Leveraging large-scale datasets and single cell omics data to develop a polygenic score for cisplatin-induced ototoxicity.

BACKGROUND: Cisplatin-induced ototoxicity (CIO), characterized by irreversible and progressive bilateral hearing loss, is a prevalent adverse effect of cisplatin chemotherapy. Alongside clinical risk factors, genetic variants contribute to CIO and genome-wide association studies (GWAS) have highlighted the polygenicity of this adverse drug reaction. Polygenic scores (PGS), which integrate information from multiple genetic variants across the genome, offer a promising tool for the identification of individuals who are at higher risk for CIO. Integrating large-scale hearing loss GWAS data with single cell omics data holds potential to overcome limitations related to small sample sizes associated with CIO studies, enabling the creation of PGSs to predict CIO risk. RESULTS: We utilized a large-scale hearing loss GWAS and murine inner ear single nuclei RNA-sequencing (snRNA-seq) data to develop two polygenic scores: a hearing loss PGS (PGSHL) and a biologically informed PGS for CIO (PGSCIO). The PGSCIO included only variants which mapped to genes that were differentially expressed within cochlear cells that showed differential abundance in the murine snRNA-seq data post-cisplatin treatment. Evaluation of the association of these PGSs with CIO in our target CIO cohort revealed that PGSCIO demonstrated superior performance (P = 5.54 × 10- 5) relative to PGSHL (P = 2.93 × 10- 3). PGSCIO was also associated with CIO in our test cohort (P = 0.04), while the PGSHL did not show a significant association with CIO (P = 0.52). CONCLUSION: This study developed the first PGS for CIO using a large-scale hearing loss dataset and a biologically informed filter generated from cisplatin-treated murine inner ear snRNA-seq data. This innovative approach offers new avenues for developing PGSs for pharmacogenomic traits, which could contribute to the implementation of tailored therapeutic interventions. Further, our approach facilitated the identification of specific cochlear cells that may play critical roles in CIO. These novel insights will guide future research aimed at developing targeted therapeutic strategies to prevent CIO.

Perspectives of an NCI T32 Training Program Designed to Train a Diverse Workforce in Cancer Health Equity Research.

With cancer health disparities on the rise in the United States (USA), there is an increased need for novel approaches to address these challenges. One such approach that may help address these disparities is increasing diversity in the biomedical research workforce. The Cancer Health Equity and Career Development Program (CHECDP) embodies this approach by recruiting and training underrepresented minorities in cancer research to develop the skills and training needed to be competitive for independent research careers, thus diversifying the biomedical research workforce. The training model that CHECDP employs is unique with its funding through the NCI training mechanism, its strong institutional support, and its participant-driven curriculum. The curriculum includes educational, career, and leadership opportunities that are continuously evaluated for sustained impact. The program has been comprised of mostly under-represented minorities that have been propelled to independent careers with a high rate of funded career development awards. Our T32 program serves as a model of success for other programs seeking to diversify the biomedical research workforce and reduce cancer health disparities.

Selective induction of senescence in cancer cells through near-infrared light treatment via mitochondrial modulation.

Photobiomodulation, utilising non-ionising light in the visible and near-infrared (NIR) spectrum, has been suggested as a potential method for enhancing tissue repair, reducing inflammation and possibly mitigating cancer-therapy-associated side effects. NIR light is suggested to be absorbed intracellularly, mainly by chromophores within the mitochondria. This study examines the impact of 734 nm NIR light on cellular senescence. Cancer (MCF7 and A549) and non-cancer (MCF10A and IMR-90) cell populations were subjected to 63 mJ/cm2 NIR-light exposure for 6 days. Senescence levels were quantified by measuring active senescence-associated beta-galactosidase. Exposure to NIR light significantly increases senescence levels in cancer (10.0%-203.2%) but not in non-cancer cells (p > 0.05). Changes in senescence were associated with significant modulation of mitochondrial homeostasis, including increased levels of reactive oxygen species (p < 0.05) and mitochondrial membrane potential (p < 0.05) post-NIR-light treatment. These results suggest that NIR light modulates cellular chemistry, arresting the proliferation of cancer cells via senescence induction while sparing non-cancer cells.

Use of cannulated screws in the treatment of unicondylar humeral condylar fractures in dogs.

