The effect of hormones insulin and glucagon on ubiquitin modifications elucidated by proteomics in liver cells.

AIMS: Insulin action is intertwined with changing levels of glucose and counter-regulatory hormone glucagon. While insulin lowers blood sugar level, glucagon raises it by promoting the breakdown of the stored glycogen in liver and releases glucose into the bloodstream. The hormones insulin and glucagon are key in the pathogenesis of type 2 diabetes (T2D). Insulin resistance is a primary predisposing factor for diabetes. Phosphorylation of insulin signaling molecules is altered in the insulin-resistant state. However, ubiquitin (Ub) modifications in insulin-resistant state are relatively understudied. To dissect the underlying mechanisms, we performed a proteomics study on hepatoma cells to study the regulation of ubiquitination by insulin and glucagon. MATERIALS AND METHODS: We performed western blotting, immunoprecipitations, and affinity pull down using tandem Ub binding entities (TUBE) reagents on hepatoma cells treated with insulin or glucagon. Next, we performed MS/MS analysis on Ub-linkage specific affinity pull down samples. Gene ontology analysis and protein-protein interaction network analysis was performed using DAVID GO and STRING db, respectively. KEY FINDINGS: The ubiquitination pattern of total Ub, K48-linked Ub, and K63-linked Ub was altered with the treatment of hormones insulin and glucagon. Ubiquitination in immunoprecipitated samples showed enrichment with total Ub and K48-linked Ub but not with K63-linked Ub. Ubiquitination by treatment with hormones mainly enriched key signaling pathways MAPK, Akt, oxidative stress etc. SIGNIFICANCE: Our study identified key altered proteins and signal transduction pathways which aids in understanding the mechanisms of hormonal action on ubiquitination and identify new therapeutic targets for T2D.

Innate Immune Mechanism of Neutrophil Extracellular Trap Formation is Impaired in at-Risk Term Low Birth Weight Newborns.

Low birth weight (LBW) is a leading cause of newborn's mortality however the underlying defects in cellular immunity and immune mechanisms leading to severe neonatal infections in term LBW (tLBW) newborns are not well understood. Neutrophil extracellular traps (NETs), or NETosis, is an innate immune defense mechanism of neutrophils involved in trapping and killing of microbes. The efficiency of NET formation in cord blood derived neutrophils of tLBW and normal birth weight (NBW) newborns in the presence of toll like receptor (TLR) agonist inductions was evaluated. The NET formation was observed to be substantially impaired in tLBW newborns along with NET proteins expression, extracellular deoxyribonucleic acid (DNA) release and reactive oxygen species generation. The placental tissues from tLBW newborns delivery also showed minimal NETosis. These findings suggest impaired NET formation to be an important factor underlying the deficient immune status of tLBW newborns making them susceptible to life- threatening infections.

Catastrophic acute failure of pelvic fixation in adult spinal deformity requiring revision surgery: a multicenter review of incidence, failure mechanisms, and risk factors.

OBJECTIVE: There are few prior reports of acute pelvic instrumentation failure in spinal deformity surgery. The objective of this study was to determine if a previously identified mechanism and rate of pelvic fixation failure were present across multiple institutions, and to determine risk factors for these types of failures. METHODS: Thirteen academic medical centers performed a retrospective review of 18 months of consecutive adult spinal fusions extending 3 or more levels, which included new pelvic screws at the time of surgery. Acute pelvic fixation failure was defined as occurring within 6 months of the index surgery and requiring surgical revision. RESULTS: Failure occurred in 37 (5%) of 779 cases and consisted of either slippage of the rods or displacement of the set screws from the screw tulip head (17 cases), screw shaft fracture (9 cases), screw loosening (9 cases), and/or resultant kyphotic fracture of the sacrum (6 cases). Revision strategies involved new pelvic fixation and/or multiple rod constructs. Six patients (16%) who underwent revision with fewer than 4 rods to the pelvis sustained a second acute failure, but no secondary failures occurred when at least 4 rods were used. In the univariate analysis, the magnitude of surgical correction was higher in the failure cohort (higher preoperative T1-pelvic angle [T1PA], presence of a 3-column osteotomy; p < 0.05). Uncorrected postoperative deformity increased failure risk (pelvic incidence-lumbar lordosis mismatch > 10°, higher postoperative T1PA; p < 0.05). Use of pelvic screws less than 8.5 mm in diameter also increased the likelihood of failure (p < 0.05). In the multivariate analysis, a larger preoperative global deformity as measured by T1PA was associated with failure, male patients were more likely to experience failure than female patients, and there was a strong association with implant manufacturer (p < 0.05). Anterior column support with an L5-S1 interbody fusion was protective against failure (p < 0.05). CONCLUSIONS: Acute catastrophic failures involved large-magnitude surgical corrections and likely resulted from high mechanical strain on the pelvic instrumentation. Patients with large corrections may benefit from anterior structural support placed at the most caudal motion segment and multiple rods connecting to more than 2 pelvic fixation points. If failure occurs, salvage with a minimum of 4 rods and 4 pelvic fixation points can be successful.

