Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a and mobile phone microscopy.

The December 2019 outbreak of a novel respiratory virus, SARS-CoV-2, has become an ongoing global pandemic due in part to the challenge of identifying symptomatic, asymptomatic, and pre-symptomatic carriers of the virus. CRISPR diagnostics can augment gold-standard PCR-based testing if they can be made rapid, portable, and accurate. Here, we report the development of an amplification-free CRISPR-Cas13a assay for direct detection of SARS-CoV-2 from nasal swab RNA that can be read with a mobile phone microscope. The assay achieved ∼100 copies/µL sensitivity in under 30 min of measurement time and accurately detected pre-extracted RNA from a set of positive clinical samples in under 5 min. We combined crRNAs targeting SARS-CoV-2 RNA to improve sensitivity and specificity and directly quantified viral load using enzyme kinetics. Integrated with a reader device based on a mobile phone, this assay has the potential to enable rapid, low-cost, point-of-care screening for SARS-CoV-2.

Programming multicellular assembly with synthetic cell adhesion molecules.

Cell adhesion molecules are ubiquitous in multicellular organisms, specifying precise cell-cell interactions in processes as diverse as tissue development, immune cell trafficking and the wiring of the nervous system1-4. Here we show that a wide array of synthetic cell adhesion molecules can be generated by combining orthogonal extracellular interactions with intracellular domains from native adhesion molecules, such as cadherins and integrins. The resulting molecules yield customized cell-cell interactions with adhesion properties that are similar to native interactions. The identity of the intracellular domain of the synthetic cell adhesion molecules specifies interface morphology and mechanics, whereas diverse homotypic or heterotypic extracellular interaction domains independently specify the connectivity between cells. This toolkit of orthogonal adhesion molecules enables the rationally programmed assembly of multicellular architectures, as well as systematic remodelling of native tissues. The modularity of synthetic cell adhesion molecules provides fundamental insights into how distinct classes of cell-cell interfaces may have evolved. Overall, these tools offer powerful abilities for cell and tissue engineering and for systematically studying multicellular organization.

Toward telomere-to-telomere cat genomes for precision medicine and conservation biology.

Genomic data from species of the cat family Felidae promise to stimulate veterinary and human medical advances, and clarify the coherence of genome organization. We describe how interspecies hybrids have been instrumental in the genetic analysis of cats, from the first genetic maps to propelling cat genomes toward the T2T standard set by the human genome project. Genotype-to-phenotype mapping in cat models has revealed dozens of health-related genetic variants, the molecular basis for mammalian pigmentation and patterning, and species-specific adaptations. Improved genomic surveillance of natural and captive populations across the cat family tree will increase our understanding of the genetic architecture of traits, population dynamics, and guide a future of genome-enabled biodiversity conservation.

Higher abatacept exposure after transplant decreases acute GVHD risk without increasing adverse events.

In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease (aGVHD) after unrelated-donor hematopoietic cell transplant (HCT), leading to US Food and Drug Administration approval. Here, we performed a determination of abatacept pharmacokinetics (PK), which enabled an examination of how abatacept exposure-response relationships affected clinical outcomes. We performed a population PK analysis of IV abatacept using nonlinear mixed-effect modeling and assessed the association between abatacept exposure and key transplant outcomes. We tested the association between the trough after dose 1 (Ctrough_1) and grade (GR) 2 or 4 aGVHD (GR2-4 aGVHD) through day +100. An optimal Ctrough_1 threshold was identified via recursive partitioning and classification tree analysis. This demonstrated that abatacept PK was characterized by a 2-compartment model with first-order elimination. The ABA2 dosing regimen was based on previous work targeting a steady-state abatacept trough of 10 µg/mL. However, a higher Ctrough_1 (≥39 µg/mL, attained in ∼60% of patients on ABA2) was associated with a favorable GR2-4 aGVHD risk (hazard ratio, 0.35; 95% confidence interval, 0.19-0.65; P < .001), with a Ctrough_1 <39 µg/mL associated with GR2-4 aGVHD risk indistinguishable from placebo (P = .37). Importantly, no significant association was found between Ctrough_1 and key safety indicators, including relapse, and cytomegalovirus or Epstein-Barr virus viremia. These data demonstrate that a higher abatacept Ctrough_1 (≥39 µg/mL) was associated with a favorable GR2-4 aGVHD risk, without any observed exposure-toxicity relationships. This trial was registered at www.clinicaltrials.gov as #NCT01743131.