OBJECTIVE: To describe unicondylar humeral fracture (UHF) repair using cannulated transcondylar screws, report postoperative fracture reduction, healing, and complication rates. STUDY DESIGN: Retrospective. ANIMALS: A total of 49 client owned dogs with UHF. METHODS: Surgical technique and approach (i.e., open, limited open, or minimally invasive) were recorded. Articular step defect (ASD) and gap (Gap) at the humeral condylar articular surface were measured on pre- and postoperative images and reported as percentages. Fracture healing was graded on follow-up radiographs. Functional outcome was based on client questionnaire over the phone. General linear models were used to assess the impact of surgical approach on %ASD, %Gap, whereas Cox regression was used to assess prognostic factors of full fracture healing. RESULTS: A total of 49 fractures repaired with a transcondylar screw with or without an antirotational pin(s) were included. Surgical approach did not have an impact on postoperative %ASD, %Gap or development of complications. The overall complication rate was 26% (11/42), with no revision surgery necessary. Of the dogs that encountered complications, 50% required pin and/or screw removal after fracture healing. For 29 dogs with a minimum of four-month owner telephone questionnaire follow-up, 90% reported no lameness and only three reported intermittent lameness. Achieving complete fracture healing was affected by increased postoperative %ASD (p = .033). CONCLUSION: The UHFs repaired by transcondylar cannulated screws had acceptable outcomes and fracture reduction with complication rates being similar regardless of the surgical approach. CLINICAL SIGNIFICANCE: Cannulated screws can be implanted with varying surgical approaches to successfully repair UHFs with comparable clinical outcome to previous reports.

An original study assessing biomarker success rate in breast cancer recurrence biomarker research.

BACKGROUND: Breast cancer is the second most common cause of cancer mortality worldwide. Biomarker discovery has led to advances in understanding molecular phenotyping and thus has a great potential for precision management of this diverse disease. Despite increased interest in the biomarker field, only a small number of breast cancer biomarkers are known to be clinically useful. Therefore, it is very important to characterise the success rate of biomarkers in this field and study potential reasons for the deficit. We therefore aim to achieve quantitative characterisation of the biomarker translation gap by tracking the progress of prognostic biomarkers associated with breast cancer recurrence. METHODS: An electronic systematic search was conducted in Medline and Embase databases using keywords and mesh headings associated with breast cancer recurrence biomarkers (1940-2023). Abstracts were screened, and primary clinical studies involving breast cancer recurrence biomarkers were selected. Upon identification of relevant literature, we extracted the biomarker name, date of publication and journal name. All analyses were performed using IBM SPSS Statistics and GraphPad prism (La Jolla, California, USA). RESULTS: A total of 19,195 articles were identified, from which 4597 articles reported breast cancer biomarkers associated with recurrence. Upon data extraction, 2437 individual biomarkers were identified. Out of these, 23 are currently recommended for clinical use, which corresponds to only 0.94% of all discovered biomarkers. CONCLUSIONS: This study characterised for the first time the translational gap in the field of recurrence-related breast cancer biomarkers, indicating that only 0.94% of identified biomarkers were recommended for clinical use. This denotes an evident barrier in the biomarker research field and emphasises the need for a clearer route from biomarker discovery through to implementation.

Antibody and siRNA Nanocarriers to Suppress Wnt Signaling, Tumor Growth, and Lung Metastasis in Triple-Negative Breast Cancer.

The paucity of targeted therapies for triple-negative breast cancer (TNBC) causes patients with this aggressive disease to suffer a poor clinical prognosis. A promising target for therapeutic intervention is the Wnt signaling pathway, which is activated in TNBC cells when extracellular Wnt ligands bind overexpressed Frizzled7 (FZD7) transmembrane receptors. This stabilizes intracellular ß-catenin proteins that in turn promote transcription of oncogenes that drive tumor growth and metastasis. To suppress Wnt signaling in TNBC cells, we developed therapeutic nanoparticles (NPs) functionalized with FZD7 antibodies and ß-catenin small interfering RNAs (siRNAs). The antibodies enable TNBC cell-specific binding and inhibit Wnt signaling by locking FZD7 receptors in a ligand unresponsive state, while the siRNAs suppress ß-catenin through RNA interference. Compared to NPs coated with antibodies or siRNAs individually, NPs coated with both agents more potently reduce the expression of several Wnt related genes in TNBC cells, leading to greater inhibition of cell proliferation, migration, and spheroid formation. In two murine models of metastatic TNBC, the dual antibody/siRNA nanocarriers outperformed controls in terms of inhibiting tumor growth, metastasis, and recurrence. These findings demonstrate suppressing Wnt signaling at both the receptor and mRNA levels via antibody/siRNA nanocarriers is a promising approach to combat TNBC.

