Discovery of Potent and Selective Covalent Inhibitors of HER2WT and HER2YVMA.

HER2 overexpression and amplification have been identified as oncogenic drivers, and the development of therapies to treat tumors harboring these markers has received considerable attention. Activation of HER2 signaling and subsequent cell growth can also be induced by HER2 mutations, including the common YVMA insertion in exon 20 within the kinase domain. Enhertu is currently the only approved treatment for HER2 mutant tumors in NSCLC. TKIs tested in this space have suffered from off-target activity, primarily due to EGFRWT inhibition or attenuated activity against HER2 mutants. The goal of this work was to identify a TKI that would provide robust inhibition of oncogenic HER2WT and HER2 mutants while sparing EGFRWT activity. Herein, we describe the development of a potent, covalent inhibitor of HER2WT and the YVMA insertion mutant while providing oral bioavailability and avoiding the inhibition of EGFRWT.

CD4+ CAR-T cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR-T cell therapy.

Multiple myeloma is characterized by frequent clinical relapses following conventional therapy. Recently, chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) has been established as a treatment option for patients with relapsed or refractory disease. However, while >70% of patients initially respond to this treatment, clinical relapse and disease progression occur in most cases. Recent studies showed persistent expression of BCMA at the time of relapse, indicating that immune intrinsic mechanisms may contribute to this resistance. While there were no pre-existing T cell features associated with clinical outcomes, we found that patients with a durable response to CAR-T cell treatment had greater persistence of their CAR-T cells compared to patients with transient clinical responses. They also possessed a significantly higher proportion of CD8+ T effector memory cells. In contrast, patients with short-lived responses to treatment have increased frequencies of cytotoxic CD4+ CAR-T cells. These cells expand in vivo early after infusion but express exhaustion markers (HAVCR2 and TIGIT) and remain polyclonal. Finally, we demonstrate that non-classical monocytes are enriched in the myeloma niche and may induce CAR-T cell dysfunction through mechanisms that include TGFß. These findings shed new light on the role of cytotoxic CD4+ T cells in disease progression after CAR-T cell therapy.

A time out for prayer.

Compassionate care of the surgical patient recognizes the wholeness of each individual. Patients and their caregivers come to healthcare providers with the hope of relief from pain and suffering and aspirations for the potential to feel well or be "normal" again. Many lean on their personal faith and prayer for spiritual comfort and petitions for healing. We discuss a case in which prayer is incorporated into the surgical Time Out, a scenario not uncommon in faith-based hospitals, and offer a framework to evaluate the practice that incorporates ethical principles of beneficence, non-maleficence, patient/parental autonomy, justice, and the fiduciary responsibility of the healthcare provider.

Revision Dual Mobility Constructs With Unmatched Acetabular and Femoral Components Do Not Increase Failure Rate.

BACKGROUND: Dual mobility (DM) constructs for revision total hip arthroplasty (THA) have continued to grow in popularity to mitigate instability. This benefit comes at the cost of potential unique modes of failure, and there are theoretical concerns that combining femoral and acetabular components from different manufacturers could lead to increased failure rates. We aimed to investigate rates of reoperation between matched and unmatched DM implants used in revision THA. METHODS: We retrospectively reviewed 217 revision THAs performed with DM constructs between July 2012 and September 2021 at a single institution. Dual mobility (DM) constructs were classified as "matched" if the acetabular and femoral components were manufactured by the same company. They were classified as "unmatched" if the acetabular and femoral components were manufactured by different companies. The primary outcome was reoperation for any reason. RESULTS: There were 136 matched DM constructs and 81 unmatched constructs. Average follow-up was 4.6 years (range, 2.0 to 9.6 years). There was no difference in reoperation rate between matched and unmatched groups (11.0 versus 13.6%, P = .576). The most common reasons for reoperation in both groups were instability and periprosthetic joint infection. There was 1 revision for intraprosthetic dislocation in the matched group. CONCLUSIONS: The use of unmatched DM components in revision THA was common and did not increase the risk of reoperation at an average of 4.6-year follow-up. This information can be helpful in operative planning, but further research on long-term survival will be necessary.

