Publications by authors named "Thomas J Hopkins"

28 Publications

  • Page 1 of 1

Percutaneous Peripheral Nerve Stimulation of the Medial Branch Nerves for the Treatment of Chronic Axial Back Pain in Patients After Radiofrequency Ablation.

Pain Med 2021 03;22(3):548-560

SPR Therapeutics, Inc., Cleveland, Ohio, USA.

Objective: Lumbar radiofrequency ablation is a commonly used intervention for chronic back pain. However, the pain typically returns, and though retreatment may be successful, the procedure involves destruction of the medial branch nerves, which denervates the multifidus. Repeated procedures typically have diminishing returns, which can lead to opioid use, surgery, or implantation of permanent neuromodulation systems. The objective of this report is to demonstrate the potential use of percutaneous peripheral nerve stimulation (PNS) as a minimally invasive, nondestructive, motor-sparing alternative to repeat radiofrequency ablation and more invasive surgical procedures.

Design: Prospective, multicenter trial.

Methods: Individuals with a return of chronic axial pain after radiofrequency ablation underwent implantation of percutaneous PNS leads targeting the medial branch nerves. Stimulation was delivered for up to 60 days, after which the leads were removed. Participants were followed up to 5 months after the start of PNS. Outcomes included pain intensity, disability, and pain interference.

Results: Highly clinically significant (≥50%) reductions in average pain intensity were reported by a majority of participants (67%, n = 10/15) after 2 months with PNS, and a majority experienced clinically significant improvements in functional outcomes, as measured by disability (87%, n = 13/15) and pain interference (80%, n = 12/15). Five months after PNS, 93% (n = 14/15) reported clinically meaningful improvement in one or more outcome measures, and a majority experienced clinically meaningful improvements in all three outcomes (i.e., pain intensity, disability, and pain interference).

Conclusions: Percutaneous PNS has the potential to shift the pain management paradigm by providing an effective, nondestructive, motor-sparing neuromodulation treatment.
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http://dx.doi.org/10.1093/pm/pnaa432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971467PMC
March 2021

Duloxetine for the reduction of opioid use in elective orthopedic surgery: a systematic review and meta-analysis.

Int J Clin Pharm 2021 Apr 18;43(2):394-403. Epub 2021 Jan 18.

Sacred Heart University, 5151 Park Ave, Fairfield, CT, 06825, USA.

Background Duloxetine is currently approved for chronic pain management; however, despite some evidence, its utility in acute, postoperative pain remains unclear Aim of the review This systematic review and meta-analysis is to determine if duloxetine 60 mg given perioperatively, is safe and effective at reducing postoperative opioid consumption and reported pain following elective orthopedic surgery. Method CINAHL, Medline, Cochrane Central Registry for Clinical Trials, Google Scholar, and Clinicaltrials.gov were searched using a predetermined search strategy from inception to January 15, 2019. Covidence.org was used to screen, select, and extract data by two independent reviewers. Individual study bias was assessed using the Cochrane Risk of Bias tool. Opioid consumption data were converted to oral morphine milligram equivalents (MME) and exported to RevMan where meta-analysis was conducted using a DerSimonian and Laird random effects model. Results Six randomized-controlled trials were included in the literature review of postoperative pain and adverse effects. Five studies were utilized for the meta-analysis of postoperative opioid consumption; totaling 314 patients. Postoperative pain analysis showed variable statistical significance with overall lower pain scores with duloxetine. Adverse effects included an increase in insomnia with duloxetine but lower rates of nausea and vomiting. Meta-analysis revealed statistically significant [mean difference (95% CI)] lower total opioid use with duloxetine postoperatively at 24 h [- 31.9 MME (- 54.22 to - 9.6), p = 0.005], 48 h [- 30.90 MME (- 59.66 to - 2.15), p = 0.04] and overall [- 31.68 MME (- 46.62 to - 16.74), p < 0.0001]. Conclusion These results suggest that adding perioperative administration duloxetine 60 mg to a multimodal analgesia regimen within the orthopedic surgery setting significantly lowers total postoperative opioid consumption and reduces pain without significant adverse effects.
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http://dx.doi.org/10.1007/s11096-020-01216-9DOI Listing
April 2021

Top Ten Tips Palliative Care Clinicians Should Know About Interventional Pain and Procedures.

J Palliat Med 2020 10 27;23(10):1386-1391. Epub 2020 Aug 27.

Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA.

Pain is a common symptom for patients with advanced illness. Palliative care (PC) clinicians are experts in pharmacologic and nonpharmacologic treatment of pain and other symptoms for these patients. True multimodal pain control should include consideration of interventional procedures and pumps to improve difficult-to-manage pain. This article, written by clinicians with expertise in interventional pain and PC, outlines and explains many of the adjunctive and interventional therapies that can be considered for patients with pain in the setting of serious illness. Only by understanding and considering all available options can we ensure that our patients are receiving optimal care.
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http://dx.doi.org/10.1089/jpm.2020.0487DOI Listing
October 2020

Perioperative Anesthetic Techniques to Reduce Surgical Morbidity After Amputation.

