IU Indianapolis ScholarWorks :: Browsing by Author "Natoli, Roman M."

Browsing by Author "Natoli, Roman M."

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A Novel Use of a Schanz Pin-Rectal Foreign Body Extraction: A Case Report
(JOCR, 2024) Chang, Joshua H.; Haag, Luke; Mohanty, Sanjay; Natoli, Roman M.; Surgery, School of Medicine
Introduction: Retained rectal foreign bodies (RFBs) can be difficult to extract, forcing the surgeon to get creative. This is the first case report utilizing orthopedic drilling and joystick manipulation techniques for foreign body extraction. Case report: A 63-year-old male presented to the emergency department with a pool ball in his rectum for two days. Extraction attempts under anesthesia both transanally and through a low midline laparotomy were unsuccessful due to the patient's pelvic anatomy. Orthopedic surgery was consulted to see if any manipulation or resection of the pelvis might aid in extraction. Ultimately, a Schanz pin was drilled retrogradely from the rectum into the pool ball and successfully manipulated the pool ball out of the patient. Conclusion: Techniques such as drilling and joystick manipulation are common in orthopedic surgery but rarely used in other surgical fields. This case presented a novel use of a Schanz pin in RFB extraction. Application of orthopedic surgical technique in a colorectal surgery in this case saved the patient from more invasive interventions such as pubic symphysiotomy or ischial tuberosity resection.
A Reproducible Cartilage Impact Model to Generate Post-Traumatic Osteoarthritis in the Rabbit
(MyJove Corporation, 2023-11-21) Dilley, Julian; Noori-Dokht, Hessam; Seetharam, Abhijit; Bello, Margaret; Nanavaty, Aaron; Natoli, Roman M.; McKinley, Todd; Bault, Zachary; Wagner, Diane; Sankar, Uma; Anatomy, Cell Biology and Physiology, School of Medicine
Post-traumatic osteoarthritis (PTOA) is responsible for 12% of all osteoarthritis cases in the United States. PTOA can be initiated by a single traumatic event, such as a high-impact load acting on articular cartilage, or by joint instability, as occurs with anterior cruciate ligament rupture. There are no effective therapeutics to prevent PTOA currently. Developing a reliable animal model of PTOA is necessary to better understand the mechanisms by which cartilage damage proceeds and to investigate novel treatment strategies to alleviate or prevent the progression of PTOA. This protocol describes an open, drop tower-based rabbit femoral condyle impact model to induce cartilage damage. This model delivered peak loads of 579.1 ± 71.1 N, and peak stresses of 81.9 ± 10.1 MPa with a time-to-peak load of 2.4 ± 0.5 ms. Articular cartilage from impacted medial femoral condyles (MFCs) had higher rates of apoptotic cells (p = 0.0058) and possessed higher Osteoarthritis Research Society International (OARSI) scores of 3.38 ± 1.43 compared to the non-impacted contralateral MFCs (0.56 ± 0.42), and other cartilage surfaces of the impacted knee (p < 0.0001). No differences in OARSI scores were detected among the non-impacted articular surfaces (p > 0.05).
