Comparison of Narcotic Prescribing Habits Between Trainee and Attending Orthopaedic Surgeons

Background: Orthopaedic surgeons are among the highest prescribing physicians of narcotics to opioidnaïve patients. Despite the current opioid epidemic, few studies have specifically quantified the appropriate amount of opioids necessary for postoperative pain control. We hypothesized a significant variability in the quantity of postoperative opioids prescribed among trainee (ie, residents and fellows) and attending surgeons at a single institution. Methods: Postoperative narcotic prescribing habits were assessed using an anonymous survey. Ultimately, 28 trainee physicians and 17 attending physicians responded to the survey (86.5%). The survey recorded the amount of 5-mg oxycodone tablets that were commonly prescribed to manage pain after various typical orthopaedic procedures (eg, total knee arthroplasty). Non-narcotic analgesic use was also measured. Mean, standard deviation, and variance values were calculated, with significance set at α = 0.05. Results: After the following procedures, the respondents reported prescribing the following quantities of 5-mg oxycodone tablets: total knee arthroplasty, 56 (SD, 16); total hip arthroplasty, 53 (SD, 13); anterior cruciate ligament reconstruction, 38 (SD, 16); partial meniscectomy, 23 (SD, 14); arthroscopic rotator cuff repair, 39 (SD, 16); carpal tunnel release, 10 (SD, 10); A1 pulley release for treating trigger finger, 9 (SD, 9); open reduction and internal fixation (ORIF) for treating distal radius fractures, 32 (SD, 16); and ORIF for treating ankle fractures, 39 (SD, 15). Statistically significant variation existed between trainee and attending physicians for total hip arthroplasty and A1 pulley release. There was no difference for acetaminophen or nonsteroidal anti-inflammatory drugs, with about 70% of patients receiving at least one of these adjuncts. Conclusions: Variability exists in postoperative opioid prescribing habits between trainee and attending physicians at the academic training institution we accessed. In light of the ongoing opioid epidemic, institutions may benefit from standardized postoperative pain protocols

Multimodal Analgesia in Orthopaedic Surgery and Presentation of a Comprehensive Postoperative Pain Protocol: A Review

Rising opioid use in the United States has now been termed an epidemic. Opioid use is associated with considerable morbidity, mortality, and cost to the healthcare system. Orthopaedic surgeons play a key role in the opioid epidemic by prescribing postoperative narcotics. Although our understanding of the quantity of narcotics to prescribe postoperatively for analgesia is progressing, there is still a paucity of data focused on routine postoperative pain protocols. The purpose of this article is to review the current options for both opioid and non-opioid analgesia and put forth a multisubspecialty orthopaedic protocol of postoperative pain. On the basis of study findings and the individual experiences of surgeons within our orthopaedic department, our comprehensive pain protocol includes the following considerations: use of non-steroidal antiinflammatory drugs on an individual basis, limited use of benzodiazepines, use of diazepam in only pediatric patients undergoing major procedures, lower doses of gabapentin after hip and knee arthroplasty, higher doses of gabapentin after spine procedures, general use of oxycodone owing to its accessibility, use of isolated opioids rather than combined forms, and close collaboration with anesthesiologists for determining use of peripheral nerve block. Our resultant comprehensive pain protocol can provide orthopaedic surgeons with a framework to build upon, which will benefit greatly from future studies that examine narcotic use with specific procedures

Patient Compliance With Follow-Up After Open Reduction and Internal Fixation for Treating Malleolar Ankle Fractures: A Retrospective Review

Background: Compliance with follow-up after orthopaedic procedures is variable and does not always occur as recommended. Various factors such as medical, financial, cultural, and logistical reasons may contribute to this lack of compliance. The purpose of this study was to determine follow-up compliance of patients who had undergone open reduction and internal fixation (ORIF) for treating closed malleolar ankle fractures. Methods: Medical records of patients who underwent ORIF for treating closed malleolar ankle fractures by the senior author (RAM) were reviewed to evaluate compliance with postoperative follow-up (n = 267). Inclusion criteria were patients with isolated, acute, closed fractures (n = 229). Patients were considered to have followed up appropriately if they returned to clinic after a removable cast boot was issued at 4 to 8 weeks postoperatively. A 2-tailed t test was performed to analyze age and visual analogue scale score at the time of obtaining the removable cast boot. Chi-square testing was performed to analyze the other variables studied. Results: Of the 229 patients included, a total of 183 complied with follow-up whereas 46 did not. Younger age, male sex, and living greater than 160.9 km (100 mi) from the hospital were statistically significant variables associated with decreased compliance with follow-up. Conclusions: In our patient population, 80% of patients followed up in clinic as scheduled. The remaining 20% did not adhere with scheduled followup either before or after obtaining a removable cast boot. Younger age, male sex, and living greater than 100 miles from the hospital were associated with decreased compliance. Consideration should be paid to these factors when treating patients with ankle fractures

Preclinical evaluation of cancer immune therapy using patient-derived tumor antigen-specific T cells in a novel xenograft platform.