A case of bilateral pneumothorax following computer-tomography guided transthoracic biopsy in a woman with suspected pulmonary cancer.

Computer-tomography-guided needle biopsies are useful for diagnosing, staging, and classification of peripheral pulmonary nodules. However, the procedure carries a risk of iatrogenic pneumothorax. This report describes a patient-case where a woman had undergone a computer-tomography guided biopsy. Approximately 4 hours following discharge the patient was admitted to the emergency ward with severe chest pain and dyspnea. Chest x-ray revealed bilateral pneumothorax and subcutaneous emphysema at the biopsy site. Pleural drainage was administered on the patient's right side. Another chest x-ray following drainage showed regression of pneumothorax on both sides thus indicating communicating pleural cavities. Medical history revealed that the patient had been thymectomized 2 years earlier and a computer tomography visualized that the patient lacked mediastinal separation of the two pleural cavities. It is possible that patients with a history of mediastinal or thoracic surgery should be observed longer following procedures carrying risk of iatrogenic pneumothorax.

The Microbiome of Osteoarthritic Hip and Knee Joints: A Prospective Multicenter Investigation.

BACKGROUND: Recent advances in high-throughput DNA sequencing technologies have made it possible to characterize the microbial profile in anatomical sites previously assumed to be sterile. We used this approach to explore the microbial composition within joints of osteoarthritic patients. METHODS: This prospective multicenter study recruited 113 patients undergoing hip or knee arthroplasty between 2017 and 2019. Demographics and prior intra-articular injections were noted. Matched synovial fluid, tissue, and swab specimens were obtained and shipped to a centralized laboratory for testing. Following DNA extraction, microbial 16S-rRNA sequencing was performed. RESULTS: Comparisons of paired specimens indicated that each was a comparable measure for microbiological sampling of the joint. Swab specimens were modestly different in bacterial composition from synovial fluid and tissue. The 5 most abundant genera were Escherichia, Cutibacterium, Staphylococcus, Acinetobacter, and Pseudomonas. Although sample size varied, the hospital of origin explained a significant portion (18.5%) of the variance in the microbial composition of the joint, and corticosteroid injection within 6 months before arthroplasty was associated with elevated abundance of several lineages. CONCLUSIONS: The findings revealed that prior intra-articular injection and the operative hospital environment may influence the microbial composition of the joint. Furthermore, the most common species observed in this study were not among the most common in previous skin microbiome studies, suggesting that the microbial profiles detected are not likely explained solely by skin contamination. Further research is needed to determine the relationship between the hospital and a "closed" microbiome environment. These findings contribute to establishing the baseline microbial signal and identifying contributing variables in the osteoarthritic joint, which will be valuable as a comparator in the contexts of infection and long-term arthroplasty success. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Child-Pugh Class B or C Liver Disease Increases the Risk of Early Mortality in Patients With Hepatitis C Undergoing Elective Total Joint Arthroplasty Regardless of Treatment Status.