AANA J 2020 Aug;88(4):325-332

is the program director and associate clinical professor at Duke University's Nurse Anesthesia Program. E-mail:

Anesthetic modalities to mitigate the development of phantom limb pain have not been standardized into an evidence-based, multimodal anesthesia protocol to promote improved patient outcomes. This quality improvement project involved the implementation of a lower extremity, amputation-specific anesthesia protocol. In the postimplementation group, 94 patients were anesthetized for their amputation using an Amputation Improved Recovery Enhanced Recovery After Surgery (ERAS) protocol. Patient outcomes before and after protocol implementation were compared. The rate of continuous peripheral nerve block placement was higher in the postimplementation group (37.2%) than the preimplementation group (29.6%, P = .337). The 2 groups did not differ on average pain scores and morphine equivalent consumption rates per patient during hospitalization. The postimplementation group had significantly lower mean pain scores during the first 24 hours after amputation (P = .046); fewer postoperative complications (P = .001), amputation revisions (P = .003), 30-day hospital readmissions (P = .049), and readmissions related to amputation surgery (P = .019); and higher rates of early phantom limb pain that resolved during hospitalization (P = .012). Use of a standardized anesthetic protocol designed for patients undergoing amputation improved patient outcomes. Trials of this protocol elsewhere may contribute to improved recovery for patients undergoing amputations.
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August 2020

Occurrence of Symptomatic Hypotension in Patients Undergoing Breast Free Flaps: Is Enhanced Recovery after Surgery to Blame?

Plast Reconstr Surg 2020 03;145(3):606-616

From the Division of Plastic, Maxillofacial, and Oral Surgery, Department of General Surgery, and the Department of Anesthesia, Duke University Hospital; Duke University School of Medicine; and the Department of Biostatistics and Bioinformatics, Duke University Medical Center.

Background: Enhanced recovery after surgery (ERAS) initiatives improve postoperative function and expedite recovery, leading to a decrease in length of stay. The authors noted a high rate of postoperative symptomatic hypotension in patients undergoing abdominal free flap breast reconstruction and wished to explore this observation.

Methods: Subjects undergoing abdominal free flap breast reconstruction at the authors' institution from 2013 to 2017 were identified. The ERAS protocol was initiated in 2015 at the authors' hospital; thus, 99 patients underwent traditional management and 138 patients underwent ERAS management. Demographics and perioperative data were collected and analyzed. Postoperative symptomatic hypotension was defined as mean arterial pressure below 80 percent of baseline with symptoms requiring evaluation.

Results: A significantly higher rate of postoperative symptomatic hypotension was observed in the ERAS cohort compared with the traditional management cohort (4 percent versus 22 percent; p < 0.0001). Patients in the ERAS cohort received significantly less intraoperative intravenous fluid (4467 ml versus 3505 ml; p < 0.0001) and had a significantly increased amount of intraoperative time spent with low blood pressure (22 percent versus 32 percent; p =0.002). Postoperatively, the ERAS cohort had significantly lower heart rate (77 beats per minute versus 88 beats per minute; p < 0.0001) and mean arterial pressure (71 mmHg versus 78 mmHg; p < 0.0001), with no difference in urine output or adverse events.

Conclusions: The authors report that ERAS implementation in abdominal free flap breast reconstruction may result in a unique physiologic state with low mean arterial pressure, low heart rate, and normal urine output, resulting in postoperative symptomatic hypotension. Awareness of this early postoperative finding can help better direct fluid resuscitation and prevent episodes of symptomatic hypotension.

Clinical Question/level Of Evidence: Therapeutic, III.
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http://dx.doi.org/10.1097/PRS.0000000000006537DOI Listing
March 2020

Undersedation During Total Hip Arthroplasty Reduction Results in Worse Patient Outcomes.

J Arthroplasty 2019 Dec 19;34(12):3061-3064. Epub 2019 Jul 19.

Department of Orthopaedic Surgery at Duke University Hospital, Durham, NC.

Background: Total hip arthroplasty (THA) dislocation is a common reason for presentation to the emergency department (ED) postoperatively. Prior literature has shown that propofol conscious sedation provides the fewest complications and the shortest time to reduction. However, we are aware of no prior reports exploring sedative dosing regimens. We hypothesized that "undersedated" patients would have worse outcomes compared to appropriately sedated patients based on dose.

Methods: This is a retrospective review of isolated propofol conscious sedation performed in the ED for closed reduction of THA dislocations from 2013 to 2019. Prior authors have used at least 0.5 mg/kg/dose for sedation with propofol. Therefore, to allow a 10% rounding error, a dose of less than 0.45 mg/kg/dose was considered undersedated. Demographic information was collected and outcomes including sedation time, number of doses, complications, and successful reductions were analyzed in univariable and multivariable analyses.

Results: A total of 79 THAs were included for analysis with mean age 65.5 (16.2) years and weight 84.1 (21.3) kg. Thirty-seven (46.8%) patients had undergone revision surgery and 44 (55.7%) previously had a dislocation. A total of 39 patients were undersedated. There was no significant difference in demographics or arthroplasty-specific variables between undersedated and "protocol" sedation patients. In multivariable analysis, undersedated patients had significantly longer sedation time (P = .020), more re-doses (by mean 3 doses; P < .001), and greater total dose (P = .002). These patients were also more likely to have failed ED closed reduction (10.3% vs 0.0%; P = .038). One complication of a skin tear from countertraction was observed in an undersedated patient.

Conclusion: Historically, conscious sedation for THA dislocations has been the responsibility of the emergency room clinician. In consideration of our outcomes, we advocate for a multidisciplinary team to create a sedation protocol, emphasizing the need to maintain a dosing regimen of 0.5 mg/kg/dose to improve the care of THA patients.
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http://dx.doi.org/10.1016/j.arth.2019.07.020DOI Listing
December 2019

Paradox of age: older patients receive higher age-adjusted minimum alveolar concentration fractions of volatile anaesthetics yet display higher bispectral index values.

