vs. 0.04 (0.00, 0.06) ; p < 0.01). ESP group also had lower total in hospital opioid use (0.57 (IQR 0.42, 0.73) vs.0.82 (0.71, 0.91); p < 0.01), and shorter duration of post discharge opioid use (6 days (IQR 5,8) vs. 9 days (IQR 7,12) (p < 0.01). After IPTW adjustment, ESP continued to be associated with shorter LOS (difference -1.20, 95% CI: -1.38, -1.01, p < 0.01) and decreased odds for opioid use beyond POD7 (OR 0.11, 95% CI: 0.05, 0.24); p < 0.01). However, total in hospital opioid use in MEq/kg (POD0-2) was now similar between groups (difference -0.02 (95% CI: -0.09, -0.04); p = 0.50). The EPI group had higher incidence of emesis (29% v 4%, p < 0.01), while ESP had higher catheter malfunction rates (23% v 0%; p < 0.01) but both groups had comparable ED visits/readmissions., Discussion/conclusion: Compared to EPI, multimodal ambulatory ESP protocol decreased LOS and postoperative opioid use, with comparable ED visits/readmissions. Disadvantages included higher postoperative pain scores, longer block times and higher catheter leakage/malfunction., Levels of Evidence: Level III., (Copyright © 2022. Published by Elsevier Inc.)

Competing Interests: Competing interests: None declared.

Ambient (outdoor) air pollution is a key risk factor for health for which effective policy plays an important preventative role. Australian federal and related state air quality standards have historically relied on international evidence for guidance, which may not accurately reflect the Australian context. However, there has been a large increase in Australian epidemiological studies over recent years. The aim of this study is to provide an updated systematic literature review of peer-reviewed epidemiological studies that examined the health impacts of outdoor air pollution in Australia, including short- and long-term exposure. Following PRISMA guidelines, we conducted a systematic literature review. Broad search terms were applied to two databases (PubMed and Web of Science) and Google Scholar. Quality assessment and risk of bias were assessed using standard metrics. Included studies were summarised by tabulating key study characteristics, grouped by health outcomes. In total, 72 studies were included in the review. Sixty-four (89%) studies used daily or hourly pollutant concentrations to examine short-term exposure impacts, of which 59 (92%) revealed significant associations with one or more health outcomes, including cardio-respiratory, all-cause mortality or morbidity and birth outcomes. Eight (11%) studies used annual average pollutant concentrations to investigate the long-term exposure finding significant associations with asthma, reduced lung function, atopy and cardio-respiratory mortality across five studies. The remaining three studies found no significant association with asthma, mortality and a range of self-reported diseases, respectively. Ambient air pollution has substantial health impacts in Australia. The body of domestic evidence has increased markedly since national air quality standards were first set in the 1990s, which could be drawn on by policy-makers when revising the existing standards, or considering new standards., (© 2021 Royal Australasian College of Physicians.)

Trends in pediatric pain management are moving toward thinking beyond opioids. Regional anesthetic techniques, such as quadratus lumborum and erector spinae plane blocks, demonstrate efficacy and safety in pediatric populations. Extremity blocks with motor-sparing characteristics also are used. Adjuvants may be added to pediatric peripheral nerve blocks to increase duration of action and improve block efficacy. For medical management, pediatric pain management frequently uses nonopioid medications. These opioid-sparing medications and regional techniques are used to facilitate enhanced recovery after surgery in pediatric surgical patients. Virtual reality is a field where technology can aid in managing acute pain in pediatric patients., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Smoke exposure from bushfires, such as those experienced in Australia during 2019-2020, can reach levels up to 10 times those deemed hazardous. Short-term and extended exposure to high levels of air pollution can be associated with adverse health effects, although the most recent fires have brought into sharp focus that several important knowledge gaps remain. In this article, we briefly identify and discuss the existing Australian evidence base and make suggestions for future research., (© 2020 Asian Pacific Society of Respirology.)