BACKGROUND: Patients with hepatitis C virus (HCV) undergoing primary elective total joint arthroplasty (TJA) are at increased risk of postoperative complications. Patients with chronic liver disease and cirrhosis, specifically Child-Pugh Class B and C, who are undergoing general surgery have high 2-year mortality risks, approaching 60% to 80%. However, the role of Child-Pugh and Model for End-Stage Liver Disease classifications of liver status in predicting survivorship among patients with HCV undergoing elective arthroplasty has not been elucidated. QUESTION/PURPOSE: What factors are independently associated with early mortality (< 2 years) in patients with HCV undergoing arthroplasty? METHODS: We performed a retrospective study at three tertiary academic medical centers and identified patients with HCV undergoing primary elective TJA between January 2005 and December 2019. Patients who underwent revision TJA and simultaneous primary TJA were excluded. A total of 226 patients were eligible for inclusion in the study. A further 25% (57) were excluded because they were lost to follow-up before the minimum study requirement of 2 years of follow-up or had incomplete datasets. After the inclusion and exclusion criteria were applied, the final cohort consisted of 75% (169 of 226) of the initial patient population eligible for analysis. The mean follow-up duration was 53 ± 29 months. We compared confounding variables for mortality between patients with early mortality (16 patients) and surviving patients (153 patients), including comorbidities, HCV and liver characteristics, HCV treatment, and postoperative medical and surgical complications. Patients with early postoperative mortality were more likely to have an associated advanced Child-Pugh classification and comorbidities including peripheral vascular disease, end-stage renal disease, heart failure, and chronic obstructive pulmonary disease. However, both groups had similar 90-day and 1-year medical complication risks including myocardial infarction, stroke, pulmonary embolism, and reoperations for periprosthetic joint infection and mechanical failure. A multivariable regression analysis was performed to identify independent factors associated with early mortality, incorporating all significant variables with p < 0.05 present in the univariate analysis. RESULTS: After accounting for significant variables in the univariate analysis such as peripheral vascular disease, end-stage renal disease, heart failure, chronic obstructive pulmonary disease, and liver fibrosis staging, Child-Pugh Class B or C classification was found to be the sole factor independently associated with increased odds of early (within 2 years) mortality in patients with HCV undergoing elective TJA (adjusted odds ratio 29 [95% confidence interval 5 to 174]; p < 0.001). The risk of early mortality in patients with Child-Pugh Class B or C was 64% (seven of 11) compared with 6% (nine of 158) in patients with Child-Pugh Class A (p < 0.001). CONCLUSION: Patients with HCV and a Child-Pugh Class B or C at the time of elective TJA had substantially increased odds of death, regardless of liver function, cirrhosis, age, Model for End-Stage Liver Disease level, HCV treatment, and viral load status. This is similar to the risk of early mortality observed in patients with chronic liver disease undergoing abdominal and cardiac surgery. Surgeons should avoid these major elective procedures in patients with Child-Pugh Class B or C whenever possible. For patients who feel their arthritic symptoms and pain are unbearable, surgeons need to be clear that the risk of death is considerably elevated. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparison of Static and Articulating Spacers After Periprosthetic Joint Infection.

INTRODUCTION: There is no consensus on whether articulating or static spacers are superior during two-stage exchange arthroplasty for periprosthetic joint infection. We aimed to compare surgical time, need for extensile exposure, surgical costs, and treatment success for articulating and static spacers. METHODS: This was a retrospective review of 229 periprosthetic joint infections treated with two-stage exchange with a minimum of one-year follow-up. For articulating and static spacers, we compared the need for extensile exposure during reimplantation and treatment failure based on an updated definition. Surgical time and costs at both stages were also compared. Subgroup analysis was performed for total knee and hip arthroplasties. RESULTS: There was no difference in the surgical time for spacer insertion; however, articulating spacers demonstrated reduced surgical time during reimplantation (181 vs. 234 minutes, P < 0.001). In multivariate analysis, there was no difference in extensile exposures (odds ratio 2.20, P = 0.081), but treatment failure was more likely for static spacers (odds ratio 2.17, P = 0.009). Overall surgical costs for two-stage exchange were similar between groups (23,782 vs. 23,766, P = 0.495). CONCLUSION: Articulating spacers demonstrated shorter surgical times and a trend toward decreased extensile exposures during reimplantation. They also had higher treatment success rates and similar surgical costs for overall two-stage exchange.

Standardized perioperative care reduces colorectal surgical site infection in children: A Western Pediatric Surgery Research Consortium multicenter analysis.

