Background Reverse total shoulder arthroplasty (RTSA) has become an increasingly popular surgery for patients with rotator cuff arthropathy, unreconstructible proximal humeral fracture, and end-stage glenohumeral arthritis. The increased annual volume of RTSAs has resulted in more postoperative complications and revision rates between 3.3% and 10.1%. Postoperative infection is one of the most common complications requiring revision surgery after primary RTSA. This study assesses patient-specific risk factors for development of early infection after primary RTSA in a single high-volume shoulder arthroplasty institution. Methods From 2014 to 2019, 902 consecutive primary RTSAs were performed for surgical treatment of rotator cuff arthropathy, glenohumeral arthritis, inflammatory arthropathy, and/or dislocation. Excluding proximal humeral or scapula fractures, 756 cases met the inclusion criteria and had a minimum of 3-month follow-up. All surgeries were performed using the same surgical technique and received similar antibiotic prophylaxis. Age, patient demographics, medical history, smoking history, and prior ipsilateral shoulder treatment and/or surgery were recorded. Multivariable logistic regression analysis was used to determine risk factors associated with development of postoperative shoulder infection. Results Thirty-five patients did not meet minimum follow-up criteria and were lost to follow-up. Overall, of 721, 22 patients (3%) developed a postoperative ipsilateral shoulder infection. Previous nonarthroplasty surgery and history of rheumatoid arthritis were significantly associated with the development of postoperative shoulder infection. Amongst 196 patients who had previous nonarthroplasty shoulder surgery, there were 12 postoperative shoulder infections (6%) compared with those without previous shoulder surgery (10 of 525, 2%) ( P = .003). Among 58 patients with rheumatoid arthritis, there were 5 postoperative shoulder infections (9%) compared with patients without rheumatoid arthritis (17 of 663, 3%) ( P = .010). Patient age, gender, smoking status, history of diabetes mellitus, history of cancer/immunosuppression, and prior cortisone injection did not demonstrate significant associations with the development of postoperative infection. Conclusion Prior nonarthroplasty shoulder surgery and/or rheumatoid arthritis are independently associated with the development of postoperative infection after primary RTSA. Patients who demonstrate these risk factors should be appropriately evaluated and preoperatively counseled before undergoing primary RTSA. Strong consideration should be given to avoid minimally invasive nonarthroplasty surgery as a temporizing measure to delay definitive RTSA.

Case: A 68-year-old male, status post revision right reverse total shoulder arthroplasty (RTSA) for periprosthetic fracture, suffered a periprosthetic joint infection necessitating 2-stage revision. Imaging revealed 8.6 cm of ipsilateral proximal humeral bone loss (PHBL) including loss of the greater and lesser tuberosities. A 2-stage revision was performed using an antibiotic spacer, followed by a custom long-stem RTSA for definitive reconstruction. Two years postoperatively, the patient had significantly improved pain and functional range of motion. Conclusion: Custom long-stem RTSA could serve as a potentially viable reconstructive option in patients with severe PHBL.

We have identified regulators of G protein signaling (Rgs8 and Rgs16) as a new class of tumor suppressor genes in a mouse model of pancreatic ductal adenocarcinoma (PDA). PDA is the 3rd leading cause of cancer related deaths in the United States. Kras mutations (e.g. KrasG12D) are associated with over 90% of human PDA and are an early event in the multistep process leading to PDA. Kras can be activated by protein kinase and G-Protein Coupled Receptor (GPCR) signaling. Rgs proteins regulate GPCR signaling by accelerating the GTPase activity of Gq- and Gi class alpha subunits. Activating alleles of Gq that are resistant to Rgs inhibition are associated with PDA in humans. We found Rgs8 and Rgs16 are in vivo reporters of Kras activity in pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and PDA progression (DMM 8, 2015). Rgs8 and Rgs16 are expressed in PanIN and IPMN, precursors of PDA, in KC mice (LSL-KrasG12D; p48::Cre). To test if Rgs8-16 function as tumor suppressor genes, we crossed the Rgs8-16 double knockout into KC (termed KCR8-16) mice. Compared to KC, PDA initiates earlier, is more aggressive, and KCR8-16 mice die earlier. Our study suggests that Rgs8 and Rgs16 control Kras-dependent PDA initiation and progression. Note: This abstract was not presented at the meeting. Citation Format: Shreoshi Pal Choudhuri, Yalda Zolghadri, Luke Mascarenhas, Ozhan Ocal, Thomas Wilkie. Rgs8 and Rgs16 are tumor suppressor genes in mouse pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5518. doi:10.1158/1538-7445.AM2017-5518

Pancreatic ductal adenocarcinoma (PDA) has the highest death rate among major cancers, and new treatments are desperately needed. The mice we developed in this study, KCR8-16, are an excellent mouse model for identification, characterization, and in vivo validation of novel PDA therapeutics. Kras oncogenic mutations (e.g., KrasG12D) are found in over 90% of human PDA. Kras can be activated by protein kinase and G-protein coupled receptor (GPCR) signaling. Regulator of G-protein signaling (Rgs) proteins regulate GPCR signaling by accelerating the GTPase activity of Gq- and Gi class alpha subunits. Activating alleles of Gq that are resistant to Rgs inhibition are found in benign precursors of PDA in humans. We previously reported that Rgs8 and Rgs16 are in vivo reporters of Kras activity in pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and PDA progression in KIC;Rgs16::GFP mice (p48::Cre/+; KrasG12D/+; Cdkn2af/f; Rgs16GFP ) (DMM 8, 2015). To identify the role of Rgs 8 and 16 in PDA, we crossed the Rgs8-16 double knockout into pancreas-specific KrasG12D (KC) mutant mice (termed KCR8-16). We found that deletion of Rgs8 and Rgs16 in KC accelerated PDA progression. Additional pancreatic stress evoked by caerulein treatment caused immediate and pancreas-wide progression to PDA in KCR8-16 mice. Our study suggests that Rgs8 and Rgs16 act as tumor-suppressor genes in PDA initiation and progression. Moreover, KCR8-16 and KIC;Rgs16::GFP mice can be used as an excellent model for identification and rapid in vivo validation of PDA therapeutics. Citation Format: Shreoshi Pal Choudhuri, Yalda Zolghadri, Luke Mascarenhas, Thomas Wilkie. Rgs8 and Rgs16 protect against pancreatitis and PDA progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5525.