A Scoring System for Predicting Nonunion After Intramedullary Nailing of Femoral Shaft Fractures
(Wolters Kluwer, 2024-09-04) Kraus, Kent R.; Flores, Joshua W.; Slaven, James E.; Sharma, Ishani; Arnold, Payton K.; Mullis, Brian H.; Natoli, Roman M.; Orthopaedic Surgery, School of Medicine
Introduction: Femoral shaft nonunion negatively affects patient quality of life. Although multiple risk factors have been identified for femoral shaft nonunion after intramedullary nail (IMN) fixation, there is no quantitative model for predicting nonunion. Study description: The study is a retrospective cohort study of patients with femoral shaft fractures treated at two level one trauma centers who were followed to fracture union or nonunion. Patient, injury, and surgical characteristics were analyzed to create a quantitative model for nonunion risk after intramedullary nailing. Methods: Eight hundred one patients aged 18 years and older with femoral shaft fractures treated with reamed, locked IMNs were identified. Risk factors including demographics, comorbidities, surgical variables, and injury-related characteristics were evaluated. Multivariate analysis was conducted, and several variables were included in a scoring system to predict nonunion risk. Results: The overall nonunion rate was 7.62% (61/801). Multivariate analysis showed significant association among pulmonary injury (odds ratio [OR] = 2.19, P = 0.022), open fracture (OR=2.36, P = 0.02), current smoking (OR=3.05, P < 0.001), postoperative infection (OR=12.1, P = 0.007), AO/OTA fracture pattern type A or B (OR=0.43, P = 0.014), and percent cortical contact obtained intraoperatively ≥25% (OR=0.41, P = 0.021) and nonunion. The scoring system created to quantitatively stratify nonunion risk showed that a score of 3 or more yielded an OR of 6.38 for nonunion (c-statistic = 0.693, P < 0.0001). Conclusions: Femoral shaft nonunion risk is quantifiable based on several independent injury, patient, and surgical factors. This scoring system is an additional tool for clinical decision making when caring for patients with femoral shaft fractures treated with IMNs.
A Two-Stage Approach Integrating Provisional Biomaterial-Mediated Stabilization Followed by a Definitive Treatment for Managing Volumetric Muscle Loss Injuries
(MDPI, 2024-06-06) Clark, Andrew R.; Kulwatno, Jonathan; Kanovka, Sergey S.; Klarmann, George J.; Hernandez, Claudia E.; Natoli, Roman M.; McKinley, Todd O.; Potter, Benjamin K.; Dearth, Christopher L.; Goldman, Stephen M.; Orthopaedic Surgery, School of Medicine
Treatment of volumetric muscle loss (VML) faces challenges due to its unique pathobiology and lower priority in severe musculoskeletal injury management. Consequently, a need exists for multi-stage VML treatment strategies to accommodate delayed interventions owing to comorbidity management or prolonged casualty care in combat settings. To this end, polyvinyl alcohol (PVA) was used at concentrations of 5%, 7.5%, and 10% to generate provisional muscle void fillers (MVFs) of varying stiffness values (1.125 kPa, 3.700 kPa, and 7.699 kPa) to stabilize VML injuries as part of a two-stage approach. These were implanted into a rat model for a duration of 4 weeks, then explanted and either left untreated (control) or treated through minced muscle grafting (MMG). Additional benchmarks included acute MMG and unrepaired groups. At the MVF explant, the 7.5% PVA group exhibited superior neuromuscular function compared to the 5% and 10% PVA groups, the least fibrosis, and the largest median myofiber size among all groups at the 12-week endpoint. Despite the 7.5% PVA’s superiority amongst the two-stage treatment groups, neuromuscular function was neither improved nor impaired relative to acute treatment benchmarks. This suggests that the future success of a two-stage VML treatment strategy will necessitate a more effective definitive intervention.
Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro
(BMC, 2018-04-27) Natoli, Roman M.; Yu, Henry; Meislin, Megan Conti-Mica; Abbasnia, Pegah; Roper, Philip; Vuchkovska, Aleksandra; Xiao, Xianghui; Stock, Stuart R.; Callaci, John J.; Orthopaedic Surgery, School of Medicine
BACKGROUND: Alcohol consumption is a risk factor for impaired fracture healing, though the mechanism(s) by which this occurs are not well understood. Our laboratory has previously shown that episodic alcohol exposure of rodents negatively affects fracture callus development, callus biomechanics, and cellular signaling which regulates stem cell differentiation. Here, we examine whether alcohol alters chemokine expression and/or signaling activity in the mouse fracture callus during early fracture healing. METHODS: A mouse model for alcohol-impaired tibia fracture healing was utilized. Early fracture callus was examined for alcohol-effects on tissue composition, expression of chemokines involved in MSC migration to the fracture site, and biomechanics. The effects of alcohol on MSC migration and cell adhesion receptors were examined in an in vitro system. RESULTS: Mice exposed to alcohol showed decreased evidence of external callus formation, decreased callus-related osteopontin (OPN) expression levels, and decreased biomechanical stiffness. Alcohol exposure decreased rOPN-mediated MSC migration and integrin β1 receptor expression in vitro. CONCLUSIONS: The effects of alcohol exposure demonstrated here on fracture callus-associated OPN expression, rOPN-mediated MSC migration in vitro, and MSC integrin β1 receptor expression in vitro have not been previously reported. Understanding the effects of alcohol exposure on the early stages of fracture repair may allow timely initiation of treatment to mitigate the long-term complications of delayed healing and/or fracture non-union.
