Citations

BACKGROUND: Cardiac computed tomography (CT) acquired during the acute stroke imaging protocol is an emerging modality to detect cardiac thrombi. We determined its yield in patients with acute ischemic stroke. METHODS: We performed a 1-stage individual patient data meta-analysis of 4 prospective observational cohorts (AIS of HEARTS [Acute Ischemic Stroke of Heart-Related Embolic Sources Detected on Acute Cardiac CT Scans]), including patients with acute ischemic stroke who underwent ECG-gated or non–ECG-gated cardiac CT between May 2018 and June 2024. We excluded patients with transient ischemic attack or stroke mimics. The primary outcome was the proportion of patients with a thrombus on cardiac CT. Secondary outcomes were additional scan time, radiation dose, comparison with echocardiography, and 90-day outcomes. We performed logistic regression analyses to compare 90-day outcomes between patients with and without thrombus, adjusting for age, sex, history of atrial fibrillation, ischemic heart disease, chronic heart failure, stroke or transient ischemic attack, anticoagulant use, prestroke modified Rankin Scale score, National Institutes of Health Stroke Scale score, large vessel occlusions, and intravenous thrombolysis, as appropriate for each outcome. RESULTS: We included 3919 patients (median age, 74 [interquartile range (IQR), 63–82], 58% male, median National Institutes of Health Stroke Scale score 6 [IQR, 3–12]). Cardiac CT detected a thrombus in 243 (6.2%) patients. Among 1323 patients that underwent both cardiac CT and transthoracic echocardiography, cardiac CT had a higher yield than transthoracic echocardiography (odds ratio, 7.4 [95% CI, 4.0–15.1]; P <0.001). Median additional scan time was 6 minutes (IQR, 5–7) for ECG-gated and 13 seconds (IQR, 12–61) for non–ECG-gated cardiac CT. Median additional radiation dose was 2.9 mSv (IQR, 1.6–4.1). Patients with thrombi had higher 90-day mortality (33% versus 15%, adjusted odds ratio, 1.6 [95% CI, 1.1–2.3]) and worse modified Rankin Scale scores (median modified Rankin Scale score 3 versus 2, adjusted odds ratio, 1.6 [95% CI, 1.2–2.0]), but similar recurrent stroke rates (5% versus 4%, adjusted odds ratio, 1.4 [95% CI, 0.7–2.5]). CONCLUSIONS: Implementing cardiac CT into the acute stroke imaging protocol is feasible, detects thrombi in ≈6% of patients, and has a higher yield than transthoracic echocardiography. Cardiac thrombi were associated with higher mortality, but not higher stroke recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT07165093.

ABSTRACT The Burkholderia cepacia complex (BCC) is comprised of 24 species of Gram-negative bacteria that cause opportunistic infections. While antimicrobial susceptibility testing (AST) has historically been used to guide treatment for BCC infections, recent work highlighting problems with AST for these organisms led the Clinical and Laboratory Sciences Institute (CLSI) to remove disk diffusion (DD) and minimal inhibitory concentration (MIC) breakpoints for BCC from its M100 standards document. Epidemiological cut-off values (ECVs) may be helpful to clinicians in the absence of breakpoints, as they may be used to determine whether an isolate has a wild-type or non-wild-type phenotype. Here we present an analysis of BCC ECVs for ceftazidime (CAZ), levofloxacin (LVX), meropenem (MEM), minocycline (MIN), and trimethoprim-sulfamethoxazole (TMP-SMX). ECVs were calculated using MIC data from 3 previous studies and 3 independent laboratories for 1,896 BCC isolates. ECVs were 16 μg/ml for CAZ, 8 μg/ml for LVX, 16 μg/ml for MEM, and 8 μg/ml for MIN. The ECV for TMP-SMX varied depending on the analysis from 2 μg/ml, 8 μg/ml, and 16 μg/ml and therefore could not be reliably established. Challenges with establishing ECVs for BCC include limitations with the pooled MIC dataset, broad MIC distributions, and high ECVs that are above the obsolete susceptible MIC breakpoints. These challenges limit the clinical utility of ECVs for these organisms and supported removal of ECVs from the CLSI M100 standards document. IMPORTANCE The Burkholderia cepacia complex is a group of bacterial species that cause difficult-to-treat opportunistic infections. Recently, clinical breakpoints, which are used to determine whether organisms are susceptible to certain antimicrobials, were removed from Clinical and Laboratory Standards Institute (CLSI) standards for these organisms due to problems with antimicrobial susceptibility testing performance. Clinicians are now faced with the challenge of how to treat these complex infections without clinical breakpoints. Here we determine epidemiological cut-off values (ECVs) for relevant antimicrobials for the B. cepacia complex. While we established ECVs for four antimicrobials, we encountered significant challenges in our analyses, including limitations with data for these organisms and high ECVs that are not clinically useful. These challenges limit the practical use of these ECVs in helping guide clinicians on treatment and supported the eventual removal of ECVs from the CLSI M100 standards document.