Objectives: With a rapidly growing list of candidate immune-based cancer therapeutics, there is a critical need to generate highly reliable animal models to preclinically evaluate the efficacy of emerging immune-based therapies, facilitating successful clinical translation. Our aim was to design and validate a novel Methods: Tumor xenografts are established rapidly in the greater omentum of globally immunodeficient NOD- Results: The tumors progress rapidly and disseminate in the mice unless patient-derived tumor-specific T cells are introduced. An initial T cell-mediated tumor arrest is later followed by a tumor escape, which correlates with the upregulation of the checkpoint molecules programmed cell death-1 (PD-1) and lymphocyte-activation gene 3 (LAG3) on T cells. Treatment with immune-based therapies that target these checkpoints, such as anti-PD-1 antibody (nivolumab) or interleukin-12 (IL-12), prevented or delayed the tumor escape. Furthermore, IL-12 treatment suppressed PD-1 and LAG3 upregulation on T cells. Conclusion: Together, these results validate the X-mouse model and establish its potential to preclinically evaluate the therapeutic efficacy of immune-based therapies

AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice.

INTRODUCTION: Pathologic accumulation and activation of mast cells and eosinophils are implicated in allergic and inflammatory diseases. Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is an inhibitory receptor selectively expressed on mast cells, eosinophils and, at a lower extent, basophils. When engaged with an antibody, Siglec-8 can induce apoptosis of activated eosinophils and inhibit mast cell activation. AK002 is a humanized, non-fucosylated IgG1 anti-Siglec-8 antibody undergoing clinical investigation for treatment of allergic, inflammatory, and proliferative diseases. Here we examine the human tissue selectivity of AK002 and evaluate the in vitro, ex vivo, and in vivo activity of AK002 on eosinophils and mast cells. METHODS: The affinity of AK002 for Siglec-8 and CD16 was determined by biolayer interferometry. Ex vivo activity of AK002 on human eosinophils from blood and dissociated human tissue was tested in apoptosis and antibody-dependent cell-mediated cytotoxicity (ADCC) assays. The in vivo activity of a murine precursor of AK002 (mAK002) was tested in a passive systemic anaphylaxis (PSA) humanized mouse model. RESULTS: AK002 bound selectively to mast cells, eosinophils and, at a lower level, to basophils in human blood and tissue and not to other cell types examined. AK002 induced apoptosis of interleukin-5-activated blood eosinophils and demonstrated potent ADCC activity against blood eosinophils in the presence of natural killer cells. AK002 also significantly reduced eosinophils in dissociated human lung tissue. Furthermore, mAK002 prevented PSA in humanized mice through mast cell inhibition. CONCLUSION: AK002 selectively evokes potent apoptotic and ADCC activity against eosinophils and prevents systemic anaphylaxis through mast cell inhibition

AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice

INTRODUCTION: Pathologic accumulation and activation of mast cells and eosinophils are implicated in allergic and inflammatory diseases. Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is an inhibitory receptor selectively expressed on mast cells, eosinophils and, at a lower extent, basophils. When engaged with an antibody, Siglec-8 can induce apoptosis of activated eosinophils and inhibit mast cell activation. AK002 is a humanized, non-fucosylated IgG1 anti-Siglec-8 antibody undergoing clinical investigation for treatment of allergic, inflammatory, and proliferative diseases. Here we examine the human tissue selectivity of AK002 and evaluate the in vitro, ex vivo, and in vivo activity of AK002 on eosinophils and mast cells. METHODS: The affinity of AK002 for Siglec-8 and CD16 was determined by biolayer interferometry. Ex vivo activity of AK002 on human eosinophils from blood and dissociated human tissue was tested in apoptosis and antibody-dependent cell-mediated cytotoxicity (ADCC) assays. The in vivo activity of a murine precursor of AK002 (mAK002) was tested in a passive systemic anaphylaxis (PSA) humanized mouse model. RESULTS: AK002 bound selectively to mast cells, eosinophils and, at a lower level, to basophils in human blood and tissue and not to other cell types examined. AK002 induced apoptosis of interleukin-5-activated blood eosinophils and demonstrated potent ADCC activity against blood eosinophils in the presence of natural killer cells. AK002 also significantly reduced eosinophils in dissociated human lung tissue. Furthermore, mAK002 prevented PSA in humanized mice through mast cell inhibition. CONCLUSION: AK002 selectively evokes potent apoptotic and ADCC activity against eosinophils and prevents systemic anaphylaxis through mast cell inhibition

