Citations

Abstract Patients with head and neck squamous cell carcinomas (HNSCC) often have poor outcomes due to suboptimal risk management and treatment strategies; yet integrating novel prognostic biomarkers into clinical practice is challenging. Here, we report the presence of multinucleated giant cells (MGC)—a type of macrophages—in tumors from patients with HNSCC, which are associated with a favorable prognosis in treatment-naive and preoperative chemotherapy–treated patients. Importantly, MGC density increased in tumors following preoperative therapy, suggesting a role of these cells in the antitumoral response. To enable clinical translation of MGC density as a prognostic marker, we developed a deep-learning model to automate its quantification on routinely stained pathological whole slide images. Finally, we used spatial transcriptomic and proteomic approaches to describe the MGC-related tumor microenvironment and observed an increase in central memory CD4 T cells. We defined an MGC-specific signature resembling to TREM2-expressing mononuclear tumor-associated macrophages, which colocalized in keratin tumor niches. Significance: Novel individual biomarkers are needed to guide therapeutic decisions for patients with head and neck cancer. We report for the first time, granulomas of TREM2-expressing multinucleated giant macrophages in keratin-rich tumor niches, as a biomarker of favorable prognosis and developed a deep-learning model to automate its quantification on routinely stained pathological slides.

OBJECTIVE Myelopathy in the cervical spine can present with diverse symptoms, many of which can be debilitating for patients. Patients with radiculopathy symptoms demonstrate added complexity because of the overlapping symptoms and treatment considerations. The authors sought to assess outcomes in patients with myelopathy presenting with or without concurrent radiculopathy. METHODS The Quality Outcomes Database, a prospectively collected multi-institutional database, was used to analyze demographic, clinical, and surgical variables of patients presenting with myelopathy or myeloradiculopathy as a result of degenerative pathology. Outcome measures included arm (VAS-arm) and neck (VAS-neck) visual analog scale (VAS) scores, modified Japanese Orthopaedic Association (mJOA) scale score, EuroQol VAS (EQ-VAS) score, and Neck Disability Index (NDI) at 3, 12, and 24 months compared with baseline. RESULTS A total of 1015 patients were included in the study: 289 patients with myelopathy alone (M0), 239 with myeloradiculopathy but no arm pain (MRAP−), and 487 patients with myeloradiculopathy and arm pain (MRAP+). M0 patients were older than the myeloradiculopathy cohorts combined (M0 64.2 vs MRAP− + MRAP+ 59.5 years, p < 0.001), whereas MRAP+ patients had higher BMI and a greater incidence of current smoking compared with the other cohorts. There were more anterior approaches used in in MRAP+ patients and more posterior approaches used in M0 patients. In severely myelopathic patients (mJOA scale score ≤ 10), posterior approaches were used more often for M0 (p < 0.0001) and MRAP+ (p < 0.0001) patients. Patients with myelopathy and myeloradiculopathy both exhibited significant improvement at 1 and 2 years across all outcome domains. The amount of improvement did not vary based on surgical approach. In comparing cohort outcomes, postoperative outcome differences were associated with patient-reported scores at baseline. CONCLUSIONS Patients with myelopathy and those with myeloradiculopathy demonstrated significant and similar improvement in arm and neck pain scores, myelopathy, disability, and quality of life at 3 months that was sustained at 1- and 2-year follow-up intervals. More radicular symptoms and arm pain increased the likelihood of a surgeon choosing an anterior approach, whereas more severe myelopathy increased the likelihood of approaching posteriorly. Surgical approach itself was not an independent predictor of outcome.

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease provide strategies for the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in adult patients with cancer. VTE is a common and life-threatening condition in patients with cancer, and its management often requires multidisciplinary efforts. The NCCN panel is comprised of specialists spanning various fields, including cardiology, hematology, medical oncology, internal medicine, interventional radiology, and pharmacology. The content featured in this issue specifically addresses the evaluation and recommended treatment options outlined in the NCCN Guidelines for the diverse subtypes of cancer-associated VTE.

