Characterization of the need for galactofuranose during the Neurospora crassa life cycle.

Galactofuranose is a constituent of the cell walls of filamentous fungi. The galactofuranose can be found as a component of N-linked oligosaccharides, in O-linked oligosaccharides, in GPI-anchored galactomannan, and in free galactomannan. The Neurospora genome contains a single UDP-galactose mutase gene (ugm-1/NCU01824) and two UDP-galactofuranose translocases used to import UDP-galactofuranose into the lumen of the Golgi apparatus (ugt-1/NCU01826 and ugt-2/NCU01456). Our results demonstrate that loss of galactofuranose synthesis or its translocation into the lumen of the secretory pathway affects the morphology and growth rate of the vegetative hyphae, the production of conidia (asexual spores), and dramatically affects the sexual stages of the life cycle. In mutants that are unable to make galactofuranose or transport it into the lumen of the Golgi apparatus, ascospore development is aborted soon after fertilization and perithecium maturation is aborted prior to the formation of the neck and ostiole. The Neurospora genome contains three genes encoding possible galactofuranosyltransferases from the GT31 family of glycosyltransferases (gfs-1/NCU05878, gfs-2/NCU07762, and gfs-3/NCU02213) which might be involved in generating galactofuranose-containing oligosaccharide structures. Analysis of triple KO mutants in GT31 glycosyltransferases shows that these mutants have normal morphology, suggesting that these genes do not encode vital galactofuranosyltransferases.

Modifying TIMER to generate a slow-folding DsRed derivative for optimal use in quickly-dividing bacteria.

It is now well appreciated that members of pathogenic bacterial populations exhibit heterogeneity in growth rates and metabolic activity, and it is known this can impact the ability to eliminate all members of the bacterial population during antibiotic treatment. It remains unclear which pathways promote slowed bacterial growth within host tissues, primarily because it has been difficult to identify and isolate slow growing bacteria from host tissues for downstream analyses. To overcome this limitation, we have developed a novel variant of TIMER, a slow-folding fluorescent protein, named DsRed42, to identify subsets of slowly dividing bacteria within host tissues. The original TIMER folds too slowly for fluorescence accumulation in quickly replicating bacterial species (Escherichia coli, Yersinia pseudotuberculosis), however DsRed42 accumulates red fluorescence in late stationary phase cultures of E. coli and Y. pseudotuberculosis. We show DsRed42 signal also accumulates during exposure to sources of nitric oxide (NO), suggesting DsRed42 signal detects growth-arrested bacterial cells. In a mouse model of Y. pseudotuberculosis deep tissue infection, DsRed42 signal was detected, and primarily accumulates in bacteria expressing markers of stationary phase growth. There was no significant overlap between DsRed42 signal and NO-exposed subpopulations of bacteria within host tissues, suggesting NO stress was transient, allowing bacteria to recover from this stress and resume replication. This novel DsRed42 variant represents a tool that will enable additional studies of slow-growing subpopulations of bacteria, specifically within bacterial species that quickly divide.

Racial Disparities in Liver Transplantation for Hepatocellular Carcinoma: Analysis of the National Inpatient Sample From 2007 to 2014.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a deadly disease, with patients' best hope for a cure being liver transplantation; however, access to health care resources, such as donor organs, between ethnic groups has historically been unbalanced. Ensuring equitable access to donor livers is crucial to minimize disparities in HCC outcomes. As a result, we sought to better elucidate the differences in transplantation rates among various ethnic groups. MATERIALS AND METHODS: The National Inpatient Sample (NIS) was utilized to evaluate for disparities in liver transplantation in patients whose primary or secondary diagnosis was recorded as HCC or hepatoma. The study included admissions between 2007 and 2014 to centers with at least 1 documented liver transplant. RESULTS: A total of 7244 transplants were performed over 70,406 weighted admissions. Black race was associated with lower transplantation rates, with an adjusted odds ratio of 0.46 (95% confidence interval: 0.42-0.51, P <0.01) when accounting for a number of possible confounders including socioeconomic and geographic factors. CONCLUSIONS: Our study observed decreased rates of liver transplant in blacks compared with whites for HCC. Furthermore, improved economic status and private insurance had a significantly higher odds ratio for transplantation. Hospital-level studies are needed to clarify confounding factors not apparent in large administrative datasets and help better investigate factors that lead to less optimal transplant rates among blacks. Interventions may include more optimal screening policies and procedures, improved interdisciplinary management, and earlier referrals.

Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines.

Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). At present, very little is known about GalNAc-Tyr prevalence, function, or biosynthesis. Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. Localization to specific cell types and organ substructures within those tissues indicates that GalNAc-Tyr is likely regulated in a cell-specific manner. GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. Collectively, the results shed new light on this under-studied form of glycosylation and provide access to new tools that will enable expanded biochemical and clinical investigations.

Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5.

The formation of a cell wall is vital for the survival and growth of a fungal cell. Fungi express members of the GH76 family of α-1,6-mannanases which play an important role in cell wall biogenesis. In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. We show that DFG-5 has an enzymatic activity and provide evidence that it processes the α-1,6-mannose backbone of the N-linked galactomannan. Site-directed mutagenesis and complementation experiments show that D116 and D117 are located at the DFG-5 active site. D76 and E130, which are located in a groove on the opposite side of the protein, are also important for enzyme function. Cell wall glycoproteins co-purify with DFG-5 demonstrating a specific association between DFG-5 and cell wall glycoproteins. DFG-5 is able to discriminate between cell wall and secreted glycoproteins, and does not bind to the N-linked galactomannans present on secreted glycoproteins. DFG-5 plays a key role in targeting extracellular glycoproteins to their final destinations. By processing the galactomannans on cell wall proteins, DFG-5 targets them for cell wall incorporation by lichenin transferases. The N-linked galactomannans on secreted proteins are not processed by DFG-5, which targets these proteins for release into the extracellular medium.

Management of Hepatolithiasis: Review of the Literature.

PURPOSE OF REVIEW: Hepatolithiasis is a disease characterized by intrahepatic stone formation. In this article, we review the features of this disease and explore the established and emerging treatment modalities. RECENT FINDINGS: Recent reports show an increasing prevalence of hepatolithiasis, likely owed to increased immigration and shifts in the Western diet. New pharmacotherapy options are limited and are often only supportive. Endoscopic intervention still cruxes on removal of impacted stones, though new techniques such as bile duct exploratory lithotomy and lithotripsy continue to advance management. Although hepatectomy of the effected portion of the liver offers definitive therapy, alternative less invasive modalities such as combined endoscopic/interventional radiology modalities have been utilized in select patients. Additionally, liver transplant serves as an option for otherwise incurable hepatolithiasis with coexisting liver dysfunction. Multiple emerging pharmacologic and procedural interventions may provide novel treatment for hepatolithiasis. While definitive therapy remains resection of affected liver segments, these modalities offer hope for less invasive approaches in the future.

Neurospora crassa family GH72 glucanosyltransferases function to crosslink cell wall glycoprotein N-linked galactomannan to cell wall lichenin.

The formation of a glucan/chitin/glycoprotein cell wall matrix is vital for fungal survival, growth, and morphogenesis. The cell wall proteins are important cell wall components and function in adhesion, signal transduction, and as cell wall structural elements. In this report we demonstrate that Neurospora crassa GH72 glucan transferases function to crosslink cell wall glycoproteins into the cell wall. With an in vitro assay, we show that the glucan transferases are able to attach lichenin, a cell wall glucan with a repeating ß-1,4-glucose-ß-1,4-glucose-ß-1,3-glucose structure, to cell wall glycoproteins. We propose that the pathway for attachment of lichenin to the glycoprotein has four steps. First, N-linked oligosaccharides present on the glycoproteins are modified by the addition of a galactomannan. As part of our report we have characterized the structure of the galactomannan, which consists of an α-1,6-mannose backbone with galactofuranose side chains. In the second step, the galactomannan is processed by members of the GH76 α-1,6-mannanases. In the third step, the glucan transferases cleave the lichenin and create substrate-enzyme intermediates. In the final step, the transferases transfer the lichenin to the processed galactomannan. We demonstrate that the N. crassa glucan transferases have demonstrate specificity for the processed galactomannan and for lichenin. The energy from the cleaved glycosidic bond in lichenin is retained in the substrate-enzyme intermediate and used to create a new glycosidic bond between the lichenin and the processed galactomannan. The pathway effectively crosslinks glycoproteins into the fungal cell wall.