PURPOSE: Surgical site infection (SSI) remains a significant source of patient morbidity and resource utilization in children undergoing colorectal surgery. We examined the utility of a protocolized perioperative care bundle in reducing SSI in pediatric patients undergoing colorectal surgery. METHODS: We conducted a prospective cohort study of patients ≤18 years of age undergoing colorectal surgery at ten United States children's hospitals. Using a perioperative care protocol comprising eight elements, or "colon bundle", we divided patients into low (1-4 elements) or high (5-8 elements) compliance cohorts. Procedures involving colorectal repair or anastomosis with abdominal closure were included. Demographics and clinical outcomes were compared between low and high compliance cohorts. Compliance was compared with a retrospective cohort. The primary outcome was superficial SSI incidence at 30 days. RESULTS: Three hundred and thirty-six patients were included in our analysis: 138 from the low compliance cohort and 198 from the high compliance cohort. Age and gender were similar between groups. Preoperative diagnosis was similar except for more patients in the high compliance cohort having inflammatory bowel disease (18.2% versus 5.8%, p<0.01). The most common procedure performed was small bowel to colorectal anastomosis. Wound classification and procedure acuity were similar between groups. Superficial SSI at 30 days occurred less frequently among the high compliance compared to the low compliance cohort (4% versus 9.7%, p = 0.036). Median postoperative length of stay and 30-day rates of readmission, reoperation, intra-abdominal abscess and anastomotic leak requiring operation were not significantly different between groups. None of the individual colon bundle elements were independently protective against superficial SSI. CONCLUSION: Standardization of perioperative care is associated with a reduction in superficial SSI in pediatric colorectal surgery. Expansion of standardized protocols for children undergoing colorectal surgery may improve outcomes and decrease perioperative morbidity. TYPE OF STUDY: Clinical Research Paper LEVEL OF EVIDENCE: Level II.

DaBlaCa-13 Study: Oncological Outcome of Short-Term, Intensive Chemoresection With Mitomycin in Nonmuscle Invasive Bladder Cancer: Primary Outcome of a Randomized Controlled Trial.

PURPOSE: This study aimed to assess long-term follow-up after chemoresection with mitomycin (MMC), a nonsurgical treatment modality for recurrent nonmuscle invasive bladder cancer (NMIBC). At the time of recurrence, chemoresection has previously been shown to reduce the number of patients requiring a procedure (transurethral resection of bladder tumors [TURBT] or office biopsy) by more than 50%. This study investigated the number of patients requiring a procedure during initial treatment and 2-year follow-up in patients treated with short-term, intensive chemoresection with MMC compared with patients undergoing standard surgical treatment of recurrent NMIBC. METHODS: A randomized, controlled trial was conducted in two urological departments in Denmark from January 2018 to August 2021. In total, 120 patients with a history of Ta low- or high-grade NMIBC were included upon recurrence. The intervention group received intravesical MMC (40 mg/40 mL) three times a week for 2 weeks and TURBT or office biopsy only if the response was incomplete. The control group received TURBT or office biopsy and 6 weekly adjuvant instillations. The primary outcome was the number of patients undergoing a procedure within 2 years from inclusion, which was compared between groups using the chi-squared test. Recurrence-free survival was analyzed using the Kaplan-Meier method. RESULTS: Significantly fewer patients were in need of a procedure in the intervention group than in the control group: 71% (95% CI, 57 to 81) and 100% (95% CI, 94 to 100), P < .001. The 12-month recurrence-free survival was 36% (95% CI, 24 to 50) and 43% (95% CI, 30 to 56) in the intervention and control groups, respectively (P = .5). CONCLUSION: Short-term intensive chemoresection is an effective treatment strategy for recurrent NMIBC that leads to a reduced number of required procedures without compromising long-term oncological safety.

Total Joint Arthroplasty Should Not Be Delayed in Hepatitis C Patients After Successful Treatment Achieving a Sustained Viral Load.

Background: Preoperative treatment recommendations and optimal time to perform total joint arthroplasty (TJA) in patients with hepatitis C virus after treatment completion for achieving best outcomes have not been elucidated. We aim to determine (1) if undetectable viral load (UVL) prior to TJA leads to decreased postoperative complication rates, specifically periprosthetic joint infection (PJI), and (2) if delaying TJA after treatment completion has benefit in decreasing PJI. Methods: A retrospective review of all hepatitis C virus patients undergoing TJA at 3 academic tertiary care centers was conducted. A total of 270 TJAs performed from 2005 to 2019 were included, 125 with positive viral load at the time of surgery. The duration from completion of treatment regimen to TJA was recorded for the UVL cohort. The primary study outcome was PJI at 1-year follow-up. Secondary outcomes included in-hospital complications, mechanical revision TJA rates, and optimal time to TJA upon completion of treatment. Results: Patients with positive viral load at the time of TJA had longer length of stay (3.9 vs 2.9 days, P < .0001) and a higher PJI rate at 1 year postoperatively (9% vs 2%, P = .02) than UVL patients. There was no difference of in-hospital complications or revision rates for mechanical etiologies. Delaying TJA after achieving a sustained virologic response did not impact PJI rates. Conclusions: Sustained UVL prior to TJA is critical to minimize PJI irrespective of the treatment regimen utilized. Surgery can be performed with lower complication rates any time after achieving sustained virologic response. Level of Evidence: Level III, prognostic retrospective cohort study.

