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Biologics and Minimally Invasive Approach to TLIFs: What Is the Risk of Radiculitis?

Wang, Erik; Stickley, Carolyn; Manning, Jordan; Varlotta, Christopher G; Woo, Dainn; Ayres, Ethan; Abotsi, Edem; Vasquez-Montes, Dennis; Fischer, Charla R; Stieber, Jonathan; Quirno, Martin; Protopsaltis, Themistocles S; Passias, Peter G; Buckland, Aaron J
BACKGROUND: Bone morphogenetic protein (BMP) and allograft containing mesenchymal stem cells (live cell) are popular biologic substitutes for iliac crest autograft used in transforaminal lumbar interbody fusion (TLIF). Use of these agents in the pathogenesis of postoperative radiculitis remains controversial. Recent studies have independently linked minimally invasive (MIS) TLIF with increased radiculitis risk compared to open TLIF. The purpose of this study was to assess the rate of postoperative radiculitis in open and MIS TLIF patients along with its relationship to concurrent biologic adjuvant use. METHODS: Patients ≥18 years undergoing single-level TLIF from June 2012 to December 2018 with minimum 1-year follow-up were included. Outcome measures were rate of radiculitis, intra- and postoperative complications, revision surgery; length of stay (LOS), and estimated blood loss (EBL). RESULTS:= .038, N = 336) compared to other combinations of surgical approach and biologic use. CONCLUSIONS: Neither the MIS approach nor BMP use is an independent risk factor for post-TLIF radiculitis. However, risk of radiculitis significantly increases when they are used in tandem. This should be considered when selecting biological adjuvants for MIS TLIF. LEVEL OF EVIDENCE/METHODS: 3.
PMID: 33046541
ISSN: 2211-4599
CID: 4632542

170. Radiculitis: assessing the risk of biologic use in minimally invasive transforaminal lumbar interbody fusions [Meeting Abstract]

Stickley, C; Wang, E; Ayres, E W; Maglaras, C; Fischer, C R; Stieber, J R; Quirno, M; Protopsaltis, T S; Passias, P G; Buckland, A J
BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein 2 (BMP) is increasingly utilized in minimally invasive (MIS) transforaminal lumbar interbody fusions (TLIF) in order to increase rate of fusion by promoting bone growth through the induction of osteoblast differentiation, awhile reducing morbidity related to iliac crest autograft. Despite these benefits, BMP use is still controversial due to its pro-inflammatory mechanism of action and potential to cause radiculitis. PURPOSE: To assess whether BMP is a risk factor for postoperative radiculitis in TLIF. STUDY DESIGN/SETTING: Single-center retrospective cohort study. PATIENT SAMPLE: A total of 397 TLIFs from June 2012 to December 2018. OUTCOME MEASURES: Perioperative clinical characteristics, post-operative risk of radiculitis and complication, and future reoperation rates.
METHOD(S): Patients >= 18 years-old undergoing elective single-level TLIFs from 2012 to 2018 were included. Outcome measures included perioperative clinical characteristics, postoperative risk of radiculitis and complication, and future reoperation rates. Radiculitis was defined the delayed onset of radicular symptoms postoperatively in patients whom had initial resolution of radicular symptoms immediately postoperatively, in the absence of persistent neurological compression on postoperative imaging. Statistical analyses included independent t-tests and chi-square analysis. Propensity score matching was utilized to control for demographic differences between the groups. Independent predictors for post-operative radiculitis were assessed by multivariate logistic regression. Significance set at p<0.05.
RESULT(S): A total of 397 cases were included in the study (59.33 +/- 13.49 mean age, 28.98 +/- 6.29 mean BMI, 52.90% female, 2.29 +/- 1.92 average Charleston comorbidity Index). There were 223 open procedures and 174 MIS. For the entire cohort, 238 cases utilized BMP and 159 did not, with 102 MIS pairing with BMP use. The MIS TLIFs had a higher percentage of BMP use than open TLIFs (58.6% vs 25.7%, p<0.001), lower estimated blood loss (212.28 +/- 193.79 mL vs 410.91 +/- 337.98 mL, p<0.001) higher fluoroscopy dosage (52.43 +/- 48.61mGy vs 16.77 +/- 27.84mGy, p<0.001), and a lower length of stay (3.20 +/- 2.55 days vs 4.11 +/- 2.52 days, p<0.001). There were no other differences in perioperative clinical characteristics. There was a significantly higher rate of postoperative radiculitis in the MIS TLIFs compared to open (12.6% vs 6.8%, p=0.046) and use of BMP compared to no BMP (13.2% vs 6.7%, p=0.029). There was a 15.7% radiculitis rate when MIS was paired with BMP use. There were no other notable differences in complication rates or rates of reoperation. Individually, MIS had a 12.6% radiculitis rate (p=0.046) and BMP use had a 13.2% rate (p=0.029). Propensity score match controlled for the significant difference in CCI between the MIS and open groups (N=168 each). Multivariate regression indicated that MIS (p=0.314) and BMP (p=0.109) were not independent predictors individually when controlling for age, gender, and BMI. When technique was paired with biologic use the regression revealed MIS + BMP is a risk factor of post-operative radiculitis (2.265(4.753-1.079), p=0.031).
CONCLUSION(S): While BMP and MIS technique were not independent risk factors for postoperative radiculitis, there is an increased risk of radiculitis when using BMP in MIS TLIF. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
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EMBASE:2007747262
ISSN: 1878-1632
CID: 4597512

