In Vivo Intra-Articular Antibiotic Concentrations at 24 Hours After TKA Fall Below the Minimum Inhibitory Concentration for Most Bacteria: A Randomized Study of Commercially Available Bone Cement.

BACKGROUND: The use of antibiotic-loaded bone cement (ALBC) to help reduce the risk of infection after primary total knee arthroplasty (TKA) is controversial. There is a paucity of in vivo data on the elution characteristics of ALBC. We aimed to determine whether the antibiotic concentrations of 2 commercially available ALBCs met the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) for common infecting organisms. METHODS: Forty-five patients undergoing TKA were randomized to receive 1 of the following: bone cement without antibiotic (the negative control; n = 5), a commercially available formulation containing 1 g of tobramycin (n = 20), or a commercially available formulation containing 0.5 g of gentamicin (n = 20). Intra-articular drains were placed, and fluid was collected at 4 and 24 hours postoperatively. An automated immunoassay measuring antibiotic concentration was performed, and the results were compared against published MIC and MBEC thresholds. RESULTS: The ALBC treatment groups were predominantly of White (65%) or Black (32.5%) race and were 57.5% female and 42.4% male. The mean age (and standard deviation) was 72.6 ± 7.2 years in the gentamicin group and 67.6 ± 7.4 years in the tobramycin group. The mean antibiotic concentration in the tobramycin group was 55.1 ± 37.7 µg/mL at 4 hours and 19.5 ± 13.0 µg/mL at 24 hours, and the mean concentration in the gentamicin group was 38.4 ± 25.4 µg/mL at 4 hours and 17.7 ± 15.4 µg/mL at 24 hours. Time and antibiotic concentration had a negative linear correlation coefficient (r = -0.501). Most of the reference MIC levels were reached at 4 hours. However, at 24 hours, a considerable percentage of patients had concentrations below the MIC for many common pathogens, including Staphylococcus epidermidis (gentamicin: 65% to 100% of patients; tobramycin: 50% to 85%), methicillin-sensitive Staphylococcus aureus (gentamicin: 5% to 90%; tobramycin: 5% to 50%), methicillin-resistant S. aureus (gentamicin: 5% to 65%; tobramycin: 50%), Streptococcus species (gentamicin: 10% to 100%), and Cutibacterium acnes (gentamicin: 10% to 65%; tobramycin: 100%). The aforementioned ranges reflect variation in the MIC among different strains of each organism. Gentamicin concentrations reached MBEC threshold values at 4 hours only for the least virulent strains of S. aureus and Escherichia coli. Tobramycin concentrations did not reach the MBEC threshold for any of the bacteria at either time point. CONCLUSIONS: The elution of antibiotics from commercially available ALBC decreased rapidly following TKA, and only at 4 hours postoperatively did the mean antibiotic concentrations exceed the MIC for most of the pathogens. Use of commercially available ALBC may not provide substantial antimicrobial coverage following TKA. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Efficacy of Antibody Drug Conjugates Alone and in Combination with other Agents in Metastatic Urothelial Carcinoma: A Scoping Review.

INTRODUCTION: Antibody drug conjugates represent a promising class of antineoplastic agents comprised of a monoclonal antibody linked to a potent cytotoxic payload for targeted delivery of chemotherapy to tumors. Various antibody drug conjugates have demonstrated impressive efficacy in patients with metastatic urothelial carcinoma in clinical trials, leading to two FDA approved therapies and several other agents and combinations in clinical development. MATERIALS AND METHODS: A comprehensive systematic review was undertaken utilizing the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Queried databases included Ovid MEDLINE, Ovid Embase, Web of Science Core Collection and Cochrane CENTRAL Trials. The search sought to identify prospective therapeutic clinical trials in humans with metastatic urothelial carcinoma with a single-arm or randomized controlled trial design investigating antibody drug conjugate-containing regimens. RESULTS: The literature search yielded 4,929 non-duplicated articles, of which 30 manuscripts and conference abstracts were included, which derived from 15 clinical trials including 19 separate cohorts with efficacy outcome results. Eleven trials investigated ADC monotherapy, while two investigated combination regimens, and the remaining two studies were mixed. Five unique ADC targets were represented including Nectin-4, Trop-2, HER2, Tissue Factor, and SLITRK6. Twelve clinical trial cohorts required prior treatment (63%). Objective response rate was reported for all studies and ranged from 27-52% for ADC monotherapies and 34-75% for ADC plus anti-PD-1 agents. Time to event outcome reporting was highly variable. CONCLUSION: In addition to enfortumab vedotin and sacituzumab govitecan, various HER2-targeted antibody drug conjugates and ADC-anti-PD-1 combination regimens have demonstrated efficacy in clinical trials and are poised for clinical advancement.

ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis.

Immune checkpoint inhibitors (ICIs) are increasingly being used to manage multiple tumor types. Unfortunately, immune-related adverse events affect up to 60% of recipients, often leading to treatment discontinuation in settings where few alternative cancer therapies may be available. Checkpoint inhibitor induced colitis (ICI-colitis) is a common toxicity for which the underlying mechanisms are poorly defined. To better understand the changing colon-specific and peripheral immune environments over the course of progression and treatment of colitis, we collected blood and colon tissue from a patient with Merkel cell carcinoma who developed colitis on treatment with pembrolizumab. We performed single-cell RNA sequencing and T-cell receptor sequencing on samples collected before, during and after pembrolizumab and after various interventions to mitigate toxicity. We report T-cells populations defined by cytotoxicity, memory, and proliferation markers at various stages of colitis. We show preferential depletion of CD8+ T cells with biologic therapy and nominate both circulating and colon-resident T-cell subsets as potential drivers of inflammation and response to immune suppression. Our findings highlight the need for further exploration of the colon immune environment and rationalize future studies evaluating biologics for ICI-colitis, including in the context of ICI re-challenge.

Germline genetic variants are associated with development of insulin-dependent diabetes in cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically improved survival in patients with cancer but are often accompanied by severe immune-related adverse events (irAEs), which can sometimes be irreversible. Insulin-dependent diabetes is a rare, but life-altering irAE. Our purpose was to determine whether recurrent somatic or germline mutations are observed in patients who develop insulin-dependent diabetes as an irAE. METHODS: We performed RNA and whole exome sequencing on tumors from 13 patients who developed diabetes due to ICI exposure (ICI-induced diabetes mellitus, ICI-DM) compared with control patients who did not develop diabetes. RESULTS: In tumors from ICI-DM patients, we did not find differences in expression of conventional type 1 diabetes autoantigens, but we did observe significant overexpression of ORM1, PLG, and G6PC, all of which have been implicated in type 1 diabetes or are related to pancreas and islet cell function. Interestingly, we observed a missense mutation in NLRC5 in tumors of 9 of the 13 ICI-DM patients that was not observed in the control patients treated with the same drugs for the same cancers. Germline DNA from the ICI-DM patients was sequenced; all NLRC5 mutations were germline. The prevalence of NLRC5 germline variants was significantly greater than the general population (p=5.98×10-6). Although NLRC5 is implicated in development of type 1 diabetes, germline NLRC5 mutations were not found in public databases from patients with type 1 diabetes, suggesting a different mechanism of insulin-dependent diabetes in immunotherapy-treated patients with cancer. CONCLUSIONS: Validation of the NLRC5 mutation as a potential predictive biomarker is warranted, as it might improve patient selection for treatment regimens. Furthermore, this genetic alteration suggests potential mechanisms of islet cell destruction in the setting of checkpoint inhibitor therapy.

Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma.

