The effect of lumbar corticosteroid injections on postoperative infection in lumbar arthrodesis surgery.

We sought to characterize the association between lumbar corticosteroid injections and postoperative infection rate for patients in the Military Health System undergoing lumbar arthrodesis. The Military Health System Data Repository was searched for all patients undergoing lumbar arthrodesis from 2009 to 2014. Current Procedural Terminology (CPT) codes were used to identify the subset of patients who also received preoperative lumbar corticosteroid injections. These patients were stratified by timing, type, and number of injections. Infection rates were compared to the control group of patients who did not receive preoperative lumbar corticosteroid injections. The search identified 3403 patients who had undergone lumbar arthrodesis from 2009 to 2014 within the Military Health System. 612 patients had received lumbar corticosteroid injections prior to surgery (348 epidural, 264 facet). The control group consisted of the remaining 2791 patients. Overall post-operative infection rate was 1.47% with an infection rate in the injection group of 1.14% versus 1.54% in the control group. When stratified by time, infection rates ranged from 0% to 1.85% in the injection groups. No differences between injection and control groups reached statistical significance in any subgroup analysis. Post-operative infection rate is not significantly increased in patients receiving lumbar corticosteroid injections (LCSIs) prior to lumbar arthrodesis. No differences were observed in infection rates based on timing, type, or number of injections prior to surgery.

Palovarotene inhibits connective tissue progenitor cell proliferation in a rat model of combat-related heterotopic ossification.

Heterotopic ossification (HO) develops in the extremities of wounded service members and is common in the setting of high-energy penetrating injuries and blast-related amputations. No safe and effective prophylaxis modality has been identified for this patient population. Palovarotene has been shown to reduce bone formation in traumatic and genetic models of HO. The purpose of this study was to determine the effects of Palovarotene on inflammation, progenitor cell proliferation, and gene expression following a blast-related amputation in a rodent model (n = 72 animals), as well as the ability of Raman spectroscopy to detect early HO before radiographic changes are present. Treatment with Palovarotene was found to dampen the systemic inflammatory response including the cytokines IL-6 (p = 0.01), TNF-α (p = 0.001), and IFN-γ (p = 0.03) as well as the local inflammatory response via a 76% reduction in the cellular infiltration at post-operative day (POD)-7 (p = 0.03). Palovarotene decreased osteogenic connective tissue progenitor (CTP-O) colonies by as much as 98% both in vitro (p = 0.04) and in vivo (p = 0.01). Palovarotene treated animals exhibited significantly decreased expression of osteo- and chondrogenic genes by POD-7, including BMP4 (p = 0.02). Finally, Raman spectroscopy was able to detect differences between the two groups by POD-1 (p < 0.001). These results indicate that Palovarotene inhibits traumatic HO formation through multiple inter-related mechanisms including anti-inflammatory, anti-proliferative, and gene expression modulation. Further, that Raman spectroscopy is able to detect markers of early HO formation before it becomes radiographically evident, which could facilitate earlier diagnosis and treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1135-1144, 2018.

Inhibition of Mammalian Target of Rapamycin Signaling with Rapamycin Prevents Trauma-Induced Heterotopic Ossification.

A pressing clinical need exists for 63% to 65% of combat-wounded service members and 11% to 20% of civilians who develop heterotopic ossification (HO) after blast-related extremity injury and traumatic injuries, respectively. The mammalian target of rapamycin pathway is a central cellular sensor of injury. We evaluated the prophylactic effects of rapamycin, a selective inhibitor of mammalian target of rapamycin signaling, on HO formation in a rat model of blast-related, polytraumatic extremity injury. Rapamycin was administered intraperitoneally daily for 14 days at 0.5 mg/kg or 2.5 mg/kg. Ectopic bone formation was monitored by micro-computed tomography and confirmed by histologic examination. Connective tissue progenitor cells, platelet-derived growth factor receptor-α-positive cells, and α-smooth muscle actin-positive blood vessels were assayed at postoperative day 7 by colony formation and immunofluorescence. Early gene expression changes were determined by low-density microarray. There was significant attenuation of 1) total new bone and soft tissue ectopic bone with 0.5 mg/kg (38.5% and 14.7%) and 2.5 mg/kg rapamycin (90.3% and 82.9%), respectively, 2) connective tissue progenitor cells, 3) platelet-derived growth factor receptor-α-positive cells, 4) α-smooth muscle actin-positive blood vessels, and 5) of key extracellular matrix remodeling (CD44, Col1a1, integrins), osteogenesis (Sp7, Runx2, Bmp2), inflammation (Cxcl5, 10, IL6, Ccl2), and angiogenesis (Angpt2) genes. No wound healing complications were noted. Our data demonstrate the efficacy of rapamycin in inhibiting blast trauma-induced HO by a multipronged mechanism.

The effect of preoperative lumbar epidural corticosteroid injection on postoperative infection rate in patients undergoing single-level lumbar decompression.