Alternative Uses of O-Arm and Stealth Navigation Technology Over 10 Years: The University of Colorado Experience.

Intraoperative computed tomography scanning with O-arm and use of Stealth navigation can improve surgical outcomes in a variety of orthopedic subspecialties. In spine surgery, the accuracy, precision, and safety of pedicle screw and interbody implant placement has improved. This technology is now routinely used in percutaneous pedicle screw placement and minimally invasive sacroiliac joint fusion. Other applications include, but are not limited to, isthmic pars defect repair, lumbosacral pseudoarticulation resection in Bertolotti's syndrome, radiofrequency ablation, and en bloc tumor resection. Intraoperative navigation has numerous applications, and use of this technology should continue to evolve as the technology advances. [Orthopedics. 2023;46(2):e89-e97.].

Repurposing an Antiepileptic Drug for the Treatment of Glioblastoma.

PURPOSE: Glioblastoma multiforme (GBM) is a grade IV, highly proliferative, and malignant form of brain tumor with a 5-year survival rate at ~ 5%. Current treatment strategies for GBM include surgery, radiation, and chemotherapy. Major challenges in GBM management include difficulties in surgical resection due to brain's vital functions and GBM metastasis, development of resistance to temozolomide (TMZ), and protection of tumor by blood brain barrier (BBB). Therefore, we aimed to discover a novel therapeutic for GBM by targeting its metabolic reprogramming. METHOD: We screened metabolic inhibitors by their effects on GBM cell viability by MTT assay. We discovered an FDA-approved drug stiripentol (STP) in our screening of metabolic inhibitors in GBM cells. STP is used for Dravet syndrome (a rare epilepsy). We further tested efficacy of STP using proliferation assay, clonogenic assay, in vitro migration assay, cell cycle assay, apoptosis assay, and in U87 3D spheroids. We also tested the toxicity of STP, and combinations used in the study on normal human dermal fibroblasts. RESULTS: STP was effective in decreasing GBM cell viability, proliferation, clonogenic ability, and migration. Moreover, cell cycle changes were involved but robust apoptosis was absent in STP's anticancer effects. STP was effective in 3D spheroid models, and in TMZ-resistant cells. STP showed additive or synergistic effect with TMZ in different anticancer assays on GBM cells and was considerably less toxic in normal cells. CONCLUSION: Our results indicate that STP can be an effective GBM therapeutic that enhances the effects of TMZ on GBM cells. Importantly, STP reduced viability of TMZ-resistant cells. Our results warrant further studies in the mechanistic basis of STP's effects on GBM cells and the preclinical potential of STP in animal models.