INTRODUCTION: Combination immune checkpoint inhibitors (ICI) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF-R-TKI), including pembrolizumab/axitinib, are approved for first-line treatment of metastatic renal cell carcinoma (mRCC). Pembrolizumab/axitinib is associated with superior progression free survival (PFS), objective response rate (ORR), and overall survival over sunitinib. However, to date, the activity and safety of pembrolizumab/axitinib in later lines of therapy has not been reported. MATERIALS AND METHODS: Clinical data of consecutive patients receiving pembrolizumab/axitinib in the second-line or beyond for mRCC at Yale-New Haven Hospital were retrospectively collected. Best objective response was assessed using RECIST 1.1 criteria. Kaplan-Meier function was used to analyze survival. RESULTS: Thirty-eight patients were included. Median age was 64, 92.1% had clear cell mRCC, 18.4% had sarcomatoid dedifferentiation; 94.7% had prior ICI and 39.5% had prior VEGF-R-TKI. Pembrolizumab/axitinib was administered as second-line therapy in 21 (55.5%) patients, third-line in 5 (13.2%) and beyond in 12 (30.2%). Adverse events (AEs) occurred in 86.8% of patients. Grade 3-4 AEs attributed to pembrolizumab and axitinib were seen in 18.4% and 6.4% of patients, respectively. No grade 5 AEs occurred. At a median follow up of 17.1 months, median PFS was 9.7 months (95% CI, 4.1-15.3). Amongst 36 response evaluable patients, the ORR was 25.0% (all partial) and disease control rate (including stable disease for at least 6 months) was 66.6%. The most frequent treatment sequence was first-line nivolumab/ipilimumab followed by second-line pembrolizumab/axitinib (n = 17, 44.7%); among this cohort, median PFS with pembrolizumab/axitinib was 11.1 (95% CI, 8.4-13.7) months, with an ORR of 31.4%. CONCLUSION: Combination pembrolizumab/axitinib among previously treated mRCC patients has activity, with AE rates comparable to those reported in the first line. Prospective studies evaluating ICI-VEGF-R-TKI combinations beyond first-line are warranted to identify the most beneficial treatment sequencing in mRCC.

The effects of tourniquet on cement penetration in total knee arthroplasty.

PURPOSE: Aseptic loosening is a common cause of implant failure following total knee arthroplasty (TKA). Cement penetration depth is a known factor that determines an implant's "strength" and plays an important role in preventing aseptic loosening. Tourniquet use is thought to facilitate cement penetration, but its use has mixed reviews. The aim of this study was to compare cement penetration depth between tourniquet and tourniquet-less TKA patients. METHODS: A multicenter retrospective review was conducted. Patients were randomized preoperatively to undergo TKA with or without the use of an intraoperative tourniquet. The variables collected were cement penetration measurements in millimeters (mm) within a 1-month post-operative period, length of stay (LOS), and baseline demographics. Measurements were taken by two independent raters and made in accordance to the zones described by the Knee Society Radiographic Evaluation System and methodology used in previous studies. RESULTS: A total of 357 TKA patients were studied. No demographic differences were found between tourniquet (n = 189) and tourniquet-less (n = 168) cohorts. However, the tourniquet cohort had statistically, but not clinically, greater average cement penetration depth [2.4 ± 0.6 mm (range 1.2-4.1 mm) vs. 2.2 ± 0.5 mm (range 1.0-4.3 mm, p = 0.01)]. Moreover, the tourniquet cohort had a significantly greater proportion of patients with an average penetration depth within the accepted zone of 2 mm or greater (78.9% vs. 67.3%, p = 0.02). CONCLUSION: Tourniquet use does not affect average penetration depth but increases the likelihood of achieving optimal cement penetration depth. Further study is warranted to determine whether this increased likelihood of optimal cement penetration depth yields lower revision rates.

Should We Aim to Help Patients "Feel Better" or "Feel Good" After Total Hip Arthroplasty? Determining Factors Affecting the Achievement of the Minimal Clinically Important Difference and Patient Acceptable Symptom State.

BACKGROUND: Recent attempts have been made to use preoperative patient-reported outcome measure (PROM) thresholds as prior authorization criteria based on the assumption that patients who have higher baseline scores are less likely to achieve the minimal clinically important difference (MCID). This study aimed to identify factors affecting the achievement of MCID and patient acceptable symptom state (PASS) after total hip arthroplasty (THA), and to determine the overlap between the two outcomes. METHODS: We identified 3,581 primary, unilateral THAs performed at a single practice in 2015-2019. PROMs including Hip Disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS-JR) and 12-item Short Form Health Survey were collected preoperatively and 1-year postoperatively. The likelihood of attaining PASS according to attainment of MCID was assessed. Multivariable regression was used to identify independent predictors of MCID and PASS. RESULTS: In total, 79.8% achieved MCID and 73.6% achieved PASS for HOOS-JR. Approximately 1 in 7 patients who achieved MCID did not eventually achieve PASS. Worse preoperative HOOS-JR (odd ratio 0.933) was associated with MCID attainment. Better preoperative HOOS-JR (odd ratio 1.015) was associated with PASS attainment. Men, lower body mass index, better American Society of Anesthesiologists score, and better preoperative 12-item Short Form Health Survey mental score were predictors of MCID and PASS. Age, race, ethnicity, Charlson Comorbidity Index, and smoking status were not significant predictors. CONCLUSION: Preoperative PROMs were associated with achieving MCID and PASS after THA, albeit in opposite directions. Clinicians should strive to help patients "feel better" and "feel good" after surgery. Preoperative PROMs should not solely be used to prioritize access to care.

Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab.

Purpose: Immune-mediated adverse events (imAEs) may be associated with response to immune checkpoint inhibitors. We assessed the relationship between imAE development and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab (anti-programmed cell death ligand-1 [PD-L1]) alone or in combination with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4). Methods: The analysis used individual patient-level data from 307 and 310 patients in the monotherapy and combination arms of MYSTIC, respectively. We evaluated the association between treatment efficacy and development of imAEs using univariate and multivariate survival analyses. Using machine learning, we built a predictive model utilizing baseline clinical and laboratory features to identify patients at risk of developing imAEs and further evaluated patient survival based on a threshold index extracted from the model. Results: Patients who developed any grade of imAE had improved overall survival versus patients without (hazard ratio [HR] 0.51; 95% confidence interval [CI]: 0.41-0.62). imAE development was associated with improved overall survival (HR 0.54; 95% CI 0.44-0.66) in a multivariate Cox proportional hazard model considering patient demographic features and baseline characteristics. Higher odds of imAE development were observed (odds ratio 3.023; 95% CI: 1.56-5.83) in responders versus non-responders in patients treated with immunotherapy. Based on baseline characteristics, the random forest classification algorithm was used to formulate a predictive model to identify patients at increased risk of developing imAEs during treatment. Conclusion: Post-hoc exploratory analysis found that the efficacy of immunotherapy was improved in patients who developed on-treatment imAEs. This was independent of severity of imAEs or the need for steroid treatment, which is important in allowing patients to remain on treatment and derive optimal clinical benefit. Further research is warranted to establish the correlation between incidence of imAEs and efficacy in this patient population.

Making a Joint Decision Regarding the Timing of Surgery for Elective Arthroplasty Surgery After Being Infected With COVID-19: A Systematic Review.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has caused a substantial number of patients to have their elective arthroplasty surgeries rescheduled. While it is established that patients with COVID-19 who are undergoing surgery have a significantly higher risk of experiencing postoperative complications and mortality, it is not well-known at what time after testing positive the risk of postoperative complications or mortality returns to normal. METHODS: PubMed (MEDLINE), Excerpta Medica dataBASE, and professional society websites were systematically reviewed on March 7, 2022 to identify studies and guidelines on the optimal timeframe to reschedule patients for elective surgery after preoperatively testing positive for COVID-19. Outcomes included postoperative complications such as mortality, pneumonia, acute respiratory distress syndrome, septic shock, and pulmonary embolism. RESULTS: A total of 14 studies and professional society guidelines met the inclusion criteria for this systematic review. Patients with asymptomatic COVID-19 should be rescheduled 4-8 weeks after testing positive (as long as they do not develop symptoms in the interim), patients with mild/moderate COVID-19 should be rescheduled 6-8 weeks after testing positive (with complete resolution of symptoms), and patients with severe/critical COVID-19 should be rescheduled at a minimum of 12 weeks after hospital discharge (with complete resolution of symptoms). CONCLUSIONS: Given the negative association between preoperative COVID-19 and postoperative complications, patients should have elective arthroplasty surgery rescheduled at differing timeframes based on their symptoms. In addition, a multidisciplinary and patient-centered approach to rescheduling patients is recommended. Further study is needed to examine the impact of novel COVID-19 variants and vaccination on timeframes for rescheduling surgery.

The Paradox of Patient-Reported Outcome Measures: Should We Prioritize "Feeling Better" or "Feeling Good" After Total Knee Arthroplasty?