Background: Stable osteochondritis dissecans (OCD) lesions are primarily treated nonoperatively. Nonoperative treatment includes several recommendations, including the use of an unloader brace. However, little is known about the clinical effectiveness of unloader bracing and its influence on OCD healing, return to sports, and patient-reported outcomes (PROs). The purpose of this investigation was to evaluate the impact of unloader bracing on patients with stable medial femoral condyle (MFC) OCD lesions treated nonoperatively. Purpose: To investigate the influence of valgus unloader bracing on the success of treating stable MFC OCD with nonoperative treatment strategies. Study Design: Cohort study; Level of evidence, 2. Methods: The authors used a prospective cohort of patients receiving nonoperative care for stable MFC knee OCD lesions. The primary variable of interest was the efficacy of bracing. The primary outcomes were transition from nonoperative care to surgical intervention, return-to-play (RTP) clearance, and PROs. Bivariate testing was used to determine if there were differences between groups. Chi-square testing was used to determine if there were differences in rates of transition to surgery by group. The timing of the transition by each group was assessed using a Wilcoxon rank-sum test, given the nonparametric nature of the data. Kaplan-Meier survival analysis was used to calculate time at risk, incidence rate, and survival times for each group. Results: A total of 185 knees (bracing group: 123 [66.5%] knees; no-bracing group: 62 [33.5%] knees) were analyzed. Overall, 142 (76.8%) knees were successfully treated nonoperatively. Transition to surgery occurred in 43 (23.2%) knees. There were no differences in transition to surgery by groups, with no differences seen by group. Of the knees that did not transition to surgical care, 65 (71.4%) in the bracing group and 38 (74.5%) in the no-bracing group received RTP clearance ( P = .693). PRO scores were similar between the 2 groups at the time of RTP clearance. Conclusion: The inclusion of an unloader brace in the nonoperative treatment for stable MFC OCD lesions did not decrease the likelihood of patients undergoing surgical intervention or improve their PRO scores at the time of RTP clearance. Registration: NCT02771496 (ClinicalTrials.gov identifier).