Background: Laparoscopy for ventriculoperitoneal shunt creation might offer smaller incisions and more reliable placement. We assessed the reliability and cost-effectiveness of this technique compared with mini-laparotomy shunt placement., Methods: All patients undergoing ventriculoperitoneal shunt creation between November 2013 and September 2017 at a single academic institution were evaluated. Individual cases were assessed for the use of laparoscopy for peritoneal shunt placement (laparoscopy) versus mini-laparotomy for peritoneal shunt placement (open). The direct hospital costs for the laparoscopy and open groups were compared for elective shunt placement from the Vizient database. These direct costs were the proportion of the admission cost attributed to surgery. The primary endpoints included costs and revision of the peritoneal catheter within 12 months of the index procedure., Results: A total of 68 patients met the inclusion criteria. Most cases (n = 40; 58.8%) had been performed with laparoscopy, with 28 performed using an open peritoneal approach. Three patients had required ≥1 distal shunt revision: 2 laparoscopy patients (5.0%; 1 had required a second revision) and 1 open patient (3.6%). No statistically significant differences were found for the patients requiring distal shunt revision between the 2 groups (P = 1.000; Fisher's exact test). The direct cost ($9461) of ventriculoperitoneal shunt creation with laparoscopy was greater than that with an open approach ($8247; P = 0.033)., Conclusions: Both laparoscopy and open peritoneal shunt creation are safe procedures, with a 12-month distal revision rate in the present series of ~4%. Laparoscopy provided no relative improvement in safety or complication avoidance but had resulted in a mean increase in costs of >$1200 per patient., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study investigated the feasibility and preliminary effectiveness of a pilot program designed to address subjective memory complaints among Veterans. The program, Brain Boosters, consisted of 10 once-weekly group sessions, during which psychoeducation and cognitive enhancement strategies were used to target memory concerns and related processes, specifically attentional difficulties. Given that memory complaints often are associated with psychiatric comorbidities, sessions also incorporated strategies for reducing symptoms of depression, posttraumatic stress, and insomnia. Controlling for age, we examined pre- to posttreatment change in symptom ratings for 96 Veterans (aged 22 to 87 years) who participated in the Brain Boosters program. The effect of Brain Boosters on memory complaints interacted with age: younger (but not older) Veterans reported reductions in memory impairment from pre- to posttreatment. Additionally, irrespective of age, from pre- to posttreatment Veterans reported fewer attentional difficulties and fewer depression symptoms. Ratings of posttraumatic stress and insomnia symptoms did not change, although insomnia was negatively associated with age. Linear regression controlling for age revealed that reductions in attention problems predicted reductions in perceived memory impairment. Findings from this exploratory, uncontrolled pilot study suggest that a psychoeducational cognitive enhancement group is feasible to conduct in a heterogeneous Veteran population, and may be associated with improvements in perceived memory functioning for younger Veterans, and in attention and depression symptoms for Veterans across age groups. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Despite recent advances in our understanding of synaptic transmission associated with epileptogenesis, the molecular mechanisms that control seizure frequency in patients with temporal lobe epilepsy (TLE) remain obscure. RNA-Seq was performed on hippocampal tissue resected from 12 medically intractable TLE patients with pre-surgery seizure frequencies ranging from 0.33 to 120 seizures per month. Differential expression (DE) analysis of individuals with low (LSF, mean = 4 seizure/month) versus high (HSF, mean = 60 seizures/month) seizure frequency identified 979 genes with ≥2-fold change in transcript abundance (FDR-adjusted p-value ö0.05). Comparisons with post-mortem controls revealed a large number of downregulated genes in the HSF (1676) versus LSF (399) groups. More than 50 signaling pathways were inferred to be deactivated or activated, with Signal Transduction as the central hub in the pathway network. While neuroinflammation pathways were activated in both groups, key neuronal system pathways were systematically deactivated in the HSF group, including calcium, CREB and Opioid signaling. We also infer that enhanced expression of a signaling cascade promoting synaptic downscaling may have played a key role in maintaining a higher seizure threshold in the LSF cohort. These results suggest that therapeutic approaches targeting synaptic scaling pathways may aid in the treatment of seizures in TLE., (Published by Elsevier B.V.)

Background: The border between the United States (US) and Mexico is an international boundary spanning 3000 km, where unauthorized crossings occur regularly. We examine patterns of neurotrauma, health care utilization, and financial costs at our level 1 trauma center incurred by patients from wall-jumping into the US., Objective: To determine the clinical and socioeconomic consequences from neurotrauma as a result of jumping over the US-Mexico border wall., Methods: Medical records of patients at (Banner University of Arizona Medical Center - Tucson) were retrospectively reviewed from January 2012 through December 2017. Demographics, clinical status, radiographic findings, treatment, length of stay, and financial data were analyzed for all patients suffering neurotrauma during that time., Results: Over 6 yr, 64 patients sustained cranial or spinal injuries directly from jumping or falling onto US soil from the border wall. Fifty (78%) suffered spinal injuries, 15 (23%) experienced cranial injury, and 1 patient had both. Total medical charges were available in 36 patients and summed $3.6 M, of which 22% was reimbursed, an amount significantly lower than expected from more conventional trauma. Neurotrauma steadily declined over the 6-yr observation period, dropping in 2017 to 6% of rates observed in 2012., Conclusion: In the Southern US, neurotrauma from unauthorized border crossings occurs commonly as a result of wall-jumping. These injuries represent a clinical and costly extreme of border-related trauma, and future efforts from both sides of the border wall are needed to decrease the detrimental impacts felt both by immigrants and surrounding health care systems., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Objective: The objective of this study was to evaluate the existing Spetzler-Martin (SM), Spetzler-Ponce (SP), and Lawton-Young (LY) grading systems for cerebellar arteriovenous malformations (AVMs) and to propose a new grading system to estimate the risks associated with these lesions., Methods: Data for patients with cerebellar AVMs treated microsurgically in two tertiary medical centers were retrospectively reviewed. Data from patients at institution 1 were collected from September 1999 to February 2013, and at institution 2 from October 2008 to October 2015. Patient outcomes were classified as favorable (modified Rankin Scale [mRS] score 0-2) or poor (mRS score 3-6) at the time of discharge. Using chi-square and logistic regression analysis, variables associated with poor outcomes were assigned risk points to design the proposed grading system. The proposed system included neurological status prior to treatment (poor, +2 points), emergency surgery (+1 point), age > 60 years (+1 point), and deep venous drainage (deep, +1 point). Risk point totals of 0-1 comprised grade 1, 2-3 grade 2, and 4-5 grade 3., Results: A total of 125 cerebellar AVMs of 1328 brain AVMs were reviewed in 125 patients, 120 of which were treated microsurgically and included in the study. With our proposed grading system, we found poor outcomes differed significantly between each grade (p < 0.001), while with the SM, SP, and LY grading systems they did not (p = 0.22, p = 0.25, and p = 1, respectively). Logistic regression revealed grade 2 had 3.3 times the risk of experiencing a poor outcome (p = 0.008), while grade 3 had 9.9 times the risk (p < 0.001). The proposed grading system demonstrated a superior level of predictive accuracy (area under the receiver operating characteristic curve [AUROC] of 0.72) compared with the SM, SP, and LY grading systems (AUROC of 0.61, 0.57, and 0.51, respectively)., Conclusions: The authors propose a novel grading system for cerebellar AVMs based on emergency surgery, venous drainage, preoperative neurological status, and age that provides a superior prognostication power than the formerly proposed SM, SP, and LY grading systems. This grading system is clinically predictive of patient outcomes and can be used to better guide vascular neurosurgeons in clinical decision-making.

