Citations

ABSTRACT At the 42nd Annual Meeting of the American Association of Clinical Anatomists (AACA) in Bellevue, Washington, June 2025, two inaugural events—the Clinical Anatomy Fireside Chat (CAFC) and the Clinical Anatomy Symposium: Head and Neck 2025 (CAS)—fostered rich dialogue on the evolving role and operational definition of clinical anatomy. Experts from various clinical and anatomical disciplines explored the meaning of clinical anatomy, highlighting the absence of a universal definition despite its frequent use in education and research. Through these interdisciplinary discussions, a consensus emerged: clinical anatomy is not defined solely by the possession of clinical credentials but by the integration of anatomical knowledge and clinical relevance, achieved most effectively through collaboration. Clinical anatomy education and research require different depths of clinical knowledge depending on the audience and objective, and meaningful collaboration can bridge gaps in expertise. The symposium further illustrated that high‐quality clinical anatomy emerges from mutual respect and reciprocal insight between clinicians and anatomists. This article presents a consensus statement developed by AACA representatives and invited speakers, affirming that collaboration is not only foundational to the practice of clinical anatomy but also fundamental to its definition. These conclusions aim to guide future educational models, research strategies, and interdisciplinary partnerships in the field of clinical anatomy.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

ABSTRACT Determining an appropriate sample size in human cadaveric studies remains a long‐standing and unresolved challenge. Unlike other basic science fields, anatomical research is constrained by factors such as limited human donor availability, cultural considerations, and ethical restrictions. Despite these limitations, researchers are often asked to justify sample sizes, yet no standardized guidelines currently exist. To quantitatively assess sample sizes in recent human cadaveric studies and propose evidence‐based recommendations for future research, a PubMed search was conducted on February 26, 2024, using the term human cadaveric study . The articles published in 2023 and 2024 were screened, yielding 770 eligible studies. Data extracted included the total sample size, number of classified groups, and journal impact factor (IF). Descriptive statistics, linear regression, and correlation analyses were performed. Continuous variables were summarized using medians and interquartile ranges (IQR). The median sample size was 11.5 (IQR: 7–20), and 47.9% of studies used 10 or fewer specimens. The median number of classified groups was 3 (IQR: 2–4). Linear regression showed that studies dividing specimens into 2–6 groups often failed to meet the recommended sample size per group based on regression modeling. No significant correlation was found between sample size and journal IF ( r = −0.062, p = 0.115). Most cadaveric studies rely on small sample sizes due to inherent constraints, yet many still attempt a subgroup analysis without sufficient statistical power. Although flexibility is essential in anatomical research, we recommend a minimum total sample size of 10 for basic studies and at least five samples per group for those involving classification. Cadaveric sample size alone does not predict journal impact, highlighting the importance of methodological rigor over quantity.

Abstract In recent years, there has been increasing interest in the possible prognostic impact of concomitant medications in patients with cancer treated with immunotherapy combinations. This real‐world analysis aims to evaluate the impact of concomitant medications on survival outcomes in patients with advanced biliary tract cancer (BTCs) treated with cisplatin, gemcitabine and durvalumab (CGD) therapy. The study cohort included patients with a diagnosis of advanced BTCs who were taking concomitant medications for their comorbidities before the start of CGD. The primary objectives were overall survival (OS) and progression‐free survival (PFS). The initial population consisted of 666 patients, who were retrospectively collected from 41 sites in 12 countries. Data on concomitant medications were available for 493 patients. After a median follow‐up of 8.8 months (95% CI: 7.8–9.8), patients who did not take steroids (prednisone >10 mg/day or equivalent) or nonsteroidal anti‐inflammatory drugs (NSAIDs) and opioids, before the start of CGD, had longer OS and PFS in univariate analysis. The multivariate analysis confirmed longer OS for patients who did not take steroids. Patients who did not take steroids had an OS of 14.8 months (95% CI: 13.1–29.1) versus 5.0 months (95% CI: 2.14–11.32) of patients who took prednisone >10 mg/day or equivalent. No differences were reported in terms of overall response rate (ORR), disease control rate (DCR) ( p = 1.0 and p = .16, respectively), and safety profile between the two groups. Our analysis suggests that patients who did not receive steroids before the start of GCD had longer survival and highlighted the relevance of balancing concomitant medications and chemoimmunotherapy.

