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Key Points Genetic testing in CKD showed diagnostic and clinical utility in the year following reporting of test results. Genetic testing was helpful for or changed management in 86% of patients with a positive finding and 42% with a negative finding. Clinical utility was seen across 12 clinical cohorts, including CKD of unknown etiology and hypertension or diabetes-related nephropathy. Background CKD is a significant public health burden, affecting >800 million people worldwide with significant cost to the health care system. CKD is a disease process with substantial genetic and phenotypic heterogeneity that can obscure a definitive diagnosis, resulting in suboptimal management. Recent guidelines support greater adoption of genetic testing in CKD. We assessed the diagnostic and clinical utility in the year following broad-panel CKD genetic testing. Methods The Renasight Clinical Application, Review, and Evaluation (RenaCARE) study (NCT05846113) was a single-arm, interventional, prospective, multicenter study evaluating the utility of genetic testing with a 385-gene panel on the diagnosis and management of CKD. Clinical history was collected before testing, and nephrologists responded to questionnaires at both 1 month and 1 year after testing. The impact of genetic testing on CKD diagnosis and management were assessed in active study patients at the 1-year time point. Results In a cohort of 1388 CKD patients with 13 pretest clinical categories of CKD, 335 (24%) patients had a positive genetic finding; 1174 had a questionnaire completed at 1 year and were included in the analysis. Genetic testing was reported helpful for clinical management and/or led to a change in management in 86% of patients with a positive test finding and 42% of patients with a negative test finding. In addition, genetic testing resulted in a change in the physician estimation of the 5-year prognosis for 55% of patients with a positive test finding and 18% of those with a negative test finding. Conclusions Supporting the previous results of the RenaCARE study at 1 month, this report demonstrated that genetic testing was helpful in the clinical management and estimated prognosis of patients with CKD. Clinical Trial registry name and registration number: ClinicalTrials.gov, NCT05846113.

Background Robotic-assisted TKA may allow for more reproducible balancing and implant positioning. However, few RCTs have directly compared modern robotic-assisted TKA to conventional TKA. Questions/purposes (1) Do patients undergoing robotic-assisted TKA perform better on the Timed Up and Go (TUG) test and Stair Climb test (SCT) than patients undergoing conventional TKA at 1 and 6 months after surgery? (2) Do patients undergoing robotic-assisted TKA demonstrate better patient-reported outcomes, including Knee Injury and Osteoarthritis Outcome Score (KOOS), EQ-5D, and VAS scores, than patients undergoing conventional TKA at 1 and 6 months after surgery? (3) Do patients undergoing robotic-assisted TKA demonstrate better radiographic alignment and position than patients undergoing conventional TKA? Methods In this double-blind RCT, 60 patients were randomized to robotic-assisted TKA (n = 30) or conventional TKA (n = 30) without the use of a tensioning device. All care was otherwise standardized, using mechanical alignment guides. The primary outcome measures were the TUG and SCT tests; results were collected by a blinded observer at 6 months postoperatively. These time points were chosen based on the maximal early improvement in patient-reported outcomes and bimodal distribution of the TUG and SCT tests, worsening in the immediate postoperative period, and improving within the first 6 months. Secondary outcome measures were KOOS, EQ-5D, and VAS scores; radiographic measurements; and operative time. Standard bivariate statistical analysis was conducted. The mean ± SD age of the cohort was 66 ± 7 years, with no differences between groups (p = 0.21). Ninety-three percent (28 of 30) of patients in the robotic-assisted group were White versus 97% (29 of 30) in the conventional TKA group (p > 0.99). Women made up 57% (17) of the robotic-assisted cohort and 60% (18) of the conventional TKA cohort. No differences were noted between the robotic-assisted and conventional TKA groups in BMI, Charlson comorbidity index, or American Society of Anesthesiologists (ASA) classification. Results Patients undergoing robotic-assisted TKA did not perform better than those who underwent conventional TKA on the TUG (11 versus 11 seconds; p = 0.88) or SCT (15 versus 15 seconds; p = 0.93) tests. Patients undergoing robotic-assisted TKA did not demonstrate better mean ± SD scores on the KOOS pain subscale than patients undergoing conventional TKA (86 ± 14 versus 80 ± 17; p = 0.15). Patients undergoing robotic-assisted TKA did not demonstrate better radiographic alignment and position than patients undergoing conventional TKA based on hip-knee-ankle angle (178° versus 178°; p = 0.89). No differences between the two groups were noted at the 1-month follow-up in TUG and SCT test results. Conclusion In this study, patients who underwent robotically assisted TKA did no better in terms of function, patient-reported outcomes, or radiographic measures than did patients who underwent conventional TKA. Until or unless future studies demonstrate benefits of robotically assisted TKA that are large enough for patients to perceive, we recommend against its use. Level of Evidence Level I, therapeutic study.