Burnout in Urological Education: An In-Depth Study of Residents and Fellows in the 2021 AUA Census.

PURPOSE: Our goal was to explore the current trends in burnout, career choice regret, and well-being needs among urology residents and fellows, with specific emphasis on identifying key factors associated with burnout. MATERIALS AND METHODS: The AUA Workforce Workgroup collaborated with the AUA Data Team to analyze data from the 2021 AUA Census, comprising a total of 243 residents and fellows. Key demographics, benefits and resources, career choice and debt, and burnout levels were analyzed, focusing on variables like gender, PGY (postgraduate year) level, debt burden, and personal health appointments. RESULTS: Overall, 48% of residents and 33% of fellows met criteria for professional burnout, with a higher incidence among PGY-2 residents (70%). Depersonalization was particularly notable, with 74% of residents reporting medium to high levels. Burnout was significantly associated with difficulty attending personal health appointments (52% vs 34%) and lack of access to on-call rooms (54% vs 36%). In contrast, having children during residency was associated with lower burnout levels (30.8% vs 49.1%). Meal plans were ranked as the most desired benefit (32%), followed by ability to attend health appointments during work hours (17%) and paid family leave (16%). Educational debt over $150,000 was carried by 53% of residents and 48% of fellows. Interestingly, burnout rates showed no statistically significant difference in response rates across genders, relationship status, amount of educational debt, presence of paid maternity or paternity leave, and type of childcare arrangements. CONCLUSIONS: Burnout remains a significant issue among urology trainees, with a complex interplay of factors like lack of personal time and provision of call rooms. The alarming rates of depersonalization and exhaustion highlight the urgency of implementing targeted interventions. Enhanced support systems, improved access to health care appointments, provision of call rooms, and debt management programs are recommended to alleviate the growing problem of professional burnout in the field of urology.

Metabolomic identification of α-ketoglutaric acid elevation in pediatric chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) is the most common cause for non-relapse mortality postallogeneic hematopoietic stem cell transplant (HSCT). However, there are no well-defined biomarkers for cGVHD or late acute GVHD (aGVHD). This study is a longitudinal evaluation of metabolomic patterns of cGVHD and late aGVHD in pediatric HSCT recipients. A quantitative analysis of plasma metabolites was performed on 222 evaluable pediatric subjects from the ABLE/PBMTC1202 study. We performed a risk-assignment analysis at day + 100 (D100) on subjects who later developed either cGVHD or late aGVHD after day 114 to non-cGVHD controls. A second analysis at diagnosis used fixed and mixed multiple regression to compare cGVHD at onset to time-matched non-cGVHD controls. A metabolomic biomarker was considered biologically relevant only if it met all 3 selection criteria: (1) P ≤ .05; (2) effect ratio of ≥1.3 or ≤0.75; and (3) receiver operator characteristic AUC ≥0.60. We found a consistent elevation in plasma α-ketoglutaric acid before (D100) and at the onset of cGVHD, not impacted by cGVHD severity, pubertal status, or previous aGVHD. In addition, late aGVHD had a unique metabolomic pattern at D100 compared with cGVHD. Additional metabolomic correlation patterns were seen with the clinical presentation of pulmonary, de novo, and progressive cGVHD. α-ketoglutaric acid emerged as the single most significant metabolite associated with cGVHD, both in the D100 risk-assignment and later diagnostic onset analysis. These distinctive metabolic patterns may lead to improved subclassification of cGVHD. Future validation of these exploratory results is needed. This trial was registered at www.clinicaltrials.gov as #NCT02067832.

Impact of rabbit anti-thymocyte globulin (ATG) exposure on outcomes after ex vivo T-cell-depleted hematopoietic cell transplantation in pediatric and young adult patients.