Study Design: A retrospective chart review. Objective: The authors aim to investigate the role of clinical and radiographic parameters in patients who underwent posterior cervical surgery, and their association with C5 palsy severity and time to recovery. Background: Postoperative C5 palsy affects 1%–30% of patients undergoing posterior decompression, with or without fusion. Causation and avoidance of this complication remain widely debated. Materials and Methods: A single institution review of patients who underwent posterior cervical spine surgery was focused on using specific Common Procedural Technology codes associated with the patient population of interest. Patients were excluded if they had inadequate pre and postoperative imaging, as well as a history of prior cervical spine surgery, concurrent anterior surgery, intradural pathology, spinal tumor, or spinal trauma. Radiographic measurements of the pre and postoperative images were completed with subsequent intraclass correlation coefficient analysis to confirm the precision of measurements. Results: Out of 105 total patients, 35 (33%) patients developed a C5 palsy. Twenty-four (69%) of those palsies completely resolved, with a median time to recovery of 8 months. Preoperative demographics and radiographic parameters demonstrated heterogeneity among those patients who did and did not have a resolution of palsy. Patients with increased change in C2–C7 lordosis (P = 0.011) after surgery were associated with decreased likelihood of recovery. Patients without a smoking history (P = 0.009) had an increased likelihood of recovering from C5 palsy. Conclusions: The degree of increased lordosis in the treatment of degenerative cervical disease plays a role in the rate of recovery from C5 palsy. This should be considered during preoperative planning in determining the amount of lordosis desired. In addition, patients without a smoking history were associated with a higher rate of recovery. Level of Evidence: Level IV.

OBJECTIVE Lumbar decompression and/or fusion surgery is a common operation for symptomatic lumbar spondylolisthesis refractory to conservative management. Multiyear follow-up of patient outcomes can be difficult to obtain but allows for identification of preoperative patient characteristics associated with durable pain relief, improved functional outcome, and higher patient satisfaction. METHODS A query of the Quality Outcomes Database (QOD) low-grade spondylolisthesis module for patients who underwent surgery for grade 1 lumbar spondylolisthesis (from July 2014 to June 2016 at the 12 highest-enrolling sites) was used to identify patient satisfaction, as measured with the North American Spine Society (NASS) questionnaire, which uses a scale of 1–4. Patients were considered satisfied if they had a score ≤ 2. Multivariable logistic regression was performed to identify baseline demographic and clinical predictors of long-term satisfaction 5 years after surgery. RESULTS Of 573 eligible patients from a cohort of 608, patient satisfaction data were available for 81.2%. Satisfaction (NASS score of 1 or 2) was reported by 389 patients (83.7%) at 5-year follow-up. Satisfied patients were predominantly White and ambulation independent and had lower baseline BMI, lower back pain levels, lower Oswestry Disability Index (ODI) scores, and greater EQ-5D index scores at baseline when compared to the unsatisfied group. No significant differences in reoperation rates between groups were reported at 5 years. On multivariate analysis, patients who were independently ambulating at baseline had greater odds of long-term satisfaction (OR 1.12, p = 0.04). Patients who had higher 5-year ODI scores (OR 0.99, p < 0.01) and were uninsured (OR 0.43, p = 0.01) were less likely to report long-term satisfaction. CONCLUSIONS Lumbar surgery for the treatment of grade 1 spondylolisthesis can provide lasting pain relief with high patient satisfaction. Baseline independent ambulation is associated with a higher long-term satisfaction rate after surgery. Higher ODI scores at 5-year follow-up and uninsured status are associated with lower postoperative long-term satisfaction.