BACKGROUND CONTEXT: Lumbar epidural corticosteroid injections (LECIs) are frequently used in the treatment of lumbar intervertebral disc herniation with radiculopathy and lumbar spinal stenosis. Although widely used, their effect on the outcomes and complications of subsequent surgery is unclear. Postoperative infection can be a morbid complication following spine surgery, and recent literature has suggested that the risk may be increased in patients undergoing lumbar spinal surgery who had previously received LECIs. PURPOSE: The purpose of this study is to define the overall postoperative infection rate in patients undergoing lumbar spine decompression surgery in the Military Health System (MHS) patient population and examine the effects of LECIs on postoperative infection rates. STUDY DESIGN/SETTING: This is a retrospective case control database study (Level III study). PATIENT SAMPLE: The sample comprised all patients in the MHS who had a LECI before single-level lumbar decompression surgery from 2009 to 2014. OUTCOME MEASURES: Postoperative infection within 90 days of surgery was used as the primary outcome measure for this study. Postoperative infection was identified using the International Classification of Diseases, 9th revision (ICD-9) diagnosis codes for postoperative infection. METHODS: The Military Health System Data Repository (MDR) database was searched for all patients who underwent single-level lumbar spine decompression surgery from 2009 to 2014 using Current Procedural Terminology (CPT) codes. Current Procedural Terminology codes were used to identify the subset of patients who received preoperative LECIs. For patients receiving an injection, cohorts were established based on the timing of the preoperative injection: <30 days, 30-90 days, 91-180 days, 181-365 days, and >365 days. An age-based cohort, composed of patients 65 years of age and older, was also analyzed. A subgroup analysis of patients receiving more than one preoperative injection was performed. Postoperative infection within 90 days of surgery was identified using ICD-9 codes, and infection rates for all groups were calculated and compared with the control group who did not receive preoperative LECIs. No external funding was received for this study. RESULTS: We identified 6,535 patients (847 preoperative LECI and 5,688 control) for analysis. The overall infection rate for patients undergoing single-level lumbar decompression surgery in the MHS was 0.81%. The rate ranged from 0% to 1.57% in the injection groups, with an overall infection rate in the injection group of 1.18% versus 0.76% in the control group. Despite an increased odds ratio of 1.57 following injection, no statistically significant differences were found between the control group and any injection group based on timing of injection, patient age, or number of preoperative injections. CONCLUSIONS: The results of this study suggest that within the MHS, preoperative LECIs do not significantly increase the risk of postoperative infection after single-level lumbar decompression. If a difference does exist, it is likely small.

Early local delivery of vancomycin suppresses ectopic bone formation in a rat model of trauma-induced heterotopic ossification.

Heterotopic ossification (HO) is a debilitating sequela of high-energy injuries. It frequently requires surgical excision once symptomatic and there is no practical prophylaxis for combat-injured patients. In this study, we examined the effect of local vancomycin powder on HO formation in a small animal model of blast-related, post-traumatic HO. Male Sprague-Dawley rats were subjected to a polytraumatic extremity injury and amputation with or without methicillin-resistant Staphylococcus aureus infection. Animals were randomized to receive a single local application of vancomycin (20 mg/kg) at the time of injury (POD-0, n = 34) or on postoperative day-3 (POD-3, n = 11). Quantitative volumetric measurement of ectopic bone was calculated at 12-weeks post-injury by micro-CT. Bone marrow and muscle tissues were also collected to determine the bacterial burden. Blood for serum cytokine analysis was collected at baseline and post-injury. Vancomycin treatment on POD-0 suppressed HO formation by 86% and prevented bone marrow and soft tissue infections. We concurrently observed a marked reduction histologically in nonviable tissue, chronic inflammatory cell infiltrates, bone infection, fibrous tissue, and areas of bone necrosis within this same cohort. Delayed treatment was significantly less efficacious. Neither treatment had a marked effect on the production of pro-inflammatory cytokines. Our study demonstrates that local vancomycin treatment at the time of injury significantly reduces HO formation in both the presence and absence of infection, with decreased efficacy if not given early. These findings further support the concept that the therapeutic window for prophylaxis is narrow, highlighting the need to develop early treatment strategies for clinical management. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2397-2406, 2017.

Use of a Dermal Regeneration Template Wound Dressing in the Treatment of Combat-Related Upper Extremity Soft Tissue Injuries.

PURPOSE: To assess the outcomes of treatment with a dermal regeneration template (DRT) in a cohort of combat casualties with severe upper extremity injuries. METHODS: Records of all active duty military patients treated with DRT at our institution between November 2009 and July 2013 were screened. Inclusion criteria were upper extremity open wounds sustained during combat, requiring split-thickness or full-thickness skin grafting for closure. The primary outcome measure was wound healing after the first attempt at definitive treatment (defined as the first application of split-thickness or full-thickness skin graft). Independent variables collected included time from injury to arrival at our facility, mechanism of injury, wound infection, tobacco use, location of wound, number of operative debridements, and patient demographics. RESULTS: A total of 60 patients with 69 wounds met the inclusion criteria. Most wounds were to the wrist or forearm (54%) or fingers (19%). All wounds were heavily contaminated, requiring a mean of 2.5 operative debridements before DRT placement. All wounds treated with full-thickness skin grafting after DRT healed completely without further complication. Split-thickness skin grafting was successful in 96% of patients. CONCLUSIONS: DRT wound dressings are a helpful adjunct in the treatment of contaminated war wounds to the upper extremity. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Use of a bioartificial dermal regeneration template for skin restoration in combat casualty injuries.