Br J Anaesth 2019 Sep 3;123(3):288-297. Epub 2019 Jul 3.

Anesthesiology Department, Duke University Medical Center, Durham, NC, USA. Electronic address:

Background: Minimum alveolar concentration (MAC) and MAC-awake decrease with age. We hypothesised that, in clinical practice, (i) end-tidal MAC fraction in older patients would decline by less than the predicted age-dependent MAC decrease (i.e. older patients would receive relatively excessive anaesthetic concentrations), and (ii) bispectral index (BIS) values would therefore be lower in older patients.

Methods: We examined the relationship between end-tidal MAC fraction, BIS values, and age in 4699 patients > 30 yr in age at a single centre using unadjusted local regression (locally estimated scatterplot smoothing), Spearman's correlation, stratification, and robust univariable and multivariable linear regression.

Results: The end-tidal MAC fraction in older patients declined by 3.01% per decade (95% confidence interval [CI]: 2.56-3.45; P<0.001), less than the 6.47% MAC decrease per decade that we found in a meta-regression analysis of published studies of age-dependent changes in MAC (P<0.001), and less than the age-dependent decrease in MAC-awake. The BIS values correlated positively with age (ρ=0.15; 95% CI: 0.12-0.17; P<0.001), and inversely with the age-adjusted end-tidal MAC (aaMAC) fraction (ρ= -0.13; 95% CI: -0.16, -0.11; P<0.001).

Conclusions: The age-dependent decline in end-tidal MAC fraction delivered in clinical practice at our institution was less than the age-dependent percentage decrease in MAC and MAC-awake determined from published studies. Despite receiving higher aaMAC fractions, older patients paradoxically showed higher BIS values. This most likely suggests that the BIS algorithm is inaccurate in older adults.
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http://dx.doi.org/10.1016/j.bja.2019.05.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104362PMC
September 2019

Preoperative Blood Management Strategy for Elective Hip and Knee Arthroplasty.

J Healthc Qual 2019 Nov/Dec;41(6):376-383

To improve quality and outcomes, a preoperative anemia clinic (PAC) was established to screen, evaluate, and manage preoperative anemia. A retrospective review of primary and revision hip and knee arthroplasty patients from August 2013 to September 2017 was conducted. Patients at "high risk" for transfusion were referred to PAC for treatment with iron, erythropoietin, or both based on anemia type. Preoperative anemia clinic referred patients were compared with a 1:3 historic propensity-matched control set of patients to help determine impact of PAC. Forty PAC patients were compared with 120 control patients. Among PAC patients, 26 (63.41%) received iron only, 3 (7.32%) received erythropoietin (EPO) only, and 12 (29.27%) received both. Preoperative hemoglobin significantly increased in the treatment group (median [interquartile range] 10.9 g/dl [10.3-11.2] vs. 12.0 g/dl [11.2-12.7]; p < .001). Four PAC patients (10.00%) received red blood cell transfusions compared with 29 (24.17%) from matched controls (p = .055). In addition, the PAC cohort had higher postoperative nadir hemoglobin levels (mean [SD] 9.7 g/dl [1.31] vs. 8.7 g/dl [1.25]; p < .001). High-risk patients appropriately treated with iron and/or EPO before surgery demonstrate a significant increase in preoperative hemoglobin, trend toward decrease perioperative transfusion, and increased hemoglobin levels postoperatively compared with matched controls.
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http://dx.doi.org/10.1097/JHQ.0000000000000207DOI Listing
July 2020

Human B-1 Cells and B-1 Cell Antibodies Change With Advancing Age.

Front Immunol 2019 19;10:483. Epub 2019 Mar 19.

Center of Molecular Immunology, Havana, Cuba.

Age-related deficits in the immune system have been associated with an increased incidence of infections, autoimmune diseases, and cancer. Human B cell populations change quantitatively and qualitatively in the elderly. However, the function of human B-1 cells, which play critical anti-microbial and housekeeping roles, have not been studied in the older age population. In the present work, we analyzed how the frequency, function and repertoire of human peripheral blood B-1 cells (CD19+CD20+CD27+CD38CD43+) change with age. Our results show that not only the percentage of B-1 cells but also their ability to spontaneously secrete IgM decreased with age. Further, expression levels of the transcription factors XBP-1 and Blimp-1 were significantly lower, while PAX-5, characteristic of non-secreting B cells, was significantly higher, in healthy donors over 65 years (old) as compared to healthy donors between 20 and 45 years (young). To further characterize the B-1 cell population in older individuals, we performed single cell sequencing analysis of IgM heavy chains from healthy young and old donors. We found reduced repertoire diversity of IgM antibodies in B-1 cells from older donors as well as differences in usage of certain VH and DH specific genes, as compared to younger. Overall, our results show impairment of the human B-1 cell population with advancing age, which might impact the quality of life and onset of disease within the elderly population.
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http://dx.doi.org/10.3389/fimmu.2019.00483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433875PMC
September 2020

A Novel Risk Calculator Predicts 90-Day Readmission Following Total Joint Arthroplasty.