Background: Cerebellar arteriovenous malformations (CAVMs) are challenging to treat given their close proximity to the brain stem, greater propensity for rupture, and greater rates of morbidity and mortality than other brain arteriovenous malformations. The present investigation sought to describe and characterize the features of these rare and unique lesions., Methods: A retrospective review of CAVM cases treated at 2 tertiary medical centers was performed. Patients surgically treated at institution 1 from September 1999 to February 2013 and institution 2 from October 2008 to October 2015 were included., Results: A total of 120 patients had been treated. Of the 120 patients, 85 (70.8%) had initially presented with hemorrhage, 45 (37.5%) of whom experienced hemorrhage requiring emergent surgery. A favorable neurological outcome was observed in 76 patients (63.3%; modified Rankin Scale score <3). The perioperative mortality was 2.5% (n = 3). The long-term mortality rate was 7.5% (n = 9). The mean follow-up time was 1.82 years. On average, the patients with large CAVMs (≥3 cm; P ≤ 0.001), who had received embolization before surgery (P = 0.04), did not have an associated aneurysm (P ≤ 0.001), or had a residual CAVM after surgery (P = 0.008) were significantly younger. Female patients had fewer CAVMs with deep venous drainage (54.3% vs. 72.3%; P = 0.049), experienced decreased mortality (1.4% vs. 16.7%; P = 0.003), and were less likely to have worse neurological status after treatment (P = 0.003)., Conclusions: CAVMs are rare lesions that exhibit unique disease characteristics. Although most patients will experience a favorable outcome, CAVMs frequently present with hemorrhage, result in high rates of morbidity and mortality, and characteristically differ depending on patient age and gender., (Copyright © 2018. Published by Elsevier Inc.)

Background: The PulseRider is an innovative stent-like device designed for the treatment of intracranial bifurcation aneurysms. The aim of this study was to assess the current evidence on safety and effectiveness of the PulseRider., Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following databases were searched: PubMed, Ovid MEDLINE, and Scopus. The search strategy consisted of "pulserider," "bifurcation aneurysm," and "endovascular" in both AND and OR combinations. Studies included were original research articles in peer-reviewed journals. The manuscripts were thoroughly examined for study design, outcomes, and results., Results: Three studies were identified describing use of the PulseRider device in the treatment of 63 patients with 63 bifurcation aneurysms. We identified 2 multicenter case series and 1 single-arm clinical trial. The majority of aneurysms treated were located at the basilar tip (37, 58.7%). All devices were successfully deployed, and there were 5 intraoperative complications (7.9%), including 2 intraoperative aneurysm ruptures, 1 vessel dissection, and 2 thrombus formations. Immediate complete aneurysm occlusion was achieved in 61.9% (39/63) of cases and at the 6-month imaging follow-up, 66.7% (42/63) achieved complete aneurysm occlusion. One recanalization was reported in 1 of the multicenter case series within the 6-month follow-up., Conclusions: The PulseRider is safe and probably effective for the treatment of intracranial bifurcation aneurysms, sometimes not amenable for stent-assisted coiling. However, current evidence is limited to a small sample and short follow-up. In addition, the device has not been compared with other treatment modalities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Near-infrared spectroscopy can interrogate functional optical signal changes in regional brain oxygenation and blood volume to nociception analogous to functional magnetic resonance imaging., Aims: This exploratory study aimed to characterize the near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin from the brain in response to nociceptive stimulation of varying intensity and duration, and after analgesic and neuromuscular paralytic in a pediatric population., Methods: We enrolled children 6 months-21 years during propofol sedation before surgery. The near-infrared spectroscopy sensor was placed on the forehead and nociception was produced from an electrical current applied to the wrist. We determined the near-infrared spectroscopy signal response to increasing current intensity and duration, and after fentanyl, sevoflurane, and neuromuscular paralytic. Heart rate and arm movement during electrical stimulation was also recorded. The near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin were calculated as optical density*time (area under curve)., Results: During electrical stimulation, nociception was evident: tachycardia and arm withdrawal was observed that disappeared after fentanyl and sevoflurane, whereas after paralytic, tachycardia persisted while arm withdrawal disappeared. The near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin increased during stimulation and decreased after stimulation; the areas under the curves were greater for stimulations 30 mA vs 15 mA (13.9 [5.6-22.2], P = .0021; 5.6 [0.8-10.5], P = .0254, and 19.8 [10.5-29.1], P = .0002 for HbO 2 , Hb, and Hb T , respectively), 50 Hz vs 1 Hz (17.2 [5.8-28.6], P = .0046; 7.5 [0.7-14.3], P = .0314, and 21.9 [4.2-39.6], P = .0177 for HbO 2 , Hb, and Hb T , respectively) and 45 seconds vs 15 seconds (16.3 [3.4-29.2], P = .0188 and 22.0 [7.5-36.5], P = .0075 for HbO 2 and Hb T , respectively); the areas under the curves were attenuated by analgesics but not by paralytic., Conclusion: Near-infrared spectroscopy detected functional activation to nociception in a broad pediatric population. The near-infrared spectroscopy response appears to represent nociceptive processing because the signals increased with noxious stimulus intensity and duration, and were blocked by analgesics but not paralytics., (© 2017 John Wiley & Sons Ltd.)