Metabolic alterations and mitochondrial dysfunction underlie hepatocellular carcinoma cell death induced by a glycogen metabolic inhibitor.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. There is an urgent need for new targets to treat HCC due to limited treatment options and drug resistance. Many cancer cells are known to have high amount of glycogen than their tissue of origin and inhibition of glycogen catabolism induces cancer cell death by apoptosis. To further understand the role of glycogen in HCC and target it for pharmacotherapy, we studied metabolic adaptations and mitochondrial function in HepG2 cells after pharmacological inhibition of glycogen phosphorylase (GP) by CP-91149 (CP). GP inhibition increased the glycogen levels in HepG2 cells without affecting overall glucose uptake. Glycolytic capacity and importantly glycolytic reserve decreased significantly. Electron microscopy revealed that CP treatment altered mitochondrial morphology leading to mitochondrial swelling with less defined cristae. A concomitant decrease in mitochondrial oxygen consumption and mitochondria-linked ATP generation was observed. Metabolomics and enzyme activity / expression studies showed a decrease in the pentose phosphate pathway. In addition, CP treatment decreased the growth of HepG2 3D tumor spheroids in a dose- and time-dependent manner. Taken together, our study provides insights into metabolic alterations and mitochondrial dysfunction accompanying apoptosis in HepG2 cells upon GP inhibition. Our study can aid in the understanding of the mechanism and development of metabolic inhibitors to treat HCC.

Blockade of Osteoclast-Mediated Bone Resorption With a RANKL-Inhibitor Enhances Bone Formation in a Rat Spinal Fusion Model.

STUDY DESIGN: Rat spine fusion model. OBJECTIVE: The present study aimed to determine whether administration of osteoprotegerin (OPG) in a rat model of spinal fusion increases bone volume, bone density, and decreases osteoclasts in the fusion mass. SUMMARY OF BACKGROUND DATA: OPG is a soluble RANK-ligand inhibitor that blocks osteoclast differentiation and activation. This makes it a potential agent to control the remodeling process and enhance bone mass during spinal fusion. MATERIALS AND METHODS: Forty-eight male Sprague-Dawley rats received a one-level spinal fusion of L4-L5 with bone allograft. Rats were then divided into four groups according to initiation of treatment: (1) saline on day 0 (saline), (2) OPG on day 0 (OPG D0), (3) OPG on day 10 (OPG D10), and (4) OPG on day 21 (OPG D21) postsurgery. After their initial injection, rats received weekly subcutaneous injections of OPG (10 mg/kg) and were euthanized six weeks postsurgery. MicroCT analysis of the fusion site and histological analysis of bone surface for quantification of osteoclast lining was performed. RESULTS: Increased bone volume in the fusion site and around the spinous process was seen in OPG D0 and OPG D10 when compared with saline. Mean trabecular thickness was greater in all groups receiving OPG compared with saline, with OPG D0 and OPG D10 having significantly greater mean trabecular thickness than OPG D21. All OPG groups had less bone surface lined with osteoclasts when compared with Saline, with OPG D0 and OPG D10 having fewer than OPG D21. CONCLUSIONS: This study indicates that OPG inhibited osteoclast bone resorption, which led to greater bone at the fusion site. Future studies investigating OPG on its own or in combination with an osteogenic factor to improve spinal fusion outcomes are warranted to further elucidate its potential therapeutic effect.

Minor Trauma Caused High-Grade Lumbosacral Spondylolisthesis After Short-Segment Lumbar Fusion: A Case Report.

CASE: Ten days after L3-L5 instrumented posterior lumbar spinal fusion, an 85-year-old woman developed Grade 4 spondylolisthesis at L5-S1 after a minor fall. She underwent posterior open reduction and internal fixation with extension of fusion from L2 to the pelvis. The preexisting hardware at L5 caused partial laceration of the right L5 nerve root. One year after surgery, computed tomography demonstrated maintenance of correction and fusion at L5-S1. CONCLUSION: High-grade lumbosacral spondylolisthesis can occur with minor trauma after short-segment lumbar fusion. Maintenance of correction and fusion is achievable with posterior open reduction and internal fixation to the pelvis alone. Preexisting hardware can damage nerve roots causing permanent neurological deficits.

Galactose-decorated liver tumor-specific nanoliposomes incorporating selective BRD4-targeted PROTAC for hepatocellular carcinoma therapy.