Importance of the Sagittal Plane in Understanding Adult Spinal Deformities

Paul, Justin; Vira, Shaleen; Quirno, Martin; Protopsaltis, Themistocles
The sagittal plane is known to be important in correction of adult spinal deformity. When surgery is indicated, the surgeon is provided with several tools and techniques to restore balance. But proper use of these tools is essential to avoid harmful complications. This article examines these tools with a focus on lumbar lordosis and the lumbopelvic junction. Positioning, releases, osteotomies, and instrumentation are considered with special attention to the alignment measurements they affect.
PMID: 29537961
ISSN: 2328-5273
CID: 2992822

Suture Anchor Repair of Complete Proximal Hamstring Ruptures A Cadaveric Biomechanical Evaluation

Campbell, K A; Quirno, M; Hamula, M; Pham, H; Weinberg, M; Kummer, F J; Jazrawi, L M; Strauss, E J
PMID: 29151008
ISSN: 2328-5273
CID: 3568422

The role of the progressive ankylosis protein (ANK) in adipogenic/osteogenic fate decision of precursor cells

Minashima, Takeshi; Quirno, Martin; Lee, You Jin; Kirsch, Thorsten
The progressive ankylosis protein (ANK) is a transmembrane protein that transports intracellular pyrophosphate (PPi) to the extracellular milieu. In this study we show increased fatty degeneration of the bone marrow of adult ank/ank mice, which lack a functional ANK protein. In addition, isolated bone marrow stromal cells (BMSCs) isolated from ank/ank mice showed a decreased proliferation rate and osteogenic differentiation potential, and an increased adipogenic differentiation potential compared to BMSCs isolated from wild type (WT) littermates. Wnt signaling pathway PCR array analysis revealed that Wnt ligands, Wnt receptors and Wnt signaling proteins that stimulate osteoblast differentiation were expressed at markedly lower levels in ank/ank BMSCs than in WT BMSCs. Lack of ANK function also resulted in impaired bone fracture healing, as indicated by a smaller callus formed and delayed bone formation in the callus site. Whereas 5weeks after fracture, the fractured bone in WT mice was further remodeled and restored to original shape, the fractured bone in ank/ank mice was not fully restored and remodeled to original shape. In conclusion, our study provides evidence that ANK plays a critical role in the adipogenic/osteogenic fate decision of adult mesenchymal precursor cells. ANK functions in precursor cells are required for osteogenic differentiation of these cells during adult bone homeostasis and repair, whereas lack of ANK functions favors adipogenic differentiation.
PMCID:5396059
PMID: 28286238
ISSN: 1873-2763
CID: 2489822

Distal femoral varus osteotomy for unloading valgus knee malalignment: a biomechanical analysis