Background: Spontaneous intracranial hemorrhage (ICH) is frequently managed in neurosurgery. Patients with durable mechanical circulatory support devices, including total artificial heart (TAH) and left ventricular assist device (LVAD), are often encountered in the setting of ICH. Although durable mechanical circulatory support devices have improved survival and quality of life for patients with advanced heart failure, ICH is one of the most feared complications following LVAD and TAH implantation. Owing to anticoagulation and clinically relevant acquired coagulopathies, ICH should be treated promptly by neurosurgeons and cardiac critical care providers. We provide an analysis of ICH in patients with mechanical circulatory support and propose a treatment algorithm., Methods: We retrospectively reviewed medical records from 2013-2016 for patients with a durable mechanical circulatory device at Banner-University of Arizona Medical Center Tucson. All patients with suspected ICH underwent computed tomography scan of the brain. Anticoagulation was managed by the cardiothoracic surgeon., Results: In 58 patients, an LVAD (n = 49), TAH (n = 10), or both (n = 1) were implanted. Both acquired von Willebrand disease and spontaneous ICH were diagnosed in 5 patients (8.6%) who underwent LVAD implantation. Seven neurosurgical procedures were performed in 2 patients. The overall mortality rate was 60%. Two patients had little or no deficits after treatment with modified Rankin Scale score of 1 and 2, respectively., Conclusions: We propose a novel treatment algorithm to manage patients with a LVAD or TAH and ICH, implemented in a multidisciplinary manner to best avoid neurologic and cardiovascular complications., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Study Design: Review of the articles., Objective: The objective of this study was to review all articles related to spinal instability to determine a consensus statement for a contemporary, practical definition applicable to thoracolumbar injuries., Summary of Background Data: Traumatic fractures of the thoracolumbar spine are common. These injuries can result in neurological deficits, disability, deformity, pain, and represent a great economic burden to society. The determination of spinal instability is an important task for spine surgeons, as treatment strategies rely heavily on this assessment. However, a clinically applicable definition of spinal stability remains elusive., Materials and Methods: A review of the Medline database between 1930 and 2014 was performed limited to papers in English. Spinal instability, thoracolumbar, and spinal stability were used as search terms. Case reports were excluded. We reviewed listed references from pertinent search results and located relevant manuscripts from these lists as well., Results: The search produced a total of 694 published articles. Twenty-five articles were eligible after abstract screening and underwent full review. A definition for spinal instability was described in only 4 of them. Definitions were primarily based on biomechanical and classification studies. No definitive parameters were outlined to define stability., Conclusions: Thirty-six years after White and Panjabi's original definition of instability, and many classification schemes later, there remains no practical and meaningful definition for spinal instability in thoracolumbar trauma. Surgeon expertise and experience remains an important factor in stability determination. We propose that, at an initial assessment, a distinction should be made between immediate and delayed instability. This designation should better guide surgeons in decision making and patient counseling.

Objective: The circle of Willis (CoW) is the foremost anastomosis and blood distribution center of the brain. Its effectiveness depends on its completion and the size and patency of its vessels. Gender-related and age-related anatomic variations in the CoW may play an important role in the pathogenesis of cerebrovascular diseases. In this study, we analyzed computed tomography angiograms (CTAs) to assess for differences in CoW completion related to gender, age, and indication for CTA., Methods: A total of 834 CTAs were retrospectively analyzed for all CoW vessels to compare the incidence of complete CoW and variation frequency based on gender, age, and indication., Results: The incidence of complete CoW was 37.1% overall. CoW completion showed a statistically significant decrease with increasing age for all age groups in both men (47.0%, 29.4%, 18.8%) and women (59.1%, 44.2%, 30.9%). Completion was greater in women (43.8%) than in men (31.2%) overall and for all age groups. These gender differences were all statistically significant except for the 18-39 years age group. The most frequent of the 28 CoW variations were absent posterior communicating artery (PCOM) bilaterally (17.1%), right PCOM (15.3%), and left PCOM (10.9%). Ischemic stroke and the 18-39 years age group of hemorrhagic stroke showed a statistically significant reduction in completion relative to trauma., Conclusions: The incidence of complete CoW is likely greater in women for all age groups and likely decreases with age in both genders. The most frequently absent vessel is likely the PCOM, either unilaterally or bilaterally. Completion may play a role in ischemic stroke and a subset of patients with hemorrhagic stroke., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: In oncological orthopedics, navigation systems are limited to use in specialized centers, because specific, expensive, software is necessary. To resolve this problem, we present a technique using general spine navigation software to resect tumors located in different segments., Materials and Methods: This technique requires a primary surgery during which screws are inserted in the segment where the bone tumor is; next, a CT scan of the entire segment is used as a guide in a second surgery where a resection is performed under navigation control. We applied this technique in four selected cases. To evaluate the procedure, we considered resolution obtained, quality of the margin and its control., Results: In all cases, 1 mm resolution was obtained; navigation allowed perfect control of the osteotomies, reaching the minimum wide margin when desired. No complications were reported and all patients were free of disease at follow-up (average 25.5 months)., Conclusions: This technique allows any bone segment to be recognized by the navigation system thanks to the introduction of screws as landmarks. The minimum number of screws required is four, but the higher the number of screws, the greater the accuracy and resolution. In our experience, five landmarks, placed distant from one another, is a good compromise. Possible disadvantages include the necessity to perform two surgeries and the need of a major surgical exposure; nevertheless, in our opinion, the advantages of better margin control justify the application of this technique in centers where an intraoperative CT scanner, synchronized with a navigation system or a dedicated software for bone tumor removal were not available.