This research deals with the development of asialoglycoprotein receptors (ASGPR) directed nanoliposomes incorporating a novel BRD4 (Bromodomain-containing protein 4) protein-targeted PROTAC (Proteolysis Targeting Chimera), ARV-825 (ARV) (GALARV), and to investigate the anticancer efficacy of GALARV for specific delivery in hepatocellular carcinoma. GALARV were prepared using the modified hydration method and characterized for their physicochemical properties as well as anticancer activity using 2D and 3D cell culture models. ARV and GALARV (93.83 ± 10.05 nm) showed significant in vitro cytotoxicity and apoptosis in hepatocellular carcinoma cells. GALARV also demonstrated a substantially higher intracellular concentration of ARV compared to non-targeted nanoliposomes (∼3 fold) and ARV alone (∼4.5 fold), showed good physical stability and negligible hemolysis. Immunoblotting results depicted substantial downregulation of target BRD4 protein, oncogenic c-Myc, apoptotic Bcl-2, and survivin proteins. Notably, GALARV treatment resulted in significant apoptosis and subsequent inhibition of the cell viability of 3D tumor spheroids of hepatocellular carcinoma. These results suggest that GALARV is a novel actively targeted PROTAC-based nanotherapeutic approach for hepatocellular carcinoma.

Nonedible Vegetable Oil-Based Polyols in Anticorrosive and Antimicrobial Polyurethane Coatings.

This review describes the preparation of nonedible vegetable oil (NEVO)-based polyols and their application in anticorrosive and antimicrobial polyurethane (PU) coatings. PUs are a class of versatile polymers made up of polyols and isocyanates. Renewable vegetable oils are promising resources for the development of ecofriendly polyols and the corresponding PUs. Researchers are interested in NEVOs because they provide an alternative to critical global food issues. The cultivation of plant resources for NEVOs can also be popularized globally by utilizing marginal land or wastelands. Polyols can be prepared from NEVOs following different conversion routes, including esterification, etherification, amidation, ozonolysis, hydrogenation, hydroformylation, thio-ene, acrylation, and epoxidation. These polyols can be incorporated into the PU network for coating applications. Metal surface corrosion and microbial growth are severe problems that cause enormous economic losses annually. These problems can be overcome by NEVO-based PU coatings, incorporating functional ingredients such as corrosion inhibitors and antimicrobial agents. The preferred coatings have great potential in high performance, smart, and functional applications, including in biomedical fields, to cope with emerging threats such as COVID-19.

Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma.

A novel treatment strategy by co-targeting c-Myc and tumor stroma was explored in vemurafenib-resistant melanoma. BRD4 proteolysis targeting chimera (ARV-825) and nintedanib co-loaded PEGylated nanoliposomes (ARNIPL) were developed to incorporate a synergistic cytotoxic ratio. Both the molecules have extremely poor aqueous solubility. A modified hydration method with citric acid was used to improve the loading of both the molecules in liposomes. ARNIPL with mean particle size 111.1 ± 6.55 nm exhibited more than 90% encapsulation efficiency for both the drugs and was found to be physically stable for a month at 4 °C. Both the molecules and ARNIPL showed significantly higher cytotoxicity, apoptosis and down-regulation of target proteins BRD4 and c-Myc in vemurafenib-resistant cell line (A375R). Vasculogenic mimicry and clonogenic potential of A375R were significantly inhibited by ARNIPL. Tumor growth inhibition in 3D spheroids with reduction of TGF-ß1 was observed with ARNIPL treatment. Therefore, ARNIPL could be a promising therapeutic approach for the treatment of vemurafenib-resistant melanoma.

A novel gene therapy for neurodegenerative Lafora disease via EPM2A-loaded DLinDMA lipoplexes.