Bone Morphogenetic Protein-2 Rapidly Heals Two Distinct Critical Sized Segmental Diaphyseal Bone Defects in a Porcine Model
(Oxford University Press, 2023) McKinley, Todd O.; Childress, Paul; Jewell, Emily; Griffin, Kaitlyn S.; Wininger, Austin E.; Tucker, Aamir; Gremah, Adam; Savaglio, Michael K.; Warden, Stuart J.; Fuchs, Robyn K.; Natoli, Roman M.; Shively, Karl D.; Anglen, Jeffrey O.; Chu, Tien-Min Gabriel; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
Introduction: Segmental bone defects (SBDs) are devastating injuries sustained by warfighters and are difficult to heal. Preclinical models that accurately simulate human conditions are necessary to investigate therapies to treat SBDs. We have developed two novel porcine SBD models that take advantage of similarities in bone healing and immunologic response to injury between pigs and humans. The purpose of this study was to investigate the efficacy of Bone Morphogenetic Protein-2 (BMP-2) to heal a critical sized defect (CSD) in two novel porcine SBD models. Materials and methods: Two CSDs were performed in Yucatan Minipigs including a 25.0-mm SBD treated with intramedullary nailing (IMN) and a 40.0-mm SBD treated with dual plating (ORIF). In control animals, the defect was filled with a custom spacer and a bovine collagen sponge impregnated with saline (IMN25 Cont, n = 8; ORIF40 Cont, n = 4). In experimental animals, the SBD was filled with a custom spacer and a bovine collage sponge impregnated with human recombinant BMP-2 (IMN25 BMP, n = 8; ORIF40 BMP, n = 4). Healing was quantified using monthly modified Radiographic Union Score for Tibia Fractures (mRUST) scores, postmortem CT scanning, and torsion testing. Results: BMP-2 restored bone healing in all eight IMN25 BMP specimens and three of four ORIF40 BMP specimens. None of the IMN25 Cont or ORIF40 Cont specimens healed. mRUST scores at the time of sacrifice increased from 9.2 (±2.4) in IMN25 Cont to 15.1 (±1.0) in IMN25 BMP specimens (P < .0001). mRUST scores increased from 8.2 (±1.1) in ORIF40 Cont to 14.3 (±1.0) in ORIF40 BMP specimens (P < .01). CT scans confirmed all BMP-2 specimens had healed and none of the control specimens had healed in both IMN and ORIF groups. BMP-2 restored 114% and 93% of intact torsional stiffness in IMN25 BMP and ORIF40 BMP specimens. Conclusions: We have developed two porcine CSD models, including fixation with IMN and with dual-plate fixation. Porcine models are particularly relevant for SBD research as the porcine immunologic response to injury closely mimics the human response. BMP-2 restored healing in both CSD models, and the effects were evident within the first month after injury. These findings support the use of both porcine CSD models to investigate new therapies to heal SBDs.
