Citations

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Study Design: This was a retrospective cohort study. Objective: The present study is the first to investigate whether cervical paraspinal sarcopenia is associated with cervicothoracic sagittal alignment parameters after posterior cervical fusion (PCF). Summary of Background Data: Few studies have investigated the association between sarcopenia and postoperative outcomes after cervical spine surgery. Methods: We retrospectively reviewed patients undergoing PCF from C2–T2 at a single institution between the years 2017–2020. Two independent reviewers utilized axial cuts of T2-weighted magnetic resonance imaging sequences to perform Goutallier classification of the bilateral semispinalis cervicis (SSC) muscles. Cervical sagittal alignment parameters were compared between subgroups based upon severity of SSC sarcopenia. Results: We identified 61 patients for inclusion in this study, including 19 patients with mild SSC sarcopenia and 42 patients with moderate or severe SSC sarcopenia. The moderate-severe sarcopenia subgroup demonstrated a significantly larger change in C2–C7 sagittal vertical axis (+6.8 mm) from the 3-month to 1-year postoperative follow-up in comparison to the mild sarcopenia subgroup (−2.0 mm; P=0.02). The subgroup of patients with moderate-severe sarcopenia also demonstrated an increase in T1–T4 kyphosis (10.9–14.2, P=0.007), T1 slope (28.2–32.4, P=0.003), and C2 slope (24.1–27.3, P=0.05) from 3-month to 1-year postoperatively and a significant decrease in C1-occiput distance (6.3–4.1, P=0.002) during this same interval. Conclusions: In a uniform cohort of patients undergoing PCF from C2–T2, SSC sarcopenia was associated with worsening cervicothoracic alignment from 3-month to 1-year postoperatively.

Abstract Intratumoral heterogeneity arising from tumor evolution poses significant challenges biologically and clinically. Dissecting this complexity may benefit from deep learning (DL) algorithms, which can infer molecular features from ubiquitous hematoxylin and eosin (H&E)–stained tissue sections. Although DL algorithms have been developed to predict some driver mutations from H&E images, the ability of these DL algorithms to resolve intratumoral mutation heterogeneity at subclonal spatial resolution is unexplored. Here, we apply DL to a paradigm of intratumoral heterogeneity, clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer. Matched IHC and H&E images were leveraged to develop DL models for predicting intratumoral genetic heterogeneity of the three most frequently mutated ccRCC genes, BAP1, PBRM1, and SETD2. DL models were generated on a large cohort (N = 1,282) and tested on several independent cohorts, including a TCGA cohort (N = 363 patients) and two tissue microarray (TMA) cohorts (N = 118 and 365 patients). These models were also expanded to a patient-derived xenograft (PDX) TMA, affording analysis of homotopic and heterotopic interactions of tumor and stroma. The status of all three genes could be inferred by DL, with BAP1 showing the highest sensitivity and performance within and across tissue samples (AUC = 0.87–0.89 on holdout). BAP1 results were validated on independent human (AUC = 0.77–0.84) and PDX (AUC = 0.80) cohorts. Finally, BAP1 predictions correlated with clinical outputs such as disease-specific survival. Overall, these data show that DL models can resolve intratumoral heterogeneity in cancer with potential diagnostic, prognostic, and biological implications. Significance: This work demonstrates the potential for deep learning analysis of histopathologic images to serve as a fast, low-cost method to assess genetic intratumoral heterogeneity. See related commentary by Song et al., p. 2672

Study Design. Retrospective cohort study. Objective. The present study is the first to assess the impact of paraspinal sarcopenia on patient-reported outcome measures (PROMs) following posterior cervical decompression and fusion (PCDF). Summary of Background Data. While the impact of sarcopenia on PROMs following lumbar spine surgery is well-established, the impact of sarcopenia on PROMs following PCDF has not been investigated. Materials and Methods. We performed a retrospective review of patients undergoing PCDF from C2 to T2 at a single institution between the years 2017 and 2020. Two independent reviewers who were blinded to the clinical outcome scores utilized axial cuts of T2-weighted magnetic resonance imaging sequences to assess fatty infiltration of the bilateral multifidus muscles at the C5–C6 level and classify patients according to the Fuchs Modification of the Goutalier grading system. PROMs were then compared between subgroups. Results. We identified 99 patients for inclusion in this study, including 28 patients with mild sarcopenia, 45 patients with moderate sarcopenia, and 26 patients with severe sarcopenia. There was no difference in any preoperative PROM between the subgroups. Mean postoperative Neck Disability Index scores were lower in the mild and moderate sarcopenia subgroups (12.8 and 13.4, respectively) than in the severe sarcopenia subgroup (21.0, P <0.001). A higher percentage of patients with severe multifidus sarcopenia reported postoperative worsening of their Neck Disability Index (10 patients, 38.5%; P =0.003), Visual Analog Scale Neck scores (7 patients, 26.9%; P =0.02), Patient-Reported Outcome Measurement Information System Physical Component Scores (10 patients, 38.5%; P =0.02), and Patient-Reported Outcome Measurement Information System Mental Component Scores (14 patients, 53.8%; P =0.02). Conclusion. Patients with more severe paraspinal sarcopenia demonstrate less improvement in neck disability and physical function postoperatively and are substantially more likely to report worsening PROMs postoperatively. Level of Evidence. 3.

AbstractWilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi‐institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P < .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event‐free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage‐specific treatment regimens.

The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org .