Aim: To develop novel cationic liposomes as a nonviral gene delivery vector for the treatment of rare diseases, such as Lafora disease - a neurodegenerative epilepsy. Materials & methods: DLinDMA and DOTAP liposomes were formulated and characterized for the delivery of gene encoding laforin and expression of functional protein in HEK293 and neuroblastoma cells. Results: Liposomes with cationic lipids DLinDMA and DOTAP showed good physicochemical characteristics. Nanosized DLinDMA liposomes demonstrated desired transfection efficiency, negligible hemolysis and minimal cytotoxicity. Western blotting confirmed successful expression and glucan phosphatase assay demonstrated the biological activity of laforin. Conclusion: Our study is a novel preclinical effort in formulating cationic lipoplexes containing plasmid DNA for the therapy of rare genetic diseases such as Lafora disease.

Three- and 4-Level Lumbar Arthrodesis Using Adjunctive Pulsed Electromagnetic Field Stimulation: A Multicenter Retrospective Evaluation of Fusion Rates and a Review of the Literature.

BACKGROUND: The incidence of 3- and 4-level lumbar arthrodesis is rising due to an aging population, and fusion rates affect clinical success in this population. Pulsed electromagnetic field (PEMF) stimulation is used as an adjunct to increase fusion rates following multilevel arthrodesis. The purpose of the study was to evaluate the fusion rates for subjects who underwent 3- and 4-level lumbar interbody arthrodesis following PEMF treatment. METHODS: In this retrospective, multicenter study, patient charts that listed 3- or 4-level lumbar arthrodesis with adjunctive use of a PEMF device were evaluated. Inclusion criteria included patients who were diagnosed with lumbar degenerative disease, spinal stenosis, and/or spondylolisthesis (grade 1 or 2). A radiographic evaluation of fusion status was performed at 12 months by the treating physicians. Fusion rates were stratified by graft material, surgical interbody approach, and certain clinical risk factors for pseudoarthrosis. RESULTS: A total of 55 patients were identified who had a 12-month follow-up. The radiographic fusion rate was 92.7% (51 patients) at 12 months. There were no significant differences in fusion rates for patients treated with allograft or autograft, for patients with different interbody approaches, or for those with or without certain clinical risk factors. CONCLUSIONS: With modern fusion techniques and PEMF, the overall fusion rate was high following 3- and 4-level lumbar arthrodesis. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: PEMF may be a useful adjunct for treatment of patients with surgical risk factors, such as multilevel arthrodesis, and clinical risk factors.

Validation of new shoulder periprosthetic joint infection criteria.

BACKGROUND: A periprosthetic joint infection (PJI) in the shoulder can be difficult to diagnose. Many variables have been used to determine a PJI. Recently, the 2018 International Consensus Meeting (ICM) on orthopedic infections gave new criteria to help identify PJI in the shoulder. With the new criteria (major and minor), the PJI definition can be categorized into definite, probable, possible, and unlikely. This study was conducted to assess the new criteria for a series of consecutive first stage revision shoulder arthroplasty cases. METHODS: All patients undergoing a first stage revision shoulder arthroplasty using a prosthesis made of antibiotic-loaded acrylic cement (PROSTALAC) spacer from 2016 through 2019 were evaluated retrospectively. All cases were performed by a single surgeon. Each case was reviewed using the 2018 shoulder ICM diagnostic criteria. Secondary factors evaluated were type of organism identified, accuracy of minor criteria, and frozen vs. permanent section accuracy. RESULTS: A total of 87 first-stage revision arthroplasty cases were reviewed. Based on the 2018 ICM criteria, there were 20 definite (30.0%), 19 probable (21.8%), 6 possible (6.9%), and 42 unlikely (48.3%) infections. Cutibacterium acnes was the most common infectious organism overall (77.3% of culture positive cases) and was present in 39.1% of cases overall. Ten patients (25.6%) grew multiple organisms. Thirty-one patients (35.6%) had a loose humeral stem, with 23 of those patients (74.2%) having a definite or probable infection (odds ratio [OR] 7.2, 95% confidence interval [CI] 2.67-19.37, P = .0001). Eleven patients (91.7%) with an elevated intraoperative synovial neutrophil cell count had a definite or probable infection. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) was elevated in patients with a definite or probable infection (OR 9.4, 95% CI 2.47-35.62, P = .0010, and OR 7.7, 95% CI 2.29-25.56, P = .0009), respectively. Discordant results between frozen and permanent sections were found in 4 patients (4.6%). CONCLUSION: The 2018 ICM shoulder infection criteria gave a new scoring system to diagnose PJI. C acnes was the most common infectious organism identified. Patients who had a loose humeral stem, elevated ESR, or elevated CRP were more likely to have either a definite or probable PJI. Frozen sections were able to accurately identify definite infections. Unexpected wound drainage and positive preoperative cultures were low-yield criteria in this series. More research into determining periprosthetic shoulder infection is needed to help identify which patients are more likely to have an infection.