Purpose: Sacrectomy is a highly demanding surgery representing the main treatment for primary tumors arising in the sacrum and pelvis. Unfortunately, it is correlated with loss of important function depending on the resection level and nerve roots sacrificed. The current literature regarding residual function after sacral resection comes from several small case series. The goal of this review is to appraise residual motor function and gait, sensitivity, bladder, bowel, and sexual function after sacrectomies, with consideration to the specific roots sacrificed., Methods: An exhaustive literature search was conducted. All manuscripts published before May 2015 regarding residual function after sacrectomy were considered; if a clear correlation between root level and functioning was not present, the paper was excluded. The review identified 15 retrospective case series, totaling 244 patients; 42 patients underwent sacrectomies sparing L4/L4, L4/L5 and L5/L5; 45 sparing both L5 and one or both S1 roots; 8 sparing both S1 and one S2; 48 sparing both S2; 11 sparing both S2 and one S3, 54 sparing both S3, 9 sparing both S3 and one or both S4, and 27 underwent unilateral variable resection., Results: Patients who underwent a sacrectomy maintained functionally normal ambulation in 56.2 % of cases when both S2 roots were spared, 94.1 % when both S3 were spared, and in 100 % of more distal resections. Normal bladder and bowel function were not present when both S2 were cut. When one S2 root was spared, normal bladder function was present in 25 % of cases; when both S2 were spared, 39.9 %; when one S3 was spared, 72.7 %; and when both S3 were spared, 83.3 %. Abnormal bowel function was present in 12.5 % of cases when both S1 and one S2 were spared; in 50.0 % of cases when both S2 were spared; and in 70 % of cases when one S3 was spared; if both S3 were spared, bowel function was normal in 94 % of cases. When even one S4 root was spared, normal bladder and bowel function were present in 100 % of cases. Unilateral sacral nerve root resection preserved normal bladder function in 75 % of cases and normal bowel function in 82.6 % of cases. Motor function depended on S1 root involvement., Conclusion: Total sacrectomy is associated with compromising important motor, bladder, bowel, sensitivity, and sexual function. Residual motor function is dependent on sparing L5 and S1 nerve roots. Bladder and bowel function is consistently compromised in higher sacrectomies; nevertheless, the probability of maintaining sufficient function increases progressively with the roots spared, especially when S3 nerve roots are spared. Unilateral resection is usually associated with more normal function. To the best of our knowledge, this is the first comprehensive literature review to analyze published reports of residual sacral nerve root function after sacrectomy.

Traumatic atlanto-occipital dislocation (AOD) is an ominous injury with high mortality and morbidity in trauma patients. Improved survival has been observed with advancements in pre-hospital and hospital care. Furthermore, high quality imaging studies are accessible at most trauma centers; these are crucial for prompt diagnosis of AOD. The objective of this study is to perform a comprehensive literature review of traumatic AOD, with specific emphasis on identifying prognostic factors for survival. A review of the literature was performed using the Medline database for all traumatic atlanto-occipital articles published between March 1959 and June 2015; 141 patients from 60 total studies met eligibility criteria for study inclusion. A binary logistic regression model was utilized to identify prognostic factors. The analysis assessed age, sex, spinal cord injury (SCI), traumatic brain injury (TBI), polytrauma injury (PI), and Traynelis AOD Classification. Only TBI was statistically significantly associated with death (OR 8.05 p<0.05); SCI did not reach statistical significance for predicting mortality in AOD patients (OR 1.25 p>0.05). Age, sex, PI, and Traynelis AOD Classification did not meet significance to predict mortality in AOD patients. We found that patients with TBI are eight times more likely to die than patients without TBI. A high degree of suspicion for AOD during pre-hospital care, as well as, prompt diagnosis and management in the trauma center play a key role in the treatment of this devastating injury. The relationship between survival and factors such as TBI and SCI should be further explored., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The role of spinal orthotic braces after surgical stabilization is not clearly defined. We systematically reviewed the published literature to determine patterns of practice, indications, and current evidence for the use of orthotic braces after surgical thoracolumbar fracture stabilization., Methods: A search was performed for publications including descriptions of postoperative management and outcomes after surgical stabilization of thoracolumbar injuries. Differences between wearing versus not wearing a postoperative brace were examined with regard to loss of deformity correction, pain, return to previous work activity, functional improvement, instrumentation failure rate, pseudoarthrosis, and the percentage of reported complications., Results: This search yielded 76 pertinent studies. Postoperative bracing (POB) was adopted in 62 studies for a median wear time of 13.3 weeks. No significant differences in terms of pain, return to work, Frankel score improvement, or instrumentation failure were found between the POB and non-POB groups. Loss of surgical kyphotic reduction was slightly greater in the POB group (4.79° vs. 3.77°; P < 0.001). The overall complication rate was also higher in the POB group (16.3% vs. 11.9%; P < 0.01). The pseudoarthrosis rate was lower in the braced group (2.4% vs. 6.0%; P < 0.001)., Conclusions: Most surgeons use braces for 3 months after surgical thoracolumbar fracture stabilization. Given the lack of clinical or biomechanical evidence for this, and the additional costs and potential discomfort to patients, further investigation is warranted to determine when and if POB for surgically stabilized thoracolumbar fractures is indicated. Controlled studies should include a careful analysis of pseudoarthrosis and complication rates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The anatomic area delineated medially by the lateral part of the L4-L5 vertebral bodies, distally by the anterior-superior surface of the sacral wing, and laterally by an imaginary line joining the base of the L4 transverse process to the proximal part of the sacroiliac joint, is of particular interest to spine surgeons. We are referring to this area as the lumbo-sacro-iliac triangle (LSIT). Knowledge of LSIT anatomy is necessary during approaches for L5 vertebral and sacral fractures, sacral and iliac tumors, and extraforaminal decompression of the L5 nerve roots., Methods: We performed an anatomic dissection of the LSIT in 3 embalmed cadavers (6 triangles), using an anterior and posterior approach., Results: We identified 3 key tissue planes: the neurological plexus plane, constituted by L4 and L5 nerve roots; an intermediate level constituted by the ileosacral tunnel; and posteriorly, by the lumbosacral ligament, and the posterior muscular plane., Conclusions: Improving anatomic knowledge of the LSIT may help surgeons decrease the risk of possible complications. When LSIT pathology is present, a lateral approach corresponding to the tip of the L4 transverse process, medially, is suggested to decrease the risk of vessel and nerve root damage., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Minimally invasive spine (MIS) surgery is gaining popularity in the elderly. With aging population and a strong desire for all patients to remain physically active, this trend will likely continue. Previous studies have reported clinical outcomes in the elderly undergoing MIS surgery; however, most of these studies encompass multiple surgeons at different sites and thus present heterogeneous experiences. In this work, we investigate the clinical outcomes and complications of all lumbar MIS procedures performed in patients over 65 years of age by a single surgeon., Methods: A retrospective analysis of a prospectively maintained database of spine surgeries was performed. Twenty-six patients who underwent 27 procedures were included., Results: Mean age at surgery was 72 years (range 64-86). The mean BMI was 30.2 kg/m(2), patients had an average of 5 comorbidities, took 9 medications, and 15% were smokers. The mean symptoms duration was 40.6 months with the numeric rating scale (NRS) and the Oswestry disability index (ODI) prior to surgery of 7.68 and 50% respectively. Six different types of procedures were performed, the most common was the interlaminar decompression and fusion (ILIF) followed by MIS laminectomy, microdiscectomy and MIS lateral fusion (XLIF). 74% of the surgeries were done at a single level. Average blood loss was 43 mL, and the mean length of stay was 1.7 days. There were three complications (11.1%): one urinary tract infection, one pulmonary embolism, and one new, postoperative weakness. At six months follow-up, there was a mean improvement of 27% in ODI, and a 5.6 improvement in NRS (both p<0.05); 90% of patients stated they would have the surgery again., Conclusion: Minimally invasive lumbar spine surgery is both safe and highly effective in the elderly population. Patient selection is of utmost importance. This data will add to the existing literature on the overall safety and effectiveness of these procedures in the elderly population.

