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Background Urinary tract infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-E. coli) may occur as outbreaks due to common-source exposures. Yet, it is currently unknown if they cluster geographically as would be expected as part of an outbreak. Methods We collected electronic health record data on all patients living in San Francisco with culture-documented community-onset E. coli bacteriuria in a safety-net public healthcare system from January 2014 to March 2020 (diagnosed E. coli bacteriuria episodes, and (2) individuals with any ESBL-E. coli bacteriuria episode, with Global and Local Moran’s I. We evaluated differences in prevalence of bacteriuria recurrence by ESBL-production by Poisson regression. Results Out of 4,304 unique individuals, we identified spatial clusters of ESBL-E. coli bacteriuria episodes (n = 461) compared to non-ESBL-E. coli bacteriuria episodes (n = 5477; Global Moran’s p E. coli were not identified (p = 0.43). Bacteriuria recurrence was more likely to occur with ESBL-E. coli (odds ratio [OR] 2.78, 95% confidence interval [95% CI] 2.10, 3.66, p E. coli bacteriuria episode (OR 2.27, 95% CI 1.82, 2.83, p E. coli bacteriuria episodes. However, this was partly explained by clustering within individuals more than between individuals, as having an ESBL-E. coli bacteriuria was associated with recurrence with ESBL-E. coli.

Background Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intra-abdominal infection (cIAI). Methods Initially, we applied an a priori DOOR prototype to electronic patient-level data from 9 phase 3 noninferiority trials for cIAI submitted to the US Food and Drug Administration between 2005 and 2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we applied the cIAI-specific DOOR endpoint to the same datasets and, for each trial, estimated the probability that a participant assigned to the study treatment would have a more desirable DOOR or component outcome than if assigned to the comparator. Results Three key findings informed the cIAI-specific DOOR endpoint: (1) a significant proportion of participants underwent additional surgical procedures related to their baseline infection; (2) infectious complications of cIAI were diverse; and (3) participants with worse outcomes experienced more infectious complications, more serious adverse events, and underwent more procedures. DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 47.4% to 50.3% and were not significantly different. Component analyses depicted risk-benefit assessments of study treatment versus comparator. Conclusions We designed and evaluated a potential DOOR endpoint for cIAI trials to further characterize overall clinical experiences of participants. Similar data-driven approaches can be utilized to create other infectious disease–specific DOOR endpoints.