Management of choroid plexus tumours: A comprehensive study from a tertiary hospital.

OBJECTIVE: Choroid plexus tumours (CPT) are rare intraventricular tumours representing less than 0.5 % of brain tumours. The tumour is commonly located in the supratentorial region, but the location varies depending on the age. We present our experience of managing these tumours in a tertiary hospital. METHODS: Retrospectively, we reviewed our operative database and recruited 80 cases of CPT who underwent surgical treatment in our institute from 1995 to 2018. We analysed the factors affecting the outcome and the perioperative complications of the choroid plexus tumour. RESULTS: A total of 80 choroid plexus tumours were recruited in our retrospective review, of which 44 were choroid plexus papilloma (CPP), 13 were atypical choroid plexus tumours (ACPP), 23 were choroid plexus carcinomas (CPC). The mean age was 16.75 (SD 16.71) in the overall cohort. Males were found to be predominant in all tumour groups (M/F: 46/34). Headache was the most common symptom (52.5 %). Hydrocephalus was seen in 53.8 % of cases. The median overall survival was 89.88 months. Gross total resection was achieved in 62.5 % cases (n = 50/80), and near-total resection in 27. 5 % cases (n = 22/80). The median overall survival was 89.88 months. The median overall survival for CPP, ACPP, CPC was 106.83, 37.37, 36.19 months, respectively. Median Event-free survival was 65.83 months. A Cox regression analysis of predictors of overall survival of atypical CPP and CPC was done, in which age, sex, location, size, the extent of the resection, and complications were considered. The extent of the resection (p = 0.01) and the size (p = 0.02) were related to overall survival CONCLUSION: CPT's are the rare intraventricular tumours, which requires aggressive resection strategies. The extent of resection offers survival benefit based on the histological grades.

Recombinant Human Bone Morphogenetic Protein-2 Improves Spine Fusion in a Vitamin D-Deficient Rat Model.

BACKGROUND: The effects of vitamin D deficiency on spinal fusion are not well studied, nor are approaches to overcoming deficiency-related detrimental effects. The purpose of this study was to (1) evaluate the effects of vitamin D deficiency on spine fusion in a rat model, and (2) determine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) can improve outcomes in deficient rats. METHODS: Sprague-Dawley rats were assigned to a vitamin D group: vitamin D sufficient (14), vitamin D deficient (16), vitamin D postoperative rescue (15). Posterolateral fusion was performed at L3-4 and L5-6, with one level receiving rhBMP-2 and the other allograft. Following 6 weeks, the spines were harvested for micro-computed tomography (micro-CT) and histological analyses. Fusion was assessed via manual palpation and micro-CT assessment. Micro-CT images were analyzed for bone microarchitecture in intact L5 vertebral bodies and within fused bone masses treated with rhBMP-2. RESULTS: There were no significant effects of vitamin D status on fusion assessments. However, the microarchitecture of native bone in the intact L5 vertebral bodies of vitamin D-sufficient rats showed significantly greater trabecular thickness (P < .001) and bone volume fraction (P < .001), with decreased trabecular spacing (P < .001), than that of vitamin D-deficient rats. Fusion masses of rhBMP-2 levels also showed significant effects of vitamin D supplementation on both bone volume fraction and trabecular thickness. Histological analysis confirmed that robust bone formation was observed in rhBMP-2-treated fusions, but not in fusion levels treated with allograft. CONCLUSIONS: Overall, vitamin D deficiency decreased trabecular bone microarchitecture, and treatment with rhBMP-2 improved outcomes across all vitamin D groups. CLINICAL RELEVANCE: Given the prevalence of vitamin D deficiency in spine surgery patients, vitamin D supplementation may be a cost-effective method for reducing the risk of pseudoarthrosis.