BACKGROUND: The use of preoperative patient-reported outcome measure (PROM) thresholds for patient selection in arthroplasty care has been questioned recently. This study aimed to identify factors affecting achievement of the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) after total knee arthroplasty (TKA) and determine the overlap between the two outcomes. METHODS: We identified 1,239 primary, unilateral TKAs performed at a single institution in 2015-2019. PROMs including the Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) and 12-item Short Form Health Survey (SF-12) were collected preoperatively and 1-year postoperatively. The likelihood of attaining PASS as per attainment of MCID was assessed. A multivariable regression was used to identify predictors of MCID and PASS. RESULTS: In total, 71.3% achieved MCID and 75.5% achieved PASS for KOOS-JR. Only 7.7% achieved MCID but not PASS, whereas almost twice this number did not achieve MCID but did achieve PASS (11.9%). Poorer preoperative KOOS-JR (OR 0.925), better SF-12 physical (OR 1.025), and mental (OR 1.027) were associated with MCID attainment. In contrast, better preoperative KOOS-JR (OR 1.030) and SF-12 mental (OR 1.025) were associated with PASS attainment. Age, gender, race, ethnicity, body mass index, Charlson index, American Society of Anesthesiologists classification, and smoking status were not significant predictors. CONCLUSION: Preoperative PROMs were associated with achieving MCID and PASS after TKA, albeit some positively and some negatively. In the era of value-based care, clinicians should not only strive to help patients "feel better" but also ensure that patients "feel good" after surgery. This study does not support the use of PROMs in prioritizing access to care.

Immune Checkpoint Inhibitor-Induced Hypophysitis and Patterns of Loss of Pituitary Function.

Background: Immune checkpoint inhibitors (ICI) are clinically active across multiple tumor types but the associated immune-related adverse events (irAEs) lead to treatment delays or discontinuation and negatively impact quality-of-life. Hypophysitis is often a permanent irAE that may affect multiple pituitary hormonal axes. Here we comprehensively characterize our institution's clinical experience with ICI-induced hypophysitis and the associated patterns of pituitary function loss. Methods: Patients with solid tumors, mostly melanoma and renal cell carcinoma (RCC), treated with ICI at Yale Cancer Center were prospectively enrolled from October 2016-May 2021. Demographics and clinical data were obtained from the medical record including type and timing of irAEs. Patients were included in this cohort if hypophysitis was diagnosed by pre-specified biochemical and clinical parameters. Results: The overall incidence of hypophysitis was 69/490 (14%) in patients with melanoma (n=58, 84%), RCC (n=10,14%), and merkel cell carcinoma (n=1, 1%) who received ipilimumab plus nivolumab (77%; 53/69), anti-PD-(L)1 (17%; 12/69), or ipilimumab monotherapy (6%; 4/69). Of the 69 patients analyzed, median time to hypophysitis on combination ICI versus anti-PD-1 was 2.8 vs. 4.1 months. The incidence of hypophysitis in patients with melanoma was 25% (46/187) with ipilimumab plus nivolumab and 5% (7/129) with anti-PD-(L)1 compared to 9% (7/77) and 8% (3/37), respectively, in patients with RCC. Patients who developed hypophysitis on combination ICI had a higher rate of headache (p=0.05) and co-occurring irAEs (p=0.01) compared anti-PD-(L1)1 monotherapy. At a median follow-up of 2.2 years, 77% of patients were alive. Objective response rates to ICI in melanoma patients were higher than previously reported for unselected populations. Central hypothyroidism and hypogonadism were the most common pituitary axes affected after the adrenal axis. In select cases, there was evidence of spontaneous rebound in free testosterone levels after an initial decline. Conclusions: We demonstrate a higher rate of ICI-induced hypophysitis than previously reported, which may be reflective of real-world practice due to increased awareness as experience with ICI has grown. In select cases, there was evidence of rebound in free testosterone and/or gonadotropins but not in adrenal axis hormones.

Are Patients With End-Stage Arthritis Willing to Delay Arthroplasty for Payer-Mandated Physical Therapy?