Quirno, Martin; Campbell, Kirk A; Singh, Brian; Hasan, Saqib; Jazrawi, Laith; Kummer, Fredrick; Strauss, Eric J
PURPOSE: To investigate the biomechanical properties of the load shifting following opening-wedge distal femoral varus osteotomies (DFVOs) and determine the osteotomy correction needed to unload the lateral compartment. METHODS: Five human cadaveric knees were tested with a load of 500 N of axial compression. Medial and lateral tibiofemoral compartment contact area and pressure were assessed utilizing a modified F-scan pressure-sensitive sensor. The knees were tested in their baseline anatomic alignment, 10 degrees valgus malalignment and following corrective DFVOs of 5 degrees , 10 degrees and 15 degrees . The load shifting effect of the various DFVO correction angles was analysed using a one-way ANOVA to determine the correction angle necessary to unload the lateral compartment. RESULTS: Gradually shifting the loading vector medially with increasing DFVO angles resulted in a decrease in the mean contact area and mean contact pressures in the lateral compartment with progressive increases in the medial compartment. The largest reduction in lateral compartment pressure and contact area was seen with the 15 degrees osteotomy with a 25 % decrease in mean contact pressure and 20 % decrease in mean maximum contact pressure and mean contact area when compared to the 10 degrees valgus-malaligned knee. For the 10 degrees valgus knee, a 15 degrees correction resulted in near-normal contact pressures and areas compared with the knee in normal anatomic alignment. CONCLUSION: Progressive unloading of the lateral tibiofemoral compartment occurred with increasing DFVO correction angles. Clinically, when performing a DFVO for valgus malalignment, surgeons should consider overcorrecting the osteotomy by 5 degrees to restore near-normal contact pressures and contact areas in the lateral compartment rather than the traditional teaching of correcting to neutral alignment.
PMID: 25894751
ISSN: 1433-7347
CID: 1543152

Current Evidence of Minimally Invasive Spine Surgery in the Treatment of Lumbar Disc Herniations

Quirno, Martin; Vira, Shaleen; Errico, Thomas
With the advent of new instrumentation and better imaging techniques that allowed less tissue trauma compared with traditional open procedures, while providing adequate or enhanced visualization of the pathologic site and based upon the successful experience of outpatient spine surgery to assist early ambulation, the trend and evolution toward ''minimal access'' or minimally invasive spine surgery began to develop with greater intensity. Many surgical techniques have flourished with the promise of delivering a safe and efficient alternative, including chemonucleolysis, manual percutaneous discectomy (MPD), automated percutaneous lumbar discectomy (APLD), and percutaneous lumbar laser discectomy (PLLD). Unfortunately, most of these techniques have been demonstrated to be inefficient with high complication rates. Only modifications of the original open discectomy in which direct visualization of the disc is obtained through either microscopic or endoscopic techniques have proven to be successful. This review outlines the historical journey that has inspired the development of these techniques and delineates the progressive clinical experience gained from their advent.
PMID: 26977554
ISSN: 2328-5273
CID: 2047192

The Effects of Amicar and TXA on Lumbar Spine Fusion in an Animal Model

Cuellar, Jason M; Yoo, Andrew; Tovar, Nick; Coelho, Paulo G; Jimbo, Ryo; Vandeweghe, Stefan; Kirsch, Thorsten; Quirno, Martin; Errico, Thomas J
STRUCTURED ABSTRACT: Study Design. Animal modelObjective. Determine whether Amicar and TXA inhibit spine fusion volumeSummary of Background Data. Amicar and TXA are antifibrinolytics used to reduce perioperative bleeding. Prior in vitro data showed that antifibrinolytics reduce osteoblast bone mineralization. This study tested whether antifibrinolytics Amicar and TXA inhibit spine fusion.Methods. Posterolateral L4-L6 fusion was performed in fifty mice, randomized into groups of ten, that received the following treatment before and after surgery: (1) Saline; (2) TXA 100mg/kg; (3) TXA 1000mg/kg; (4) Amicar 100 mg/kg; (5) Amicar 1000 mg/kg. High-resolution plane radiography was performed after 5 weeks and micro-CT was performed at the end of the 12-week study. Radiographs were graded using the Lenke scale. Micro-CT was used to quantify fusion mass bone volume. One-way analysis of variance (ANOVA) by ranks with Kruskal-Wallis testing was used to compare the radiographic scores. One-way ANOVA with least-significant differences (LSD) post-hoc testing was used to compare the micro-CT bone volume.Results. The average (+/- SD) bone volume/total volume (%) measured in the saline, TXA 100 mg/kg, TXA 1000 mg/kg, Amicar 100 mg/kg and Amicar 1000 mg/kg groups were 10.8+/-2.3, 9.7+/-2.2, 13.4+/-3.2, 15.5+/-5.2 and 17.9+/-3.5%, respectively. There was a significant difference in the Amicar 100 mg/kg (p < 0.05) and Amicar 1000 mg/kg (p < 0.001) groups compared to saline. There was greater bone volume in the Amicar groups compared to the TXA group (p < 0.001). There was more bone volume in the TXA 1000 mg/kg group compared to TXA 100 mg/kg (p < 0.05) but the bone volume in neither of the TXA groups was different to saline (p = 0.49). There were no between-group differences observed using plane radiographic scoring.Conclusions. Amicar significantly enhanced the fusion bone mass in a dose-dependent manner while TXA did not have a significant effect on fusion compared to saline control.These data are in contrast to prior in vitro data that antifibrinolytics inhibit osteoblast bone mineralization.
PMID: 24979407
ISSN: 0362-2436
CID: 1061592