Military personnel who survive combat injuries frequently have large soft tissue wounds complicated by concomitant injuries and contamination. These devastating wounds present a therapeutic challenge to not only restore the protective skin barrier but also to preserve tendon and muscle excursion, provide protective padding around nerves and restore adequate joint motion. Accordingly, regenerative medicine modalities that can accomplish these goals are of great interest. The use of bioartificial dermal regeneration templates (DRT), such as Integra DRT (Integra Lifesciences Corporation, Plainsboro, NJ, USA), in the management of complex soft tissue injuries has an important role in the reconstruction of war wounds. These DRTs provide initial wound coverage and help establish a well-vascularized wound bed suitable for definitive soft tissue coverage.

Informed consent training improves surgery resident performance in simulated encounters with standardized patients.

BACKGROUND: Although informed consent is vital to patient-physician communication, little training is provided to surgical trainees. We hypothesized that highlighting critical aspects of informed consent would improve resident performance. METHODS: Eighty (out of 88) surgical postgraduate year 1 surgical residents were randomly assigned to one of the 2 cases (laparoscopic cholecystectomy or ventral herniorrhaphy) and instructed to obtain and document informed consent with a standardized patient (SP) followed by a didactic training session. The residents then obtained and documented informed consent with the other case with the other SP. SPs graded encounters ("Checklist"); trained raters graded notes. Repeated measures multivariate analysis of variance (MANOVA) was used to determine differences between pre- and post-training and Checklist versus "Note" scores. RESULTS: Statistically significant pre- to post differences for Note (P < .01) and Checklist (P < .01) along with significant differences between Note and Checklist (P < .01) were noted. CONCLUSIONS: Training improved surgery residents' ability to discuss and document informed consent. Despite this improvement, significant differences between discussion and documentation persisted. Documentation training is a future area for improvement.

Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis.

PURPOSE: We analyzed the urothelium of cats diagnosed with feline interstitial cystitis to determine whether abnormalities in protein expression patterns could be detected and whether the expression pattern was similar to that in patients with human interstitial cystitis/bladder pain syndrome. The proteins analyzed are involved in cell adhesion and barrier function, comprise the glycosaminoglycan layer or are differentiation markers. MATERIALS AND METHODS: Formalin fixed biopsies from 8 cats with feline interstitial cystitis and from 7 healthy control cats were labeled by immunohistochemistry and scored with a modified version of a system previously used for human samples. Cluster analysis was performed to investigate relationships between markers and samples. RESULTS: Of the feline interstitial cystitis bladders 89% showed abnormal protein expression and chondroitin sulfate patterns while only 27% of normal tissues showed slight abnormalities. Abnormalities were found in most feline interstitial cystitis samples, including biglycan in 87.5%, chondroitin sulfate, decorin, E-cadherin and keratin-20 in 100%, uroplakin in 50% and ZO-1 in 87.5%. In feline interstitial cystitis bladders about 75% of chondroitin sulfate, biglycan and decorin samples demonstrated absent luminal staining or no staining. Cluster analysis revealed that feline interstitial cystitis and normal samples could be clearly separated into 2 groups, showing that the urothelium of cats with feline interstitial cystitis is altered from normal urothelium. CONCLUSIONS: Feline interstitial cystitis produces changes in luminal glycosaminoglycan and several proteins similar to that in patients, suggesting some commonality in mechanism. Results support the use of feline interstitial cystitis as a model of human interstitial cystitis.

Intensity modulated radiation therapy (IMRT) for the treatment of unicentric Castlemans disease: a case report and review of the use of radiotherapy in the literature.

BACKGROUND: Surgical resection is considered standard therapy for cases of resectable unicentric Castleman's disease (UCD). Unresectable cases of UCD do not have a consensus regarding the optimal treatment approach, but have utilized steroids, observation, chemotherapy, and radiotherapy. Here we discuss a patient presentation of UCD treated with an advanced radiotherapy technique, IMRT. CASE REPORT: A 47 year old female was found to have an intra-thoracic posterior UCD and was determined not to be a good surgical candidate. She was referred for radiotherapy and was treated using IMRT to a total dose of 4320 cGy in 180 cGy fractions including a scheduled 10 day break. Following the break, the patient's treatment was replanned at which the initial treatment volume was reduced by 50.9% for the duration of the treatment course. Radiation Therapy Oncology Group (RTOG) grade III pneumonitis developed which was managed medically. Neither disease progression nor late effects have occurred. CONCLUSIONS: The use of IMRT and planned treatment break was successful in the treatment of a case of UCD, and should be considered for other unresectable cases.