BACKGROUND: Payer coverage policies have recently begun requiring physical therapy (PT) prior to total hip arthroplasty and total knee arthroplasty (TKA). It remains controversial if such a mandate is appropriate for patients with end-stage, symptomatic osteoarthritis. The purpose of this study is to assess if such patients are amenable to delaying surgery for a trial of PT. METHODS: All patients scheduled for elective primary total hip arthroplasty and TKA in a 3-month period by 1 of 7 surgeons at a single institution were contacted and asked to participate in a survey. Participation in PT within the prior 6 months was noted. Patients were asked if they would be willing to delay surgery for a PT trial as a nonsurgical option to improve their symptoms. The primary reason for their answer was also recorded. RESULTS: In total, 200 patients were successfully contacted and agreed to participate. The mean age was 66 years, 47% were male, the mean body mass index was 31 kg/m2, and 66% were scheduled for TKA. In total, 157 patients (79%) stated they had not done PT in the preceding 6 months, and 185 patients (93%) stated they would not want to delay surgery for mandatory PT. The most common reasons for refusing PT were "surgery is inevitable" (44%) and "unlikely to improve pain" (29%). CONCLUSION: Patients with end-stage hip and knee osteoarthritis who are otherwise candidates for surgery appear overwhelmingly opposed to mandatory preoperative PT, mostly due to a lack of perceived efficacy in providing long-term symptom relief compared to total joint arhtroplasty.

Stress and Strain During Total Joint Arthroplasty Are Not Impacted by Hand Dominance or Operative Laterality in Orthopedic Surgeons.

BACKGROUND: Orthopedic surgeons experience significant musculoskeletal pain and work-related injuries while performing total joint arthroplasty (TJA). We sought to investigate the impact of operative extremity and surgeon limb dominance on surgeon physiologic stress and energy expenditure during TJA. METHODS: This was a prospective cohort study conducted at a tertiary academic practice. Cardiorespiratory data was recorded continuously in 3 high-volume arthroplasty surgeons using a smart garment that measured heart rate (HR), HR variability, respiratory rate, minute ventilation, and energy expenditure (calories) during conventional total knee (TKA) and total hip arthroplasty (THA). RESULTS: Surgeon 1 and 2 (right-handed) performed 21 right TKAs, 10 left TKAs, 13 right THAs, and 10 left THAs. Surgeon 3 (left-handed) performed 6 right TKAs, 9 left TKAs, 16 right THAs, and 10 left THAs. While performing TKA or THA, limb laterality had no significant impact on operative time and no significant differences existed in HR, HR variability, respiratory rate, minute ventilation, or energy expenditure for any right-handed or left-handed surgeons, regardless of the operative limb laterality. While performing TKA, consistently standing on the side of hand dominance was associated with decreased strain and stress, compared to always standing on the operative side. CONCLUSION: This study suggests that surgeon hand dominance and operative limb laterality do not impact energy expenditure or physiologic strain during TJA. However, consistently standing on the side of hand dominance in TKA may lead to decreased physiologic strain and stress during surgery. Further study utilizing wearable technology during TJA may provide orthopedic surgeons with information about modifiable factors that contribute to differences in physiological parameters during surgery.

Increased Rates of Tibial Aseptic Loosening in Primary Cemented Total Knee Arthroplasty With a Short Native Tibial Stem Design.

BACKGROUND: Emerging evidence has suggested that both obesity and a short, native tibial stem (TS) design may be associated with early aseptic loosening in total knee arthroplasty. The use of short, fully cemented stem extensions may mitigate this risk. As such, we devised a multicenter study to confirm or negate these claims. METHODS: A search of our institutional research databases was done. A minimum 2-year time from index procedure was selected. Cohorts were created according to patient body mass index and the presence (stemmed tibia [ST]) or absence (nonstemmed tibia [NST]) of a short TS extension. Kaplan-Meier survival analyses for aseptic loosening and log-rank tests were done. RESULTS: A total of 1,350 patients were identified (ST = 500, NST = 850). The mean time to the final follow-up in cases without aseptic loosening for the ST cohort was 3.5 years (2.8-6.3) and 5.0 years (2.9-6.3) for the NST cohort (P < 0.001). Kaplan-Meier survival analysis at 6 years was superior for the ST cohort (100%, 98.5%; P = 0.025), and a trend toward superior 5-year survival was observed for body mass index <40 kg/m2 (99.1%, 93.2%; P = 0.066). The mean time to aseptic loosening was 2.4 years (0.9-4.5), with approximately 40% occurring within the first 2 years. CONCLUSIONS: Short, native TS design is associated with early aseptic loosening in primary cemented total knee arthroplasty. This can be mitigated through the use of an ST. More cost-effective solutions include (1) use of implants with longer native stem designs or (2) redesign of short TS implants.