BACKGROUND AIMS: Traditional weight-based dosing of rabbit anti-thymocyte globulin (rATG) used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host disease (GVHD) and graft rejection leads to variable exposures. High exposures induce delayed CD4+immune reconstitution (CD4+IR) and greater mortality. We sought to determine the impact of rATG exposure in children and young adults receiving various types of EX-VIVO T-cell-depleted (EX-VIVO-TCD) HCT. METHODS: Patients receiving their first EX-VIVO-TCD HCT (CliniMACS CD34+, Isolex or soybean lectin agglutination), with removal of residual T cells by E-rosette depletion (E-) between 2008 and 2018 at Memorial Sloan Kettering Cancer Center were retrospectively analyzed. rATG exposure post-HCT was estimated (AU*d/L) using a validated population pharmacokinetic model. Previously defined rATG-exposures, <30, 30-55, ≥55 AU*d/L, were related with outcomes of interest. Cox proportional hazard and cause-specific models were used for analyses. RESULTS: In total, 180 patients (median age 11 years; range 0.1-44 years) were included, malignant 124 (69%) and nonmalignant 56 (31%). Median post-HCT rATG exposure was 32 (0-104) AU*d/L. Exposure <30 AU*d/L was associated with a 3-fold greater probability of CD4+IR (P < 0.001); 2- to 4-fold lower risk of death (P = 0.002); and 3- to 4-fold lower risk of non-relapse mortality (NRM) (P = 0.02). Cumulative incidence of NRM was 8-fold lower in patients who attained CD4+IR compared with those who did not (P < 0.0001). There was no relation between rATG exposure and aGVHD (P = 0.33) or relapse (P = 0.23). Effect of rATG exposure on outcomes was similar in three EX-VIVO-TCD methods. CONCLUSIONS: Individualizing rATG dosing to target a low rATG exposure post-HCT while maintaining total cumulative exposure may better predict CD4+IR, reduce NRM and increase overall survival, independent of the EX-VIVO-TCD method.

Two novel assays demonstrate persistent daratumumab exposure in a pediatric patient with delayed engraftment following allogeneic hematopoietic stem cell transplantation.

BACKGROUND AIMS: Daratumumab, a human IgG monoclonal antibody targeting CD38, is a promising treatment for pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL). We describe a case of delayed engraftment following a mismatched, unrelated donor hematopoietic stem cell transplant (HSCT) in a 14-year-old female with relapsed T-ALL, treated with daratumumab and chemotherapy. By Day 28 post-HSCT, the patient had no neutrophil engraftment but full donor myeloid chimerism. METHODS: We developed two novel, semi-quantitative, antibody-based assays to measure the patient's bound and plasma daratumumab levels to determine if prolonged drug exposure may have contributed to her slow engraftment. RESULTS: Daratumumab levels were significantly elevated more than 30 days after the patient's final infusion, and levels inversely correlated with her white blood cell counts. To clear daratumumab, the patient underwent several rounds of plasmapheresis and subsequently engrafted. CONCLUSIONS: This is the first report of both delayed daratumumab clearance and delayed stem cell engraftment following daratumumab treatment in a pediatric patient. Further investigation is needed to elucidate the optimal dosing of daratumumab for treatment of acute leukemias in pediatric populations as well as daratumumab's potential effects on hematopoietic stem cells and stem cell engraftment following allogenic HSCT.

Open Access Publication in Total Knee Arthroplasty Is Associated With Increased Social Media Attention, but Is Not Associated With Increased Citations.