Background Desirability of outcome ranking (DOOR) uses an ordinal ranking system to evaluate global outcomes in clinical trial participants by incorporating safety and efficacy assessments into a single endpoint. In this study, we developed and applied a DOOR endpoint for cIAI clinical trials. Methods We reviewed 10 Phase 3 noninferiority trials for cIAI with electronic patient-level data (n=5473 participants) submitted to the FDA between 2005-2021. Extending previous work [CID. 2019:68(10):1691-8)], we developed an expanded cIAI-specific DOOR endpoint based on clinically meaningful events captured in trial datasets and those that were unique to patients with cIAI. Using this DOOR endpoint, we assigned each participant a DOOR rank, estimated the probability that a participant in the study treatment arm in each trial would have a more desirable DOOR rank than if assigned to the comparator arm, and analyzed individual components of clinical experience in each trial. Results Based on analysis of available data, we noted heterogeneity in definitions of “indeterminate” clinical outcomes, and significant diversity and increased incidence of infectious complications (ICs), serious adverse events (SAEs), and surgical/percutaneous procedures in participants without clinical cure. These informed the expansion of the DOOR endpoint for cIAI to include clinical efficacy outcomes, ICs, SAEs, and additional procedures (Table 1). The DOOR distributions between treatment and comparator arms in all 10 trials were similar. DOOR probability estimates for the 10 trials ranged from 44.5% to 50.3% but were not nominally statistically significant. Component analyses in two trials showed that the study treatment was nominally statistically inferior to the comparator with regard to SAEs and clinical failure, respectively (Fig. 1b, 1c). Table 1.cIAI-Specific DOOR EndpointFigure 1.Forest plot listing the DOOR probabilities and probability for each DOOR component from 3 trials. Trial 1 has no significant differences between the treatment arms in the component analysis (A). The study treatment arm was shown to be nominally statistically inferior for SAEs in Trial 2 (B) and for clinical failure in Trial 3 (C). Conclusion We developed a cIAI-specific DOOR endpoint to better elucidate the events that participants experienced in these trials. The component analysis allowed more nuanced evaluation of the factors that contributed to the composite DOOR probability estimate and provided a visual display of the risk-benefit assessment of a study treatment vs. the comparator. Our study was limited by its retrospective approach and trial design heterogeneity. Disclosures Deborah Collyar, B.Sci, Apellis Pharmaceuticals, Inc.: Advisor/Consultant|Kinnate Biopharma: Advisor/Consultant|M2GEN: Advisor/Consultant|Maxis Clinical Sciences: Advisor/Consultant|Parexel: Honoraria|Pfizer: Honoraria|Roundtable Analytics, Inc.: Ownership Interest Sarah B. Doernberg, MD, MAS, Basilea: Clincal events committee|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Regeneron: Grant/Research Support|Shinogi: Clincal events committee Scott R. Evans, Ph.D., M.S., Abbvie: DSMB|Akouos: DSMB|Apellis: DSMB|AstraZeneca: Advisor/Consultant|Atricure: Advisor/Consultant|Becton Dickenson: Advisor/Consultant|Breast International Group: DSMB|Candel: DSMB|ChemoCentrix: Advisor/Consultant|Clover: DSMB|DayOneBio: DSMB|DeGruyter: Editor|Duke University: DSMB|Endologix: Advisor/Consultant|FHI Clinical: DSMB|Genentech: Advisor/Consultant|Horizon: Advisor/Consultant|International Drug Development Institute: Advisor/Consultant|Janssen: Advisor/Consultant|Lung Biotech: DSMB|Neovasc: Advisor/Consultant|NIH: Grant/Research Support|Nobel Pharma: Advisor/Consultant|Nuvelution: DSMB|Pfizer: DSMB|Rakuten: DSMB|Roche: DSMB|Roivant: Advisor/Consultant|SAB Biopharm: DSMB|SVB Leerink: Advisor/Consultant|Takeda: DSMB|Taylor & Francis: Book royalties|Teva: DSMB|Tracon: DSMB|University of Penn: DSMB|Vir: DSMB Thomas L. Holland, MD, Aridis: Advisor/Consultant|Lysovant: Advisor/Consultant Henry Chambers, MD, Merck: DSMB member|Merck: Stocks/Bonds|Moderna: Stocks/Bonds Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds Sumathi Nambiar, MD MPH, Johnson and Johnson: Stocks/Bonds Helen W. Boucher, MD, American Society of Microbiology: Honoraria|Elsevier: Honoraria|Sanford Guide: Honoraria.

Background The combination of CZA-ATM is frequently used to treat patients with metallo-β-lactamase (MBL)-producing Enterobacterales (EB) infections, but its safety has not been established in controlled trials. This phase 1 study evaluated the safety of the optimal CZA-ATM regimens identified in the hollow fiber infection model of MBL-producing EB (PMID: 32464664). Methods The phase I, open-label, single center study enrolled healthy adults aged 18-45 years (NCT03978091). Subjects were sequentially assigned to 1 of 6 Cohorts and administered investigational product(s) (IP) for 7 days (Table 1). Study safety was monitored by assessments of adverse events (AEs), vital signs, and clinical laboratory safety tests. Results Of 48 subjects enrolled, 50% were female and 60% were Black. The mean (SD) age was 33.5 (6.2) years and mean (SD) weight was 75.7 (12.1) kg. The number of subjects who had ≥ 1 AE and experienced ≥ 1 IP related AE was 46 (96%) and 41 (85%), respectively. Frequency of IP related AEs by MedDRA system organ class, severity, and Cohort are shown in Figure 1. The occurrence of IP related investigation AEs were more frequent in the combination vs single IP Cohorts (Table 2). The most common IP related investigation AEs were ALT/AST elevations (35%) with 94% occurring in subjects who received ATM alone or in combination. The incidence of ALT/AST elevation AEs in the combination Cohorts were comparable to the ATM alone Cohorts. In the ATM single IP Cohorts, 3 subjects experienced severe ALT/AST elevation AEs, which halted the study. All subjects who experienced ALT/AST elevations were asymptomatic, had no other clinical findings suggestive of liver injury, and all resolved without intervention. Most other IP related AEs were of mild severity and similar across Cohorts except prolonged prothrombin time (PT) AEs, which was more frequent in combination Cohorts. Conclusion Clinicians should only consider using CZA-ATM when the benefits outweigh the risks. If CZA-ATM is prescribed, clinicians are advised to monitor for hepatic injury. Close monitoring of coagulation parameters may also be prudent with CZA-ATM. Future comparator-controlled randomized clinical trials are required to better define the safety and efficacy of the CZA-ATM regimens. Disclosures Thomas Lodise, Jr., Pharm.D., PhD, BioFire Diagnostics: Grant/Research Support|cidara: Advisor/Consultant|cidara: Honoraria|Entasis: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Paratek: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant|Venatrox: Advisor/Consultant J Nicholas O'Donnell, Pharm.D., Merck & Co, Inc: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support Stephen Balevic, MD, Purdue Pharma: Grant/Research Support|UCB: Advisor/Consultant Jeffrey Guptill, MD, argenx: Stocks/Bonds Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds henry chambers, MD, Merck: DSMB member|Merck: Stocks/Bonds|Moderna: Stocks/Bonds.