Imaging joint infections using D-methyl-11C-methionine PET/MRI: initial experience in humans.

PURPOSE: Non-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl-11C-methionine (D-11C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D-11C-Met in patients with suspected prosthetic joint infections. METHODS: 614.5 ± 100.2 MBq of D-11C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUVmax and SUVpeak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling. RESULTS: D-11C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D-11C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUVmax and SUVpeak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P < 0.01). Furthermore, higher distribution volume and binding potential were observed in suspected infections compared to the unaffected joints. CONCLUSION: D-11C-Met has a favorable radiation profile, minimal background uptake, and fast urinary extraction. Furthermore, D-11C-Met showed increased uptake in areas of suspected infection, making this a promising approach. Validation in larger clinical trials with a rigorous gold standard is still required.

An Enhanced Understanding of Culture-Negative Periprosthetic Joint Infection with Next-Generation Sequencing: A Multicenter Study.

BACKGROUND: The challenges of culture-negative periprosthetic joint infection (PJI) have led to the emergence of molecular methods of pathogen identification, including next-generation sequencing (NGS). While its increased sensitivity compared with traditional culture techniques is well documented, it is not fully known which organisms could be expected to be detected with use of NGS. The aim of this study was to describe the NGS profile of culture-negative PJI. METHODS: Patients undergoing revision hip or knee arthroplasty from June 2016 to August 2020 at 14 institutions were prospectively recruited. Patients meeting International Consensus Meeting (ICM) criteria for PJI were included in this study. Intraoperative samples were obtained and concurrently sent for both routine culture and NGS. Patients for whom NGS was positive and standard culture was negative were included in our analysis. RESULTS: The overall cohort included 301 patients who met the ICM criteria for PJI. Of these patients, 85 (28.2%) were culture-negative. A pathogen could be identified by NGS in 56 (65.9%) of these culture-negative patients. Seventeen species were identified as common based on a study-wide incidence threshold of 5%. NGS revealed a polymicrobial infection in 91.1% of culture-negative PJI cases, with the set of common species contributing to 82.4% of polymicrobial profiles. Escherichia coli, Cutibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus ranked highest in terms of incidence and study-wide mean relative abundance and were most frequently the dominant organism when occurring in polymicrobial infections. CONCLUSIONS: NGS provides a more comprehensive picture of the microbial profile of infection that is often missed by traditional culture. Examining the profile of PJI in a multicenter cohort using NGS, this study demonstrated that approximately two-thirds of culture-negative PJIs had identifiable opportunistically pathogenic organisms, and furthermore, the majority of infections were polymicrobial. LEVEL OF EVIDENCE: Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Simultaneous endoscopic and video-assisted retroperitoneal debridement in walled-off pancreatic necrosis using a laparoscopic access platform: Two case reports.

BACKGROUND: Infected walled-off necrosis is a potentially life-threatening complication of necrotizing pancreatitis. While some patients can be treated by drainage alone, many patients also need evacuation of the infected debris. Central necroses in relation to the pancreatic bed are easily reached via an endoscopic transluminal approach, whereas necroses that involve the paracolic gutters and the pelvis are most efficiently treated via a percutaneous approach. Large and complex necroses may need a combination of the two methods. CASE SUMMARY: Transluminal and percutaneous drainage followed by simultaneous endoscopic and modified video-assisted retroperitoneal debridement was carried out in two patients with very large (32-38 cm), infected walled-off necroses using a laparoscopic access platform. After 34 d and 86 d and a total of 9 and 14 procedures, respectively, complete regression of the walled-off necroses was achieved. The laparoscopic access platform improved both access to the cavities as well as the overview. Simultaneous transluminal and percutaneous necrosectomy are feasible with the laparoscopic access platform serving as a useful adjunctive. CONCLUSION: This approach may be necessary to control infection and achieve regression in some patients with complex collections.

