Citations

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202 ) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

Summary: While the current approach to precursor hematologic conditions is to “watch and wait,” this may change with the development of therapies that are safe and extend survival or delay the onset of symptomatic disease. The goal of future therapies in precursor hematologic conditions is to improve survival and prevent or delay the development of symptomatic disease while maximizing safety. Clinical trial considerations in this field include identifying an appropriate at-risk population, safety assessments, dose selection, primary and secondary trial endpoints including surrogate endpoints, control arms, and quality-of-life metrics, all of which may enable more precise benefit–risk assessment.

Objective: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). Background: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. Methods: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. Results: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population (https://rediscover.unipi.it/). Conclusions: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Abstract Labral tears most commonly occur anteriorly between the 12‐ and 3‐o'clock positions, with the 12‐o'clock position denoted as superior and the 3‐o'clock position denoted as anterior. When approaching the 3‐o'clock position and beyond, suture anchor placement becomes difficult given the challenging arthroscopic trajectory and an overall thin anterior rim of cortical bone for anchor purchase, resulting in a narrow angle of safe drilling. The purpose of this technical note is to present a safe and reproducible method of suture anchor placement during acetabular labral repair approaching the 3‐ and 4‐o'clock positions, with the 12‐o'clock position representing the superior anatomic location and the 3‐o'clock position representing the anterior anatomic location regardless of hip laterality. We use an inside‐out anchor placement technique to place far medial anchors, which differs from the conventional techniques (e.g., outside‐in technique) in which anchor placement is performed along the external margin of the acetabular labrum. Technique Video video See video under supplementary data.

Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was, however, often employed in combination with other drugs, such as the antiviral remdesivir and glucocorticoids. The possible effect of such interaction has never been investigated systematically. To assess the safety and efficacy of CCP combined with other agents for treatment of patients hospitalized for COVID-19, a systematic literature search using appropriate Medical Subject Heading (MeSH) terms was performed through PubMed, EMBASE, Cochrane central, medRxiv and bioRxiv. The main outcomes considered were mortality and safety of CCP combined with other treatments versus CCP alone. This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Measure of treatment effect was the risk ratio (RR) together with 95% confidence intervals (CIs). A total of 11 studies (8 randomized controlled trials [RCTs] and 3 observational) were included in the systematic review, 4 studies with CCP combined with remdesivir and 6 studies with CCP combined with corticosteroids, all involving hospitalized patients. One RCT reported information on both remdesivir and steroids use with CCP. The use of CCP combined with remdesivir was associated with a significantly reduced risk of death (RR 0.74; 95% CI 0.56–0.97; p = 0.03; moderate certainty of evidence), while the use of steroids with CCP did not modify the mortality risk (RR 0.72; 95% CI 0.34–1.51; p = 0.38; very low certainty of evidence). Not enough safety data were retrieved form the systematic literature analysis. The current evidence from the literature suggests a potential beneficial effect on mortality of combined CCP plus remdesivir compared to CCP alone in hospitalized COVID-19 patients. No significant clinical interaction was found between CCP and steroids.

AbstractBackgroundComputed tomography (CT) is routinely used to guide cryoablation procedures. Notably, CT‐guidance provides 3D localization of cryoprobes and can be used to delineate frozen tissue during ablation. However, metal‐induced artifacts from ablation probes can make accurate probe placement challenging and degrade the ice ball conspicuity, which in combination could lead to undertreatment of potentially curable lesions.PurposeIn this work, we propose an image‐based neural network (CNN) model for metal artifact reduction for CT‐guided interventional procedures.MethodsAn image domain metal artifact simulation framework was developed and validated for deep‐learning‐based metal artifact reduction for interventional oncology (MARIO). CT scans were acquired for 19 different cryoablation probe configurations. The probe configurations varied in the number of probes and the relative orientations. A combination of intensity thresholding and masking based on maximum intensity projections (MIPs) was used to segment both the probes only and probes + artifact in each phantom image. Each of the probe and probe + artifact images were then inserted into 19 unique patient exams, in the image domain, to simulate metal artifact appearance for CT‐guided interventional oncology procedures. The resulting 361 pairs of simulated image volumes were partitioned into disjoint training and test datasets of 304 and 57 volumes, respectively. From the training partition, 116 600 image patches with a shape of 128 × 128 × 5 pixels were randomly extracted to be used for training data. The input images consisted of a superposition of the patient and probe + artifact images. The target images consisted of a superposition of the patient and probe only images. This dataset was used to optimize a U‐Net type model. The trained model was then applied to 50 independent, previously unseen CT images obtained during renal cryoablations. Three board‐certified radiologists with experience in CT‐guided ablations performed a blinded review of the MARIO images. A total of 100 images (50 original, 50 MARIO processed) were assessed across different aspects of image quality on a 4‐point likert‐type item. Statistical analyses were performed using Wilcoxon signed‐rank test for paired samples.ResultsReader scores were significantly higher for MARIO processed images compared to the original images across all metrics (all p < 0.001). The average scores of the overall image quality, iceball conspicuity, overall metal artifact, needle tip visualization, target region confidence, and worst metal artifact, needle tip visualization, iceball conspicuity, and target region confidence improved by 34.91%, 36.29%, 39.94%, 34.17%, 35.13%, and 45.70%, respectively.ConclusionsThe proposed method of image‐based metal artifact simulation can be used to train a MARIO algorithm to effectively reduce probe‐related metal artifacts in CT‐guided cryoablation procedures.