Background Scant PK data are available with CZA-ATM in combination. Occurrence of ALT/AST elevations are common with ATM, and it is unknown if it is exacerbated by use of CZA-ATM. This analysis of COMBINE sought to describe the popPK of CZA-ATM and to assess the association between ATM exposures and ALT/AST elevations. Methods COMBINE was a Phase I study of 48 healthy subjects aged 18-45 years (NCT03978091). Subjects were enrolled into 1 of 6 Cohorts (Table 1). Drug(s) were administered for 7 D and intensive plasma and urine PK sampling was performed. PopPK models were developed for ceftazidime (CAZ), avibactam (AVI), and ATM. Empirical Bayesian estimates from the ATM PopPK model were used to simulate ATM day 1 (D1) exposures. Associations between D1 ATM exposures and highest observed ALT/AST were assessed with curvilinear regression (CR) and generalized linear models (GLM). Results Of enrolled 48 subjects, 35% had ALT/AST elevations; 94% occurred in ATM/CZA-ATM Cohorts. Two severe study product related ALT/AST AEs were observed with in the continuous infusion (CI) ATM Cohort. All subjects with ALT/ATS elevations were asymptomatic with no other signs of liver injury. In the ATM PopPK model, CZA-ATM administration reduced ATM non-renal clearance (CLNR) by 1 L/hr (16% of total CL) (Table 2). Administration of CAZ-ATM had a negligible effect on total CAZ CL in the CAZ PopPK model and CZA-ATM was not a covariate in final AVI PopPK model. In the CR, no ATM exposure-ALT/AST associations were identified in overall analyses. Associations (R2=0.18-0.22, p< 0.05) between D1 AUC and ALT/AST were observed in CR analyses restricted to the intermittent infusion (II) ATM Cohorts (Figure 1). In GLM, D1 AUC was significantly associated with ALT/AST in the ATM II Cohort analyses. Administration of CZA-ATM was not associated with ALT/AST in the GLM analyses. Figure 1 Conclusion Administration of CZA-ATM was found to reduce ATM CL, resulting in higher daily ATM AUCs, but did not exacerbate AST/ALT elevations relative to ATM alone. The observed association between ATM AUC and ALT/AST elevations in subjects who received II ATM suggest the risks vs benefits of using II of ATM 8 g/daily vs 6 g/daily with CZA should be considered. Use of CI ATM should be used with caution given the 2 severe ALT/ASTs in the CI ATM Cohort. Disclosures Thomas Lodise, Jr., Pharm.D., PhD, BioFire Diagnostics: Grant/Research Support|cidara: Advisor/Consultant|cidara: Honoraria|Entasis: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Paratek: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant|Venatrox: Advisor/Consultant J Nicholas O'Donnell, Pharm.D., Merck & Co, Inc: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support Stephen Balevic, MD, Purdue Pharma: Grant/Research Support|UCB: Advisor/Consultant Jeffrey Guptill, MD, argenx: Stocks/Bonds Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds henry chambers, MD, Merck: DSMB member|Merck: Stocks/Bonds|Moderna: Stocks/Bonds.