Background Although flow diverters (FDs) have benefited from several technical improvements, recently concerns have arisen regarding the braid stability after implantation. Thus, we investigated frequency, predictive factors, and clinical impact of the phenomenon of FD braid deformation (FDBD). Methods Consecutive intracranial aneurysms (IAs) treated with various FDs, between January 2018 and July 2023, were reviewed to identify FDBD (defined as the deformation of a FD without any external force applied to it). Patient, aneurysm, procedural, and FD characteristics were retrieved and analyzed using univariate and multivariable analyses. Morbidity is defined as a score of +1 in the modified Rankin Scale at 3 months. Results In total, 245 FD procedures (271 FDs implanted; 25 multiple IAs treated with 1 FD) in 228 patients; FDBD was observed in 36/245 cases (14.7%), mainly at follow-up angiography (32/36, 88.9%); fish-mouthing was the most frequent FDBD. Morbidity was related to fish-mouthing and braid collapse and was significantly higher in the FDBD group after retreatment (p=0.04). Drawn filled tubing with platinum (DFT) (adjusted odds ratio (aOR)=7.0, 95% CI 3.0 to 17.5; p<0.001) and FD diameter (aOR=2.2, 95% CI 1.3 to 4.1; p<0.01) were identified as independent predictors of FDBD. The metal alloy composing the FD (p=0.13) and coated surfaces were not significantly associated with FDBD (p=0.54 in multivariable analysis). Conclusions FDBD is a frequent phenomenon observed in about 15% of cases, and it was responsible for higher morbidity. Only FD characteristics (DFT and FD diameter) were independent determinants of FDBD. Future research should focus on the impact of novel braid configurations and materials on braid stability.

Background: Understanding interactions between multiple risk factors for shoulder and elbow injuries in Major League Baseball (MLB) pitchers is important to identify potential avenues by which risk can be reduced while minimizing impact on player performance. Purpose: To apply a novel game theory–based approach to develop a machine-learning model predictive of next-season shoulder and elbow injuries in MLB pitchers and use this model to understand interdependencies and interaction effects between the most important risk factors. Study Design: Case-control study; Level of evidence, 3. Methods: Pitcher demographics, workload measures, pitch-tracking metrics, and injury data between 2017 and 2022 were used to construct a database of MLB pitcher-years, where each item in the database corresponded to a pitcher's information and metrics for that year. An extreme gradient boosting machine-learning model was trained to predict next-season shoulder and elbow injuries utilizing Shapley additive explanation values to quantify feature importance as well as interdependencies and interaction effects between predictive variables. Results: A total of 3808 pitcher-years were included in this analysis; 606 (15.9%) of these involved a shoulder or elbow injury resulting in placement on the MLB injured list. Of the >65 candidate features (including workload, demographic, and pitch-tracking metrics), the most important contributors to predicting shoulder/elbow injury were increased: pitch velocity (all pitch types), utilization of sliders (SLs), fastball (FB) spin rate, FB horizontal movement, and player age. The strongest game theory interaction effects were that higher FB velocity did not alter a younger pitcher's predicted risk of shoulder/elbow injury versus older pitchers, risk of shoulder/elbow injury increased with the number of high-velocity pitches thrown (regardless of pitch type and in an additive fashion), and FB velocity <95 mph (<152.9 kph) demonstrated strong negative interaction effects with higher SL percentage, suggesting that the overall predicted risk of injury for pitchers throwing a high number of SLs could be attenuated by lower FB velocity. Conclusion: Pitch-tracking metrics were substantially more predictive of future injury than player demographics and workload metrics. There were many significant game theory interdependencies of injury risk. Notably, the increased risk of injury that was conferred by throwing with a high velocity was even further magnified if the pitchers were also older, threw a high percentage of SLs, and/or threw a greater number of pitches.