Surgeons Experience Greater Cardiorespiratory Strain and Stress During Total Hip Arthroplasty Than Total Knee Arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are physically demanding, with a high prevalence of work-related injuries among arthroplasty surgeons. It is unknown whether there are differences in cardiorespiratory output for surgeons while performing THA and TKA. The objective of this study is to characterize whether differences in surgeon physiological response exist while performing primary THA vs TKA. METHODS: This is a prospective cohort study including 3 high-volume, fellowship-trained arthroplasty surgeons who wore a smart garment that recorded cardiorespiratory data on operative days during which they were performing primary conventional TKA and THA. Variables collected included patient body mass index (BMI), operative time (minutes), heart rate, heart rate variability, respiratory rate, minute ventilation, and energy expenditure (calories). RESULTS: Seventy-six consecutive cases (49 THAs and 27 TKAs) were studied. Patient BMI was similar between the 2 cohorts (P > .05), while operative time was significantly longer in TKAs (60.4 ± 12.0 vs 53.6 ± 11.8; P = .029). During THA, surgeons had a significantly higher heart rate (95.7 ± 9.1 vs 90.2 ± 8.9; P = .012), energy expenditure per minute (4.6 ± 1.23 vs 3.8 ± 1.2; P = .007), and minute ventilation (19.0 ± 3.0 vs 15.5 ± 3.3; P < .001) compared to TKA. CONCLUSION: Surgeons experience significantly higher physiological strain and stress while performing THA. While scheduling THAs and TKAs, surgeons should consider the higher physical demand associated with THAs and ensure adequate personal preparation and sequence of cases.

A Simple Algorithmic Approach Allows the Safe Use of Cephalosporin in "Penicillin-Allergic" Patients without the Need for Allergy Testing.

BACKGROUND: Patients who report a penicillin allergy are often given second-line antibiotic prophylaxis during total joint arthroplasty (TJA), with only a minority of patients undergoing additional consultations and allergy testing. In an effort to increase the use of cephalosporin prophylaxis in TJA, the present study aimed to assess the effectiveness of a simple, protocol-driven penicillin allergy screening program without the need for additional work-up. METHODS: Following implementation of a questionnaire-based screening protocol in May 2019, all patients scheduled for primary TJA were risk-stratified into low or high-risk categories. The low-risk cohort received cefazolin, and the high-risk cohort received non-cefazolin antibiotics. Patients were monitored prospectively, and data on antibiotic usage and adverse outcomes were documented. The protocol group (n = 2,078) was propensity score matched 1:1 with a control group that included patients who underwent TJA in the same institution prior to implementation of the protocol. The primary end point was the efficacy of the protocol in reducing unnecessary use of non-cephalosporin antibiotics for prophylaxis. Secondary outcomes included the rate of surgical site infections and allergic reactions to the administered antibiotic. RESULTS: A total of 357 patients (17.2%) reported a penicillin allergy in the protocol group compared with 310 patients (14.9%) with a recorded allergy in the control group (p = 0.052). The number of patients who received non-cephalosporin antibiotics was significantly lower in the protocol group (5.7% compared with 15.2% in the control group; p < 0.001), whereas there was no difference in the rate of total allergic reactions (0.8% compared with 0.7%, respectively; p = 0.857). Of the 239 low-risk patients (66.9%) in the protocol group, only 3 (1.3%) experienced a mild cutaneous reaction following cefazolin administration. There were no differences in the rates of superficial wound, deep periprosthetic, or Clostridioides difficile infections between the protocol and control groups. CONCLUSIONS: A simple screening protocol allowed two-thirds of patients with a self-reported allergy to receive cefazolin without the need for additional consultations or testing. We believe this protocol can be safely implemented to increase the rate of cefazolin usage without a corresponding increase in the number of allergic reactions. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Routine Postoperative Chemistry Panels Are Not Necessary for Most Total Joint Arthroplasty Patients.