Optimizing the aryl-triazole of cjoc42 for enhanced gankyrin binding and anti-cancer activity.

Gankyrin is an oncoprotein overexpressed in numerous cancer types and appears to play a key role in regulating cell proliferation, cell growth, and cell migration. These roles are largely due to gankyrin's protein-protein interaction with the 26S proteasome. We previously published a study exploring the aryl sulfonate ester of cjoc42 in an effort to enhance gankyrin binding and inhibit cancer cell proliferation. In order to further improve the gankyrin binding ability of the cjoc42 scaffold, an extensive SAR for the aryl-triazole moiety of cjoc42 was developed. Our cjoc42 derivatives exhibited enhanced gankyrin binding, as well as enhanced antiproliferative activity against Hep3B, HepG2, A549, and MDA-MB-231 cancer cell lines.

Early results of reverse total shoulder arthroplasty using a patient-matched glenoid implant for severe glenoid bone deficiency.

BACKGROUND: Reverse total shoulder arthroplasty (rTSA) in the presence of significant glenoid bone loss remains a challenge. This study presents preliminary clinical and radiographic outcomes of primary and revision rTSA using a patient-matched, 3-dimensionally printed custom metal glenoid implant to address severe glenoid bone deficiency. METHODS: Between September 2017 and November 2018, 19 patients with severe glenoid bone deficiency underwent primary (n = 9) or revision rTSA (n = 10) using the Comprehensive Vault Reconstruction System (VRS) (Zimmer Biomet, Warsaw, IN, USA) at a single institution. Preoperative and postoperative values for the Disabilities of the Arm, Shoulder and Hand score, Constant score, American Shoulder and Elbow Surgeons score, Simple Shoulder Test score, Single Assessment Numeric Evaluation score, and visual analog scale pain score and active range of motion were compared using the Wilcoxon signed rank test with the level of statistical significance set at P < .05. RESULTS: Complications occurred in 4 patients (21%), including a nondisplaced greater tuberosity fracture treated conservatively in 1, intraoperative cortical perforation during humeral cement removal treated with an allograft strut in 1, and recurrent instability and hematoma formation treated with humeral component revision in 1. One patient with an early periprosthetic infection was treated with component removal and antibiotic spacer placement at an outside facility and was subsequently lost to follow-up. Eighteen patients with 1-year minimum clinical and radiographic follow-up were evaluated (mean, 18.2 months; range, 12-27 months). Significant improvements were noted in the mean Disabilities of the Arm, Shoulder and Hand score (57.4 ± 16.5 vs. 29.4 ± 19.5, P < .001), mean Constant score (24.6 ± 10.2 vs. 60.4 ± 14.5, P < .001), mean American Shoulder and Elbow Surgeons score (32 ± 18.2 vs. 79 ± 15.6, P < .001), mean Simple Shoulder Test score (4.5 ± 2.6 vs. 9.3 ± 1.8, P < .001), mean Single Assessment Numeric Evaluation score (25.4 ± 13.7 vs. 72.2 ± 17.8, P < .001), mean visual analog scale pain score (6.2 ± 2.9 vs. 0.7 ± 1.3, P < .001), mean active forward flexion (53° ± 27° vs. 124° ± 23°, P < .001), and mean active abduction (42° ± 17° to 77° ± 15°, P < .001). Mean external rotation changed from 17° ± 19° to 32° ± 24° (P = .06). No radiographic evidence of component loosening, scapular notching, or hardware failure was observed at last follow-up in any patient. CONCLUSION: The preliminary results of rTSA using the VRS to manage severe glenoid bone deficiency are promising, but longer follow-up is necessary to determine the longevity of this implant.