Purpose: Accurate survival estimation is prerequisite to determine the most appropriate treatment for patients with metastatic spine disease. Several authors have proposed classification systems analyzing clinical and radiological parameters, such as, performance status, metastasis localization, and primary tumor histotype, but the modified Tokuhashi score (mTS) is the most widely used. Although it is regarded as one of the most complete and accurate systems, it does not take the effectiveness of new therapeutic strategies into consideration, contributing to a progressive loss of accuracy. The purpose of this review is to verify the ability of the mTS to accurately estimate metastatic spine patient survival, nearly 10 years after it was introduced., Methods: A literature review was conducted to evaluate mTS accuracy to predict metastatic spine patient survival., Results: Ten studies were selected, representing 1686 patients. The total predictive accuracy of the mTS was 63.00%; for patients expected to survive less than 6 months (group I), it was 64.10%; 6-12 months (group II), 55.32%; and more than 12 months (group III), 77.21%. A progressive decrease in accuracy over time was statistically significant in groups I and II., Conclusions: The mTS is suggestive of actual survival for patients with a good prognosis. It is less accurate for patients with an estimated survival of less than 12 months. The decreasing trend in mTS accuracy over time will likely further reduce mTS utility. An important opportunity exists to develop new instruments to assist spine surgeons and oncologists to choose appropriate surgical or non-surgical treatment modalities for patients with metastatic spine disease.

Primary bone tumors of the spine are rare entities with a poor prognosis if left untreated. En bloc excision is the preferred surgical approach to minimize the rate of recurrence. Paraspinal primary bone tumors are even less common. In this technical note the authors present an approach to the en bloc resection of primary bone tumors of the paraspinal thoracic region with posterior vertebral body hemiosteotomies and lateral thoracotomy. They also describe 2 illustrative cases.

We evaluated the anatomical considerations specific to the high anterior retropharyngeal approach to the cervical spine. Surgical exposure of the anterior upper cervical spine can sometimes be challenging due to the surrounding neurovascular structures. Using three adult cadavers, we performed high anterior retropharyngeal cervical dissection of the left and right side for a total of six approaches (six sides). During the dissection, all important neurovascular elements were noted and photographed, and anatomical relationships to the spinal vertebral bodies and disc spaces were analyzed. There are certain anatomic considerations that are unique to the high anterior cervical spine. The unique structures include the hypoglossal nerve and the superior thyroid artery/nerve. Only the superior thyroid artery in this region has numerous anatomical variations. Awareness of other structures, including the carotid artery, recurrent laryngeal nerve, and esophagus also remains important. Awareness of the anatomical structures in the anterior upper cervical spine is essential for performing safe anterior upper cervical spinal surgery, avoiding serious complications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