BACKGROUND: The routine use of traditional chemistry-7 (chem-7) laboratory tests following total joint arthroplasty (TJA) has been called into question with the advent of short-stay procedures. Our objective was to determine the incidence, risk factors, and clinical interventions associated with inpatient abnormal routine postoperative chem-7 panels. METHODS: From 2015 to 2017, 3,162 patients underwent a total of 3,721 TJA procedures, including primary total hip arthroplasty (THA) (n = 1,939; 52.1%) or primary total knee arthroplasty (TKA) (n = 1,782; 47.9%). Patients underwent routine preoperative and postoperative chem-7 testing. Clinical interventions were identified. With use of mixed-effects multivariate logistic regression, potential risk factors for abnormal chemistry panel values (including preoperative chem-7 results, type of surgery, age, sex, race, comorbidities, American Society of Anesthesiologists [ASA] score, and medications) were analyzed. RESULTS: The rates of abnormal preoperative laboratory results were 3.4% for sodium (Na+), 7.4% for potassium (K+), 15.8% for blood urea nitrogen (BUN), and 26.4% for creatinine (Cr). The incidence of abnormal postoperative results was low for K+ (9.7%) and higher for Na+ (25.6%), BUN (55.6%), and Cr (27.9%). Preoperative abnormal laboratory results were a significant predictor of a postoperative abnormality for Na+ (odds ratio [OR] = 2.15; 95% confidence interval [CI] = 1.82 to 2.54), K+ (OR = 4.22; 95% CI = 3.03 to 5.88), and Cr (OR = 3.00; 95% CI = 2.45 to 3.68). Bilateral TJA was associated with increased odds of abnormal postoperative Na+ (OR = 1.56; 95% CI = 1.44 to 1.68). Renal disease was associated with increased odds of abnormal postoperative Cr (OR = 15.21; 95% CI = 5.67 to 40.77). Patients taking loop diuretics had increased odds of abnormal postoperative K+ (OR = 2.10; 95% CI = 1.42 to 3.11) and Cr (OR = 2.28; 95% CI = 1.56 to 3.33). Regarding intervention, 6.7% of hypokalemic patients received potassium chloride (KCl) fluid/tablets. Forty percent of hyponatremic patients received sodium chloride (NaCl) fluid/tablets. The electrolyte-related medicine consultation rate was 0.3% (13 of 3,721). CONCLUSIONS: On the basis of our findings, we recommend postoperative chem-7 testing for patients with an abnormal preoperative laboratory result (Na+, K+, BUN, Cr), preexisting renal disease, bilateral TJA, and prescribed angiotensin-converting enzyme inhibitors (ACE), angiotensin II receptor blockers (ARB), and diuretics. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Canceled Total Joint Arthroplasty: Who, What, When, and Why?

BACKGROUND: Unexpected cancelation of scheduled total joint arthroplasty (TJA) procedures creates patient distress and disruption for the clinical team. The purpose of this study is to identify the etiology and fate of cancelations for scheduled TJAs. METHODS: A consecutive series of 11,670 patients at a single institution from 2013 to 2017 was reviewed in March 2020. All patients who were scheduled for a primary total hip arthroplasty or total knee arthroplasty and subsequently canceled were identified. The etiology of cancelation and time to rescheduling were recorded. RESULTS: Of the 505 (4.3%) canceled patients, 209 (42%) were due to medical reasons. Three hundred ninety-one patients (77%) eventually underwent their procedure at a mean delay of 165 days (19-1908). Only 53 (25%) patients canceled for a medical reason underwent further diagnostic or therapeutic intervention for their medical condition. When compared to patient-driven cancelations, those canceled for medical reasons had a higher mean Charlson Comorbidity Index (0.82 vs 0.39, P < .001), were canceled closer to the scheduled surgery date (8.55 vs 18.1 days, P < .001), and were more likely to eventually undergo surgery (86% vs 73%, P = .004). CONCLUSION: Canceled elective TJA surgeries are most often due to a medical concern, however only a minority of these patients undergo intervention for that medical condition. To minimize the risk of cancelation, healthcare providers may consider early referral of medically complex patients to the patient's primary care physician. After cancelation, patients should have a clearly defined path to return to the operative schedule to prevent further delays.