Pre-existing Toxoplasma gondii infection increases susceptibility to pentylenetetrazol-induced seizures independent of traumatic brain injury in mice

IntroductionPost-traumatic epilepsy (PTE) is a debilitating chronic outcome of traumatic brain injury (TBI), and neuroinflammation is implicated in increased seizure susceptibility and epileptogenesis. However, how common clinical factors, such as infection, may modify neuroinflammation and PTE development has been understudied. The neurotropic parasite, Toxoplasma gondii (T. gondii) incurably infects one-third of the world’s population. Thus, many TBI patients have a pre-existing T. gondii infection at the time of injury. T. gondii infection results in chronic low-grade inflammation and altered signaling pathways within the brain, and preliminary clinical evidence suggest that it may be a risk factor for epilepsy. Despite this, no studies have considered how a pre-existing T. gondii infection may alter the development of PTE.MethodsThis study aimed to provide insight into this knowledge gap by assessing how a pre-existing T. gondii infection alters susceptibility to, and severity of, pentylenetetrazol (PTZ)-induced seizures (i.e., a surrogate marker of epileptogenesis/PTE) at a chronic stage of TBI recovery. We hypothesized that T. gondii will increase the likelihood and severity of seizures following PTZ administration, and that this would occur in the presence of intensified neuroinflammation. To test this, 6-week old male and female C57BL/6 Jax mice were intraperitoneally injected with 50,000 T. gondii tachyzoites or with the PBS vehicle only. At 12-weeks old, mice either received a severe TBI via controlled cortical impact or sham injury. At 18-weeks post-injury, mice were administered 40 mg/kg PTZ and video-recorded for evaluation of seizure susceptibility. Fresh cortical tissue was then collected for gene expression analyses.ResultsAlthough no synergistic effects were evident between infection and TBI, chronic T. gondii infection alone had robust effects on the PTZ-seizure response and gene expression of markers related to inflammatory, oxidative stress, and glutamatergic pathways. In addition to this, females were more susceptible to PTZ-induced seizures than males. While TBI did not impact PTZ responses, injury effects were evident at the molecular level.DiscussionOur data suggests that a pre-existing T. gondii infection is an important modifier of seizure susceptibility independent of brain injury, and considerable attention should be directed toward delineating the mechanisms underlying this pro-epileptogenic factor

The Soybean Genome Database (SoyGD): a browser for display of duplicated, polyploid, regions and sequence tagged sites on the integrated physical and genetic maps of Glycine max

Genomes that have been highly conserved following increases in ploidy (by duplication or hybridization) like Glycine max (soybean) present challenges during genome analysis. At the Soybean Genome Database (SoyGD) genome browser has, since 2002, integrated and served the publicly available soybean physical map, bacterial artificial chromosome (BAC) fingerprint database and genetic map associated genomic data. The browser shows both build 3 and build 4 contiguous sets of clones (contigs) of the soybean physical map. Build 4 consisted of 2854 contigs that encompassed 1.05 Gb and 404 high-quality DNA markers that anchored 742 contigs. Many DNA markers anchored sets of 2–8 different contigs. Each contig in the set represented a homologous region of related sequences. GBrowse was adapted to show sets of homologous contigs at all potential anchor points, spread laterally and prevented from overlapping. About 8064 minimum tiling path (MTP2) clones provided 13 473 BAC end sequences (BES) to decorate the physical map. Analyses of BES placed 2111 gene models, 40 marker anchors and 1053 new microsatellite markers on the map. Estimated sequence tag probes from 201 low-copy gene families located 613 paralogs. The genome browser portal showed each data type as a separate track. Tetraploid, octoploid, diploid and homologous regions are shown clearly in relation to an integrated genetic and physical map