Citations

Background: The number of multiply revised anterior cruciate ligament reconstructions (rrACLRs) performed each year continues to increase. The most reliable graft type and surgical technique in the young, active patient remains to be determined. Purpose: To determine the outcomes of rrACLR using quadriceps tendon (QT) autograft with lateral extra-articular tenodesis (LET). Study Design: Case series; Level of evidence, 4. Methods: A retrospective review was performed of all competitive athletes undergoing rrACLR with QT autograft and LET at a single institution with a minimum follow-up of 2 years. Patient demographics, physical examination, and radiological findings, and previous surgical details were documented. Patient outcomes were noted, including the International Knee Documentation Committee (IKDC) and Lysholm scores, ability to return to sport and return at the same level of play, retear rate, and other complications. Results: A total of 19 rrACLRs were performed and met inclusion criteria in the 10-year study period. All participants were high school, collegiate, or professional athletes with a mean age of 22 years, and 63.2% were female. The mean follow-up was 42.3 months, and IKDC scores increased from 51.6 preoperatively to 74.7 at the final follow-up ( P < .001). Likewise, the Lysholm score increased significantly from a preoperative value of 53.6 to 76.8 at the final follow-up ( P < .001). Return to play was possible in 52.6% of the patients at a mean of 11.5 months, with 31.6% returning to the same or higher level of play. One (5.3%) patient experienced a recurrent ACL tear, and 2 (10.5%) experienced a contralateral tear. Arthrofibrosis requiring surgical intervention occurred in 26.3% of the athletes. Conclusion: Short- to midterm results demonstrated that competitive athletes who received an rrACLR using a QT autograft with LET had statistically significant improvements in both IKDC and Lysholm scores, with more than half of patients being able to return to sport and nearly a third returning at the same or higher level of play. In the setting of a third ACL reconstruction, quadriceps tendon autograft with LET is a reasonable option even in high-risk patients.

Abstract Purpose While immunotherapy has transformed treatment in multiple solid tumors, its efficacy in high-grade glioma remains limited. Understanding the molecular and clinical factors that influence glioma’s response to immunotherapy is essential to improving outcomes. Methods We identified patients with recurrent glioblastoma or astrocytoma, IDH-mutant grade 4, who had been treated with checkpoint inhibitor (CPI), virus therapy, or cell therapy and determined the association between their molecular, clinical, and demographic characteristics and survival outcomes. Results We identified 66 patients, 57 glioblastoma and 9 astrocytoma, IDH-mutant grade 4; 38 were treated with CPI, 22 with virus therapy, and 6 with cell therapy. PIK3CA mutation was associated with shorter PFS and OS (p = 0.022, 0.073, respectively) among all patients and a shorter OS among CPI-treated patients (p = 0.004). Tumor tissue without the mutation had less PD-1 expression in CD3+/CD8 + T cells. In CPI-treated patients, IDH1/2 mutation was associated with a shorter OS (p = 0.002), and mutations in RB1 and TERT promoter were associated with a shorter PFS (p-value = 0.00056, 0.022, respectively). Length of CPI therapy of more than 6 months was associated with increased PFS and OS (p = 0.048, 0.062, respectively), while steroid use at baseline was associated with a shorter OS (p = 0.00023). Multifocal disease was associated with shorter PFS and OS durations (p = 0.0017, 0.0013, respectively) among all patients. Conclusions In high-grade glioma, PIK3CA, IDH1/2, RB1, and TERT promoter mutations may be associated with a poor response to immunotherapy. Our results may provide the rationale for clinical trials combining PI3K and IDH inhibitors with CPI in high-grade glioma.

Précis: Using a CNN-enhanced platform, 60-4 visual fields identified peripheral glaucomatous defects missed by central testing in mild cases; facial contour correction showed these defects occurred exclusively outside the temporal visual field. Purpose: To develop a methodology to separate facial contour-induced visual field defects from defects related to glaucoma in patients with peripheral field defects. Methods: Ninety-seven eyes from 50 patients previously diagnosed with glaucoma were enrolled in the study. Thirty-one (62%) participants were male, and 86% were white. The study involved patients with glaucoma who underwent visual field testing using standard automated perimetry, including 10-2, 24-2, 30-2, and 60-4 visual fields. A convolutional neural network (CNN)-enhanced platform, previously developed to identify facial contour-dependent defects in healthy subjects, was used to analyze the visual field data. Patients: The study included 97 eyes from 50 patients with glaucoma, with the majority having primary open angle glaucoma. Results: In 90 out of 97 eyes, there were 60-4 visual field defects. However, 20 (22%) of these eyes did not have glaucomatous defects on the 10-2 or 30-2 visual fields. All patients with 60-4 defects in the absence of more central defects had mild glaucoma, and these eyes comprised 38% of the mild glaucoma group. 60-4 visual field increased the sensitivity of identifying glaucoma in mild disease. Without facial contour, the 60-4 visual field mean threshold summation was 1099.6±346.6 dB, and decreased to 1057±331 dB when accounting for facial contour, which affected 8.03%±4.02% of test points. Facial contour-dependent visual field defects were exclusively found outside the temporal visual field. Conclusion: The study demonstrated the potential utility of 60-4 visual fields for identifying early functional glaucomatous changes that may not be detected by more central visual field tests (10-2 or 30-2). It may be important to consider peripheral visual field defects, which can be affected by facial contour, in the diagnosis and monitoring of glaucoma, particularly in mild cases.