A Copper10-Paclitaxel crystal; a medicinally active drug delivery platform.

Paclitaxel is a well-known cancer drug that functions as a mitotic inhibitor. This work focuses on a copper based crystal that encapsulates the pharmaceutical agent and serves as a drug delivery agent. A Copper10-Pacitaxil1 chloride (CU10PAC1) complex is synthesized and tested against the National Cancer Institute's sixty cell line panel. The 10:1 ratio results in a crystal that was examined by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spec (MALDI-TOF-MS), Scanning Electron Microscopy (SEM) and Proton (1H) and Carbon (13C) Nuclear Magnetic Resonance (NMR). The potential attributes of a copper based crystal as an in vivo drug carrier for Paclitaxel are discussed.

Biomimetic Proteoglycans Mimic Macromolecular Architecture and Water Uptake of Natural Proteoglycans.

Aging and degeneration of human tissue come with the loss of tissue water retention and associated changes in physical properties partially due to degradation and subsequent loss of proteoglycans. We demonstrated a novel method of fabrication of biomimetic proteoglycans, which mimic the three-dimensional bottlebrush architecture and physical behavior of natural proteoglycans responsible for tissue hydration and structural integrity. Biomimetic proteoglycans are synthesized by an end-on attachment of natural chondroitin sulfate bristles to a synthetic poly(acryloyl chloride) backbone. Atomic force microscopy imaging suggested three-dimensional core-bristle architecture, and hydrodynamic size of biomimetic proteoglycans was estimated at 61.3 ± 12.3 nm using dynamic light scattering. Water uptake results indicated that biomimetic proteoglycans had a ∼50% increased water uptake compared to native aggrecan and chondroitin sulfate alone. The biomimetic proteoglycans are cytocompatible in the physiological ranges of concentrations and could be potentially used to repair damaged or diseased tissue with depleted proteoglycan content.

Myocardial Viability and Revascularization: Current Understanding and Future Directions.

The initial observation of functional recovery in dysfunctional myocardium following revascularization led to the introduction of the concept of hibernating myocardium. Since then, the pathophysiologic basis of hibernating myocardium has been well described. Multiple imaging modalities have been utilized to prospectively detect viable myocardium and thus predict its functional recovery following revascularization. It has been hypothesized that viability imaging will be instrumental in the selection of patients with ischemic cardiomyopathy likely to benefit from revascularization. Multiple observational studies built a large body of evidence supporting this concept. However, data from prospective studies failed to substantiate utility of viability testing. This review aims to summarize the current literature and describe the role of viability imaging in current clinical practice as well as future directions.

Double outlet left atrium: successful management of a rare entity.

Double-outlet left atrium is an extremely rare congenital ventriculo-atrial mal-alignment anomaly, wherein, the left atrium drains into both ventricles, through either a common atrioventricular valve or two separate atrioventricular valves. The only egress from the right atrium is through an inter-atrial communication. We present a 16-month-old male, diagnosed to have double outlet left atrium and describe its surgical management.

Evaluation of lymphopenia as a predictor of postoperative mortality and major complications in patients undergoing surgery for metastatic spine tumors.