The James A. Rand Young Investigator's Award: Keeping It Simple: Are all Musculoskeletal Infection Society Tests Useful to Diagnose Periprosthetic Joint Infection?

BACKGROUND: Current data evaluating the clinical value and cost-effectiveness of advanced diagnostic tests for periprosthetic joint infection (PJI) diagnosis, including alpha-defensin and synovial C-reactive protein (CRP), is conflicting. This study aimed to evaluate the adequacy of preoperative and intraoperative PJI workups without utilizing these tests. METHODS: This retrospective analysis identified all patients who underwent revision total knee or hip arthroplasty (rTKA and rTHA, respectively) for suspected PJI between 2018 and 2020 and had a minimum follow-up of 2 years. Perioperative data and lab results were collected, and cases were dichotomized based on whether they met the 2018 Musculoskeletal Infection Society (MSIS) criteria for PJI. In total, 204 rTKA and 158 rTHA cases suspected of PJI were reviewed. RESULTS: Nearly 100% of the cases were categorized as "infected" for meeting the 2018 MSIS criteria without utilization of alpha-defensin or synovial CRP (rTKA: n = 193, 94.6%; rTHA: n = 156, 98.7%). Most cases were classified as PJI preoperatively by meeting either the major MSIS or the combinational minor MSIS criteria of traditional lab tests (rTKA: n = 177, 86.8%; rTHA: n = 143, 90.5%). A subset of cases was classified as PJI by meeting combinational preoperative and intraoperative MSIS criteria (rTKA: 16, 7.8%; rTHA: 13, 8.2%). Only 3.6% of all cases were considered "inconclusive" using preoperative and intraoperative data. CONCLUSIONS: Given the high rate of cases satisfying PJI criteria during preoperative workup using our available tests, the synovial alpha-defensin and synovial CRP tests may not be necessary in the routine diagnostic workup of PJI. We suggest that the primary PJI workup process should be based on a stepwise algorithmic approach with the most economical testing necessary to determine a diagnosis first. The use of advanced, commercialized, and costly biomarkers should be utilized only when traditional testing is indeterminate.

Membrane-Cloaked Nanoparticles for RNA Interference of ß-Catenin in Triple-Negative Breast Cancer.

There is an outstanding need for targeted therapies for triple-negative breast cancer (TNBC), an aggressive breast cancer subtype. Since TNBC's rapid growth and metastasis are driven by hyperactive Wnt signaling, suppressing the key-pathway mediator ß-catenin through RNA interference may improve patient outcomes. However, small interfering ribonucleic acid (siRNA) molecules require a carrier to elicit targeted gene silencing. Here, we show that 4T1 cancer cell membrane wrapped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) can deliver siRNA into TNBC cells, silence ß-catenin expression, and reduce the cells' tumorigenic qualities. Compared to unwrapped and nontargeted NPs, the cancer cell membrane wrapped nanoparticles (CCNPs) exhibit dramatically improved uptake by TNBC cells versus breast epithelial cells and greater gene silencing at mRNA and protein levels. Congruently, ß-catenin siRNA-loaded CCNPs significantly activate senescence in 2D cultured TNBC cells and reduce proliferation in 3D spheroids. This work advances the development of nucleic acid carriers for targeted RNA interference therapy.

The use of sniffer dogs for early detection of cancer: a One Health approach.

This review, which is part of the "Currents in One Health" series, describes and evaluates the current research on the utilization of trained medical scent detection, aka "sniffer" dogs for the detection of diseases, with particular emphasis on neoplasia, both within human and veterinary patients. A recent study by the authors that used sniffer dogs to detect differences in saliva from dogs diagnosed with various neoplastic processes compared with healthy control dogs is described. The concept of One Health is explored by the description of previous studies that have utilized sniffer dogs in the detection of human neoplasia (focusing on lung, prostate, and breast cancer) and veterinary neoplasia and demonstrating that further research in this arena can benefit multiple species. Future avenues of research and utilization of these findings are outlined. The companion Currents in One Health by Ungar et al, JAVMA, January 2024, addresses the use of sniffer dogs to detect human COVID-19 infections.

A One Health perspective: COVID-sniffing dogs can be effective and efficient as public health guardians.