BACKGROUND: Open access (OA) publication is growing in total joint arthroplasty literature. While OA manuscripts are free to view, these publications require a fee from authors. This study aimed to compare social media attention and citation rates between OA and non-OA publications in the total knee arthroplasty (TKA) literature. METHODS: There were 9,606 publications included, with 4,669 (48.61%) as OA articles. The TKA articles were identified from 2016 to 2022. Articles were grouped as OA or non-OA and Altmetric Attention Score (AAS), a weighted count of social media attention, and the Mendeley readership were analyzed using negative binomial regressions while adjusting for days since publication. RESULTS: The OA articles had greater mean AAS (13.45 versus 8.42, P = .012) and Mendeley readership (43.91 versus 36.72, P < .001). OA was not an independent predictor of number of citations when compared to non-OA articles (13.98 versus 13.63, P = .914). Subgroup analysis of studies in the top 10 arthroplasty journals showed OA was not an independent predictor of AAS (13.51 versus 9.53, P = .084) or number of citations (19.51 versus 18.74, P = .495) but was an independent predictor of Mendeley readership (49.05 versus 40.25, P < .003). CONCLUSION: The OA publications in the TKA literature were associated with increased social media attention, but not overall citations. This association was not observed among the top 10 journals. Authors may use these results to weigh the relative importance of readership, citations, and online engagement to the cost of OA publication.

Over the Past Decade, Preoperative Anemia Has Become a Greater Predictor of Transfusions After Total Knee Arthroplasty.

BACKGROUND: With advancements in perioperative blood management and the use of tranexamic acid, the rate of transfusions after total knee arthroplasty (TKA) has substantially decreased. As these principles are refined, other modifiable risk factors, such as preoperative anemia, may play an increasingly important role in transfusion risk for patients undergoing TKA. METHODS: A multicenter, national database was utilized to identify patients undergoing TKA from 2010 to 2021. Anemia was defined by World Health Organization definitions as < 12 g/dL for women and < 13 g/dL for men. A predictive model was created using backwards elimination logistic regression to predict transfusion risk, controlling for demographic and medical covariates. The coefficient of anemia was then analyzed for each year. The trend over time was fitted with a best-fit linear regression equation. RESULTS: There were 509,117 patients who underwent TKA, and had a mean age of 67 years (range, 18 to 89). There were 57,716 (11%) patients who were anemic preoperatively, and 15,426 (3%) of patients required a transfusion. Rate of transfusion decreased from 10.6% in 2010 to 0.6% in 2021. The odds ratio associated with anemia as a predictor of transfusion increased from 3.1 (95% confidence interval: 2.1 to 4.6) in 2010 to 14.0 (95% confidence interval: 8.9 to 24) in 2021. CONCLUSIONS: The results of this study demonstrate that the importance of preoperative anemia as a predictor of transfusion has increased over the past decade as rates of transfusion have decreased. As perioperative blood management protocols improve, preoperative anemia should be considered an important focus of intervention to reduce the risk of transfusion prior to TKA. LEVEL OF EVIDENCE: III.

Publishing on Topical Subjects in Total Joint Arthroplasty Is Associated With Increased Social Media Attention.

BACKGROUND: Social media platforms are often used for research dissemination and collaboration. Given the increased prevalence of online-only publications, understanding what drives research dissemination is important. Here, we analyzed factors associated with increased social media attention among peer-reviewed publications in total knee arthroplasty, total hip arthroplasty, and unicompartmental knee arthroplasty. METHODS: We analyzed publications about total knee arthroplasty, total hip arthroplasty, or unicompartmental knee arthroplasty from 2010 to 2022 using a national database. We analyzed a weighted count of social media mentions, using negative binomial regressions adjusting for days since publication. Publications on "hot topics" in arthroplasty were examined including navigation/robotics, COVID-19, race/ethnicity, body mass index, and reimbursement. There were 9,542 publications included, 4,216 (44%) were open access (OA), 338 (3.5%) included navigation, 32 (0.34%) discussed race/ethnicity, 20 (0.2%) discussed COVID-19, 3,840 (40%) were randomized studies, 30 (0.3%) discussed reimbursement, and 2,867 (30%) were in top-10 orthopaedic journals. RESULTS: Factors associated with higher weighted score included studies about COVID-19 (50 versus 6.0, P < .001), race/ethnicity (15.8 versus 6.0, P < .001), OA status (6.3 versus 5.8, P = .001), and randomized studies (6.5 versus 5.7, P < .001). Studies from top-10 journals had a lower score (5.8 versus 6.2, P = .025), as did studies about body mass index (3.4 versus 6.1, P = .001). Studies about navigation and reimbursement did not have significantly different scores. CONCLUSIONS: Studies on COVID-19, race/ethnicity, randomized studies, and OA publication were associated with increased social media while those in top-10 orthopaedic journals had lower scores. LEVEL OF EVIDENCE: Level IV, Prognostic Study.