OBJECTIVE: Lymphopenia is often seen in advanced metastatic disease and has been associated with poor postoperative outcomes. Limited research has been done to validate this metric in patients with spinal metastases. The objective of this study was to evaluate the capability of preoperative lymphopenia to predict 30-day mortality, overall survival (OS), and major complications in patients undergoing surgery for metastatic spine tumors. METHODS: A total of 153 patients who underwent surgery for metastatic spine tumor between 2012 and 2022 and met the inclusion criteria were examined. Electronic medical record chart review was conducted to obtain patient demographics, comorbidities, preoperative laboratory values, survival time, and postoperative complications. Preoperative lymphopenia was defined as < 1.0 K/µL based on the institution's laboratory cutoff value and within 30 days prior to surgery. The primary outcome was 30-day mortality. Secondary outcomes were OS up to 2 years and 30-day postoperative major complications. Outcomes were assessed with logistic regression. Survival analyses were done using the Kaplan-Meier method with log-rank test and Cox regression. Receiver operating characteristic curves were plotted to classify the predictive ability of lymphocyte count as a continuous variable on outcome measures. RESULTS: Lymphopenia was identified in 47% of patients (72 of 153). The overall 30-day mortality rate was 9% (13 of 153). In logistic regression analysis, lymphopenia was not associated with 30-day mortality (OR 1.35, 95% CI 0.43-4.21; p = 0.609). The mean OS in this sample was 15.6 months (95% CI 13.9-17.3 months), with no significant difference between patients with lymphopenia and those with no lymphopenia (p = 0.157). Cox regression analysis did not show an association between lymphopenia and survival (HR 1.44, 95% CI 0.87-2.39; p = 0.161). The major complication rate was 26% (39 of 153). In univariable logistic regression analysis, lymphopenia was not associated with the development of a major complication (OR 1.44, 95% CI 0.70-3.00; p = 0.326). Finally, receiver operating characteristic curves generated poor discrimination between lymphocyte count and all outcomes, including 30-day mortality (area under the curve 0.600, p = 0.232). CONCLUSIONS: This study does not support prior research that had shown an independent association between low preoperative lymphocyte level and poor postoperative outcomes following surgery for metastatic spine tumors. Although lymphopenia may be used to predict outcomes in other tumor-related surgeries, this metric may not hold a similar predictive capability in the population undergoing surgery for metastatic spine tumors. Further research into reliable prognostic tools is needed.

Characterization of Neurospora crassa GH16, GH17, and GH72 gene families of cell wall crosslinking enzymes.

GH16 chitin transferases, GH17 ß-1,3-glucan transferases, and GH72 ß-1,3-glucan/lichenin transferases are important fungal cell wall crosslinking enzymes. The Neurospora crassa genome encodes three genes from the GH17 gene family and five members in the GH16 subfamily 18 and 19 fungal chitin transferases. We created deletion mutants lacking all three GH17 genes and determined that they had wild type morphology and are more sensitive to cell wall perturbation reagents than the wild type. We also created deletion mutants lacking all five GH16 subfamily 18 and 19 genes and found that they had wild type morphology and are more sensitive to cell wall perturbation reagents than the wild type. We conclude that GH16 and GH17 enzymes play roles in cell wall biogenesis. In N. crassa, GH72 enzymes have been reported to be lichenin transferases, while in other fungi they have been shown to be the ß-1,3-glucan transferases. Neurospora triple GH72 deletions give rise to a tight colonial morphology, sensitivity to cell wall perturbation reagents, and release of cell wall proteins into the medium. To ask if GH72 and GH17 enzymes might be redundant in N. crassa, we created sextuple mutants lacking the three GH72 genes and the three GH17 genes and found that they were indistinguishable from the GH72 triple mutant. We also found that a recombinant GH72 enzyme is able to form a lichenin-enzyme intermediate demonstrating that GH72 enzymes are lichenin transferases. The N. crassa GH72 enzymes are lichenin transferases and are not redundant with the GH17 ß-1,3-glucan transferases.

Herpes Virus Pseudotumor in a Patient with HIV Immunosuppression.