J Bone Joint Surg Am 2019 Mar;101(6):547-556

Department of Orthopaedic Surgery (D.E.G., S.P.R., D.E.A., M.P.B., and T.M.S.), Department of Anesthesiology (T.J.H.), and Performance Services (C.B.H.), Duke University Medical Center, Durham, North Carolina.

Background: A reliable prediction tool for 90-day adverse events not only would provide patients with valuable estimates of their individual risk perioperatively, but would also give health-care systems a method to enable them to anticipate and potentially mitigate postoperative complications. Predictive accuracy, however, has been challenging to achieve. We hypothesized that a broad range of patient and procedure characteristics could adequately predict 90-day readmission after total joint arthroplasty (TJA).

Methods: The electronic medical records on 10,155 primary unilateral total hip (4,585, 45%) and knee (5,570, 55%) arthroplasties performed at a single institution from June 2013 to January 2018 were retrospectively reviewed. In addition to 90-day readmission status, >50 candidate predictor variables were extracted from these records with use of structured query language (SQL). These variables included a wide variety of preoperative demographic/social factors, intraoperative metrics, postoperative laboratory results, and the 30 standardized Elixhauser comorbidity variables. The patient cohort was randomly divided into derivation (80%) and validation (20%) cohorts, and backward stepwise elimination identified important factors for subsequent inclusion in a multivariable logistic regression model.

Results: Overall, subsequent 90-day readmission was recorded for 503 cases (5.0%), and parameter selection identified 17 variables for inclusion in a multivariable logistic regression model on the basis of their predictive ability. These included 5 preoperative parameters (American Society of Anesthesiologists [ASA] score, age, operatively treated joint, insurance type, and smoking status), duration of surgery, 2 postoperative laboratory results (hemoglobin and blood-urea-nitrogen [BUN] level), and 9 Elixhauser comorbidities. The regression model demonstrated adequate predictive discrimination for 90-day readmission after TJA (area under the curve [AUC]: 0.7047) and was incorporated into static and dynamic nomograms for interactive visualization of patient risk in a clinical or administrative setting.

Conclusions: A novel risk calculator incorporating a broad range of patient factors adequately predicts the likelihood of 90-day readmission following TJA. Identifying at-risk patients will allow providers to anticipate adverse outcomes and modulate postoperative care accordingly prior to discharge.

Level Of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.18.00843DOI Listing
March 2019

American Society for Enhanced Recovery (ASER) and Perioperative Quality Initiative (POQI) joint consensus statement on measurement to maintain and improve quality of enhanced recovery pathways for elective colorectal surgery.

Perioper Med (Lond) 2017 17;6. Epub 2017 Mar 17.

Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina USA.

Background: This article sets out a framework for measurement of quality of care relevant to enhanced recovery pathways (ERPs) in elective colorectal surgery. The proposed framework is based on established measurement systems and/or theories, and provides an overview of the different approaches for improving clinical monitoring, and enhancing quality improvement or research in varied settings with different levels of available resources.

Methods: Using a structure-process-outcome framework, we make recommendations for three hierarchical tiers of data collection.

Discussion: Core, Quality Improvement, and Best Practice datasets are proposed. The suggested datasets incorporate patient data to describe case-mix, process measures to describe delivery of enhanced recovery and clinical outcomes. The fundamental importance of routine collection of data for the initiation, maintenance, and enhancement of enhanced recovery pathways is emphasized.
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http://dx.doi.org/10.1186/s13741-017-0062-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356230PMC
March 2017

Human B-1 and B-2 B Cells Develop from Lin-CD34+CD38lo Stem Cells.

J Immunol 2016 11 7;197(10):3950-3958. Epub 2016 Oct 7.

Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030;

The B-1 B cell population is an important bridge between innate and adaptive immunity primarily because B-1 cells produce natural Ab. Murine B-1 and B-2 cells arise from distinct progenitors; however, in humans, in part because it has been difficult to discriminate between them phenotypically, efforts to pinpoint the developmental origins of human B-1 and B-2 cells have lagged. To characterize progenitors of human B-1 and B-2 cells, we separated cord blood and bone marrow LinCD34 hematopoietic stem cells into LinCD34CD38 and LinCD34CD38 populations. We found that transplanted LinCD34CD38 cells, but not LinCD34CD38 cells, generated a CD19 B cell population after transfer into immunodeficient NOD.Cg-Prkdc Il2rg/SxJ neonates. The emergent CD19 B cell population was found in spleen, bone marrow, and peritoneal cavity of humanized mice and included distinct populations displaying the B-1 or the B-2 cell phenotype. Engrafted splenic B-1 cells exhibited a mature phenotype, as evidenced by low-to-intermediate expression levels of CD24 and CD38. The engrafted B-1 cell population expressed a VH-DH-JH composition similar to cord blood B-1 cells, including frequent use of VH4-34 (8 versus 10%, respectively). Among patients with hematologic malignancies who underwent hematopoietic stem cell transplantation, B-1 cells were found in the circulation as early as 8 wk posttransplantation. Altogether, our data demonstrate that human B-1 and B-2 cells develop from a LinCD34CD38 stem cell population, and engrafted B-1 cells in humanized mice exhibit an Ig-usage pattern comparable to B-1 cells in cord blood.
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http://dx.doi.org/10.4049/jimmunol.1600630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363078PMC
November 2016

Associations between ASA Physical Status and postoperative mortality at 48 h: a contemporary dataset analysis compared to a historical cohort.

Perioper Med (Lond) 2016 20;5:29. Epub 2016 Oct 20.