Background: Cardiac CT acquired during the acute stroke imaging protocol is an emerging diagnostic modality to detect cardiac thrombi. We aimed to determine its diagnostic yield in a large, international, multicenter study. Methods: We performed an individual patient data meta-analysis by pooling prospective and retrospective observational data of patients with acute ischemic stroke (AIS) who underwent cardiac CT (ECG-gated or non-ECG-gated) as part of the acute imaging protocol between May 2018 and June 2024. We excluded patients with a TIA or stroke mimic. The primary outcome was the proportion of patients with a cardiac thrombus detected on cardiac CT. Secondary outcomes were additional scan time and radiation dose, comparison of yield with echocardiography, and 90-day mortality and recurrent ischemic stroke rates. Results: We included 3940 patients from 4 hospitals (median age 74 [IQR 63-82], 58.0% male, median NIHSS 6 [IQR 3-12], median time onset to hospital arrival 100 minutes [IQR 62-185]). Atrial fibrillation at baseline was present in 23.1% patients, and 29.6% had a large vessel occlusion. Cardiac CT was non-diagnostic in 17 (0.4%) patients. In total, cardiac CT detected 254 cardiac thrombi in 243/3923 (6.2%) patients. Thrombi were located in the left atrial appendage (n=193), left atrium (n=19), and left ventricle (n=42). Of 95/243 (39.1%) patients with a cardiac thrombus that underwent echocardiography (median interval cardiac CT-echocardiography: 2 days), transthoracic echocardiography detected a thrombus in 18/92 (19.6%) patients and transesophageal echocardiography in 2/5 (40.0%) patients. The diagnostic yield in patients that underwent both modalities was higher for cardiac CT (OR 7.5 [CI 4.0-15.3], p<0.001). Median additional scan time was 6 minutes (IQR 5-7) for ECG-gated and 17 seconds (IQR 15-63) for non-ECG-gated cardiac CT. Median additional radiation dose was 5.4mSv (IQR 3.0-7.6). Patients with a cardiac thrombus on cardiac CT had higher 90-day mortality than those without a thrombus (33.3% vs 14.6%, p<0.001). We found no difference in 90-day recurrent stroke rate (5.4% vs 4.4%, p=0.50). Conclusion: Routine cardiac CT performed during the acute stroke imaging protocol detects a cardiac thrombus in 1 out of 16 patients with AIS, with a 7-times higher yield than routine echocardiography. Mortality rate was doubled in patients with a cardiac thrombus, but 90-day stroke recurrence risk did not differ.

Background: The rate of intracardiac thrombus detection in the hyperacute phase of stroke varies from 5% to 12% between studies. Our aim was to compare the thrombus detection rate between ECG-gated and non-ECG-gated cardiac CT protocols in acute stroke patients, using data from a large, international, multicentre registry. Methods: We conducted an individual patient data meta-analysis by pooling prospective and retrospective observational data from stroke patients assessed at four comprehensive stroke centres who underwent either ECG-gated or non-ECG-gated cardiac CT (extended CT angiography or two-phase non-ECG-gated cardiac CT) as part of the acute stroke imaging protocol between May 2018 and June 2024. The primary outcome was the proportion of patients with a cardiac thrombus in gated vs non gated techniques. Results: Of 3,940 patients, 1,474 (37.4%) underwent ECG-gated and 2,466 (62.6%) non-ECG-gated cardiac CT. Patients in the ECG-gated group were younger (median age 72 [IQR 62–81] vs. 74 [IQR 64–82] years, p = 0.000) and had a lower NIHSS at baseline (median 5 [IQR 2–12] vs. 6 [IQR 3–13], p < 0.00). There was a higher rate of thrombus detection with ECG-gated CT compared to non-gated CT (7.5% vs. 5.5%, p = 0.011. The association remained significant after adjusting for age, sex, baseline NIHSS score, and baseline atrial fibrillation (adjusted OR 1.87, 95% CI 1.42–2.47, p = 0.000). ECG-gated CT was associated with lower radiation dose (3.6 vs. 6.3 mSv, p = 0.000) but longer acquisition time (5.8 vs. 0.28 min, p = 0.000). Conclusion: ECG-gated cardiac CT has a higher detection rate for intracardiac thrombus detection compared to non-ECG-gated CT in patients with acute ischemic stroke.

The NCCN Clinical Practice Guidelines (NCCN Guidelines) for Wilms Tumor (WT; nephroblastoma) cover strategies for the screening, diagnosis, and treatment of WT, which is the most frequent primary kidney tumor in children. WT can generally be separated into 2 histology types: favorable histology WT and anaplastic WT. Five-year survival is high for children with favorable histology WT who receive appropriate treatment; however, survival rates are much lower for patients who present with higher stage diffuse anaplastic WT. Treatment of WT can range from surgery alone to surgery plus intensive chemotherapy and radiation depending on whether the tumor is unilateral or bilateral, histology, and local stage. The goal of therapy is to maximize cure while minimizing long-term toxicities. The content featured in this issue covers the NCCN panel’s recommendations for overall management of both favorable histology WT and anaplastic WT.