Abstract Aims The Shock Academic Research Consortium (SHARC) recently proposed pragmatic consensus definitions to standardize classification of cardiogenic shock (CS) in registries and clinical trials. We aimed to describe contemporary CS epidemiology using the SHARC definitions in a cardiac intensive care unit (CICU) population. Methods and results The Critical Care Cardiology Trials Network (CCCTN) is a multinational research network of advanced CICUs coordinated by the TIMI Study Group (Boston, MA). Cardiogenic shock was defined as a cardiac disorder resulting in SBP &lt; 90 mmHg for ≥30 min [or the need for vasopressors, inotropes, or mechanical circulatory support (MCS) to maintain SBP ≥ 90 mmHg] with evidence of hypoperfusion. Primary aetiologic categories included acute myocardial infarction-related CS (AMI-CS), heart failure-related CS (HF-CS), and non-myocardial (secondary) CS. Post-cardiotomy CS was not included. Heart failure-related CS was further subcategorized as de novo vs. acute-on-chronic HF-CS. Patients with both cardiogenic and non-cardiogenic components of shock were classified separately as mixed CS. Of 8974 patients meeting shock criteria (2017–23), 65% had isolated CS and 17% had mixed shock. Among patients with CS (n = 5869), 27% had AMI-CS (65% STEMI), 59% HF-CS (72% acute-on-chronic, 28% de novo), and 14% secondary CS. Patients with AMI-CS and de novo HF-CS were most likely to have had concomitant cardiac arrest (P &lt; 0.001). Patients with AMI-CS and mixed CS were most likely to present in more severe shock stages (SCAI D or E; P &lt; 0.001). Temporary MCS use was highest in AMI-CS (59%). In-hospital mortality was highest in mixed CS (48%), followed by AMI-CS (41%), similar in de novo HF-CS (31%) and secondary CS (31%), and lowest in acute-on-chronic HF-CS (25%; P &lt; 0.001). Conclusion SHARC consensus definitions for CS classification can be pragmatically applied in contemporary registries and reveal discrete subpopulations of CS with distinct phenotypes and outcomes that may be relevant to clinical practice and future research.

Background: Assessment of orthopaedic surgery trainees is traditionally based on subjective evaluation by faculty. The recent push for value-based health care has placed a premium on improving patient outcomes. As a result, surgical training evaluations for orthopaedic trainees are evolving to include more objective measures to evaluate competency. Purpose: To develop and subsequently demonstrate the efficacy of a novel surgical skills assessment for orthopaedic sports medicine fellows. Study Design: Case series; Level of evidence, 4. Methods: A team of 14 fellowship-trained orthopaedic sports medicine surgeons developed objective scoring rubrics for anterior cruciate ligament reconstruction (ACLR) and rotator cuff repair (RCR) using a modified Delphi process. Rubrics were designed based on 10 surgical steps with a grading scale (1-5) based on core competencies with a maximum summative score of 50. Fourteen orthopaedic fellows across a regionally diverse group of sports medicine–accredited fellowship programs were invited to complete both an ACLR and RCR in a surgical skills laboratory at the beginning and end of their fellowship year. Individual surgical steps, overall performance, and total procedure time were evaluated by a single sports medicine surgeon for both sessions. Results: Thirteen of 14 fellows completed both pre- and post-fellowship assessments. For the ACLR procedure, the pre-fellowship mean summative score was 25.4 (SD, 4.4) and the post-fellowship mean summative score was 38.6 (SD, 4.1), which was a statistically significant improvement ( P < .001). For the RCR procedure, the pre-fellowship mean summative score was 26.6 (SD, 5.4) and the post-fellowship mean summative score was 38.8 (SD, 4.3), which was also a statistically significant improvement ( P < .001). The mean time to completion for the ACLR procedure was 82.3 minutes (SD, 4.3 minutes) pre-fellowship, which improved to 69.7 minutes (SD, 11.6 minutes) post-fellowship ( P = .002). The mean time to completion for the RCR procedure was 85.5 minutes (SD, 5.0 minutes) pre-fellowship, which improved to 76.4 minutes (SD, 7.0 minutes) post-fellowship ( P < .001). Conclusion: This surgical skills program represents the first standardized and reproducible instrument for the evaluation of 2 arthroscopic sports medicine procedures in the United States. Orthopaedic sports medicine fellows improved significantly in aggregate over their fellowship year with regard to the ACLR and RCR. The described program has the potential to serve as both a training tool and formal orthopaedic sports medicine fellow assessment.