Citations

ABSTRACT Background Head and neck squamous cell carcinoma remains challenging due to high recurrence rates and poor survival outcomes. Developing precise technologies for disease burden assessment, treatment response, and minimal residual disease (MRD) surveillance is crucial for improving prognosis. Methods This review explores the potential of liquid biopsy for MRD and recurrence detection. A novel liquid TNM (LiTNM) staging system is introduced, integrating biomarkers from saliva, surgical drain lymphatic fluid (SLF), and peripheral blood. Results Proximal liquid biopsies, particularly saliva and SLF, offer advantages due to their proximity to the tumor microenvironment. Saliva demonstrates high sensitivity in HPV‐associated oropharyngeal cancers, while SLF holds potential in identifying early postoperative recurrence. Despite these advancements, standardization and validation remain challenges. Conclusions Liquid biopsy approaches show promise for postoperative disease monitoring, yet their clinical implementation remains in the early stages. The proposed LiTNM staging system could complement TNM staging by providing a molecular framework for risk stratification. However, rigorous prospective studies are necessary to validate its clinical utility and facilitate adoption.

OBJECTIVE Previous research suggests elective surgical procedures performed later in the week have worse outcomes. This study investigated whether the day of the week on which elective anterior cervical discectomy and fusion (ACDF) surgery was performed impacts clinical outcomes. METHODS Using data from the Quality Outcomes Database, a nationwide, multicenter prospective registry, this study included patients undergoing elective ACDF for cervical spondylosis. Patients were categorized into groups based on the surgery day (early week, Monday and Tuesday; late week, Thursday and Friday). Analyzed outcomes included postoperative complications, readmissions, reoperations, and patient-reported outcomes. Statistical methods included the independent t-test, Pearson’s chi-square test, and multivariable logistic regression. RESULTS The study analyzed 19,818 patients, with 41.7% undergoing surgery early in the week and 36.9% later. There were no significant differences in 30-day mortality, readmissions, or reoperations between the two groups. Early-week surgical procedures were associated with a higher incidence of postoperative dysphagia requiring nasogastric tubes (0.6% vs 0.3%, p = 0.02) and a higher incidence of vocal cord paralysis (0.5% vs 0.3%, p = 0.01). The data indicate a surgical selection bias with more complex surgical procedures and higher risk patients typically scheduled earlier in the week, which likely contributed to the increased rates of dysphagia. Conversely, patients who underwent operations on Fridays were more likely to be discharged on the same day compared to those earlier in the week (p = 0.02), without a significant difference in length of stay overall. Surgical procedures performed later in the week were more likely to be performed at ambulatory surgical centers rather than inpatient facilities (p < 0.01), indicating a strategic selection of healthier patients for end-of-week procedures. CONCLUSIONS The day of elective ACDF surgery does not affect mortality, readmissions, or reoperation rates. However, early-week surgical procedures may see slightly higher rates of postoperative dysphagia and vocal cord paralysis, likely due to the scheduling of more complex cases or higher risk patients during these days. Overall, the authors’ data confirm that day of surgery does not influence overall patient recovery significantly. This information is useful for surgical planning and for providing patient reassurance that the day of the week does not significantly impact surgical outcomes.

ABSTRACT Understanding lung cancer evolution can identify tools for intercepting its growth. In a landscape analysis of 1024 lung adenocarcinomas (LUAD) with deep whole-genome sequencing integrated with multiomic data, we identified 542 LUAD that displayed diverse clonal architecture. In this group, we observed an interplay between mobile elements, endogenous and exogenous mutational processes, distinct driver genes, and epidemiological features. Our results revealed divergent evolutionary trajectories based on tobacco smoking exposure, ancestry, and sex. LUAD from smokers showed an abundance of tobacco-related C:G>A:T driver mutations in KRAS plus short subclonal diversification. LUAD in never smokers showed early occurrence of copy number alterations and EGFR mutations associated with SBS5 and SBS40a mutational signatures. Tumors harboring EGFR mutations exhibited long latency, particularly in females of European-ancestry (EU_N). In EU_N, EGFR mutations preceded the occurrence of other driver genes, including TP53 and RBM10. Tumors from Asian never smokers showed a short clonal evolution and presented with heterogeneous repetitive patterns for the inferred mutational order. Importantly, we found that the mutational signature ID2 is a marker of a previously unrecognized mechanism for LUAD evolution. Tumors with ID2 showed short latency and high L1 retrotransposon activity linked to L1 promoter demethylation. These tumors exhibited an aggressive phenotype, characterized by increased genomic instability, elevated hypoxia scores, low burden of neoantigens, propensity to develop metastasis, and poor overall survival. Re-activated L1 retrotransposition-induced mutagenesis can contribute to the origin of the mutational signature ID2, including through the regulation of the transcriptional factor ZNF695 , a member of the KZFP family. The complex nature of LUAD evolution creates both challenges and opportunities for screening and treatment plans.