ABSTRACTA core tenant of the Geriatric Emergency care Applied Research Network 2.0—Advancing Dementia Care (GEAR 2.0‐ADC) is the inclusion of community members during all stages of clinical research. As such, we deliberately integrated and supported patient and public involvement in the evaluation and selection of GEAR 2.0‐ADC Pilot Research Grants by developing and adapting traditional grant application review structures, with input from community members, to create the GEAR 2.0‐ADC Community Review Committee approach. Community members, including persons living with dementia, effectively participated in all three rounds of research grant application review and selection, complementing the traditional scientific review process. The structure and flexibility of the GEAR 2.0‐ADC Community Review Committee approach serve as a model for patient and public grant application review involvement with strong potential for applications across grant reviews in other medical specialties.

Abstract Background Noninvasive prenatal screening for common autosomal trisomies, sex chromosome aneuploidies and microdeletions vary by methodology and laboratory practice. The fetal portion of all cell-free DNA in the maternal circulation defines the fetal fraction (FF). The minimum specimen FF levels for reporting results vary between laboratories as well as the screening target (e.g., common trisomies vs select microdeletions). This variability can lead to confusion for both healthcare providers and patients. Methods Participants in the College of American Pathologists Non-Invasive Prenatal Testing 2021-B Exercise provided FF estimates for 3 manufactured samples. Responses to supplemental questions were also collected and analyzed. Results Overall, 72 of 77 participants responded. FF was measured by 66 participants using sequence counts (40), single nucleotide polymorphisms (15), fragment length (24), and Y chromosome sequences (24). Nearly half (48%) used multiple methods. For common trisomies, minimum FFs were none or &lt;1% (n = 7), 1.0% to 3.9% (n = 35), 4.0% to 6.9% (n = 23), and ≥7.0% (n = 1); 4 participants did not measure FF. Challenge-specific FFs were variable with CVs of 13%, 15%, and 36%; the latter rate appears due to that sample’s fetal karyotype of 47,XYY. Comparing adjusted FF results for the 3 samples shows that 85% of participant results were within 20% of the consensus. Conclusions Using multiple methods to estimate FF was common, and cutoff levels for sample suitability varied widely. Within-laboratory FFs were less variable than between laboratories. Current FF estimates from clinical laboratories are not standardized and should be considered laboratory-specific.

Abstract Background Robotic Whipple holds the promise to overcome safety concerns associated with laparoscopy, paving the way for widespread implementation of minimal-invasive surgery in this complex procedure. However, randomized data comparing robot vs. open Whipple demonstrate more pancreas-specific complications and R1-resections in the robotic arm. Recent international consensus identified establishing benchmarks as critical to ensure safe adoption of the robot. Benchmarking is a validated quality improvement tool, enabling comparison of surgical performance. Aims The aim was to define benchmarks for outcome parameters in robotic Whipple. Methods We analyzed consecutive patients undergoing robotic Whipple from January 2020 until December 2023 in 11 centers across 4 continents, with a minimum one-year follow-up. Centers had to perform ≥15 cases/year and have mounted their learning curve. Benchmark criteria included benign or resectable malignant disease without neoadjuvant therapy, arterial resection, major co-morbidities, or significant previous abdominal surgery. Medians across centers represented benchmark cutoffs. Results Eleven centers performed 1’037 Whipple procedures, of which 603 (58%) were benchmark cases. One third (n=192) were pancreatic ductal adenocarcinoma (PDAC) patients. Key benchmarks at 6 months included ≤1.2% mortality, ≤24.2% major complications, and ≤ 8.7 points Comprehensive Complication Index®. Pancreas-specific cutoffs included ≤13.0% postoperative pancreatic fistula (POPF) B/C and ≤3.4% post-pancreatectomy hemorrhage B/C, with 100% R0-resection and ≥19 harvested lymph nodes in PDAC patients. One-year actuarial overall and recurrence-free survival was 87% and 77%. In the entire cohort POPF B/C occurred in 16% (n=195). Independent POPF predictors included duct diameter ≤4mm (OR 1.79 95%CI [1.27-2.55]), anticoagulation (OR 3.68 95%CI [2.14-6.24]), and indication other than PDAC (OR 3.17, 95%CI [2.13-4.85]). Conclusion This study establishes benchmarks for key outcomes in robotic Whipple, demonstrating oncologic adequacy and morbidity comparable to open surgery. Risk factors for POPF in open surgery also hold true in the robotic approach.