Faculty Bibliography

PURPOSE/OBJECTIVE:The aim of this study was to characterize if the use of surgical drains or length of drain placement following spine surgery increases the risk of post-operative infection. METHODS:Records of patients undergoing elective spinal surgery at a tertiary care center were collected between May 5, 2016 and August 16, 2018. Pre-operative baseline characteristics were recorded including patient's demographics and comorbidities. Intraoperative procedure information was documented related to procedure type, blood loss, and antibiotics used. Following surgery, patients were then further subdivided into two groups: patients who were discharged with a spinal surgical site drain and patients who did not receive a drain. Post-operative surgical variables included length of stay (LOS), drain length, number of antibiotics given, and type of post-operative infection. Univariate and multivariate statistical analysis was conducted. RESULTS:A total of 671 patients were included in the current study, 386 (57.5%) with and 285 (42.5%) without the drain. The overall infection rate was 5.7% with 6.22% among patients with the drain compared to 4.91% in patients without drain. The univariate analysis identified the following variables to be significantly associated with the infection: total number of surgical levels, spinal region, blood loss, redosing of antibiotics, length of stay, length of drain placement, and number of antibiotics (P < 0.05). However, the multivariate analysis none of the predictors was significant. CONCLUSIONS:The current study shows that the placement of drain does not increase rate of infection, irrespective of levels, length of surgery, or approach.

Background/UNASSIGNED:Mycosis fungoides (MF) and Sézary syndrome (SS) are subtypes of primary cutaneous lymphomas and represent complex diseases regarding their physiopathology and management. Depending on the stage of the disease, different treatment regimens are applied, but there is no consensus on an optimal approach. Prognosis for patients with early stage MF is favorable, but significantly worsens in advanced disease and in SS, where patients frequently relapse and require multiple therapies. Methods/UNASSIGNED:. HUT-78, HUT-102, and MyLa cells were treated with NEO212 under different conditions, and drug effects on proliferation, viability, and apoptosis were characterized. Results/UNASSIGNED:NEO212 inhibited proliferation, diminished viability, and stimulated apoptosis in all cell lines, although with varying degrees of potency in the different cell lines. It down-regulated c-myc and cyclin D1 proteins, which are required for cell proliferation, but triggered endoplasmic reticulum stress and activation of caspases. Pretreatment of cells with antioxidants ascorbic acid and beta-mercaptoethanol prevented these NEO212-induced effects. Conclusions/UNASSIGNED:NEO212 exerted promising anticancer effects on SS and MF cell lines. The generation of reactive oxygen species (ROS) appears to play a key role in the NEO212-induced cell death process, because the blockage of ROS with antioxidants prevented caspase activation. We propose that NEO212 should be investigated further toward clinical testing in these tumor types.

OBJECT/OBJECTIVE:The objective of this study was to compare the incidence of degeneration and need for subsequent fusion surgery between patients who were treated nonsurgically and patients treated with fusion after a diagnosis of thoracic-or lumbar-level fracture without degenerative disease. METHODS:The authors performed a retrospective study of Orthopedic United Healthcare patients diagnosed with thoracic or lumbar fracture. Patients were filtered into thoracic and lumbar fracture groups using diagnostic codes and then assigned to one of 2 treatment subgroups (fusion surgery or no surgery) on the basis of procedural codes. Disc degeneration and follow-up surgery were recorded. Chi-square statistical analysis was used. RESULTS:Of 3699 patients diagnosed with a thoracic fracture, 117 (3.2%) underwent thoracic fusion and 3215 (86.9%) were treated nonsurgically. Within 3 years, 147 (4.6%) patients from the nonsurgical subgroup and fewer than 11 (0.9%-8.5%) from the fusion subgroup were diagnosed with thoracic disc degeneration. From the nonsurgical subgroup, 11 (0.3%) patients underwent a thoracic surgery related to disc degeneration compared with zero from the fusion group (p > 0.05). Of 5016 patients diagnosed with lumbar fracture, 150 (3.0%) underwent fusion and 4371 (87.1%) had no surgery. Within 3 years, 503 patients (11.5%) from the nonsurgical subgroup and 35 (23.3%) from the fusion subgroup were diagnosed with lumbar disc degeneration (p < 0.05). From the nonsurgical subgroup, 42 (1.0%) went on to have surgery related to disc degeneration, compared with fewer than 11 (0.7%-6.7%) from the fusion subgroup (values not precise due to privacy limitations). CONCLUSIONS:Fusion surgery for thoracic fracture does not appear to increase the likelihood of undergoing future surgery. In the lumbar region, initial fusion surgery appears to increase the incidence of disc degeneration and could potentially necessitate future surgeries.

Delineation of tumor margins is a critical and challenging objective during brain cancer surgery. A tumor-targeting deep-blue nanoparticle-based visible contrast agent is described, which, for the first time, offers in vivo tumor-specific visible color staining. This technology thus enables color-guided tumor resection in real time, with no need for extra equipment or special lighting conditions. The visual contrast agent consists of polyacrylamide nanoparticles covalently linked to Coomassie Blue molecules (for nonleachable blue color contrast), which are surface-conjugated with polyethylene glycol and F3 peptides for efficient in vivo circulation and tumor targeting, respectively.