Abstract This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53mut) myeloid neoplasms (MNs). Of 580 MNs harboring TP53mut with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.4%), 92 (15.9%), and 75 (12.9%) were classified as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) with low blasts (MDS-LB), MDS with excess blasts (MDS-EB)-2, and -EB1 according to the revised fourth edition of the World Health Organization (WHO) classification, respectively. Hierarchical analysis identified the following 4 risk groups with distinct survival: (1) MDS-LB, (2) MDS-EB1/EB2/AML VAF &lt;10%, (3) MDS-EB1/EB2 VAF ≥10%, and (4) AML VAF ≥10%. We next evaluated the impact of allelic status, VAF, and complex karyotype (CK). In our cohort, the significance of biallelic status was limited to MDS with &lt;5% blasts and not for blasts 5% to 9%, as proposed by the International Consensus Classification (ICC), or 5% to 19%, as proposed by the fifth edition of the WHO (WHO-5). MDS-EB1 and -EB2 with VAF ≥10% had comparable survival (9.6 vs 7.2 months; P = .12), regardless of allelic status. Contrary to the ICC proposal, MDS-EB1/EB2 with VAF &lt;10% and CK had poor survival compared with those without CK, comparable to MDS-EB1/EB2 with VAF ≥10% (5.6 vs 26.2 vs 6.3 months; P = .003). Survival of TP53mut AML was poor (median 3.9 months) regardless of allelic/CK status. Thus, using ICC or WHO-5 may underestimate prognosis of MDS with blasts 5% to 19% and 5% to 9%, respectively. Collectively, the hierarchical model acknowledges poor survival of 91.9% TP53mut MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.

Background: Nonoperative and operative management techniques after anterior cruciate ligament (ACL) injury are both appropriate treatment options for selected patients. However, the subsequent development of posttraumatic knee osteoarthritis (PTOA) remains an area of active study. Purpose: To compare the risk of PTOA between patients treated without surgery and with ACL reconstruction (ACLR) after primary ACL disruption using a machine learning causal inference model. Study Design: Cohort study; Level of evidence, 3. Methods: A geographic database identified patients undergoing ACLR between 1990 and 2016 with minimum 7.5-year follow-up. Variables collected include age, sex, body mass index, activity level, occupation, relevant comorbid diagnoses, radiographic findings, injury characteristics, and clinical course. Treatment effects of ACLR on the development of PTOA and progression to total knee arthroplasty (TKA) were analyzed with machine learning models (MLMs) in a causal inference estimator (targeted maximum likelihood estimation, TMLE), while controlling for confounders. Results: The study included 1194 patients with a minimum follow-up of 7.5 years, among whom 974 underwent primary reconstruction and 220 underwent nonoperative treatment. A total of 215 (22%) patients developed symptomatic PTOA in the ACLR group compared with 140 (64%) in the nonoperative treatment group ( P < .001), whereas 25 (3%) patients underwent TKA in the ACLR group compared with 50 (23%) in the nonoperative treatment group ( P < .001). Patients in the ACLR group had delayed TKA compared with patients in the nonoperative treatment group (193.4 vs 166.0 months, respectively; P = .02). TMLE evaluation revealed that reconstruction decreased the risk of PTOA by 11% (95% CI, 8%-13%; P < .001) compared with nonoperative treatment but did not demonstrate a significant effect on the rate of progression to TKA. Survival analysis with random forest algorithm demonstrated significant delay to the onset of PTOA as well as time to progression of TKA in patients undergoing ACLR. Additional risk factors for the development of PTOA, irrespective of treatment, included older age at injury, greater body mass index, total number of arthroscopic knee surgeries, and residual laxity at follow-up. Conclusion: MLMs in a causal inference estimator found ACLR to exert a significant treatment effect in reducing the rate of development of PTOA by 11% compared with nonoperative treatment. ACLR also delayed the onset of PTOA and progression to TKA.