Scent-detection dogs have been used for decades to locate drugs, explosives, toxic waste, and more. Scent dogs have been trained to alert for seizures and hypoglycemia, locate cadavers, and screen for viruses, bacterial infections, and numerous cancers. These capable dogs warrant a more significant role in public health protection. The purpose of this preliminary study was to determine whether dogs could be trained to accurately identify coronavirus disease 2019 (COVID-19) infections in humans. In previously published studies, dogs were trained to identify the scent of COVID-19 in inert samples with high sensitivity and specificity. In this study, 2 dogs were trained to identify the scent in live individuals (vs inert samples, as used in previous studies), a faster and more efficient screening method. These dogs tested out at 94% to 96% positive and negative agreement compared to PCR testing. These results recommend the use of scent dogs for public health applications and warrant investigation for other applications beyond COVID-19. This study is included as part of the Currents in One Health series. A partner article by Pellin et al, AJVR, January 2024, describes and evaluates the current research on the utilization of trained scent-detection dogs for the detection of disease within human and veterinary patients.

Indications, Clinical Outcomes, and Re-Revisions Following Revision Total Hip Arthroplasty - Does Age Matter?

BACKGROUND: Younger age is associated with increased revision incidence following primary total hip arthroplasty, though the association between age and repeat revision following revision total hip arthroplasty (rTHA) has not been described. This study aimed to describe the incidences and indications for subsequent revision (re-revision) following rTHA based on age. METHODS: Patients undergoing aseptic rTHA from 2011 to 2021 with minimum 1-year follow-up were retrospectively reviewed. Patients were stratified into 3 groups based on age at the time of index rTHA (ie, <55 years, 55 to 74 years, and >74 years). Perioperative characteristics, complications, and re-revisions were compared between groups. RESULTS: Of 694 included rTHAs, those in the >74 age group were more likely to undergo rTHA for periprosthetic fracture (P < .001) while those in the <55 age group were more likely to undergo rTHA for metallosis/taper corrosion (P = .028). Readmissions (P = .759) and emergency department visits (P = .498) within 90 days were comparable across ages. Rates of re-revision were comparable at 90 days (P = .495), 1 year (P = .443), and 2 years (P = .204). Kaplan-Meier analysis of all-cause re-revision at latest follow-up showed a nonstatistically significant trend toward increasing re-revisions in the <55 and 55 to 74 age groups. Using logistic regressions, smoking and index rTHA for instability were independently associated with re-revision, while age at index surgery was not. CONCLUSIONS: While indications for rTHA differ across age groups, rates of 2-year re-revision are statistically comparable between groups. Further studies are warranted to understand the association between age, activity, and re-revision rates after 5 years postoperatively.

Patient comfort discussing sensitive behavioral health topics.

BACKGROUND: : Following implementation of routine screening for depression in primary care, screening for other behavioral health issues is expanding. However, prior to implementing additional screening it is important to consider patient comfort answering sensitive questions related to behavioral health topics to determine screening acceptability and effectiveness. METHODS: : A self-report survey was completed by U.S. adults over the age of 18 (n = 378) using Amazon Mechanical Turk. The survey assessed comfort discussing demographics, physical health, behavioral health, oral health, and living conditions with medical providers. Comfort levels of behavioral health topics were compared to comfort discussing depression symptoms and reasons for discomfort discussing topics were also surveyed. RESULTS: : There were significant differences in comfort level discussing various behavioral health issues (F(8) = 51.70, P < .001). Participants reported being more comfortable discussing cigarette smoking and less comfortable discussing trauma, intimate partner violence (IPV) and gun ownership compared to depression. Privacy and perceived irrelevance were the most common reasons for discomfort. CONCLUSIONS: : Accurate indices of patient behavioral health are essential for patient care. However, patients may be uncomfortable discussing some topics such as trauma, IPV, and gun ownership that patients view as private and/or unrelated to their treatment. Patient comfort may increase through provider trainings that focus on communication skills training, clear administrative procedures that allow for privacy and adequate time for discussions, and community education that underscores how these issues impact physical health.

Combination cancer imaging and phototherapy mediated by membrane-wrapped nanoparticles.