Osteoporosis and Total Knee Arthroplasty: Higher 5-Year Implant-Related Complications.

BACKGROUND: The risk of revision surgery in patients who have osteoporosis after total knee arthroplasty (TKA) is understudied. Our aim was to compare the 5-year cumulative risk of revision surgery after TKA in patients who have preoperative osteoporosis. METHODS: A national administrative claims database was queried for patients undergoing primary TKA from 2010 to 2021. There were 418,054 patients included, and 41,760 (10%) had osteoporosis. The 5-year incidence of revision surgery was examined for all-causes, periprosthetic fracture (PPF), aseptic loosening, and periprosthetic joint infection (PJI). A multivariable analysis was conducted using Cox proportional hazards models. Hazards ratios (HRs) were reported with 95% confidence intervals (CIs). RESULTS: The 5-year rate of all-cause revision surgery was higher for patients who had osteoporosis (HR 1.1, 95% CI: 1.0 to 1.2), however, the highest risk of revision surgery was seen for PPF (HR 1.8, 95% CI: 1.6 to 2.1). Patients who had osteoporosis also had elevated risk of revision surgery for PJI (HR 1.2, 95% CI: 1.1 to 1.3) and aseptic loosening (HR 1.2, 95% CI: 1.1 to 1.3). Osteoporosis was independently associated with PJI and aseptic loosening at a higher rate in obese patients. CONCLUSIONS: In unadjusted survival analysis, those who had osteoporosis have a marginally lower risk of all-cause revision surgery. However, after controlling for age, sex and comorbidities, patients who had osteoporosis have a nearly 2-fold increased risk of 5-year revision for PPF after TKA, and mildly increased risk of revision for all causes, aseptic loosening, and PJI. Obesity may also modulate this association. Future studies should determine the extent to which treatment of osteoporosis modifies these postoperative outcomes.

Risk Factors Associated With Quadriceps Tendon Extensor Mechanism Disruption Following Total Knee Arthroplasty.

BACKGROUND: Quadriceps tendon extensor mechanism disruption is an infrequent but devastating complication after total knee arthroplasty (TKA). Our knowledge of specific risk factors for this complication is limited by the current literature. Thus, this study aimed to identify potential risk factors for quadriceps tendon extensor mechanism disruption following TKA. METHODS: A retrospective cohort analysis was performed using the PearlDiver Administrative Claims Database. Patients undergoing TKA without a prior history of quadriceps tendon extensor mechanism disruption were identified. Quadriceps tendon extensor mechanism disruption included rupture of the quadriceps tendon, patellar tendon, or fracture of the patella. Patients who had a minimum of 5 years of follow-up after TKA were included. A total of 126,819 patients were included. Among them, 517 cases of quadriceps tendon extensor mechanism disruption occurred (incidence 0.41%). Hypothesized risk factors were compared between those who had postoperative quadriceps tendon extensor mechanism disruption and those who did not. RESULTS: On multivariate analysis, increased Charlson Comorbidity Index (odds ratio (OR): 1.10, 95% confidence interval (CI) [1.07 to 1.13]; P < .001), obesity (OR: 1.49, 95% CI [1.24 to 1.79]; P < .001), and fluoroquinolone use any time after TKA (OR: 1.24, 95% CI [1.01 to 1.52]; P = .036) were significantly associated with quadriceps tendon extensor mechanism disruption. CONCLUSIONS: Our study identified the incidence of quadriceps tendon extensor mechanism disruption following TKA as 0.41%. Identified risk factors for quadriceps tendon extensor mechanism disruption after TKA include an increased Charlson Comorbidity Index, obesity, and use of fluoroquinolones postoperatively.

Can You Pay Your Way to Readership? Free to Publish Open Access Formats Receive Greater Readership and Citations Than Paid Open Access Formats in Total Knee Arthroplasty Literature.