ABSTRACTThe goal of the present study was to investigate the effect of positioning a soft flexible tube‐based actuator parallel or orthogonal to the principle muscle fibre direction, on measurements of the stiffness of upper trapezius (UT) muscle obtained using magnetic resonance elastography (MRE). The effects of using three different vibration frequencies (60 Hz, 80 Hz and 100 Hz) and studying left and right sides of the body were also investigated. The relevant MRE datasets were acquired on a 1.5 T MRI system using a 2D gradient‐echo (GRE) MRE sequence, and corresponding wave images produced using multimodel direct inversion (MMDI) were analysed by two observers using the manual caliper technique. Except for two of the 108 individual datasets, when the agreement was moderate, there was substantial to perfect agreement between wave quality scores obtained by the two observers, with an identical mean value. Similarly, and again with only two exceptions, there was good to excellent agreement between the measurements of UT stiffness obtained by the two observers. UT stiffness values obtained when the acoustic waves were propagating along the principle muscle fibre direction were significantly higher than when the waves were propagating orthogonal to the principle muscle fibre direction at all vibration frequencies (p < 0.005), and only for the former was a significant dispersion effect observed whereby stiffness increased as frequency increased (p < 0.05). No significant asymmetry was observed in measurements of UT stiffness obtained for the left and right sides of the body (p = 0.29). In conclusion, the new soft and flexible tube‐based actuator is comfortable and produced very good wave propagation in UT when positioned in either orientation. However, it is recommended for wave propagation to be induced in the principle fibre direction and there was found to be no advantage in using a vibration frequency above 60 Hz.

AbstractBackgroundTraditionally, there has been a reluctance to use weight training with female gymnasts due to concerns that it could cause detrimental increases in muscle mass and impede flexibility. Recent literature has demonstrated that strength training has no significant effect on flexibility and can improve athletic performance.ObjectiveTo assess in a pilot study the perceptions of collegiate gymnasts and coaches toward strength training after starting inaugural strength and conditioning training.DesignSurvey‐based study.SettingNational Collegiate Athletics Association Division I women's gymnastics program at a public university in California.ParticipantsOf the 23 gymnasts surveyed, 17 (74%) responded to the survey. Of the two coaches surveyed, both (100%) responded to the survey.InterventionsNot applicable.Main Outcome MeasuresDescriptive statistics characterizing demographics, characteristics of gymnasts' strength and conditioning program, and perceptions regarding the safety of strength training and its impact on performance, body shape, flexibility, and injury rates.ResultsMost gymnasts agreed (35%) or strongly agreed (59%) that weight training may improve performance. All gymnasts disagreed (59%) or strongly disagreed (41%) that weight training is not safe; 41% disagreed, 29% strongly disagreed, and 17% agreed that weight training may negatively affect body shape. Most gymnasts disagreed (59%) or strongly disagreed (18%) that weight training decreases flexibility; four (24%) felt neutral. Eighty three percent (59% strongly agree, 24% agree) felt that weight training had a positive impact on performance. More than half of the gymnasts either agreed (24%) or strongly agreed (29%) they had fewer injuries the season after implementing weight training, compared to prior seasons. Both coaches similarly endorsed the safety of strength training and its potential to improve performance.ConclusionsIn this pilot study, collegiate gymnasts and coaches expressed generally positive perceptions toward the safety of strength training and its effect on performance. A small number of gymnasts expressed concerns regarding the effects of weight training on body shape and flexibility.