Background: In rare cases, HSV infections can present as pseudotumors that are often mistaken as malignancies in patients with an uncontrolled HIV infection. Herpes simplex virus type 2 (HSV-2) infection rates range from 60% to 90% in individuals coinfected with HIV. Case Presentation. A 48-year-old patient presented with a large fungating mass near her right inferior vulva with a hardness of surrounding tissues. The mass was 4 cm × 3 cm in size and was excised in the operating room. The pathology was negative for malignancy; however, it showed lymphoplasmacytic proliferation with immunostaining positive for HSV virus. Conclusion: Atypical HSV pseudotumors should be considered in the differential diagnosis for an immunosuppressed patient who presents with a genital mass lesion.

A Paraurethral Aggressive (Deep) Angiomyxoma.

Background: Aggressive angiomyxomas (AAs) are rare mesenchymal tumors that are histologically composed of myxoid stroma and vasculature. AAs are typically located in the pelvis and perineum and occur more frequently in females of reproductive age. Case Presentation. In this report, we outline a patient who had a paraurethral tumor with histopathology showing a circumscribed hypocellular lesion with myxoid stroma and abundant vasculature, consistent with the diagnosis of aggressive angiomyxoma. The mass was excised with resolution of symptoms and the patient was advised to continue close follow-up with her gynecologist and endocrinologist to monitor for recurrence. Conclusion: Due to its rarity, aggressive angiomyxomas are often misdiagnosed as cysts, hernias, lipomas, or cancerous lesions. Although benign, close follow-ups are crucial to monitor for recurrences or metastasis.

Analysis of clinical risk models vs. clinician's assessment for prediction of coronary artery disease among predominantly female population.

INTRODUCTION: Multiple risk models are used to predict the presence of obstructive coronary artery disease (CAD) in patients with chest pain. We aimed to compare the performance of these models to an experienced cardiologist's assessment utilizing coronary angiography (CA) as a reference. MATERIALS AND METHODS: We prospectively enrolled patients without known CAD referred for elective CA. We assessed pretest probability of CAD using the following risk models: Diamond-Forrester (original and updated), Duke Clinical score, ACC/AHA, CAD consortium (basic and clinical) and PROMISE minimal risk tool. All patients completed self-administrative Rose angina questionnaire. Independently, an experienced cardiologist assessed the patients to provide a binary prediction of obstructive CAD prior to CA. Obstructive CAD was defined as >80% stenosis in epicardial coronary arteries by visual assessment, or fractional flow reserve <0.80 in intermediate lesions (30-80%). RESULTS: A total of 150 patients were recruited (100 women, 50 men). Mean age was 58 (32-78) years. Obstructive CAD was found in 31 patients (21%). The area under the curve (AUC) for all the clinical risk prediction models (except the Duke Clinical Score, AUC 0.73, P = 0.07) was significantly lower compared with the clinician's assessment (AUC 0.51-0.65 vs. 0.81, respectively, P < 0.01). The clinician's assessment had sensitivity comparable to the Duke Clinical score, which was higher than all other clinical models. There was no difference in prediction performance on the basis of sex in this predominantly female population. DISCUSSION/CONCLUSION: In stable patients with chest pain and suspected CAD, current clinical risk models which are universally based upon the characteristics of the chest pain, show suboptimal performance in predicting obstructive CAD. These findings have important clinical implications, as current appropriateness criteria for recommending CA are on the basis of these risk models.

Cardiac catheterization in patients with end-stage liver disease: safety and outcomes.