Department of Anesthesiology, Duke University Hospital, Durham, NC USA.

Background: In this study, we examined the association between American Society of Anesthesiologists Physical Status (ASA PS) designation and 48-h mortality for both elective and emergent procedures in a large contemporary dataset (patient encounters between 2009 and 2014) and compared this association with data from a landmark study published by Vacanti et al. in 1970.

Methods: Patient history, hospital characteristics, anesthetic approach, surgical procedure, efficiency and quality indicators, and patient outcomes were prospectively collected for 732,704 consecutive patient encounters between January 1, 2009, and December 31, 2014, at 233 anesthetizing locations across 19 facilities in two US states and stored in the Quantum™ Clinical Navigation System (QCNS) database. The outcome (death within 48 h of procedure) was tabulated against ASA PS designations separately for patients with and without "E" status labels. To maintain consistency with the historical cohort from the landmark study performed by Vacanti et al. on adult men at US naval hospitals in 1970, we then created a comparison cohort in the contemporary dataset that consisted of 242,103 adult male patients (with/without E designations) undergoing elective and emergent procedures. Differences in the relationship between ASA PS and 48-h mortality in the historical and contemporary cohorts were assessed for patients undergoing elective and emergent procedures.

Results: As reported nearly five decades ago, we found a significant trend toward increased mortality with increasing ASA PS for patients undergoing both elective and emergent procedures in a large contemporary cohort ( < 0.0001). Additionally, the overall mortality rate at 48 h was significantly higher among patients undergoing emergent compared to elective procedures in the large contemporary cohort (1.27 versus 0.03 %,  < 0.0001). In the comparative analysis with the historical cohort that focused on adult males, we found the overall 48-h mortality rate was significantly lower among patients undergoing elective procedures in the contemporary cohort (0.05 % now versus 0.24 % in 1970,  < 0.0001) but not significantly lower among those undergoing emergent procedures (1.88 % now versus 1.22 % in 1970,  < 0.0001).

Conclusions: The association between increasing ASA PS designation (1-5) and mortality within 48 h of surgery is significant for patients undergoing both elective and emergent procedures in a contemporary dataset consisting of over 700,000 patient encounters. Emergency surgery was associated with a higher risk of patient death within 48 h of surgery in this contemporary dataset. These data trends are similar to those observed nearly five decades ago in a landmark study evaluating the association between ASA PS and 48-h surgical mortality on adult men at US naval hospitals. When a comparison cohort was created from the contemporary dataset and compared to this landmark historical cohort, the absolute 48-h mortality rate was significantly lower in the contemporary cohort for elective procedures but not significantly lower for emergency procedures. The underlying implications of these findings remain to be determined.
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http://dx.doi.org/10.1186/s13741-016-0054-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072352PMC
October 2016

Age-Related Decline in Natural IgM Function: Diversification and Selection of the B-1a Cell Pool with Age.

J Immunol 2016 05 20;196(10):4348-57. Epub 2016 Apr 20.

Center for Oncology and Cell Biology, Feinstein Institute for Medical Research, Hofstra Northwell School of Medicine, Manhasset, NY 11030; Department of Medicine, Hofstra Northwell School of Medicine, Manhasset, NY 11030; and Department of Molecular Medicine, Hofstra Northwell School of Medicine, Manhasset, NY 11030.

Streptococcus pneumoniae is the most common cause of pneumonia, which claims the lives of people over the age of 65 y seven times more frequently than those aged 5-49 y. B-1a cells provide immediate and essential protection from S. pneumoniae through production of natural Ig, which has minimal insertion of N-region additions added by the enzyme TdT. In experiments with SCID mice infected with S. pneumoniae, we found passive transfer of IgG-depleted serum from aged (18-24 mo old) mice had no effect whereas IgG-depleted serum from young (3 mo old) mice was protective. This suggests protective natural IgM changes with age. Using single cell PCR we found N-region addition, which is initially low in fetal-derived B-1a cell IgM developing in the absence of TdT, increased in 7- to 24-mo-old mice as compared with 3-mo-old mice. To determine the mechanism responsible for the age related change in B-1a cell IgM, we established a mixed chimera system in which mice were reconstituted with allotype-marked mature peritoneal B-1a cells and adult bone marrow cells. We demonstrated even in the presence of mature peritoneal B-1a cells, adult bone marrow contributed to the mature B-1a cell pool. More importantly, using this system we found over a 10-mo-period peritoneal B-1a cell IgM changed, showing the number of cells lacking N-region additions at both junctions fell from 49 to 29% of sequences. These results strongly suggest selection-induced skewing alters B-1a cell-derived natural Ab, which may in turn be responsible for the loss of natural IgM-mediated protection against pneumococcal infection.
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http://dx.doi.org/10.4049/jimmunol.1600073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874569PMC
May 2016

Thoracic Nerve Root Entrapment by Intrathecal Catheter Coiling: Case Report and Review of the Literature.

Pain Physician 2016 Mar;19(3):E499-504

Department of Neurosurgery, Duke University Medical Center, Durham, NC.

Background: Intrathecal catheter placement has long-term therapeutic benefits in the management of chronic, intractable pain. Despite the diverse clinical applicability and rising prevalence of implantable drug delivery systems in pain medicine, the spectrum of complications associated with intrathecal catheterization remains largely understudied and underreported in the literature.