Clinical outcomes following endoscopic or video-assisted retroperitoneal management of acute pancreatitis with large (>15 cm) walled-off pancreatic necrosis: Retrospective, single tertiary center cohort study.

OBJECTIVE: Acute pancreatitis with walled-off necrosis (WON) is associated with considerable morbidity and mortality. Previous studies have evaluated outcomes in WON collections of limited size, while data about large WON with long-term follow-up are lacking. We aimed to report our experience in managing large WON. METHODS: Between 2010 and 2020, consecutive patients with large (>15 cm) WON were identified from a prospectively maintained database. Patients with chronic pancreatitis or an index intervention 90 days or more from the debut of symptoms were excluded. We registered clinical and technical outcomes following minimally invasive treatment in WON >15 cm. Follow-up was a minimum of 1 year. RESULTS: Overall, 144 patients with WON >15 cm, with a median age of 60 (interquartile range [IQR] 49-69) years, were included. The median WON size was 19.2 cm (IQR 16.8-22.1). Most patients were treated with endoscopic transluminal drainage (93%). The median length of stay was 53 days (IQR 39-76) and 61 (42%) patients needed intensive care support during their hospital stay. As 143 patients (99%) were managed using endoscopic or video-assisted retroperitoneal techniques, only one (0.7%) patient needed an open necrosectomy. Procedure-related adverse events occurred in 10 (7%) patients. Overall, 24 patients (17%) died during admission, all due to multiorgan failure. The median follow-up was 35 months (IQR 15-63.5). Complete resolution was achieved in all remaining patients. CONCLUSION: Minimally invasive treatment of large WON is feasible, with a minimal need for surgery and acceptable rates of morbidity and mortality.

Short- and Long-Term Outcomes After Multimodal Treatment of Pancreatic Duct Leakage in Patients With Chronic Pancreatitis.

OBJECTIVES: In patients with chronic pancreatitis, pancreatic duct leakage is associated with a prolonged disease course and serious complications. We aimed to assess the efficacy of this multimodal treatment of pancreatic duct leakage. METHODS: In a retrospective design, patients with chronic pancreatitis, an amylase content greater than 200 U/L in either ascites or pleural fluid and treated between 2011 and 2020, were evaluated. The primary end point was treatment success. RESULTS: Twenty-seven patients (22 males, median age 60, median American Society of Anesthesiologists score 3) were included.Endoscopic retrograde pancreatography was performed in 23 patients (85%) with transpapillary stenting of the main pancreatic duct in 22 patients (96%). Pancreatic sphincterotomy and dilation of the main pancreatic duct were done in 14 patients (61%) and 17 patients (74%), respectively. Twelve patients (44%) were treated with somatostatin analogs, parenteral nutrition, and were "nil by mouth" for a median of 11 days (range, 4-34 days). Six patients (22%) had extracorporeal shock wave lithotripsy due to pancreatic duct stones. One patient (4%) was referred for surgery. All 23 patients (100%) were treated with success after a median of 21 days (range, 5-80 days). CONCLUSIONS: Multimodal treatment of pancreatic duct leakage is effective, with minimal need for surgery.

Infection and Mechanical Complications Are Risk Factors for New Diagnosis of a Mental Health Disorder After Total Joint Arthroplasty.