Purpose To establish international expert consensus on surgical techniques, complications, and rehabilitation protocols for lateral extra‐articular procedures (LEAPs) performed adjunctively with anterior cruciate ligament reconstruction. Methods Fifty‐five knee surgeons from 17 countries on 5 continents completed a 3‐round modified Delphi process. In the final round, 16 statements on LEAP techniques and complications were scored on a 5‐point Likert scale; ≥75% “agree/strongly agree” constituted consensus. When appropriate, strength of recommendation was graded. Statements lacking support were revised until consensus or abandonment. Results Six statements achieved unanimous consensus (100%), 2 had strong consensus (90%‐99.9%), and 3 reached consensus (75%‐89.9%); 4 were removed. Key technical recommendations were as follows: (1) in iliotibial band procedures, the graft strip should pass beneath the lateral collateral ligament; (2) an anatomic technique is mandatory for anterolateral ligament reconstruction; and (3) no single LEAP is clinically superior to another. Unanimous agreement indicated that modern LEAPs do not increase lateral compartment osteoarthritis risk, carry a low complication rate, and do not necessitate changes to rehabilitation or return‐to‐play timelines. Conclusions Consensus defined core surgical principles and confirmed the safety of adding LEAPs to anterior cruciate ligament reconstruction. When an iliotibial band graft is used, it should be routed deep to the lateral collateral ligament and fixed between 0° and 60° of knee flexion under low tension. For anterolateral ligament reconstruction, femoral fixation should be in full extension at a posterior‐proximal point relative to the lateral epicondyle. Although no single LEAP proved superiority, adherence to these principles permits safe, effective surgery without altering standard rehabilitation or return‐to‐sport protocols and without increasing osteoarthritis risk. Level of Evidence Level V, expert opinion.

Purpose To define expert consensus on whether and how lateral extra‐articular procedures (LEAPs) should accompany anterior cruciate ligament (ACL) reconstruction to optimize outcomes in ACL‐deficient knees. Methods Fifty‐five knee surgeons from 17 countries on 5 continents completed a 3‐round modified Delphi process. Twenty‐one statements on patient selection for combined ACL reconstruction (ACLR) + LEAPs were graded on 5‐point Likert scales; ≥75% “agree/strongly agree” signified consensus. Strength of recommendation was ranked, and statements failing the threshold were revised or discarded after discussion. Results One statement achieved unanimous agreement (100%): it is strongly recommended to add a LEAP for active patients ≤25 years receiving hamstring‐autograft ACLR to reduce graft failure. Strong consensus (≥90%) supported LEAPs in primary ACLR when grade 3 pivot shift (97.9%), knee hyperextension (97.9%), skeletally immature status (79.5%), revision ACLR (91.5%), return to pivoting sports (93.2%), active patients ≤25 years using nonhamstring grafts (90.7%), grade 3 Lachman test (90%), and when multiple relative risk factors coexist (statement 36, 97.1%). Consensus (75%‐89.9%) favored LEAPs for chronic symptomatic ACL deficiency (86.1%), posterior tibial slope >12° (85.7%), and a history of contralateral ACL injury (88.9%). Eight statements did not reach consensus regarding small‐diameter autografts, female athletes, imaging signs of anterolateral injury (e.g., Segond fracture, lateral femoral‐notch sign), and concomitant meniscal procedures. One statement on LEAPs with primary ACL repair was withdrawn because the project focused on reconstruction. Conclusions International experts strongly recommend adding a LEAP in young active patients undergoing hamstring‐autograft ACLR and in cases of high‐grade rotational or anterior laxity, knee hyperextension, revision surgery, or returning to pivoting sports. Unresolved issues include small graft size, female athletes, imaging findings of rotational instability, and concurrent meniscal procedures, highlighting priorities for future research. Level of Evidence Level V, expert opinion.