Background: Hip arthroscopy in patients with borderline hip dysplasia has satisfactory outcomes at short-term follow-up; however, the data on midterm outcomes are inconsistent, and failure rates are high in some studies, limiting understanding of the role and utility of hip arthroscopy in this patient cohort. Purpose: To provide an up-to-date, evidence-based review of the clinical outcomes of primary hip arthroscopy in patients with frank or borderline hip dysplasia at ≥5-year follow-up and report the failure rate and progression to total hip arthroplasty in this cohort. Study Design: Systematic review; Level of evidence, 4. Methods: A comprehensive literature search was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were included if they evaluated outcomes of primary hip arthroscopy in patients with lateral center-edge angle (LCEA) <25° at ≥5-year follow-up. Risk of bias assessment was performed using the methodological index for non-randomized studies scoring system. Level of evidence was determined using criteria from the Oxford Centre for Evidence-Based Medicine. Results: Nine studies were included in this review. Patients with LCEA <25° demonstrated satisfactory clinical outcomes, high patient satisfaction, and significant postoperative improvements in patient-reported outcomes (PROs) at follow-up ranging from a ≥5 to 10 years. Studies comparing patients with dysplasia to those without did not demonstrate significant differences in preoperative, postoperative, or delta PROs or in failure, reoperation, or revision rates. There was no overall significant correlation between outcomes and LCEA stratification. Conclusion: Hip arthroscopy in carefully selected patients with LCEA <25° can be successful at mid- to long-term follow-up and may provide clinical outcomes and failure rates comparable with patients with normal LCEA, understanding that this is a singular, 2-dimensional radiographic measure that does not differentiate instability from impingement or combinations thereof, warranting future studies delineating these differences. These findings suggest that hip dysplasia may not be an absolute contraindication for isolated hip arthroscopy and may serve as a viable intervention with consideration of staged future periacetabular osteotomy (PAO). Importantly, this review does not suggest that hip arthroscopy alters the natural history of dysplasia; therefore, patients with dysplasia should be counseled on the potential utility of PAO by appropriate hip preservation specialists.

Background: Matrix-induced autologous chondrocyte implantation (MACI) is an established cell-based therapy for the treatment of chondral defects of the knee. As long-term outcomes are now being reported in the literature, it is important to systematically review available evidence to better inform clinical practice. Purpose: To report (1) subjective patient-reported outcomes (PROs) and (2) the rate of graft failure, reoperation, and progression to total knee arthroplasty (TKA) after undergoing MACI of the knee at a minimum 10-year follow-up. Study Design: Systematic review; Level of evidence, 4. Methods: A comprehensive search of Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus from 2008 to September 15, 2022, was conducted in the English language. Study eligibility criteria included (1) full-text articles in the English language, (2) patients undergoing a MACI within the knee, (3) clinical outcomes reported, and (4) a minimum 10-year follow-up. Results: In total, 168 patients (99 male, 69 female; mean age, 37 years [range, 15-63 years]; mean body mass index, 26.2 [range, 18.6-39.4]) representing 188 treated chondral defects at a minimum 10-year follow-up after MACI were included in this review. Significant and durable long-term improvements were observed across multiple PRO measures. Follow-up magnetic resonance imaging (MRI), when performed, also demonstrated satisfactory defect fill and an intact graft in the majority of patients. The all-cause reoperation rate was 9.0%, with an overall 7.4% rate of progression to TKA at 10 to 17 years of follow-up. Conclusion: At a minimum 10-year follow-up, patients undergoing MACI for knee chondral defects demonstrated significant and durable improvements in PROs, satisfactory defect fill on MRI-based assessment, and low rates of reoperation and TKA. These data support the use of MACI as a long-term treatment of focal cartilage defects of the knee.

Abstract Meniscal extrusion (ME) is a valuable, noninvasive diagnostic tool for meniscus pathology. In addition, ultrasound can allow for instant results in the office. However, ME is a fragile metric in the degree of millimeters. The inconsistent techniques used by different authors in the literature and the additional operator variability that ultrasound technology introduces make it important a systematic approach is used. The purpose of this study is to propose a reproducible technique. The current authors recommend having the patient in (1) 30° of knee flexion while weight‐bearing, (2) capturing the image at the posterior border of the medial collateral ligament, (3) using a reference line parallel to the articular margin of the tibia, and (4) measuring ME at the coronal midpoint of the outermost edge of the meniscus. Technique Video video See video under supplementary data.