BACKGROUND: Prior studies have demonstrated that depression is an independent risk factor for developing a prosthetic joint infection (PJI) after total joint arthroplasty (TJA). To our knowledge, there is no literature examining whether PJI or aseptic failure increases the risk of developing a new mental health diagnosis. METHODS: PearlDiver Patient Database (Colorado Springs, CO) was used to identify 80,826 patients who underwent TJA without a pre-existing diagnosis of depression, anxiety, a stress and/or adjustment disorder, and/or current use of a selective serotonin reuptake inhibitor within the year prior to surgery. The odds of developing a new mental health issue or being prescribed a selective serotonin reuptake inhibitor within 1 year of an uncomplicated TJA was compared to those who developed PJI or mechanical failure within 90 days after TJA as well as to those who subsequently underwent revision surgery within 30 days of either complication using Fisher's exact test and Baptista-Pike. RESULTS: A total of 6474 (8%) patients were diagnosed with a new mental health issue after TJA. PJI or mechanical failure led to significantly higher odds of new diagnoses with an odds ratio of 1.67 (95% confidence interval = 1.26, 2.22) and 1.57 (1.24, 2.00), respectively. Undergoing revision surgery for PJI or mechanical failure increased the odds of developing a new mental health diagnosis to 2.10 (1.29, 3.42) and 2.24 (1.36, 3.72), respectively. There was no significant difference comparing those who developed PJI vs those who sustained mechanical complications. CONCLUSION: Patients who sustain complications after TJA are at increased odds of receiving a new mental health diagnosis, an effect further amplified if revision surgery is required.

External Validation Demonstrates Limited Clinical Utility of a Preoperative Prognostic Calculator for Periprosthetic Joint Infection.

BACKGROUND: Preoperative calculation of treatment failure risk in patients undergoing surgery for periprosthetic joint infection (PJI) is imperative to allow for medical optimization and targeted prevention. A preoperative prognostic model for PJI treatment failure was previously developed, and this study sought to externally validate the model. METHODS: A retrospective review was performed of 380 PJIs treated at two institutions. The model was used to calculate the risk of treatment failure, and receiver operating characteristic curves were generated to calculate the area under the curve (AUC) for each institution. RESULTS: When applying this model to institution 1, an AUC of 0.795 (95% confidence interval [CI]: 0.693-0.897) was found, whereas institution 2 had an AUC of 0.592 (95% CI: 0.502-0.683). Comparing all institutions in which the model had been applied to, we found institution 2 represented a significantly sicker population and different infection profile. CONCLUSION: In this cohort study, we externally validated the prior published model for institution 1. However, institution 2 had a decreased AUC using the prior model and represented a sicker and less homogenous cohort compared with institution 1. When matching for chronicity of the infection, the AUC of the model was not affected. This study highlights the impact of comorbidities and their distributions on PJI prognosis and brings to question the clinical utility of the algorithm which requires further external validation.

2020 Mark Coventry Award: Microorganism-directed oral antibiotics reduce the rate of failure due to further infection after two-stage revision hip or knee arthroplasty for chronic infection: a multicentre randomized controlled trial at a minimum of two years.

AIMS: The aim of this study was to determine if a three-month course of microorganism-directed oral antibiotics reduces the rate of failure due to further infection following two-stage revision for chronic prosthetic joint infection (PJI) of the hip and knee. METHODS: A total of 185 patients undergoing a two-stage revision in seven different centres were prospectively enrolled. Of these patients, 93 were randomized to receive microorganism-directed oral antibiotics for three months following reimplantation; 88 were randomized to receive no antibiotics, and four were withdrawn before randomization. Of the 181 randomized patients, 28 were lost to follow-up, six died before two years follow-up, and five with culture negative infections were excluded. The remaining 142 patients were followed for a mean of 3.3 years (2.0 to 7.6) with failure due to a further infection as the primary endpoint. Patients who were treated with antibiotics were also assessed for their adherence to the medication regime and for side effects to antibiotics. RESULTS: Nine of 72 patients (12.5%) who received antibiotics failed due to further infection compared with 20 of 70 patients (28.6%) who did not receive antibiotics (p = 0.012). Five patients (6.9%) in the treatment group experienced adverse effects related to the administered antibiotics severe enough to warrant discontinuation. CONCLUSION: This multicentre randomized controlled trial showed that a three-month course of microorganism-directed, oral antibiotics significantly reduced the rate of failure due to further infection following a two-stage revision of total hip or knee arthroplasty for chronic PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):3-9.