Abstract Background Cisplatin, gemcitabine, and durvalumab combination is a standard first-line treatment for advanced biliary tract cancer. This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced biliary tract cancer treated with cisplatin, gemcitabine, and durvalumab in real-world clinical practice. Methods Patients with unresectable, locally advanced, or metastatic biliary tract cancer treated with cisplatin and gemcitabine plus durvalumab across 39 centers in 11 countries in Europe, the United States, and Asia were included in this analysis. Results The cohort included 513 patients with advanced biliary tract cancer. The 5 most frequently altered genes were TP53 (22.1%), KRAS (13.7%), CDKN2A/B (13.6%), ARID1A (12.2%), and IDH1 (9.2%). In multivariate analysis, SMAD4 mutations were associated with improved progression-free survival (PFS) (hazard ratio [HR] = 0.49, P = .018) and overall survival (HR = 0.11, P = .023), while TP53 mutations were linked to worse PFS (HR = 1.62, P = .0047) and TERT mutations to worse overall survival (HR = 8.92, P = .0012). No other genomic alterations were statistically associated with outcomes. Subgroup analysis showed that TP53 mutations negatively affected PFS and overall survival in intrahepatic cholangiocarcinoma, while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma. No gene alterations were linked to outcomes in gallbladder cancer. Conclusions This large-scale analysis, with comprehensive molecular profiling, supports the positive prognostic impact of SMAD4 mutations for PFS and overall survival and highlights the negative prognostic roles of TP53 (PFS) and TERT (overall survival) mutations, providing valuable insights for personalized treatment strategies in biliary tract cancer.

Purpose To develop an expert consensus statement on the diagnosis, management, and rehabilitation of medial meniscal root tears (MMRTs) using a modified Delphi technique. Methods A working group developed statements on MMRT diagnosis, nonoperative management, surgical indications, surgical management, alignment, and rehabilitation using modified Delphi techniques. Fifty‐six experts were surveyed over 3 rounds to reach consensus, with agreement measured on a 5‐point Likert scale. Statements were included, revised, or excluded on the basis of predefined thresholds (≥75% agreement, <20% disagreement). Experts suggested revisions or new statements in the first 2 rounds, and final consensus statements were included. Results All 56 experts completed 3 survey rounds. Experts agreed that root tears may occur with no known history of trauma, typically in older patients, and that it should be diagnosed with an magnetic resonance imaging. In symptomatic patients with MMRTs without advanced osteoarthritis should be repaired using an anatomic transtibial pull‐out technique (performing a pie‐crusting technique can be helpful for visualization). Nonoperative management is advised for patients with advanced osteoarthritis. High tibial osteotomy may be considered for significant varus malalignment during MMRT repair. The only statement without consensus was the management of asymptomatic MMRTs with mild medial compartment cartilage wear, indicating ongoing debate. Conclusions Overall, 98% of statements reached consensus. There is agreement that magnetic resonance imaging is the gold standard for diagnosis. Symptomatic MMRTs without advanced osteoarthritis should be repaired early using an anatomic transtibial pull‐out technique. End‐stage knee osteoarthritis warrants nonoperative management of MMRTs, and a structured postoperative protocol with limited weightbearing and range of motion is essential after repair. No agreement was reached on managing asymptomatic MMRTs in patients without significant medial compartment degeneration. Meniscal centralization sutures may help in cases of substantial extrusion, but their routine use is debated. Level of Evidence Level V, consensus of expert opinion.