Investigate the efficacy and safety of multipattern incobotulinumtoxinA injections in children/adolescents with lower-limb cerebral palsy (CP)-related spasticity.Phase 3 double-blind study in children/adolescents (Gross Motor Function Classification System - Expanded and Revised I-V) with unilateral or bilateral spastic CP and Ashworth Scale (AS) plantar flexor (PF) scores ⩾ 2 randomized (1:1:2) to incobotulinumtoxinA (4, 12, 16 U/kg, maximum 100, 300, 400 U, respectively) for two 12- to 36-week injection cycles. Two clinical patterns were treated. Pes equinus (bilateral or unilateral) was mandatory; if unilateral, treatment included flexed knee or adducted thigh.Primary: AS-PF change from baseline to 4 weeks; Coprimary: investigator-rated Global Impression of Change Scale (GICS)-PF at 4 weeks; Secondary: investigator's, patient's, and parent's/caregiver's GICS, Gross Motor Function Measure-66 (GMFM-66).Among 311 patients, AS-PF and AS scores in all treated clinical patterns improved from baseline to 4-weeks post-injection and cumulatively across injection cycles. GICS-PF and GICS scores confirmed global spasticity improvements. GMFM-66 scores indicated better motor function. No significant differences between doses were evident. Treatment was well-tolerated, with no unexpected treatment-related adverse events or neutralising antibody development.Children/adolescents with lower-limb spasticity experienced multipattern benefits from incobotulinumtoxinA, which was safe and well-tolerated in doses up to 16 U/kg, maximum 400 U.

Background: Treatment options for pediatric and adolescent anterior cruciate ligament (ACL) injuries include early operative, delayed operative, and nonoperative management. Currently, there is a lack of consensus regarding the optimal treatment for these injuries. Purpose/Hypothesis: The purpose was to determine the optimal treatment strategy for ACL injuries in pediatric and adolescent patients. We hypothesized that (1) early ACL reconstruction results in fewer meniscal tears than delayed reconstruction but yields no difference in knee stability and (2) when compared with nonoperative management, any operative management results in fewer meniscal tears and cartilage injuries, greater knee stability, and higher return-to-sport rates. Study Design: Systematic review and meta-analysis; Level of evidence, 4. Methods: A systematic search of databases was performed including PubMed, Embase, and Cochrane Library using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were a pediatric and adolescent patient population (≤19 years old at surgery), the reporting of clinical outcomes after treatment of primary ACL injury, and original scientific research article. Exclusion criteria were revision ACL reconstruction, tibial spine avulsion fracture, case report or small case series (Results: A total of 30 studies containing 50 cohorts and representing 1176 patients met our criteria. With respect to nonoperative treatment, knee instability was observed in 20% to 100%, and return to preinjury level of sports ranged from 6% to 50% at final follow-up. Regarding operative treatment, meta-analysis results favored early ACL reconstruction over delayed reconstruction (>12 weeks) for the presence of any meniscal tear (odds ratio, 0.23; P = .006) and irreparable meniscal tear (odds ratio, 0.31; P = .001). Comparison of any side-to-side differences in KT-1000 arthrometer testing did not favor early or delayed ACL reconstruction in either continuous mean differences ( P = .413) or proportion with difference ≥3 mm ( P = .181). Return to preinjury level of competition rates for early and delayed ACL reconstruction ranged from 57% to 100%. Conclusion: Delaying ACL reconstruction in pediatric or adolescent patients for >12 weeks significantly increased the risk of meniscal injuries and irreparable meniscal tears; however, early and delayed operative treatment achieved satisfactory knee stability. Nonoperative management resulted in high rates of residual knee instability, increased risk of meniscal tears, and comparatively low rates of return to sports.