Distinguishing a tumor from non-neoplastic tissue is a challenging task during cancer surgery. Several attempts have been made to use visible or fluorescent agents to aid in the visualization of a tumor during surgery. We describe a novel method to delineate brain tumors, using a highly sensitive photoacoustic imaging technique that is enhanced by tumor-targeting blue nanoparticles serving as a contrast agent. Experiments on phantoms and on rat brains, ex vivo, demonstrate the high sensitivity of photoacoustic imaging in delineating tumors containing contrast agent at a concentration much lower than needed for visualization by the naked eye. The limit of detection of the system for the nanoparticles is about 0.77 μg/mL in water (equivalent to 0.84 μmol/L Coomassie Blue dye). The present exploratory study suggests that photoacoustic imaging, when used with strongly optical absorbing contrast agents, could facilitate cancer surgery intraoperatively by revealing the distribution and extent of the tumor.

The evaluation of candidate optical contrast agents for brain tumor delineation in ex vivo models may not accurately predict their activity in vivo. This study describes an in vivo model system designed to assess optical contrast agents for brain tumor delineation. The brain tumor window (BTW) model was created by performing biparietal craniectomies on 8-week-old Sprague-Dawley rats, injecting 9L glioma cells into the cortex and bonding a cover slip to the cranial defect with cyanoacrylate glue. Tumor growth was followed serially and occurred in an exponential fashion. Once tumors on the cortical surface achieved a 1mm radius, intravenous contrast agents were injected while the appearance of the cortical surface was recorded. Computerized image analysis was used to quantitatively evaluate visible differences between tumor and normal brain. Tumor margins became readily apparent following contrast administration in the BTW model. Based on red component intensity, tumor delineation improved fourfold at 50 min post-contrast administration in the BTW model (P<0.002). In summary, window placement overlying an implanted glioma is technically possible and well tolerated in the rat. The BTW model is a valid system for assessing the in vivo activity of optical contrast agents.

OBJECTIVE:Optical contrast agents for brain tumor delineation have been previously evaluated in ex vivo specimens from animals with implanted gliomas and may not reflect the true visual parameters encountered during surgery. This study describes a novel model system designed to evaluate optical contrast agents for tumor delineation in vivo. METHODS:Biparietal craniectomies were performed on 8-week-old Sprague-Dawley rats. 9L glioma cells were injected intraparenchymally. A cover slip was bonded to the cranial defect with cyanoacrylate glue. When the tumor radius reached 1 mm, Coomassie Blue was administered intravenously while the appearance of the cortical surface was recorded. Computerized image analysis of the red/green/blue color components was used to quantify visible differences between tumor and nonneoplastic tissue and to compare delineation in the brain tumor window (BTW) model with the conventional 9L glioma model. RESULTS:The tumor margin in the BTW model was poorly defined before contrast administration but readily apparent after contrast administration. Based on red component intensity, tumor delineation improved 4-fold at 50 minutes after contrast administration in the BTW model (P < .002). The conventional 9L glioma model overestimated the degree of delineation compared with the BTW model at the same dose of Coomassie Blue (P < .03). CONCLUSION/CONCLUSIONS:Window placement overlying an implanted glioma is technically possible and well tolerated in the rat. The BTW model is a valid system for evaluating optical contrast agents designed to delineate brain tumor margins. To our knowledge, we have described the first in vivo model system for evaluating optical contrast agents for tumor delineation.

OBJECTIVE:To synthesize and complete in vitro characterization of a novel, tumor-targeted nanodevice for visible intraoperative delineation of brain tumors. METHODS:The ability of dye-loaded polyacrylamide nanoparticles (NP) containing methylene blue, Coomassie blue, or indocyanine green to cause color change in the 9L glioma cell lines was evaluated. Cells were incubated with dye-loaded NPs, photographed, and analyzed colorimetrically. Confocal microscopy was used to determine subcellular localization of NPs in treated cells. RESULTS:Incubation of glioma cell lines with dye-loaded NPs resulted in clearly visible, quantifiable cell tagging in a dose- and time-dependent manner. Dye-loaded NPs were observed to bind to the surface and become internalized by glioma cells. Coating the NP surface with F3, a peptide that binds to the tumor cell surface receptor nucleolin, significantly increased NP affinity for glioma cells. F3 targeting also significantly increased the rate of cell tagging by dye-loaded NPs. Finally, F3-targeted NPs demonstrated specificity for targeting various cancer cell lines based on their surface expression of cell surface nucleolin. CONCLUSION/CONCLUSIONS:F3-targeted dye-loaded NPs efficiently cause definitive color change in glioma cells. This report represents the first use of targeted NPs to cause a visible color change in tumor cell lines. Similar nanodevices may be used in the future to enable visible intraoperative tumor delineation during tumor resection.

Mice are a nocturnal species, whose social behaviors occur primarily during the dark phase of the circadian cycle. However, laboratory rodents are frequently tested during their light phase, for practical reasons. We investigated the question of whether light phase testing presents a methodological pitfall for investigating mouse social approach behaviors. Three lines of mice were systematically compared. One cohort of each line was raised in a conventional lighting schedule and tested during the light phase, under white light illumination; another cohort was raised in a reverse lighting schedule and tested during their dark phase, under dim red light. Male C57BL/6J (B6) displayed high levels of sociability in our three-chambered automated social approach task when tested in either phase. BTBR T+ tf/J (BTBR) displayed low levels of sociability in either phase. Five cohorts of vasopressin receptor subtype 1b (Avpr1b) null mutants, heterozygotes, and wildtype littermate controls were tested in the same social approach paradigm: three in the dark phase and two in the light phase. All three genotypes displayed normal sociability in four out of the five replications. In the juvenile play test, testing phase had no effect on play soliciting behaviors in Avpr1b mice, but had modest effects on nose sniff and huddling. Taken together, these findings indicate that testing phase is not a crucial factor for studying some forms of social approach in juvenile and adult mice.