INTRODUCTION: Patients with end-stage liver disease (ESLD) awaiting transplant are at increased risk of bleeding. Nevertheless, these patients routinely undergo cardiac catheterization for various indications. Safety and outcomes of cardiac catheterization in these patients are not well reported. METHODS: In a case-control study 43 patients with ESLD who underwent angiography for liver transplant work-up were compared to 43 age and gender-matched controls with no liver dysfunction. In-hospital outcomes and procedural variables were compared. RESULTS: Patients with ESLD had a lower baseline hemoglobin (12.1 ± 2.1 vs. 13.7 ± 1.8, P < 0.0005), lower platelet counts (86.8 ± 66 vs. 247 ± 80, P < 0.0001) and higher international normalized ratio (INR) (1.4 ± 0.2 vs. 1.1 ± 0.2, P < 0.0001) than controls. Among ESLD group, five (11.6%) patients received platelet transfusions, one received blood transfusion, and three patients (7%) with INR > 1.6 received fresh frozen plasma (FFP) compared with none in the control group. Smaller size (four French) vascular sheaths were used more frequently in the group with ESLD (16% vs. 4%, P = 0.04). There were no significant vascular or bleeding complications in either group. CONCLUSIONS: Elective cardiac catheterization can be safely performed in patients with ESLD with outcomes (vascular and bleeding complications, length of hospital stay and in-hospital mortality) similar to patients without liver disease despite significant thrombocytopenia and elevated INR in patients with ESLD. Practices such as platelet transfusion for platelets <60,000 µL, prophylactic FFP transfusion for INR ≥ 1.6, less frequent use of antiplatelet therapy and more frequent use of smaller vascular sheaths may have contributed to the safety of cardiac catheterization in ESLD patients.

Lumbar Intervertebral Spacer With Cement Augmentation of Endplates and Integrated Screws as a Fixation Device in an Osteoporotic Model: An In Vitro Kinematic and Load-to-Failure Study.

BACKGROUND: Integrated lateral lumbar interbody fusion (LLIF) devices have been shown to successfully stabilize the spine and avoid complications related to posterior fixation. However, LLIF has increased subsidence risk in osteoporotic patients. Cement augmentation through cannulated pedicle screws enhances pedicle fixation and cage-endplate interface yet involves a posterior approach. Lateral application of cement with integrated LLIF fixation has been introduced and requires characterization. The present study set out to evaluate kinematic and load-to-failure properties of a novel cement augmentation technique with an integrated LLIF device, alone and with unilateral pedicle fixation, compared with bilateral pedicle screws and nonintegrated LLIF (BPS + S). METHODS: Twelve specimens (L3-S1) underwent discectomy at L4-L5. Specimens were separated into 3 groups: (1) BPS + S; (2) polymethyl methacrylate (PMMA) augmentation, integrated LLIF, and unilateral pedicle screws (PMMA + UPS + iS); and (3) PMMA and integrated LLIF (PMMA + iSA) without posterior fixation. Flexion-extension, lateral bending, and axial rotation were applied. A compressive load was applied to L4-L5 segments until failure. An analysis was performed (P < .05). RESULTS: Operative constructs significantly reduced motion relative to intact specimens in all motion planes (P < .05). BPS + S provided the most stability, reducing motion by 71.6%-86.4%, followed by PMMA + UPS + iS (68.1%-79.4%) and PMMA + iSA (62.9%-81.9%); no significant differences were found (P > .05). PMMA + UPS + iS provided the greatest resistance to failure (2290 N), followed by PMMA + iSA (1970 N) and BPS + S (1390 N); no significant differences were observed (P > .05). CONCLUSIONS: Cement augmentation of vertebral endplates via the lateral approach with integrated LLIF moderately improved cage-endplate strength compared to BPS + S in an osteoporotic model; unilateral pedicle fixation further improved failure load. Reconstruction before and after application of unilateral pedicle screws and rods was biomechanically equivalent to anteroposterior reconstruction. Overall, initial results suggest that integrated LLIF with cement augmentation may be a viable alternative in the presence of osteoporosis.

Comprehensive Evaluation of Accessory Rod Position, Rod Material and Diameter, Use of Cross-connectors, and Anterior Column Support in a Pedicle Subtraction Osteotomy Model: Part I: Effects on Apical Rod Strain: An In Vitro and In Silico Biomechanical Study.