Breaststroker’s knee is an overuse syndrome resulting from similar repetitive movements in competitive swimmers that has been described in the orthopedic literature. The typical symptoms are medial knee pain with tenderness to palpation at the tibial collateral ligament or inferomedial patella. Despite these localizing symptoms on clinical exam, arthroscopic studies have failed to demonstrate a specific structural abnormality corresponding to this syndrome, although some have reported thickened medial synovial plica, medial-predominant synovitis or patellofemoral cartilage loss in association knee pain with breaststroke swimmers. We present a case of medial knee pain in a young breaststroke swimmer with magnetic resonance imaging (MRI) findings of marrow edema in the anterior aspect of the medial femoral condyle. To our knowledge, this is the first reported case of MRI findings in breaststroker’s knee .

Among patients with methicillin-resistant Staphylococcus aureus bacteremia, vancomycin-associated acute kidney injury increased as a function of the day 2 area under the curve (AUC), even for daily AUCs within the recommended therapeutic range (400–600). Further data are needed to determine if daily AUCs

Purpose: The purpose of this study was to develop consensus for the surgical indications of anterior distal femur hemiepiphysiodesis in children with cerebral palsy using expert surgeon opinion through a modified Delphi technique. Methods: The panel used a 5-level Likert-type scale to record agreement or disagreement with 27 statements regarding anterior distal femur hemiepiphysiodesis. Consensus was defined as at least 80% of responses being in the highest or lowest 2 of the Likert-type ratings. General agreement was defined as 60%–79% falling into the highest or lowest 2 ratings. Results: For anterior distal femur hemiepiphysiodesis, 27 statements were surveyed: consensus or general agreement among the panelists was achieved for 22 of 27 statements (22/27, 82%) and 5 statements had no agreement (5/27, 18%). There was general consensus that anterior distal femur hemiepiphysiodesis is indicated for ambulatory children with cerebral palsy, with at least 2 years growth remaining, and smaller (Conclusion: Anterior distal femur hemiepiphysiodesis can be used to treat fixed knee flexion contractures in the setting of crouch gait, but other associated lever arm dysfunctions must be addressed by single-event multilevel surgery. Level of evidence: V

Objectives: The most common presentation of knee osteochondritis dissecans (OCD) is a stable lesion on the lateral aspect of the medial femoral condyle (MFC) in an adolescent or pre-adolescent athlete. The standard of care for primary treatment is non-operative, and includes rest/activity modification and often weight bearing protection or bracing. Failed conservative management often leads arthroscopy and drilling of the lesion. Two different primary drilling techniques have been utilized, but no prospective studies have compared their relative effectiveness. The study hypothesis was that retro-articular drilling (RAD), the slightly newer technique, would not be inferior to trans-articular (TAD), with regard to rate of healing, time to return to sports (RTS), and patient-reported outcome scores (PROs). Methods: Skeletally immature (n=113) patients presenting with MRI-confirmed stable OCD of the MFC who did not demonstrate substantial healing after a minimum of 3 months of non-operative treatment were prospectively enrolled by one of seventeen surgeon-investigators (at 14 centers, representing all major geographic regions in the U.S.) and randomized to TAD or RAD. Post-operatively, serial radiographs were obtained every 6 weeks to assess healing, and PROs were obtained at 6 months, 12 months, and 24 months. Twelve patients were closed out at time of surgery due to lesion instability detected during arthroscopy. Power analysis determined that in order to detect a difference in 2-year IKDC score between RA and TA groups with 80% power, sample sizes of 37 subjects per group would be required if the true standard deviation were 15. This analysis was based on conducting an independent samples Student’s t-test with alpha set to 5%. Results: Ninety-one study subjects were included, consisting of 51 TAD and 40 RAD patients, respectively, with the two groups being similar in age (12.6 years vs. 11.9 years), sex distribution (45% vs. 27% female, p=0.081), and 2-year PRO response rate (both 90%). No significant differences between TAD and RAD were detected in follow-up Pedi-IKDC, Lysholm, Marx knee activity score, or KOOS QOL scores (Table 1). Revision/additional OCD surgery occurred in 10% of patients in RAD and 4% in TAD (p=0.40). 73% of TAD patients reached a ‘healed’ status at a mean of 1.15 years, compared with 60% RAD patients at a mean of 1.21 years. Conclusions: While both primary forms of OCD drilling (TAD and RAD) showed consistent post-operative healing, achieving a completely ‘healed’ status was often a more prolonged process, taking approximately 1 year, despite clinical improvement and RTS being achieved much sooner. PROs were similar between drilling techniques. Significantly higher powered studies are needed to better elucidate the greater revision surgery rates in RAD compared with TAD, but overall risk is low and absolute risk only 6%. The current data support either drilling technique, which may be technically simpler, without the need for fluoroscopy, with TAD, and may be more protective of the chondral articular surface with RAD.