BACKGROUND: As publishing with open access is becoming increasingly popular within orthopaedics, understanding the types of publishing options available and what each may deliver is critically important. Hybrid articles require a high article processing charge. Open journal articles have a lower fee, while closed license articles are freely accessible at no charge. Open repository articles are peer-reviewed manuscripts posted freely online. The purpose of this study was to determine the relationship between article type and resulting citations, social media attention, and readership in total knee arthroplasty (TKA) literature. METHODS: Open access TKA journal articles published since 2016 were found using the Altmetric Explorer Database. Data gathered included the Altmetric Attention Score (attention), Mendeley Readership Score (readership), and citations per article. Articles were grouped by type: open journal, hybrid, closed license, and open repository. Results were analyzed using descriptive statistics and Tukey's analysis; α = 0.05. RESULTS: A total of 9,606 publications were included. The open repository had the greatest mean citations (14.40), while open journal (9.55) had fewer than all other categories (P < .001). Hybrid had the greatest mean attention (10.35), and open journal (6.16) had a lower mean attention than all other categories (P ≤ .002). Open repository had the greatest mean readership (44.68), and open journal (34.00) had a lower mean readership than all other categories (P ≤ .012). The mean publication fee for paid publication options was $1,792 United States dollars. CONCLUSIONS: In open access TKA literature, free-to-publish open repositories had the greatest mean citations and readership. Free publication options, open repositories and closed licenses, had greater readership compared to paid publication options.

Osteoporotic Patients Undergoing Total Hip Arthroplasty Have a Similar 5-Year Cumulative Incidence Rate of Periprosthetic Fracture Regardless of Cemented Versus Cementless Femoral Stem Fixation.

BACKGROUND: In osteoporotic patients, surgeons may utilize cemented femoral fixation to minimize risk of fracture. The purpose of this study was to compare 5-year implant survivability in patients who have osteoporosis who underwent elective total hip arthroplasty (THA) with cementless versus cemented fixation. METHODS: A retrospective analysis of patients who have osteoporosis undergoing THA with either cemented or cementless femoral fixation was conducted using a national administrative claims database. Of the 18,431 identified THA patients who have osteoporosis, 15,867 (86.1%) underwent cementless fixation. The primary outcome was a comparison of the 5-year cumulative incidences of aseptic revision, mechanical loosening, and periprosthetic fracture (PPF). Kaplan-Meier and Multivariable Cox Proportional Hazard Ratio analyses were used, controlling for femoral fixation method, age, sex, a comorbidity scale, use of osteoporosis medication, and important comorbidity. RESULTS: There was no difference in aseptic revision (Hazard's Ratio (HR): 1.13; 95% Confidence Interval (CI): 0.79 to 1.62; P value: .500) and PPF (HR: 0.96; 95% CI: 0.64 to 1.44; P value: .858) within 5 years of THA between fixation cohorts. However, patients who had cemented fixation were more likely to suffer mechanical loosening with 5 years post-THA (HR: 1.79; 95% CI: 1.17 to 2.71; P-value: .007). CONCLUSIONS: We found a similar 5-year rate of PPF when comparing patients who underwent cementless versus cemented femoral fixation for elective THA regardless of preoperative diagnosis of osteoporosis. While existing registry data support the use of cemented fixation in elderly patients, a more thorough understanding of the interplay between age, osteoporosis, and implant design is needed to delineate in whom cemented fixation is most warranted for PPF prevention.

The Definition of Anemia Matters When Using Preoperative Hemoglobin as a Screening Tool Prior to Total Hip and Knee Arthroplasty.