STUDY DESIGN: In silico finite element study. OBJECTIVE: The aim of this study was to evaluate the effect of six construct factors on apical rod strain in an in silico pedicle subtraction osteotomy (PSO) model: traditional inline and alternative Ames-Deviren-Gupta (ADG) multi-rod techniques, number of accessory rods (three- vs. four-rod), rod material (cobalt-chrome [CoCr] or stainless steel [SS] vs. titanium [Ti]), rod diameter (5.5 vs. 6.35 mm), and use of cross-connectors (CC), or anterior column support (ACS). SUMMARY OF BACKGROUND DATA: Rod fracture following lumbar PSO is frequently reported. Clinicians may modulate reconstructs with multiple rods, rod position, rod material and diameter, and with CC or ACS to reduce mechanical demand or rod contouring. A comprehensive evaluation of these features on rod strain is lacking. METHODS: A finite element model (T12-S1) with intervertebral discs and ligaments was created and validated with cadaveric motion data. Apical rod strain of primary and accessory rods was collected for 96 constructs across all six construct factors, and normalized to the Ti two-rod control. RESULTS: Regardless of construct features, CoCr and SS material reduced strain across all rods by 49.1% and 38.1%, respectively; increasing rod diameter from 5.5 mm to 6.35 mm rods reduced strain by 32.0%. Use of CC or lumbosacral ACS minimally affected apical rod strain (<2% difference from constructs without CC or ACS). Compared to the ADG technique, traditional inline reconstruction reduced primary rod strain by 32.2%; however, ADG primary rod required 14.2° less rod contouring. The inline technique produced asymmetrical loading between left and right rods, only when three rods were used. CONCLUSION: The number of rods and position of accessory rods affected strain distribution on posterior fixation. Increasing rod diameter and using CoCr rods was most effective in reducing rod strain. Neither CC nor lumbosacral ACS affected apical rod strain. LEVEL OF EVIDENCE: N/A.

Comprehensive In Silico Evaluation of Accessory Rod Position, Rod Material and Diameter, Use of Cross-connectors, and Anterior Column Support in a Pedicle Subtraction Osteotomy Model: Part II: Effects on Lumbosacral Rod and Screw Strain.

STUDY DESIGN: In silico finite element study. OBJECTIVE: The aim of this study was to evaluate effects of six construct factors on rod and screw strain at the lumbosacral junction in an in silico pedicle subtraction osteotomy (PSO) model: traditional inline and alternative Ames-Deviren-Gupta (ADG) multi-rod techniques, number of accessory rods (three-rod vs. four-rod), rod material (cobalt-chrome [CoCr] or stainless steel [SS] vs. titanium [Ti]), rod diameter (5.5 vs. 6.35 mm), and use of cross-connectors (CC), or anterior column support (ACS). SUMMARY OF BACKGROUND DATA: Implant failure and pseudoarthrosis at the lumbosacral junction following PSO are frequently reported. Clinicians may modulate reconstructs with multiple rods, rod position, rod material, and diameter, and with CC or ACS to reduce mechanical demand. An evaluation of these features' effects on rod and screw strains is lacking. METHODS: A finite element model (T12-S1) with intervertebral discs and ligaments was created and validated with cadaveric motion data. Lumbosacral rod and screw strain data were collected for 96 constructs across all six construct factors and normalized to the Ti 2-Rod control. RESULTS: The inline technique resulted in 12.5% to 51.3% more rod strain and decreased screw strain (88.3% to 95%) compared to ADG at the lumbosacral junction. An asymmetrical strain distribution was observed in the three-rod inline technique in comparison to four-rod, which was more evenly distributed. Regardless of construct features, rod strain was significantly decreased by rod material (CoCr > SS > Ti), and increasing rod diameter from 5.5 mm to 6.35 mm reduced strain by 9.9% to 22.1%. ACS resulted in significant reduction of rod (37.8%-59.8%) and screw strains (23.2%-65.8%). CONCLUSION: Increasing rod diameter, using CoCr rods, and ACS were the most effective methods in reducing rod strain at the lumbosacral junction. The inline technique decreased screw strain and increased rod strain compared to ADG. LEVEL OF EVIDENCE: N/A.