Aim Cefazolin, a first generation cephalosporin, is the standard of care for perioperative antibiotic prophylaxis in hip and knee arthroplasty patients. Research has shown that prosthetic joint infection (PJI) rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis. Cefazolin contains an R1 side chain that has not shown cross reactivity with other cephalosporins. Despite these data, the declaration of a cephalosporin allergy causes uncertainty regarding the optimal antibiotic choice in these patients. The purpose of this study was to determine the safety of administering perioperative cefazolin in patients with a cephalosporin allergy undergoing joint arthroplasty. Methods We identified all patients (n=1267) with a documented cephalosporin allergy who underwent total hip or knee arthroplasty at a high volume academic medical center from 2016-2024. We compared patients who received perioperative cefazolin despite the presence of a cephalosporin allergy (n=481) to patients who received alternative antibiotic prophylaxis (n=786). The primary outcome measure was the incidence of IgE mediated allergic reactions within the first 72 hours postoperatively. Secondary outcomes included 90-day complication rates including PJI, C. difficile infection, adverse events and readmission. Results The incidence of allergic reaction in cephalosporin allergic patients who received cefazolin was 0.0% (0/481) compared to 0.51% (4/786) in patients who received alternative antibiotics prophylaxis (p=0.12). There were no significant differences in the incidences of PJI (0.23% vs. 0.30%; p=0.83), C. difficile infection (0.0% vs. 0.0%) or readmission (3.95% vs. 4.34%; p=0.75) within 90 days. There was one adverse event related to cefazolin administration which was urethral irritation and was self-limited. There were three adverse events related to alternative antibiotic prophylaxis including cutaneous manifestations, GI distress and headache in a patient with idiopathic intracranial hypertension. All four allergic reactions in the alternative antibiotic prophylaxis cohort required supportive treatment with IV corticosteroids, fluids and antihistamines. Conclusion In this cohort of hip and knee arthroplasty patients, cefazolin administration in the setting of a cephalosporin allergy resulted in a 0.0% incidence of IgE mediated allergic reactions. These data and the fact that cefazolin's unique R1 side chain is not shared by any other cephalosporins suggests that cefazolin can safely be administered to most patients with a documented cephalosporin allergy.

Objective: In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application. Summary Background Data: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment. Methods: A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes. Results: ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients. Conclusions: Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.

OBJECTIVE The COVID-19 pandemic led to many changes across medical organizations and graduate medical education programs nationwide including the rapid implementation of telemedicine as a modality for delivering health care. The purpose of this study was to investigate the telemedicine experiences of residents and fellows with their self-reported level of preparedness, impact on their education including precepting, skill development, and patient-physician relationships, and perceptions of telehealth platforms and curricula in the future. METHODS A total of 365 Mayo Clinic residents and fellows across three sites (Florida, Arizona, and Minnesota) were identified as trainees who conducted at least one telemedicine encounter from January 1, 2020 to June 30, 2020 and were sent an electronic survey by e-mail. RESULTS There was a total of 103 completed surveys across various specialties with 58.3% female respondents, 63.1% residents, 35.0% fellows and 77.7% of respondents who attended medical school in the United States. Most trainees reported having very little to no exposure to telemedicine in their medical careers before the pandemic. The majority were satisfied with their first telemedicine encounter and found precepting comparable to in-person visits. The trainees in this study had a favorable view with 98.1% believing telemedicine will play a more prevalent role in the future and most agreed this should be included in medical school and residency training. CONCLUSION Our survey found that after the implementation of telemedicine during the COVID-19 pandemic, the experiences of trainees at a multi-site academic center were overall positive. More research is needed on the perceptions of skill development (physical exam and history taking) during a telemedicine encounter and outlining an optimal telemedicine curriculum that can improve confidence in trainees.

ObjectiveTo develop evidence‐based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient‐important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate‐to‐severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA).MethodsWe developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations.ResultsThe panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality.ConclusionThis guideline provides evidence‐based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate‐to‐severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient‐important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.

ObjectiveTo develop evidence‐based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient‐important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate‐to‐severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA).MethodsWe developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations.ResultsThe panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality.ConclusionThis guideline provides evidence‐based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate‐to‐severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient‐important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.

Advances in computer science and data-analytic methods are driving a new era in mental health research and application. Artificial intelligence (AI) technologies hold the potential to enhance the assessment, diagnosis, and treatment of people experiencing mental health problems and to increase the reach and impact of mental health care. However, AI applications will not mitigate mental health disparities if they are built from historical data that reflect underlying social biases and inequities. AI models biased against sensitive classes could reinforce and even perpetuate existing inequities if these models create legacies that differentially impact who is diagnosed and treated, and how effectively. The current article reviews the health-equity implications of applying AI to mental health problems, outlines state-of-the-art methods for assessing and mitigating algorithmic bias, and presents a call to action to guide the development of fair-aware AI in psychological science.