Cancer is a devastating health problem with inadequate treatment options. Many conventional treatments for solid-tumor cancers lack tumor specificity, which results in low efficacy and off-target damage to healthy tissues. Nanoparticle (NP)-mediated photothermal therapy (PTT) is a promising minimally invasive treatment for solid-tumor cancers that has entered clinical trials. Traditionally, NPs used for PTT are coated with passivating agents and/or targeting ligands, but alternative coatings are being explored to enhance tumor specific delivery. In particular, cell-derived membranes have emerged as promising coatings that improve the biointerfacing of photoactive NPs, which reduces their immune recognition, prolongs their systemic circulation and increases their tumor accumulation, allowing for more effective PTT. To maximize treatment success, membrane-wrapped nanoparticles (MWNPs) that enable dual tumor imaging and PTT are being explored. These multifunctional theranostic NPs can be used to enhance tumor detection and/or ensure a sufficient quantity of NPs that have arrived in the tumor prior to laser irradiation. This review summarizes the current state-of-the-art in engineering MWNPs for combination cancer imaging and PTT and discusses considerations for the path toward clinical translation.

A Plasmodium falciparum genetic cross reveals the contributions of pfcrt and plasmepsin II/III to piperaquine drug resistance.

Piperaquine (PPQ) is widely used in combination with dihydroartemisinin (DHA) as a first-line treatment against malaria parasites. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and increased copies of plasmepsin II/III (pm2/3). We generated a cross between a Cambodia-derived multi-drug resistant KEL1/PLA1 lineage isolate (KH004) and a drug susceptible parasite isolated in Malawi (Mal31). Mal31 harbors a wild-type (3D7-like) pfcrt allele and a single copy of pm2/3, while KH004 has a chloroquine-resistant (Dd2-like) pfcrt allele with an additional G367C substitution and four copies of pm2/3. We recovered 104 unique recombinant progeny and examined a targeted set of progeny representing all possible combinations of variants at pfcrt and pm2/3 for detailed analysis of competitive fitness and a range of PPQ susceptibility phenotypes, including PPQ survival assay (PSA), area under the dose-response curve (AUC), and a limited point IC50 (LP-IC50). We find that inheritance of the KH004 pfcrt allele is required for PPQ resistance, whereas copy number variation in pm2/3 further enhances resistance but does not confer resistance in the absence of PPQ-R-associated mutations in pfcrt. Deeper investigation of genotype-phenotype relationships demonstrates that progeny clones from experimental crosses can be used to understand the relative contributions of pfcrt, pm2/3, and parasite genetic background, to a range of PPQ-related traits and confirm the critical role of the PfCRT G367C substitution in PPQ resistance.

Clinical outcomes in cats with renal carcinoma undergoing nephrectomy: A retrospective study.

Renal carcinomas (RC) are uncommonly encountered in feline medicine. Limited information regarding clinical presentation and postoperative outcomes is available. The purpose of this multi-institutional, retrospective study was to describe the presenting features and clinical outcomes of cats with RC undergoing nephrectomy. Thirty-six client-owned cats were included. Medical records from participating institutions were searched to identify cats that had a histopathologic diagnosis of RC and underwent nephrectomy from January 2001 to October 2021. The most common presenting complaints were weight loss (36.1%) and hyporexia (30.6%). Based on preoperative imaging and intraoperative findings, eight cats had suspected metastasis at the time of surgery (22.2%). Twenty-eight cats survived to discharge (77.8%). Median progression free interval (PFI) could not be determined, as only six cats developed suspected recurrence (16.7%) and seven cats developed suspected metastasis (19.4%). The all-cause median survival time (MST) was 203 days (95% confidence interval [CI]: 84, 1379 days). When cases that died prior to discharge were excluded, MST increased to 1217 days (95% CI: 127, 1641 days). One-year, two-year, and three-year survival rates were all 40.4%. Neither renal tumour histologic subtype nor the presence of preoperative azotemia, anaemia, erythrocytosis, haematuria, or suspected metastasis at diagnosis were found to influence survival. For cats surviving to discharge, prolonged survival times were possible. Further studies are necessary to elucidate other potential prognostic factors, the utility of postoperative adjuvant treatment, and to identify cats at-risk of mortality in the perioperative period.

Cancer Cell Membrane Wrapped Nanoparticles for the Delivery of a Bcl-2 Inhibitor to Triple-Negative Breast Cancer.