Annexin A6 Interacts With p65 and Stimulates NF-kappaB Activity and Catabolic Events in Articular Chondrocytes

Campbell, Kirk A; Minashima, Takeshi; Zhang, Ying; Hadley, Scott; Lee, You Jin; Giovinazzo, Joseph; Quirno, Martin; Kirsch, Thorsten
OBJECTIVE: ANXA6, the gene for annexin A6, is highly expressed in osteoarthritic (OA) articular chondrocytes but not in healthy articular chondrocytes. This study was undertaken to determine whether annexin A6 affects catabolic events in these cells. METHODS: Articular chondrocytes were isolated from Anxa6-knockout mice, wild-type (WT) mice, and human articular cartilage in which ANXA6 was overexpressed. Cells were treated with interleukin-1beta (IL-1beta) or tumor necrosis factor alpha (TNFalpha), and expression of catabolic genes and activation of NF-kappaB were determined by real-time polymerase chain reaction and luciferase reporter assay. Anxa6(-/-) and WT mouse knee joints were injected with IL-1beta or the medial collateral ligament was transected and partial resection of the medial meniscus was performed to determine the role of Anxa6 in IL-1beta-mediated cartilage destruction and OA progression. The mechanism by which Anxa6 stimulates NF-kappaB activity was determined by coimmunoprecipitation and immunoblot analysis of nuclear and cytoplasmic fractions of IL-1beta-treated Anxa6(-/-) and WT mouse chondrocytes for p65 and Anxa6. RESULTS: Loss of Anxa6 resulted in decreased NF-kappaB activation and catabolic marker messenger RNA (mRNA) levels in IL-1beta- or TNFalpha-treated articular chondrocytes, whereas overexpression of ANXA6 resulted in increased NF-kappaB activity and catabolic marker mRNA levels. Annexin A6 interacted with p65, and loss of Anxa6 caused decreased nuclear translocation and retention of the active p50/p65 NF-kappaB complex. Cartilage destruction in Anxa6(-/-) mouse knee joints after IL-1beta injection or partial medial meniscectomy was reduced as compared to that in WT mouse joints. CONCLUSION: Our data define a role of annexin A6 in the modulation of NF-kappaB activity and in the stimulation of catabolic events in articular chondrocytes.
PMID: 24022118
ISSN: 0004-3591
CID: 666062

Preventing venous thromboembolism in major orthopaedic surgery

Campbell, K A; Quirno, M; Day, M S; Strauss, E J
Despite advances in thromboprophylaxis, venous thromboembolism remains a significant problem in major orthopaedic surgery, associated with significant morbidity and high cost of treatment. Virchow's triad, as well as patient and procedural risk factors, put many orthopaedic surgery patients at high risk. Diagnosis is based on clinical suspicion in combination with imaging such as ultrasound. Options for prophylaxis include aspirin, warfarin, low-molecular weight heparins and direct inhibitors of coagulation factors. In this review, we discuss the latest American Academy of Orthopaedic Surgeons (AAOS) and American College of Chest Physicians (ACCP) guidelines for prevention of venous thromboembolism and their implications for practice. 1940-7041 2013 Wolters Kluwer Health
EMBASE:2013598206
ISSN: 1940-7041
CID: 557952