Objective: To report a case of thoracic nerve root entrapment resulting from intrathecal catheter migration.

Study Design: Case report.

Setting: Inpatient hospital service.

Results/ Case Report: A 60-year-old man status post implanted intrathecal (IT) catheter for intractable low back pain secondary to failed back surgery syndrome returned to the operating room for removal of IT pump trial catheter after experiencing relapse of preoperative pain and pump occlusion. Initial attempt at ambulatory removal of the catheter was aborted after the patient reported acute onset of lower extremity radiculopathic pain during the extraction. Noncontrast computed tomography (CT) subsequently revealed that the catheter had ascended and coiled around the T10 nerve root. The patient was taken back to the operating room for removal of the catheter under fluoroscopic guidance, with possible laminectomy for direct visualization. Removal was ultimately achieved with slow continuous tension, with complete resolution of the patient's new radicular symptoms.

Limitations: This report describes a single case report.

Conclusion: This case demonstrates that any existing loops in the intrathecal catheter during initial implantation should be immediately re-addressed, as they can precipitate nerve root entrapment and irritation. Reduction of the loop or extrication of the catheter should be attempted under continuous fluoroscopic guidance to prevent further neurosurgical morbidity.
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March 2016

Distinctions among Circulating Antibody-Secreting Cell Populations, Including B-1 Cells, in Human Adult Peripheral Blood.

J Immunol 2016 Feb 6;196(3):1060-9. Epub 2016 Jan 6.

Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030;

Human Ab-secreting cell (ASC) populations in circulation are not well studied. In addition to B-1 (CD20(+)CD27(+)CD38(lo/int)CD43(+)) cell and conventional plasmablast (PB) (CD20-CD27(hi)CD38(hi)) cell populations, in this study, we identified a novel B cell population termed 20(+)38(hi) B cells (CD20(+)CD27(hi)CD38(hi)) that spontaneously secretes Ab. At steady-state, 20(+)38(hi) B cells are distinct from PBs on the basis of CD20 expression, amount of Ab production, frequency of mutation, and diversity of BCR repertoire. However, cytokine treatment of 20(+)38(hi) B cells induces loss of CD20 and acquisition of CD138, suggesting that 20(+)38(hi) B cells are precursors to PBs or pre-PBs. We then evaluated similarities and differences among CD20(+)CD27(+)CD38(lo/int)CD43(+) B-1 cells, CD20(+)CD27(hi)CD38(hi) 20(+)38(hi) B cells, CD20(-)CD27(hi)CD38(hi) PBs, and CD20(+)CD27(+)CD38(lo/int)CD43(-) memory B cells. We found that B-1 cells differ from 20(+)38(hi) B cells and PBs in a number of ways, including Ag expression, morphological appearance, transcriptional profiling, Ab skewing, Ab repertoire, and secretory response to stimulation. In terms of gene expression, B-1 cells align more closely with memory B cells than with 20(+)38(hi) B cells or PBs, but differ in that memory B cells do not express Ab secretion-related genes. We found that B-1 cell Abs use Vh4-34, which is often associated with autoreactivity, 3- to 6-fold more often than other B cell populations. Along with selective production of IgM anti-phosphoryl choline, these data suggest that human B-1 cells might be preferentially selected for autoreactivity/natural specificity. In summary, our results indicate that human healthy adult peripheral blood at steady-state consists of three distinct ASC populations.
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http://dx.doi.org/10.4049/jimmunol.1501843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351554PMC
February 2016

How do we develop and implement a preoperative anemia clinic designed to improve perioperative outcomes and reduce cost?

Transfusion 2016 Feb 23;56(2):297-303. Epub 2015 Nov 23.

Department of Anesthesiology.

Treatment of anemia is one of the four pillars of patient blood management programs. Preoperative anemia is common and associated with increased perioperative morbidity after surgery and increased rates of blood transfusion. Effective treatment of preoperative anemia, however, requires advanced screening, diagnosis, and initiation of therapy weeks before elective surgery. Here we describe the development and implementation of a preoperative anemia screening and treatment program at Duke University Hospital.
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http://dx.doi.org/10.1111/trf.13426DOI Listing
February 2016

Effective Implementation of Enhanced Recovery Pathway Programs: The Key to Disseminating Evidence into Practice.

Jt Comm J Qual Patient Saf 2015 Oct;41(10):445-6

Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.

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http://dx.doi.org/10.1016/s1553-7250(15)41057-8DOI Listing
October 2015

Deep brain stimulation of the nucleus accumbens shell attenuates cocaine reinstatement through local and antidromic activation.