CAMKK2 is Upregulated in Primary Human Osteoarthritis and its Inhibition Protects Against Chondrocyte Apoptosis
(Elsevier, 2023) Dilley, Julian E.; Seetharam, Abhijit; Ding, Xinchun; Bello, Margaret A.; Shutter, Jennifer; Burr, David B.; Natoli, Roman M.; McKinley, Todd O.; Sankar, Uma; Anatomy, Cell Biology and Physiology, School of Medicine
Objective: To investigate the role of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) in human osteoarthritis. Materials and methods: Paired osteochondral plugs and articular chondrocytes were isolated from the relatively healthier (intact) and damaged portions of human femoral heads collected from patients undergoing total hip arthroplasty for primary osteoarthritis (OA). Cartilage from femoral plugs were either flash frozen for gene expression analysis or histology and immunohistochemistry. Chondrocyte apoptosis in the presence or absence of CAMKK2 inhibition was measured using flow cytometry. CAMKK2 overexpression and knockdown in articular chondrocytes were achieved via Lentivirus- and siRNA-mediated approaches respectively, and their effect on pro-apoptotic and cartilage catabolic mechanisms was assessed by immunoblotting. Results: CAMKK2 mRNA and protein levels were elevated in articular chondrocytes from human OA cartilage compared to paired healthier intact samples. This increase was associated with elevated catabolic marker matrix metalloproteinase 13 (MMP-13), and diminished anabolic markers aggrecan (ACAN) and type II collagen (COL2A1) levels. OA chondrocytes displayed enhanced apoptosis, which was suppressed following pharmacological inhibition of CAMKK2. Levels of MMP13, pSTAT3, and the pro-apoptotic marker BAX became elevated when CAMKK2, but not its kinase-defective mutant was overexpressed, whereas knockdown of the kinase decreased the levels of these proteins. Conclusions: CAMKK2 is upregulated in human OA cartilage and is associated with elevated levels of pro-apoptotic and catabolic proteins. Inhibition or knockdown of CAMKK2 led to decreased chondrocyte apoptosis and catabolic protein levels, whereas its overexpression elevated them. CAMKK2 may be a therapeutic target to prevent or mitigate human OA.
A Comprehensive Review of Mouse Diaphyseal Femur Fracture Models
(Elsevier, 2020-07) Gunderson, Zachary J.; Campbell, Zachery R.; McKinley, Todd O.; Natoli, Roman M.; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
Complications related to treatment of long bone fractures still stand as a major challenge for orthopaedic surgeons. Elucidation of the mechanisms of bone healing and development, and the subsequent alteration of these mechanisms to improve outcomes, typically requires animal models as an intermediary between in vitro and human clinical studies. Murine models are some of the most commonly used in translational research, and mouse fracture models are particularly diverse, offering a wide variety of customization with distinct benefits and limitations depending on the study. This review critically examines three common femur fracture models in the mouse, namely cortical hole, 3-point fracture (Einhorn), and segmental bone defect. We lay out the general procedure for execution of each model, evaluate the practical implications and important advantages/disadvantages of each and describe recent innovations. Furthermore, we explore the applications that each model is best adapted for in the context of the current state of murine orthopaedic research.
Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials
(BioMed Central, 2020-09-30) Sprague, Sheila; Scott, Taryn; Dodds, Shannon; Pogorzelski, David; McKay, Paula; Harris, Anthony D.; Wood, Amber; Thabane, Lehana; Bhandari, Mohit; Mehta, Samir; Gaski, Greg; Boulton, Christina; Marcano-Fernández, Francesc; Guerra-Farfán, Ernesto; Hebden, Joan; O’Hara, Lyndsay M.; Slobogean, Gerard P.; Slobogean, Gerard P.; Sprague, Sheila; Wells, Jeffrey; Bhandari, Mohit; D’Alleyrand, Jean-Claude; Harris, Anthony D.; Mullins, Daniel C.; Thabane, Lehana; Wood, Amber; Della Rocca, Gregory J.; Hebden, Joan; Jeray, Kyle J.; Marchand, Lucas; O’Hara, Lyndsay M.; Zura, Robert; Gardner, Michael J.; Blasman, Jenna; Davies, Jonah; Liang, Stephen; Taljaard, Monica; Devereaux, P. J.; Guyatt, Gordon H.; Heels-Ansdell, Diane; Marvel, Debra; Palmer, Jana; Friedrich, Jeff; O’Hara, Nathan N.; Grissom, Frances; Gitajn, I. Leah; Morshed, Saam; O’Toole, Robert V.; Petrisor, Bradley A.; Camara, Megan; Mossuto, Franca; Joshi, Manjari G.; Fowler, Justin; Rivera, Jessica; Talbot, Max; Dodds, Shannon; Garibaldi, Alisha; Li, Silvia; Nguyen, Uyen; Pogorzelski, David; Rojas, Alejandra; Scott, Taryn; Del Fabbro, Gina; Szasz, Olivia Paige; McKay, Paula; Howe, Andrea; Rudnicki, Joshua; Demyanovich, Haley; Little, Kelly; Mullins, C. Daniel; Medeiros, Michelle; Kettering, Eric; Hale, Diamond; Eglseder, Andrew; Johnson, Aaron; Langhammer, Christopher; Lebrun, Christopher; Manson, Theodore; Nascone, Jason; Paryavi, Ebrahim; Pensy, Raymond; Pollak, Andrew; Sciadini, Marcus; Degani, Yasmin; Demyanovich, Haley K.; Joseph, Katherine; Petrisor, Brad A.; Johal, Herman; Ristevski, Bill; Williams, Dale; Denkers, Matthew; Rajaratnam, Krishan; Al-Asiri, Jamal; Leonard, Jordan; Marcano-Fernández, Francesc A.; Gallant, Jodi; Persico, Federico; Gjorgjievski, Marko; George, Annie; Natoli, Roman M.; Gaski, Greg E.; McKinley, Todd O.; Virkus, Walter W.; Sorkin, Anthony T.; Szatkowski, Jan P.; Baele, Joseph R.; Mullis, Brian H.; Hill, Lauren C.; Hudgins, Andrea; Osborn, Patrick; Pierrie, Sarah; Martinez, Eric; Kimmel, Joseph; Adams, John D.; Beckish, Michael L.; Bray, Christopher C.; Brown, Timothy R.; Cross, Andrew W.; Dew, Timothy; Faucher, Gregory K.; Gurich, Richard W.; Lazarus, David E.; Millon, S. John; Palmer, M. Jason; Porter, Scott E.; Schaller, Thomas M.; Sridhar, Michael S.; Sanders, John L.; Rudisill, L. Edwin; Garitty, Michael J.; Poole, Andrew S.; Sims, Michael L.; Walker, Clark M.; Carlisle, Robert M.; Hofer, Erin Adams; Huggins, Brandon S.; Hunter, Michael D.; Marshall, William A.; Ray, Shea Bielby; Smith, Cory D.; Altman, Kyle M.; Bedard, Julia C.; Loeffler, Markus F.; Pichiotino, Erin R.; Cole, Austin A.; Maltz, Ethan J.; Parker, Wesley; Ramsey, T. Bennett; Burnikel, Alex; Colello, Michael; Stewart, Russell; Wise, Jeremy; Moody, M. Christian; Tanner, Stephanie L.; Snider, Rebecca G.; Townsend, Christine E.; Pham, Kayla H.; Martin, Abigail; Robertson, Emily; Miclau, Theodore; Kandemir, Utku; Marmor, Meir; Matityahu, Amir; McClellan, R. Trigg; Meinberg, Eric; Shearer, David; Toogood, Paul; Ding, Anthony; Donohue, Erin; Belaye, Tigist; Berhaneselase, Eleni; Paul, Alexandra; Garg, Kartik; Gary, Joshua L.; Warner, Stephen J.; Munz, John W.; Choo, Andrew M.; Achor, Timothy S.; Routt, Milton L. “ Chip”; Rao, Mayank; Pechero, Guillermo; Miller, Adam; Hagen, Jennifer E.; Patrick, Matthew; Vlasak, Richard; Krupko, Thomas; Sadasivan, Kalia; Koenig, Chris; Bailey, Daniel; Wentworth, Daniel; Van, Chi; Schwartz, Justin; Dehghan, Niloofar; Jones, Clifford B.; Watson, J. Tracy; McKee, Michael; Karim, Ammar; Talerico, Michael; Sietsema, Debra L.; Williams, Alyse; Dykes, Tayler; Obremskey, William T.; Jahangir, Amir Alex; Sethi, Manish; Boyce, Robert; Stinner, Daniel