Purpose: There is marked variation in indications and techniques for hamstring surgery in children with cerebral palsy. There is particular uncertainty regarding the indications for hamstring transfer compared to traditional hamstring lengthening. The purpose of this study was for an international panel of experts to use the Delphi method to establish consensus indications for hamstring surgery in ambulatory children with cerebral palsy. Methods: The panel used a five-level Likert-type scale to record agreement or disagreement with statements regarding hamstring surgery, including surgical indications and techniques, post-operative care, and outcome measures. Consensus was defined as at least 80% of responses being in the highest or lowest two of the five Likert-type ratings. General agreement was defined as 60%–79% falling into the highest or lowest two ratings. There was no agreement if neither of these thresholds was reached. Results: The panel reached consensus or general agreement for 38 (84%) of 45 statements regarding hamstring surgery. The panel noted the importance of assessing pelvic tilt during gait when considering hamstring surgery, and also that lateral hamstring lengthening is rarely needed, particularly at the index surgery. They noted that repeat hamstring lengthening often has poor outcomes. The panel was divided regarding hamstring transfer surgery, with only half performing such surgery. Conclusion: The results of this study can help pediatric orthopedic surgeons optimize decision-making in their choice and practice of hamstring surgery for ambulatory children with cerebral palsy. This has the potential to reduce practice variation and significantly improve outcomes for ambulatory children with cerebral palsy. Level of evidence: level V.

Background: Imaging characteristics of osteochondritis dissecans (OCD) lesions quantified by magnetic resonance imaging (MRI) are often used to inform treatment and prognosis. However, the interrater reliability of clinician-driven MRI-based assessment of OCD lesions is not well documented. Purpose: To determine the interrater reliability of several historical and novel MRI-derived characteristics of OCD of the knee in children. Study Design: Cohort study (diagnosis); Level of evidence, 3 Methods: A total of 42 OCD lesions were evaluated by 10 fellowship-trained orthopaedic surgeons using 31 different MRI characteristics, characterizing lesion size and location, condylar size, cartilage status, the interface between parent and progeny bone, and features of both the parent and the progeny bone. Interrater reliability was determined via intraclass correlation coefficients (ICCs) with 2-way random modeling, Fleiss kappa, or Krippendorff alpha as appropriate for each variable. Results: Raters were reliable when the lesion was measured in the coronal plane (ICC, 0.77). Almost perfect agreement was achieved for condylar size (ICC, 0.93), substantial agreement for physeal patency (ICC, 0.79), and moderate agreement for joint effusion (ICC, 0.56) and cartilage status (ICC, 0.50). Overall, raters showed significant variability regarding interface characteristics (ICC, 0.25), progeny (ICC range, 0.03 to 0.62), and parent bone measurements and qualities (ICC range, –0.02 to 0.65), with reliability being moderate at best for these measurements. Conclusion: This multicenter study determined the interrater reliability of MRI characteristics of OCD lesions in children. Although several measurements provided acceptable reliability, many MRI features of OCD that inform treatment decisions were unreliable. Further work will be needed to refine the unreliable characteristics and to assess the ability of those reliable characteristics to predict clinical lesion instability and prognosis.