Overexpression of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) is correlated with poor survival outcomes in triple-negative breast cancer (TNBC), making Bcl-2 inhibition a promising strategy to treat this aggressive disease. Unfortunately, Bcl-2 inhibitors developed to date have limited clinical success against solid tumors, owing to poor bioavailability, insufficient tumor delivery, and off-target toxicity. To circumvent these problems, we loaded the Bcl-2 inhibitor ABT-737 in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) that were wrapped with phospholipid membranes derived from 4T1 murine mammary cancer cells, which mimic the growth and metastasis of human TNBC. We show that the biomimetic cancer cell membrane coating enabled the NPs to preferentially target 4T1 TNBC cells over noncancerous mammary epithelial cells in vitro and significantly increased NP accumulation in orthotopic 4T1 tumors in mice after intravenous injection by over 2-fold compared to poly(ethylene glycol)-poly(lactide-co-glycolic) (PEG-PLGA) copolymer NPs. Congruently, the ABT-737 loaded, cancer cell membrane-wrapped PLGA NPs (ABT CCNPs) induced higher levels of apoptosis in TNBC cells in vitro than ABT-737 delivered freely or in PEG-PLGA NPs. When tested in a syngeneic spontaneous metastasis model, the ABT CCNPs significantly increased apoptosis (evidenced by elevated active caspase-3 and decreased Bcl-2 staining) and decreased proliferation (denoted by reduced Ki67 staining) throughout tumors compared with saline or ABT-loaded PEG-PLGA NP controls. Moreover, the ABT CCNPs did not alter animal weight or blood composition, suggesting that the specificity afforded by the TNBC cell membrane coating mitigated the off-target adverse effects typically associated with ABT-737. Despite these promising results, the low dose of ABT CCNPs administered only modestly reduced primary tumor growth and metastatic nodule formation in the lungs relative to controls. We posit that increasing the dose of ABT CCNPs, altering the treatment schedule, or encapsulating a more potent Bcl-2 inhibitor may yield more robust effects on tumor growth and metastasis. With further development, drug-loaded biomimetic NPs may safely treat solid tumors such as TNBC that are characterized by Bcl-2 overexpression.

Axial twisting within an ending loop of a continuous suture pattern affects the biomechanical properties of knots of certain suture sizes and types.

OBJECTIVE: To determine whether axial twisting within an ending loop negatively impacts maximum load to failure and failure mode of suture knots. SAMPLES: 525 knots (15 samples each of 7 different suture types/sizes tested in 5 knot-twist configurations each). PROCEDURES: Each suture type (polydioxanone [PDO], Monoderm [polyglecaprone 25], and Nylon) and size (1, 0, 2-0, 3-0) were used to create a starting square knot, and each of the following ending square knot configurations: 0 twists, 1 twist, 4 twists, and 10 twists. Each suture was tested for failure using a universal testing machine (Instron, Instron Corp) with a 100 kg load cell at a speed of 100 mm/min. Each suture and knot was evaluated for a mode of failure using gross evaluation of the knots and video footage recorded during testing. Maximum load at failure (P-value set at .005) and failure mode (p-value set at 0.003) were recorded for each group. RESULTS: Maximum load at failure was decreased in knots tied within ending loops containing more twists for some types and sizes of the suture. With 4 twists, 0-PDO, 1 PDO, and 2-0 Nylon was more likely to fail at the knot than knots with 0 twists. All sutures containing 10 twists, except 3-0 Monoderm, were more likely to fail at the knot than knots with 0 twists. CLINICAL RELEVANCE: The number of twists within the ending loop may not increase the risk of failure at the knot; however, it can decrease the maximum load to failure at a knot, particularly as the suture size increases.

Impact of time to revision total knee arthroplasty on outcomes following aseptic failure.

INTRODUCTION: Prior studies have demonstrated an association between time to revision total knee arthroplasty (rTKA) and indication; however, the impact of early versus late revision on post-operative outcomes has not been reported. MATERIALS AND METHODS: A retrospective, observational study examined patients who underwent unilateral, aseptic rTKA at an academic orthopedic hospital between 6/2011 and 4/2020 with > 1-year of follow-up. Patients were early revisions if they were revised within 2 years of primary TKA (pTKA) or late revisions if revised after greater than 2 years. Patient demographics, surgical factors, and post-operative outcomes were compared. RESULTS: 470 rTKA were included (199 early, 271 late). Early rTKA patients were younger by 2.5 years (p = 0.002). The predominant indications for early rTKA were instability (28.6%) and arthrofibrosis/stiffness (26.6%), and the predominant indications for late rTKA were aseptic loosening (45.8%) and instability (26.2%; p < 0.001). Late rTKA had longer operative times (119.20 ± 51.94 vs. 103.93 ± 44.66 min; p < 0.001). There were no differences in rTKA type, disposition, hospital length of stay, all-cause 90-day emergency department visits and readmissions, reoperations, and number of re-revisions. CONCLUSIONS: Aseptic rTKA performed before 2 years had different indications but demonstrated similar outcomes to those performed later. Early revisions had shorter surgical times, which could be attributed to differences in rTKA indication. LEVEL OF EVIDENCE: III, retrospective observational analysis.