BACKGROUND: Preoperative anemia is common in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). Several definitions of anemia have been described, with no clear consensus on the optimal one for preoperative screening. We hypothesized that depending on the definition used preoperatively, the proportion of anemic patients identified who would require a postoperative allogeneic blood transfusion would vary significantly. METHODS: A total of 681,141 patients were identified in a national database who underwent either THA or TKA. Preoperative anemia was classified according to the World Health Organization (WHO) definition, Cleveland Clinic (CC) definition, or race, age, and sex-specific definition described by Beutler et al in 2006. The optimal preoperative (OP) hemoglobin thresholds to predict perioperative transfusions were also calculated using receiver operating characteristic curves. RESULTS: When using the WHO definition, 18% of anemic patients required a transfusion versus 14% (OP definition), 12% (CC definition), and 16% (Beutler definition). Similarly, 0.69% of anemic patients sustained a periprosthetic joint infection within 30 days using the WHO definition versus 0.59% (OP definition), 0.60% (CC definition), or 0.66% (Beutler definition). Using the WHO definition, 5.3% of patients would have sustained a major complication versus 4.5% (OP definition), 4.4% (CC definition), and 5.0% (Beutler definition). CONCLUSIONS: Variation in the definition of anemia for preoperative screening in THA and TKA results in substantial differences in discriminative ability to predict perioperative transfusions. The WHO definition identified the largest proportion of patients who ultimately received a perioperative transfusion.

The Creation of Data-Driven Preoperative Hemoglobin A1c and Same-Day Glucose Strata to Stratify Complication Risk Following Total Hip Arthroplasty.

BACKGROUND: This study identifies data-driven strata for preoperative Hemoglobin A1c (HbA1c) and same-day glucose levels that maximize differences in the likelihood of complications following total hip arthroplasty (THA). METHODS: Patients who underwent THA from 2013 to 2022 were identified using a national database. In total, 18,728 patients were identified with a mean age of 67 years (range, 18 to 80). Stratum specific likelihood ratio (SSLR) analysis determined separate strata for HbA1c and same-day glucose levels that minimized the likelihood of 90-day complications following THA. Each stratum was propensity-score matched based on age, sex, hypertension, heart failure, chronic obstructive pulmonary disease, and obesity to the lowest respective stratum. The risk ratio (RR) with respect to the lowest matched stratum was observed. RESULTS: Our SSLR analysis identified 3 data-driven HbA1c strata (4.5 to 5.9, 6.0 to 6.9, and 7.0+) and two same-day glucose strata (60 to 189 and 190+) that predicted 90-day major complications. For HbA1c, when compared to the lowest strata (4.5 to 5.9), the risk of 90-day major complications sequentially increased as the HbA1c strata increased: 6.0 to 6.9 (RR: 1.21; P = .041), 7+ (RR: 1.82; P < .001). For same-day glucose, when compared to the matched lowest strata (60 to 189), the risk of 90-day major complications was higher for the 190+ strata (RR: 1.5; P < .001). CONCLUSIONS: Our results support the use of multiple HbA1c strata that can be incorporated into preoperative risk-stratification models. Additionally, we identified a single cut-off level of 190 as a maximum target blood glucose level perioperatively.

10-Year Cumulative Incidence and Indications for Revision Total Joint Arthroplasty for Patients Who Have Ehlers-Danlos syndrome.

BACKGROUND: Long-term complications following total joint arthroplasty are not well established for patients who have Ehlers-Danlos syndrome (EDS), a group of connective tissue disorders. This study compared 10-year incidence of revision surgery after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in patients who have and do not have EDS. METHODS: A retrospective cohort analysis was conducted using a national all-payer claims database from 2010 to 2021 to identify patients who underwent primary TKA or THA. Patients who had and did not have EDS were propensity-score matched by age, sex, and a comorbidity index. Kaplan-Meier analyses and Cox proportional hazard models were utilized to determine the cumulative incidence and risks of revision experienced by patients who have and do not have EDS. RESULTS: The EDS patients who underwent TKA had a higher risk of all-cause revision (hazard ratio (HR): 1.50, 95% confidence interval (95% CI): 1.09 to 2.07, P < 0.014) and risk of revision due to instability (HR = 2.49, 95% CI: 1.37 to 4.52, P < 0.003). The EDS patients who underwent THA had a higher risk of all-cause revision (HR = 2.32, 95% CI: 1.47 to 3.65, P < 0.001), revision due to instability (HR = 4.26, 95% CI: 2.17 to 8.36, P < 0.001), and mechanical loosening (HR = 3.63, 95% CI: 2.05 to 6.44, P < 0.001). CONCLUSION: Patients who had EDS were found to have a higher incidence of revision within 10 years of undergoing TKA and THA compared to matched controls, especially for instability. Patients who have EDS should be counseled accordingly. Surgical technique and implant selection should include consideration for increased constraint in TKA and larger femoral heads or dual mobility articulations for THA.