J Neurosci 2013 Sep;33(36):14446-54

Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Accumbal deep brain stimulation (DBS) is a promising therapeutic modality for the treatment of addiction. Here, we demonstrate that DBS in the nucleus accumbens shell, but not the core, attenuates cocaine priming-induced reinstatement of drug seeking, an animal model of relapse, in male Sprague Dawley rats. Next, we compared DBS of the shell with pharmacological inactivation. Results indicated that inactivation using reagents that influenced (lidocaine) or spared (GABA receptor agonists) fibers of passage blocked cocaine reinstatement when administered into the core but not the shell. It seems unlikely, therefore, that intrashell DBS influences cocaine reinstatement by inactivating this nucleus or the fibers coursing through it. To examine potential circuit-wide changes, c-Fos immunohistochemistry was used to examine neuronal activation following DBS of the nucleus accumbens shell. Intrashell DBS increased c-Fos induction at the site of stimulation as well as in the infralimbic cortex, but had no effect on the dorsal striatum, prelimbic cortex, or ventral pallidum. Recent evidence indicates that accumbens DBS antidromically stimulates axon terminals, which ultimately activates GABAergic interneurons in cortical areas that send afferents to the shell. To test this hypothesis, GABA receptor agonists (baclofen/muscimol) were microinjected into the anterior cingulate, and prelimbic or infralimbic cortices before cocaine reinstatement. Pharmacological inactivation of all three medial prefrontal cortical subregions attenuated the reinstatement of cocaine seeking. These results are consistent with DBS of the accumbens shell attenuating cocaine reinstatement via local activation and/or activation of GABAergic interneurons in the medial prefrontal cortex via antidromic stimulation of cortico-accumbal afferents.
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http://dx.doi.org/10.1523/JNEUROSCI.4804-12.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761051PMC
September 2013

A 10-year longitudinal analysis of surgical management for acute ischemic colitis.

J Gastrointest Surg 2013 Apr 14;17(4):784-92. Epub 2012 Dec 14.

Department of General Surgery, Duke University Medical Center, Box 3443, Durham, NC 27710, USA.

Introduction: Our objective was to review our 10-year experience of surgical resection for acute ischemic colitis (IC) and to assess the predictive value of previously reported risk-stratification methods.

Methods: We retrospectively reviewed all adult patients at our institution undergoing colectomy for acute IC between 2000 and 2009. Descriptive statistics were calculated. Long-term survival was assessed using Kaplan-Meier methods and in-hospital mortality using multivariate logistic regression. Patients were risk-stratified based on previously reported methods, and discriminatory accuracy of predicting in-hospital mortality was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.

Results: A total of 115 patients were included for analysis, of which 37 % (n = 43) died in-hospital. The median survival was 4.9 months for all patients and 43.6 months for patients surviving to discharge. Seventeen patients subsequently underwent end-ostomy reversal at our institution, with in-hospital mortality of 18 % (n = 3) and ICU admission for 35 % (n = 6). The discriminatory accuracy of risk stratification in predicting in-hospital mortality based on ROC AUC was 0.75.

Conclusion: Acute IC continues to remain a very deadly disease. Patients who survive the initial acute IC insult can achieve long-term survival; however, we experienced high rates of death and complications following elective end-ostomy reversal. Risk stratification provides reasonable accuracy in predicting postoperative mortality.
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http://dx.doi.org/10.1007/s11605-012-2117-xDOI Listing
April 2013

CSK regulatory polymorphism is associated with systemic lupus erythematosus and influences B-cell signaling and activation.

Nat Genet 2012 Nov 7;44(11):1227-30. Epub 2012 Oct 7.

Center for Autoimmune and Musculoskeletal Disorders, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish, Manhasset, New York, USA.

The c-Src tyrosine kinase, Csk, physically interacts with the intracellular phosphatase Lyp (encoded by PTPN22) and can modify the activation state of downstream Src kinases, such as Lyn, in lymphocytes. We identified an association of CSK with systemic lupus erythematosus (SLE) and refined its location to the intronic polymorphism rs34933034 (odds ratio (OR) = 1.32; P = 1.04 × 10(-9)). The risk allele at this SNP is associated with increased CSK expression and augments inhibitory phosphorylation of Lyn. In carriers of the risk allele, there is increased B-cell receptor (BCR)-mediated activation of mature B cells, as well as higher concentrations of plasma immunoglobulin M (IgM), relative to individuals with the non-risk haplotype. Moreover, the fraction of transitional B cells is doubled in the cord blood of carriers of the risk allele, due to an expansion of late transitional cells in a stage targeted by selection mechanisms. This suggests that the Lyp-Csk complex increases susceptibility to lupus at multiple maturation and activation points in B cells.
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http://dx.doi.org/10.1038/ng.2439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715052PMC
November 2012

Galantamine, an acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, attenuates nicotine taking and seeking in rats.

Neuropsychopharmacology 2012 Sep 6;37(10):2310-21. Epub 2012 Jun 6.

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Current smoking cessation pharmacotherapies have limited efficacy in preventing relapse and maintaining abstinence during withdrawal. Galantamine is an acetylcholinesterase inhibitor that also acts as a positive allosteric modulator of nicotinic acetylcholine receptors. Galantamine has recently been shown to reverse nicotine withdrawal-induced cognitive impairments in mice, which suggests that galantamine may function to prevent relapse in human smokers. However, there are no studies examining whether galantamine administration modulates nicotine self-administration and/or reinstatement of nicotine seeking in rodents. The present experiments were designed to determine the effects of galantamine administration on nicotine taking and reinstatement of nicotine-seeking behavior, an animal model of relapse. Moreover, the effects of galantamine on sucrose-maintained responding and sucrose seeking were also examined to determine whether galantamine's effects generalized to other reinforced behaviors. An inverted U-shaped dose-response curve was obtained when animals self-administered different unit doses of nicotine with the highest responding for 0.03 mg/kg per infusion of nicotine. Acute galantamine administration (5.0 mg/kg, i.p.) attenuated nicotine self-administration when animals were maintained on either a fixed-ratio 5 (FR5) or progressive ratio (PR) schedule of reinforcement. Galantamine administration also attenuated the reinstatement of nicotine-seeking behavior. No significant effects of galantamine on sucrose self-administration or sucrose reinstatement were noted. Acetylcholinesterase inhibitors have also been shown to produce nausea and vomiting in humans. However, at doses required to attenuate nicotine self-administration, no effects of galantamine on nausea/malaise as measured by pica were noted. These results indicate that increased extracellular acetylcholine levels and/or nicotinic acetylcholine receptor stimulation is sufficient to attenuate nicotine taking and seeking in rats and that these effects are reinforcer selective and not due to adverse malaise symptoms such as nausea.
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http://dx.doi.org/10.1038/npp.2012.83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422495PMC
September 2012

Muscarinic acetylcholine receptors in the nucleus accumbens core and shell contribute to cocaine priming-induced reinstatement of drug seeking.