ABSTRACT The Burkholderia cepacia complex (BCC) is a group of Gram-negative bacteria that cause opportunistic infections, most notably in people with cystic fibrosis (CF), and have been associated with outbreaks caused by contaminated medical products. Antimicrobial susceptibility testing (AST) is often used to guide treatment for BCC infections, perhaps most importantly in people with CF who are being considered for lung transplant. However, recent studies have highlighted problems with AST methods. Here, we address limitations from previous studies to further evaluate BCC AST methods. We assessed the performance of reference broth microdilution (BMD), disk diffusion (DD) using Mueller-Hinton agar (MHA) from three manufacturers, agar dilution (AD), and gradient diffusion (ETEST) for ceftazidime (CAZ), levofloxacin (LVX), meropenem (MEM), minocycline (MIN), and trimethoprim-sulfamethoxazole (TMP-SMX) on a set of 205 BCC isolates. The isolate set included 100 isolates from people with CF and 105 isolates from people without CF from a variety of sources, which enabled us to systematically evaluate whether specimen source impacts AST performance. For all BCC isolates, BMD reproducibility was 93%, 98%, 99%, 98%, and 96% for CAZ, LVX, MEM, MIN, and TMP-SMX, respectively. Using BMD as the comparator method, we show that DD, AD, and ETEST perform poorly, with neither MHA manufacturer nor specimen source significantly impacting method performance. Based on our data, we recommend that routine AST should not be performed for BCC isolates. If a provider requests AST, clinical microbiology laboratories should perform Clinical and Laboratory Standards Institute reference methodology for BMD (stored frozen) and report MIC only. IMPORTANCE Antimicrobial susceptibility testing for the Burkholderia cepacia complex (BCC) is often used to determine eligibility for lung transplant in people with cystic fibrosis. However, problems with method performance have been reported. Here, we systematically evaluate the performance of reference broth microdilution, disk diffusion, agar dilution, and gradient diffusion (ETEST) for BCC organisms isolated from people with and without cystic fibrosis. We show that broth microdilution reproducibility is acceptable for levofloxacin, meropenem, minocycline, and trimethoprim-sulfamethoxazole, while ceftazidime was just below the acceptability cut-off. Regardless of specimen source, the results from disk diffusion, agar dilution, and ETEST do not correlate with broth microdilution. Based on these findings, we recommend that antimicrobial susceptibility testing should not be routinely performed for BCC, and if requested by the provider, only broth microdilution following Clinical and Laboratory Standards Institute guidelines should be used. Providers should be aware of the significant limitations of antimicrobial susceptibility testing methods for BCC.

Background: Osteochondritis dissecans (OCD) of the knee is a focal idiopathic alteration of subchondral bone and/or its precursor with risk for instability and disruption of adjacent cartilage. Treatment options focused on preventing premature osteoarthritis vary depending on multiple patient and lesion characteristics, including lesion mobility. Purpose: To differentiate lesion mobility before arthroscopy using a multivariable model that includes patient demographic characteristics and physical examination findings. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: Demographic, preoperative physical examination, and radiographic data were collected from a multicenter national prospective cohort of patients with OCD of the knee. Inclusion criteria included patients <19 years of age and patients with arthroscopically confirmed mobility status based on the Research on Osteochondritis Dissecans of the Knee arthroscopy classification. Multivariable logistic regression analysis using stepwise model selection was used to determine factors associated with the likelihood of a mobile versus an immobile lesion. A 75% partition of the data was used for model training, and 25% was used as a validation cohort. Quantitative model fit statistics were computed using the holdout data, including sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC), along with the corresponding 95% CI. Results: A total of 407 patients in the prospective cohort met inclusion criteria, and 62% were male. The mean ± SD age was 13.7 ± 2.2 years, height 161.8 ± 5.3 cm, and weight 59.2 ± 42.2 kg. Arthroscopic evaluation yielded 235 immobile and 172 mobile lesions. Multivariable analysis determined that the best model to predict lesion mobility included chronologic age ≥14 years ( P < .001), effusion on physical examination ( P < .001), and any loss of range of motion on physical examination ( P = .07), while controlling for male sex ( P = .38) and weight >54.4 kg ( P = .12). In the 25% holdout validation sample (n = 102), a sensitivity of 83%, a specificity of 82%, and an AUC of 0.89 (95% CI, 0.82-0.95) were achieved with these predictive factors. Conclusion: Age, effusion, and loss of motion can predict knee OCD lesion mobility at the time of arthroscopy. Education about lesion mobility can help with surgical planning and patient and family counseling.