Trends in Extended Oral Antibiotic Prophylaxis Utilization Following Primary and Revision Total Hip Arthroplasty From 2010 to 2022.

BACKGROUND: In patients considered high-risk for infection, extended oral antibiotic (EOA) prophylaxis has been demonstrated to reduce rates of prosthetic joint infection following total hip arthroplasty (THA). Although national guidelines regarding their use have not yet been created, the increase in literature surrounding EOA prophylaxis suggests a potential change in practice patterns. The purpose of this study was to investigate the trends in utilization of EOA prophylaxis following THA from 2010 to 2022 and identify prescription patterns. METHODS: A total of 646,059 primary THA and 51,879 aseptic revision THA patients were included in this study. Patients who underwent primary or aseptic revision THA between 2010 and 2022 were identified in a national administrative claims database. Rates and duration of EOA prescriptions were calculated. A secondary analysis examined rates of utilization across demographics, including patients considered high risk for infection. RESULTS: From 2010 to 2022, utilization of EOA increased by 366% and 298% following primary and revision THA, respectively. Of patients prescribed postoperative antibiotics, 30% and 59% were prescribed antibiotics for more than 7 days following primary and revision THA, respectively. Rates of utilization were similar between high-risk individuals and the general population. CONCLUSIONS: Rates of utilization of EOA prophylaxis after THA have increased significantly since 2010. As current trends demonstrate a wide variation in prescription patterns, including in length of antibiotic duration and in patient population prescribed, guidelines surrounding the use of EOA prophylaxis after THA are necessary to promote antibiotic stewardship while preventing rates of periprosthetic joint infection.

The Association Between Oral Bone Mineral Density-Reducing Medications and the Risk of 2-Year Implant-Related Complications Following Total Knee Arthroplasty.

BACKGROUND: Certain medications interfere with the bone remodeling process and may potentially increase the risk of complications after total knee arthroplasty (TKA). As patients undergoing TKA may be taking these bone mineral density (BMD)-reducing medications, it is unclear as to whether and which medications impact TKA outcomes. Therefore, the purpose of this study was to observe the impact of various BMD-reducing medications on 2-year implant-related complications following TKA. METHODS: A retrospective analysis of patients undergoing primary TKA was conducted using a national administrative claims database. Patients were identified if they were taking any known BMD-reducing medication and were compared to control patients. To control for confounders associated with taking multiple agents, multivariable logistic regression analyses were conducted for each 2-year outcome (all-cause revision, loosening-indicated revision, and periprosthetic fracture--indicated revision), with the output recorded as odds ratios (ORs). RESULTS: In our study, 502,927 of 1,276,209 TKA patients (39.4%) were taking at least one BMD-reducing medication perioperatively. On multivariable analysis, medications associated with a higher likelihood of 2-year all-cause revision included first- and second-generation antipsychotics (SGAs) (OR: 1.42 and 1.26, respectively), selective serotonin reuptake inhibitors (SSRIs) (OR: 1.14), glucocorticoids (1.13), and proton pump inhibitors (PPIs) (OR: 1.23) (P < .05 for all). Medications associated with a higher likelihood of 2-year periprosthetic fracture included SGAs (OR: 1.51), SSRIs (OR: 1.27), aromatase inhibitors (OR: 1.29), and PPIs (OR: 1.42) (P < .05 for all). CONCLUSIONS: Of the drug classes observed, the utilization of perioperative PPIs, SSRIs, glucocorticoids, first-generation antipsychotics, and SGAs was associated with the highest odds of all-cause revision. Our findings suggest a relationship between these medications and BMD-related complications; however, further studies should seek to determine the causality of these relationships.