There is ample evidence supporting concomitant fusion after intradural spinal tumor resection in select pediatric patients. Unfortunately, the data are scarcer in adults. The objective of this work is to review the published literature and analyze practice patterns for stabilization and fusion after intradural tumor resection in adults. We performed a literature review via PubMed for information available regarding fusion in adults with intradural spine tumors. Additionally, we manually searched the references of selected articles to add relevant articles. Finally, we retrieved the criteria for fusion (if any) in the selected studies. A total of 639 articles were found and 35 were finally selected for analysis. Of those, three were literature reviews and 32 were retrospective case series. There were a total of 1288 patients on the series with 104 of them requiring fusion (8.1%). The median follow up of all the series was 24 months (range 1.5-180).The criteria for fusion that were common in most cases series were: previous deformity (i.e. kyphosis in the cervical spine), 3 or more levels of laminectomy, laminectomy encompassing a spinal junction, "young adults" (33 ± 4.2 years), facetectomy ≥ 50% (unilateral or bilateral), persistence of deformity after 1 year of the surgery and, C2 laminectomy. There appears to be some consistent practices for fusion after intradural tumor resection in adults, but this is based on retrospective analyses of case series. Prospective or randomized trials will likely provide more evidence based support for this practice., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: The minimally invasive (MI) lateral lumbar interbody fusion (LLIF) approach has become increasingly popular for the treatment of degenerative lumbar spine disease. The neural anatomy of the lumbar plexus has been studied; however, the pertinent surgical vascular anatomy has not been examined in detail. The goal of this study is to examine the vascular structures that are relevant in relation to the MI-LLIF approach., Methods: Anatomic dissection of the lumbar spines and associated vasculature was performed in three embalmed, adult cadavers. Right and left surgeon perspective views during LLIF were for a total of six approaches. During the dissection, all vascular elements were noted and photographed, and anatomical relationships to the vertebral bodies and disc spaces were analyzed. In addition, several axial and sagittal MRI images of the lumbar spine were analyzed to complement the cadaveric analysis., Results: The aorta descends along the left anterior aspect of lumbar vertebra with an average distance of 2.1 cm (range 1.9-2.3 cm) to the center of each intervertebral disc. The vena cava descends along the right anterior aspect of lumbar vertebrates with average distance of 1.4 cm (range 1.3-1.6 cm) to the center of the intervertebral disc. Each vertebral body has two lumbar arteries (direct branches from the aorta); one exits to the left and one to the right side of the vertebral body. The lumbar arteries pass underneath the sympathetic trunk, run in the superior margin of the vertebral body and extend all the way across it, with average length of 3.8 cm (range 2.5-5 cm). The mean distance between the arteries and the inferior plate of the superior disc space is 4.2 mm (range 2-5 mm) and mean distance of 3.1 cm (range 2.8-3.8 cm) between two arteries in adjacent vertebrae. One of the cadavers had an expected normal anatomical variation where the left arteries at L3-L4 anastomosed dorsally of the vertebral bodies at the middle of the intervertebral disc., Conclusions: Understanding the vascular anatomy of the lateral and anterior lumbar spine is paramount for successfully and safely executing the LLIF procedure. It is imperative to identify anatomical variations in lumbar arteries and veins with careful assessment of the preoperative imaging.

This cadaveric study aims to reexamine the corridors to the anterior cervicothoracic junction, relative to the left brachiocephalic vein, and to present these working corridors as either supra- or infra-brachiocephalic. The anterior cervicothoracic junction incorporates the seventh cervical vertebrae through the fourth thoracic vertebrae (C7-T4) and involves critical anatomical structures. Operative approaches to this area are well described in the literature, with the predominant implementation of three surgical corridors. We used three embalmed, human, cadaveric specimens for this study. No pathology involving the cervicothoracic junction was noted. While dissecting, we tried to imitate the actual surgery. For each surgical step, photographs were taken, drawing attention to the critical structures and highlighting the different corridors to the spine relative to the left brachiocephalic vein. It is possible to access the cervicothoracic junction relative to the brachiocephalic vein from the left. The supra-brachiocephalic approach gives access to the C7-T4 vertebrae, whereas if T4-T5 is the goal, the infra-brachiocephalic approach may be utilized. In the supra-brachiocephalic approach, the brachiocephalic artery can be either medialized or lateralized as needed. A re-examination of the anterior cervicothoracic junction anatomy has allowed us to classify approaches relative to the left brachiocephalic vein. Identifying and understanding the approaches relative to this structure will assist in safe and effective spinal surgery in this area., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We reviewed the literature to determine differences in clinical outcomes for the removal or preservation of the posterior longitudinal ligament (PLL) in anterior cervical discectomy and fusion (ACDF). The outcomes are surgeon and case-dependent for both practices. A literature review was performed in PubMed from the years 1960 to 2014 to identify studies describing surgeries where the PLL was removed or preserved during ACDF. Searches were performed using Medical Subject Headings (MeSH) and references included in the reviewed articles were also considered. Additionally we searched recent articles that cited those from the original search. The search yielded 79 articles and 115 pertinent citations. These 194 articles were reviewed for specific discussions of PLL resection or preservation. Four articles containing 122 patients were included in the final analysis. In 69 patients the PLL was removed and in 53 the PLL was preserved. Both groups improved in clinical scores during follow up. One patient in the PLL removal group had a cerebrospinal fluid leak. MRI and correlative outcome data suggest that a non-ossified PLL itself does not contribute to significant cord compression. Postoperative MRI of patients with the PLL removed showed a larger spinal cord diameter. Resection of the PLL is safe and common in ACDF surgery but there does not appear to be a demonstrable clinical difference in patients where it is resected. The ultimate decision is likely surgeon and case-dependent. Randomized trials could further determine the importance of PLL removal in ACDF treated patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Atlantoaxial surgical fixation is widely employed treatment strategy for a myriad of pathologies affecting the stability of the atlantoaxial joint. The most common technique used in adults, and in certain cases in children, involves a posterior construct with C1 lateral mass screws, and C2 pars or pedicle screws. This technical note aims to provide a step-by-step guide to this procedure using cadaveric and fluoroscopic images., Methods: An embalmed, human, cadaveric, specimen was used for this study. The subject did not have obvious occipital-cervical pathology. Dissections and techniques were performed to mimic actual surgical technique. Photographs were taken during each step, and the critical aspects of each step were highlighted. Fluoroscopic images from a real patient undergoing C1/C2 fixation were also utilized to further highlight the anatomic-radiographic relationships. This study was performed without external or industry funding., Results: Photographic and radiographic pictures and drawings are presented to illustrate the pertinent anatomy and technical aspects of this technique. The nuances of each step, including complication avoidance strategies are also highlighted., Conclusions: Given the widespread utilization of this technique, described step-by-step guide is timely for surgeons and trainees alike.