Eur J Pharmacol 2011 Jan 27;650(2-3):596-604. Epub 2010 Oct 27.

Department of Pharmacology, Boston University School of Medicine, Boston, MA 02118, USA.

Muscarinic acetylcholine receptors in the nucleus accumbens play an important role in mediating the reinforcing effects of cocaine. However, there is a paucity of data regarding the role of accumbal muscarinic acetylcholine receptors in the reinstatement of cocaine-seeking behavior. The goal of these experiments was to assess the role of muscarinic acetylcholine receptors in the nucleus accumbens core and shell in cocaine and sucrose priming-induced reinstatement. Rats were initially trained to self-administer cocaine or sucrose on a fixed-ratio schedule of reinforcement. Lever-pressing behavior was then extinguished and followed by a subsequent reinstatement phase during which operant responding was induced by either a systemic injection of cocaine in cocaine-experienced rats or non-contingent delivery of sucrose pellets in subjects with a history of sucrose self-administration. Results indicated that systemic administration of the muscarinic acetylcholine receptor antagonist scopolamine (5.0 mg/kg, i.p.) dose-dependently attenuated cocaine, but not sucrose, reinstatement. Furthermore, administration of scopolamine (36.0 μg) directly into the nucleus accumbens shell or core attenuated cocaine priming-induced reinstatement. In contrast, infusion of scopolamine (36.0 μg) directly into the accumbens core, but not shell, attenuated sucrose reinstatement, which suggests that muscarinic acetylcholine receptors in these two subregions of the nucleus accumbens have differential roles in sucrose seeking. Taken together, these results indicate that cocaine priming-induced reinstatement is mediated, in part, by increased signaling through muscarinic acetylcholine receptors in the shell subregion of the nucleus accumbens. Muscarinic acetylcholine receptors in the core of the accumbens, in contrast, appear to play a more general (i.e. not cocaine specific) role in motivated behaviors.
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http://dx.doi.org/10.1016/j.ejphar.2010.10.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033040PMC
January 2011

Lumbar interbody fusion after treatment with recombinant human bone morphogenetic protein-2 added to poly(L-lactide-co-D,L-lactide) bioresorbable implants.

Neurosurg Focus 2004 Mar 15;16(3):E9. Epub 2004 Mar 15.

DBA California Spine Group, and Century City Hospital, Los Angeles, California, USA.

Object. To evaluate the effectiveness of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with a bioresorbable implant, the authors conducted a prospective study of 43 patients with degenerative lumbar disc disease who underwent transforaminal lumbar interbody fusion. Methods. The authors used Infuse bone graft, which consisted of rhBMP-2 applied to an absorbable collagen sponge and contained within a HYDROSORB Telamon bioresorbable implant to perform the fusion. Multilevel fusions were performed in 30% of the 43 patients, for a total of 57 levels. At 6 months postoperatively, x-ray films and computerized tomography (CT) scans demonstrated solid fusion in 98% of 41 patients. Improvement from the baseline Oswestry Disability Rating was demonstrated at 6 months postoperatively in 68% of the patients, based on the Oswestry Disability Questionnaire. At 12 months all 11 patients in whom CT scans were obtained showed complete bridging of bone; there were no device-related complications. Conclusions. Results in this series provide evidence of the feasibility of using HYDROSORB Telamon bioresorbable spacers in combination with Infuse bone graft for lumbar spine fusion.
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March 2004

Early findings in a pilot study of anterior cervical interbody fusion in which recombinant human bone morphogenetic protein-2 was used with poly(L-lactide-co-D,L-lactide) bioabsorbable implants.

Neurosurg Focus 2004 Mar 15;16(3):E6. Epub 2004 Mar 15.

California Spine Group, Century City Hospital, Los Angeles, California, USA.

Object: The goal of this study was to assess the efficacy of bioabsorbable interbody spacers in cervical spine fusion.

Methods: The authors report on a prospective examination of 20 patients with degenerative cervical disc disease who underwent anterior cervical fusion at 28 total levels. The authors used Infuse bone graft (that is, recombinant human bone morphogenetic protein-2 applied to an absorbable collagen sponge and contained within a Cornerstone-HSR bioabsorbable spacer. Multiple-level fusions were performed in 30% of these patients. At 3 months postfusion, radiographs and computerized tomography scans demonstrated bridging bone in 100% of the patients. Improvement from baseline scores in physical functioning, mental health, and bodily pain was demonstrated at 3 months postoperatively according to results of the Short Form-36 Version 2 health survey. There were no device-related complications.

Conclusions: The results in this series indicate that the use of Cornerstone-HSR as a bioabsorbable interbody spacer in combination with Infuse bone graft may be an alternative treatment for cervical spine fusion.
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March 2004