Citations

Hypertension is the leading modifiable risk factor for atrial fibrillation (AF) and is estimated to be present in >70% of AF patients. This Frontiers Review was prepared by 29 expert members of the AF-SCREEN International Collaboration to summarize existing evidence and knowledge gaps on links between hypertension, AF, and their cardiovascular sequelae; simultaneous screening for hypertension and AF; and the prevention of AF through antihypertensive therapy. Hypertension and AF are inextricably connected. Both are easily diagnosed, often silent, and frequently treated inadequately. Together, they additively increase the risk of ischemic stroke, heart failure, and many types of dementia, resulting in greater all-cause mortality, considerable disease burden, and increased health care expenditures. Automated upper arm cuff blood pressure devices with implemented technology can be used to simultaneously detect both hypertension and AF. However, positive screening for AF with an oscillometric blood pressure monitor still requires ECG confirmation. The current evidence suggests that high-risk individuals aged ≥65 years or with treatment-resistant hypertension could benefit from AF screening. Since antihypertensive therapy effectively lowers AF risk, particularly in individuals with left ventricular dysfunction, hypertension should be the key target for AF prediction and prevention rather than merely a comorbidity of AF. Nevertheless, several important gaps in knowledge need to be filled over the next years, including the ideal method and selection of patients for simultaneous screening of hypertension and AF and the optimal antihypertensive drug class and blood pressure targets for AF prevention.

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.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and comprehensive care of patients with MDS based on a review of recent clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts is convened at least on an annual basis. During the annual meeting, the panel evaluates new and emerging data to inform their recommendations. These NCCN Guidelines Insights review the recent updates, including treatment recommendations both for lower-risk and higher-risk MDS, preference stratification of therapeutic agents, and emerging data on novel therapeutics.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Central Nervous System Cancers provide multidisciplinary diagnostic workup, staging, and treatment recommendations for diffuse high-grade gliomas and medulloblastomas in children and adolescents. This article summarizes the studies and panel discussion that serve as the rationale for comprehensive care recommendations included in the NCCN Guidelines for Pediatric Central Nervous System Cancers.

Abstract Solid tumors develop within a complex environment called the tumor microenvironment (TME), which is sculpted by the presence of other cells, such as cancer‐associated fibroblasts (CAFs) and immune cells like macrophages (Mφs). Despite the presence of immune cells, tumor cells orchestrate a tumor‐supportive environment through intricate interaction with the components of the TME. However, the specific mechanism by which this intercellular dialogue is regulated is not fully understood. To that end, the development of an organotypic 3D breast TME‐on‐a‐chip (TMEC) model, integrated with single‐cell RNA sequencing analysis, is reported to mechanistically evaluate the progression of triple‐negative breast cancer (TNBC) cells in the presence of patient‐derived CAFs and Mφs. Extensive functional assays, including invasion and morphometric characterization, reveal the synergistic influence of CAFs and Mφs on tumor cells. Furthermore, gene expression and pathway enrichment analyses identify the involvement of the KYNU gene, suggesting a potential immune evasion mechanism through the kynurenine pathway. Lastly, the pharmacological targeting of the identified pathway is investigated.

Objectives While extracorporeal shockwave therapy (ESWT) may be an efficacious adjunctive treatment option for musculoskeletal injuries, current research is limited by significant heterogeneity within treatment protocols. This study aims to establish international expert consensus recommendations on ESWT terminology, parameters, procedural considerations, contraindications and side effects in the application of ESWT to sports injuries. Methods A systematic literature search was performed on the use of ESWT for musculoskeletal and sports medicine injuries to identify potential panellists, followed by the development of a steering committee-led questionnaire. A three-stage, modified Delphi questionnaire was provided to a panel of 41 international clinical and research experts across 13 countries. Panellists had the opportunity to suggest edits to existing statements or recommend additional statements in Round 1. Consensus was defined as≥75% agreement. Results All 41 panellists completed Rounds 1, 2 and 3. Consensus was reached on 69/118 statements (58.5%), including recommendations on terminology and fundamental concepts, indications for use, procedural aspects for tendinopathy and bone pathologies, treatment correlations with imaging, periprocedural and postprocedural considerations, absolute and relative contraindications and potential side effects. Of the 49 statements that did not reach consensus, 17/49 (34.7%) were related to procedural aspects of bone pathology. Conclusion This international panel presents recommendations on ESWT terminology, indications and treatment considerations to guide ESWT use and decision-making by sports medicine clinicians. While our panel supported the use of ESWT in the treatment of bone pathologies, certain procedural aspects of ESWT specific to these injuries did not reach consensus and require further investigation.

OBJECTIVE Cervical spondylotic myelopathy (CSM) can be associated with urinary dysfunction, leading to an inability or marked difficulty with micturition. This study aimed to evaluate the urinary dysfunction, long-term prognosis, and recovery in patients with CSM following surgical intervention. METHODS The CSM cases of the Quality Outcomes Database SpineCORe study group were analyzed. Urinary control was assessed using the modified Japanese Orthopaedic Association (mJOA) urinary function subscore. Improvement was defined as a minimum improvement of 1 point in the mJOA urinary function subscore at the 2-year follow-up. Univariate and multivariable analyses were conducted as appropriate. RESULTS Of 1141 patients, 772 (67.7%) patients were identified with a minimum 2-year follow-up mJOA score, and 249 (32.3%) of these patients reported baseline urinary dysfunction. Of those 249 patients with baseline urinary control problems, 193 (77.5%) had improvement in urinary function postoperatively, and more women than men had improved urinary control after CSM surgery (54.9% vs 45.1%, p = 0.03). Apart from sex, demographic characteristics of patients who experienced urinary function improvement versus those who did not were similar. Patients who experienced urinary function improvement had lower overall baseline mJOA scores (10.2 vs 13, p < 0.01). Both cohorts reported similar rates of postoperative satisfaction (North American Spine Society scores of 1 and 2) (89.1% vs 85.9%, p = 0.26). CONCLUSIONS Among the one-third of patients with CSM experiencing urinary dysfunction, nearly 78% achieve improved urinary function at the 2-year postoperative follow-up. Women are more likely to experience improvement in this function. Patients with and without improvements in urinary function are equally satisfied with their surgery and report similar outcomes on long-term follow-up.