Purpose: Pelvic and sacral surgeries are considered technically difficult due to the complex multidimensional anatomy and the presence of significant neurovascular structures. Knowledge of the key neurovascular anatomy is essential for safe and effective execution of partial and complete sacral resections. The goal of this anatomic, cadaveric study is to describe the pertinent neurovascular anatomy during these procedures., Methods: Three embalmed human cadaveric specimens were used. Sacrectomies and sacroiliac joint resections were simulated and the structures at risk were identified. Both anterior and posterior approaches were evaluated., Results: During sacroiliac joint resection, L5 nerve roots are at high risk for iatrogenic injury; the vasculatures at greatest risk are the common iliac vessels and internal iliac vessels with L5-S1 and S1-S2 high sacrectomies. Minor bleeding risk is associated with S2-S3 osteotomy because of the potential to damage superior gluteal vessels. S3-S4 osteotomy presents a low risk of bleeding. Adjacent nerve roots proximal to the resection level are at high risk during higher sacrectomies., Conclusions: Several sacrectomy techniques are available and selection often depends on the specific case and surgeon preference; nevertheless, anatomic knowledge is extremely important. Considering the highly variable anatomic relations of the vascular bundles, a preoperative evaluation with CT or MRI with vascular reconstruction may be helpful to decrease bleeding risk by preemptively binding the internal iliac vessels in cases where higher tumors are present. To decrease the risk of damaging nerve roots, it is recommended to perform the resection as close to the involved foramina as possible.

Purpose: The recent proliferation of minimally invasive lateral lumbar interbody fusion (LLIF) techniques has drawn attention to potential for these techniques to control or correct sagittal misalignment in adult spinal deformity. We systemically reviewed published studies related to LLIF use in adult spinal deformity treatment with emphasis on radiographic assessment of sagittal balance., Methods: A literature review was conducted to examine studies focusing on sagittal balance restoration in adult degenerative scoliosis with the LLIF approach., Results: Fourteen publications, 12 retrospective and 2 prospective, reported data regarding lumbar lordosis correction (1,266 levels in 476 patients) but only two measured global sagittal alignment., Conclusion: LLIF appears to be especially effective when the lumbar lordosis and sagittal balance correction goals are less than 10° and 5 cm, respectively. However, the review demonstrated a lack of consistent reporting on sagittal balance restoration with the MIS LLIF techniques.

We describe 3 patients who presented with radiographic signs and clinical symptoms of adjacent segment disease several years after undergoing L4-S1 posterior pedicle screw fusion. All patients underwent successful lateral lumbar interbody fusion (LLIF) at 1-2 levels above their previous constructs, using stand-alone cages, with complete resolution of radiculopathy and a significant improvement in low-back pain. In addition to a thorough analysis of these cases, we review the pertinent literature regarding treatment options for adjacent segment disease and the applications of the lateral lumbar interbody technique., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Premise of the Study: Microsatellite markers were developed in Marchantia inflexa, a haploid liverwort with unisexual individuals, to identify clonal genotypes and measure population genetic variability., Methods and Results: Twelve polymorphic primer sets were developed from three enriched genomic libraries. Primers were fluorescently labeled, and alleles were identified by fragment analysis. These primers were tested in four natural populations and revealed a moderate level of genetic variation within four populations, as indicated by the number of alleles per locus (range = 1-5)., Conclusions: Development of polymorphic markers is crucial to the identification of individuals and will allow additional research into this species, particularly on its population genetics and metapopulation dynamics.

Objective: The goal of this study was to analyze trends in the annual rates of reported medical outcomes of US copperhead (Agkistrodon contortrix) snakebites published in the annual reports of the American Association of Poison Control Centers in the course of 26 years., Methods: This was a retrospective analysis of medical outcomes for copperhead snakebite victims who developed fatal, major, moderate, minor, or no effects. The annual rates for these medical outcomes were calculated by dividing the annual number of patients in each outcome category by the total annual number of people reported as being bitten by copperheads. Poisson and negative binomial regression were used to examine trends in annual rates., Results: From 1983 through 2008, the incidence rate of copperhead snakebites causing no effect significantly decreased by 12.1%/year (incidence rate ratio [IRR] 0.879; 95% confidence interval [CI] 0.848-0.911]. From 1985 through 2008, the incidence rate of minor outcomes significantly decreased by 2.3%/year (IRR 0.977; 95% CI 0.972-0.981), whereas the rate of moderate outcomes significantly increased by 2.8%/year (IRR 1.028; 95% CI 1.024-1.033). The rate of major outcomes did not significantly change. One fatality was reported in 2001., Conclusions: Annual rates of copperhead snakebites producing no effects and minor outcomes significantly decreased, those producing moderate outcomes significantly increased, and those producing major outcomes did not significantly change in a 26-year period.