Background Selected MRSA strains become susceptible to β-lactams (e.g., oxacillin [OX]; cefazolin [CFZ]) in vitro when tested in a standard medium (cation-adjusted Mueller–Hinton Broth; CA-MHB) supplemented with NaHCO3 (“NaHCO3-responsivity”). In vivo activity of β-lactams was demonstrated for MRSA strains with this phenotype in a rabbit endocarditis model (Ersoy et al Antimicrob Agents Chemother 2019). The current study was designed to: (i) determine the prevalence of the NaHCO3-responsive phenotype in a large collection of clinical MRSA isolates; and (ii) identify genetic and phenotypic predictors of this phenotype. Methods. 58 recent MRSA bloodstream isolates representing contemporary clonal complex (CC) genotypes were screened for the NaHCO3-responsive phenotype by broth microdilution MICs in CA-MHB, with or without NaHCO3 supplementation (25–44 mM). Methods 58 recent MRSA bloodstream isolates representing contemporary clonal complex (CC) genotypes were screened for the NaHCO3-responsive phenotype by broth microdilution MICs in CA-MHB, with or without NaHCO3 supplementation (25–44 mM). Results 43/58 (74.1%) and 21/58 (36.2%) were rendered susceptible to CFZ and OX, respectively, in the presence of NaHCO3; 20 of the 21 OX-susceptible strains were also susceptible to CFZ in the presence of NaHCO3. High baseline β-lactam MICs (i.e., MICs in CA-MHB alone ≥64 µg/mL) was not predictive of NaHCO3 responsivity. The CC8 genotype was correlated with NaHCO3 responsivity for OX, but not CFZ (P < 0.05). Conclusion The NaHCO3-responsive phenotype is relatively common for both OX and especially CFZ among clinical MRSA isolates. Identification of specific genetic factors linked to this phenotype remains ongoing. Confirmation in relevant animal models that this phenotype is predictive of β-lactam efficacy in vivo could provide a solid foundation for a paradigm shift in antimicrobial susceptibility testing of MRSA. Disclosures All authors: No reported disclosures.

Shoulder and back pain in school children is associated with wearing heavy backpacks. Such pain may be attributed to the magnitude of the backpack load and the manner by which children distribute the load over their shoulders and back. The purpose of this study is to quantify the pressures under backpack straps of children while they carried a typical range of loads during varying conditions.Ten healthy children (aged, 12-14 years) wore a backpack loaded at 10%, 20%, and 30% body weight (BW). Backpacks were carried under 2 conditions, low on back or high on back. Pressure sensors (0.1 mm thick) measured pressures beneath the shoulder straps.When walking with the backpack straps over both shoulders, contact pressures were significantly greater in the low-back condition than in the high-back condition (P = 0.004). In addition, when children carried the backpack in the low-back condition, mean pressures (+/-SE) over the right shoulder were as follows: 98 +/- 31, 153 +/- 48, and 170 +/- 54 mm Hg at 10%, 20%, and 30% BW, respectively, which were significantly higher (P0.001) than those over the left shoulder (46 +/- 14, 92 +/- 29, and 90 +/- 29 mm Hg, respectively). Perceived pain with the backpack over 1 shoulder was significantly greater (P = 0.002) than that for donning with both shoulders in the low-back condition.Pressures at 10%, 20%, and 30% BW loads on the right or left shoulder, during low-back or high-back conditions, are higher than the pressure thresholds (approximately 30 mm Hg) to occlude skin blood flow. Furthermore, asymmetric and high pressures exerted for extended periods of time may help explain the shoulder and back pain attributed to backpacks.

Orthopedic surgery for patients with cerebral palsy addresses motion impairments, assuming that this will improve motor function. This study evaluates the relationships among clinical impairment measures with standardized assessments of function and disability as an initial step in testing this assumption. A total of 129 ambulatory children and adolescents across six institutions participated in a prospective evaluation that consisted of passive motion and spasticity examination of the lower extremities, three-dimensional gait temporal-spatial and kinematic analysis, and administration of the Gross Motor Function Measure (GMFM) and the Pediatric Outcomes Data Collection Instrument (PODCI). The analysis found that isolated impairment measures of motion and spasticity were only weakly related to motor function in cerebral palsy and even when averaged across multiple joints yielded no more than a fair correlation with functional scores, nor did a combination of impairments emerge that could predict substantial variance in motor function. These findings suggest that caution should be exercised when anticipating functional change through the treatment of isolated impairment and that addressing multiple impairments may be needed to produce appreciable effects.