J.; Mitchell, Phillip; Trochez, Karen; Rodriguez, Andres; Gajari, Vamshi; Rodriguez, Elsa; Pritchett, Charles; Boulton, Christina; Lowe, Jason; Wild, Jason; Ruth, John T.; Taylor, Michel; Seach, Andrea; Saeed, Sabina; Culbert, Hunter; Cruz, Alejandro; Knapp, Thomas; Hurkett, Colin; Lowney, Maya; Prayson, Michael; Venkatarayappa, Indresh; Horne, Brandon; Jerele, Jennifer; Clark, Linda; Marcano-Fernández, Francesc; Jornet-Gibert, Montsant; Martínez-Carreres, Laia; Martí-Garín, David; Serrano-Sanz, Jorge; Sánchez-Fernández, Joel; Sanz-Molero, Matsuyama; Carballo, Alejandro; Pelfort, Xavier; Acerboni-Flores, Francesc; Alavedra-Massana, Anna; Anglada-Torres, Neus; Berenguer, Alexandre; Cámara-Cabrera, Jaume; Caparros-García, Ariadna; Fillat-Gomà, Ferran; Fuentes-López, Ruben; Garcia-Rodriguez, Ramona; Gimeno-Calavia, Nuria; Graells-Alonso, Guillem; Martínez-Álvarez, Marta; Martínez-Grau, Patricia; Pellejero-García, Raúl; Ràfols-Perramon, Ona; Peñalver, Juan Manuel; Domènech, Mònica Salomó; Soler-Cano, Albert; Velasco-Barrera, Aldo; Yela-Verdú, Christian; Bueno-Ruiz, Mercedes; Sánchez-Palomino, Estrella; Guerra-Farfán, Ernesto; García, Yaiza; Romeo, Nicholas M.; Vallier, Heather A.; Breslin, Mary A.; Fraifogl, Joanne; Wilson, Eleanor S.; Wadenpfuhl, Leanne K.; Halliday, Paul G.; Viskontas, Darius G.; Apostle, Kelly L.; Boyer, Dory S.; Moola, Farhad O.; Perey, Bertrand H.; Stone, Trevor B.; Lemke, H. Michael; Zomar, Mauri; Spicer, Ella; Fan, Chen “Brenda”; Payne, Kyrsten; Phelps, Kevin; Bosse, Michael; Karunakar, Madhav; Kempton, Laurence; Sims, Stephen; Hsu, Joseph; Seymour, Rachel; Churchill, Christine; Bartel, Claire; Mayberry, Robert Miles; Brownrigg, Maggie; Girardi, Cara; Mayfield, Ada; Hymes, Robert A.; Schwartzbach, Cary C.; Schulman, Jeff E.; Malekzadeh, A. Stephen; Holzman, Michael A.; Ramsey, Lolita; on behalf of the PREP-IT Investigators; Orthopaedic Surgery, School of Medicine
An amendment to this paper has been published and can be accessed via the original article.
Cracking the Code: The Role of Peripheral Nervous System Signaling in Fracture Repair
(Springer, 2024) Morris, Ashlyn J.; Parker, Reginald S.; Nazzal, Murad K.; Natoli, Roman M.; Fehrenbacher, Jill C.; Kacena, Melissa A.; White, Fletcher A.; Orthopaedic Surgery, School of Medicine
Purpose of review: The traditionally understated role of neural regulation in fracture healing is gaining prominence, as recent findings underscore the peripheral nervous system's critical contribution to bone repair. Indeed, it is becoming more evident that the nervous system modulates every stage of fracture healing, from the onset of inflammation to repair and eventual remodeling. Recent findings: Essential to this process are neurotrophins and neuropeptides, such as substance P, calcitonin gene-related peptide, and neuropeptide Y. These molecules fulfill key roles in promoting osteogenesis, influencing inflammation, and mediating pain. The sympathetic nervous system also plays an important role in the healing process: while local sympathectomies may improve fracture healing, systemic sympathetic denervation impairs fracture healing. Furthermore, chronic activation of the sympathetic nervous system, often triggered by stress, is a potential impediment to effective fracture healing, marking an important area for further investigation. The potential to manipulate aspects of the nervous system offers promising therapeutic possibilities for improving outcomes in fracture healing. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Browsing by Author "Natoli, Roman M."

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