ABSTRACT Background Over the years, prognostic indexes have been developed to help clinicians stratify patients with biliary tract cancers (BTC) into risk groups. This study aims to identify a new prognostic index for patients with BTC treated with cisplatin, gemcitabine and durvalumab (CGD) in the first‐line setting. Patients and Methods The study population consisted of patients with BTC from 11 Eastern and Western Countries. Using multivariate analysis for overall survival (OS), we identified 5 baseline statistically significant variables: stage, carcinoembryonic antigen (CEA) levels, albumin levels, gamma glutamyl transferase (GGT) levels, neutrophil‐to‐lymphocyte ratio (NLR). Metastatic disease is a prognostic factor with a superior weight considering the HR of 3.62, while all the others can be considered prognostic factors with equivalent weight as the HRs are quite similar (HRs between 1.55 and 1.92). Based on these reasons, we developed a prognostic model called the MAGIC‐D index by assigning a score of 2 for metastatic disease, and a score of 1 for CEA increased levels, albumin decreased levels, GGT increased levels, NLR ≥ 3. Patients were stratified into three risk groups as follows: low‐risk group (Score from 0 to 2), intermediate‐risk group (Score from 3 to 4) and high‐risk group (Score from 5 to 6). At the first data cutoff (April 2024), these data were available for 319 patients that composed the training cohort used for the analysis. At the second data cutoff (May 2025), 79 patients were further enrolled and composed the validation cohort. Results Median progression‐free survival was 11.7 months in low‐risk group (20.7%), 8.7 months in intermediate‐risk group (46.4%) and 5.4 months in high‐risk group (32.9%) [low‐risk hazard ratio (HR): 0.27, intermediate‐risk HR: 0.55, high‐risk HR: 1, p < 0.0001]. Median OS was 18.4 months in low‐risk group,15.9 months in intermediate‐risk group and 7.8 months in high‐risk group (low‐risk HR: 0.17, intermediate‐risk HR: 0.43, high‐risk HR: 1, p < 0.0001). There was no difference in overall response rate (low‐risk: 31.8%, intermediate‐risk: 36.5% and high‐risk: 25.7%; p = 0.0718), while disease control rate was significantly different across the three risk groups (low‐risk: 83.3%, intermediate‐risk: 70.9% and high‐risk: 60.9%; p < 0.0001) as well as the rate of patients receiving a second‐line therapy (low‐risk: 54.5%, intermediate‐risk: 48.6% and high‐risk: 25.7%; p = 0.0061). Finally, the prognostic role in terms of OS and PFS of the MAGIC‐D index was confirmed in a validation cohort of 79 patients. Conclusion The MAGIC‐D index is an easy‐to‐use tool able to stratify patients with BTC with different prognoses undergoing first‐line therapy with CGD.

PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

AbstractStandard of care first‐line systemic treatment for advanced biliary tract cancer includes chemo‐immunotherapy with gemcitabine, cisplatin, and durvalumab, followed by maintenance durvalumab monotherapy. The present work aims to investigate the differences in baseline clinical and molecular characteristics between patients with early progression during chemo‐immunotherapy and those who reach durvalumab maintenance therapy. The study population included patients with unresectable, locally advanced, or metastatic BTC who received treatment at 38 clinical Institutions in 12 countries from July 2021 to December 2023. The primary objective of the study was to investigate whether baseline clinical and molecular characteristics differed between patients with early progression during chemo‐immunotherapy versus those reaching durvalumab maintenance therapy. Four hundred forty‐eight patients were included in this study. Two hundred twenty‐seven patients (50.7%) received maintenance with durvalumab monotherapy, whereas 221 (49.3%) did not receive maintenance therapy due to PD during first‐line chemo‐immunotherapy before completing 8 cycles. Results show that patients who received maintenance were more likely to be older (≥70 years), have an ECOG = 0, locally advanced disease, and a neutrophil‐to‐lymphocyte ratio (NLR) <3. A higher proportion of patients with BAP1 mutations received maintenance, while TP53 mutations were more common in those who progressed early. According to the present analysis, a substantial proportion of patients (50.7%) with advanced BTC who were treated with chemotherapy plus durvalumab proceeded to receive maintenance therapy with durvalumab monotherapy, with a median treatment duration of 4.4 cycles. Patients ≥70 years, with ECOG PS 0, with locally advanced disease, and with NLR <3 had a higher likelihood of receiving maintenance therapy.