Outcomes of medicaid patients undergoing TJA with previous positive urine toxicology screens.

INTRODUCTION: Previous studies have demonstrated that patients with positive preoperative urine toxicology (utox) screens prior to total joint arthroplasty (TJA) have higher readmission rates, greater complication rates, and longer hospital stays compared to patients with negative screens. The aim of this study was to investigate the effect of postponing surgery for patients with positive preoperative utox in the Medicaid population. METHODS: This retrospective, observational study reviewed the Medicaid ambulatory database at a large, academic orthopedic specialty hospital for patients with a utox screen prior to TJA from 2012 to 2020. Patients were categorized into three groups: (1) controls with negative preoperative utox or a utox consistent with prescription medications (Utox-) with TJA completed as scheduled; (2) positive preoperative utox with TJA rescheduled and surgery completed on a later date (R-utox+); (3) positive preoperative utox inconsistent with prescription medications with TJA completed as scheduled (S-utox+). Primary outcomes included mortality, 90-day readmission rate, complication rate, and length of stay. RESULTS: Of the 300 records reviewed, 185 did not meet inclusion criteria. The remaining 115 patients included 80 (69.6%) Utox-, 5 (6.3%) R-utox+, and 30 (37.5%) S-utox+. Mean follow-up time was 49.6 months. Hospital stays trended longer in the Utox- group (3.7 ± 2.0 days vs. 3.1 ± 1.6 S-utox+ vs.2.5 ± 0.4 R-utox+, p = 0.20). Compared to the R-utox+group, the S-utox+ group trended toward lower home discharge rates (p = 0.20), higher in-hospital complication rates (p = 0.85), and more all-cause 90-day emergency department visits (p = 0.57). There were no differences in postoperative opioid utilization between groups (p = 0.319). Duration of postoperative narcotic use trended toward being longer in the Utox- patients (820.7 ± 1073.8 days vs. 684.6 ± 1491.8 S-utox+ vs. 585.1 ± 948.3 R-utox+, p = 0.585). Surgical time (p = 0.045) and revision rates (p = 0.72) trended toward being higher in the S-utox+ group. CONCLUSIONS: Medicaid patients with positive preoperative utox who had surgeries postponed trended towards shorter hospital stays and greater home discharge rates. Larger studies should be conducted to analyze the implications of a positive preoperative utox on risk profiles and outcomes following TJA in the Medicaid population. Study design Retrospective cohort study.

Trained dogs can accurately discriminate between scents of saliva samples from dogs with cancer versus healthy controls.

OBJECTIVE: To determine whether dogs can be trained to utilize olfaction to differentiate between saliva samples from dogs with cancer and those from healthy control dogs. SAMPLE: Canine patient saliva samples were collected (October 2020 to July 2022) from 139 dogs diagnosed with malignant tumors and from 161 healthy dogs (control samples) for use during training and testing of the dog detection team. Samples from canine patients were collected prior to treatment with radiation therapy or chemotherapy. PROCEDURES: Six pet dogs (mean ± SD age, 5.4 ± 1.9 years) were trained for odor discrimination between healthy control and malignant tumor samples. Training of the dogs, using a reward-based positive reinforcement method, took place 1 to 3 times per week for a period of 6 months (January to June 2022). After training was complete, a subset of samples not utilized during the training sessions were selected for use during odor discrimination testing of the dog team. RESULTS: The trained dogs could accurately distinguish between samples from cancer patients versus control dogs with a mean sensitivity of 90% and mean specificity of 98%, and with mean positive and negative predictive values of 95%. CLINICAL RELEVANCE: This study serves as preliminary evidence that dogs can be trained to detect differences in scent between saliva samples from cancer and normal patients. Further studies should expand upon these results with a larger sample, varied tumor types, use of non-cancer diseases as controls, and exploration of this technique in feline patients.