Citations

Abstract Sinonasal squamous cell carcinoma (SNSCC) is an aggressive head and neck cancer of the sinonasal cavity which has not benefitted from therapeutic advances over decades 1 . Though historically attributed to inhaled carcinogens such as hardwood dust and tobacco smoking 2 , SNSCC is incidentally associated with human papillomavirus (HPV) 3,4 . Importantly, HPV is the primary oncogenic driver of >80% of anatomically adjacent oropharyngeal cancers 5 . While viral status drives clinical staging and treatment guidelines in these malignancies 6,7 , the potentially oncogenic consequences and prognostic value of host–virus interactions in SNSCC remain incompletely defined. Here, through paired host and viral whole-genome sequencing (WGS), we map the genomic footprint of HPV in SNSCC. Strikingly, lesser studied strains such as HPV45, 51, and 39 constitute driver infections in this rare but clinically credentialed cancer, where extrachromosomal DNA (ecDNA)-associated viral integration and APOBEC mutagenesis are shown to underpin somatic tumor evolution. Statement of Significance Paired host viral and whole-genome sequencing of SNSCC nominates HPV as a primary oncogenic driver of SNSCC. HPV–human ecDNA amplicons harboring noncanonical strains such as HPV45, 51 mediate viral carcinogenesis. Routine clinical diagnostic HPV panels should be expanded to capture the activity of lesser studied strains.

ABSTRACT Background Sentinel lymph node (SLN) biopsy is a critical staging tool in skin and soft tissue cancers. Although technetium lymphoscintigraphy is the most common adjunct, indocyanine green (ICG) demonstrates a promising alternative in pediatric, adolescent, and young adult (AYA) skin and soft tissue cancers. Methods and Objectives Evaluate the safety and efficacy of ICG in SLN biopsy (SLNB) in diverse pediatric and AYA solid cancers in a multi‐institutional environment. This is a prospective, observational study conducted at 13 member institutions in the Pediatric Surgical Oncology Research Collaborative between 2019 and 2023. Eligible patients underwent SLNB for primary or recurrent solid skin and soft tissue tumors. Peritumoral ICG was administered intraoperatively. Outcomes included SLN detection rates, histopathology of excised specimens, and surgeon‐reported assessment of utility. Safety was assessed through adverse event reporting. Results Forty SLNB procedures yielded 84 specimens: 13 melanoma (32.5%), 12 squamous cell carcinoma (30%), 11 non‐rhabdomyosarcoma soft tissue sarcoma (27.5%), two rhabdomyosarcoma (5%), one Ewing sarcoma (2.5%), and one malignant peripheral nerve sheath tumor (2.5%). Histologic evaluation identified 81 lymph nodes, 75 benign (89.3%) and six malignant (7.1%); three specimens were adipose tissue (3.6%). Of 81 lymph nodes, 76% were ICG‐positive. ICG had a sensitivity of 79.5%, a specificity of 33%, and a positive predictive value of 96%. All malignant nodes were ICG‐avid. There were no adverse reactions to ICG at 30 days. Conclusions ICG is a safe and effective adjunct for SLNB in pediatric and AYA soft tissue and skin malignancies.

BACKGROUND: Stoma-free survival represents a key quality-of-life outcome after surgery for locally advanced rectal cancer. Despite advances in neoadjuvant and surgical management, up to 30% of patients ultimately require a permanent fecal diversion. OBJECTIVE: To evaluate stoma-free survival and identify factors associated with permanent stoma formation in patients with locally advanced rectal cancer undergoing coloanal anastomosis. DESIGN: Retrospective cohort study. SETTINGS: Single tertiary referral center (2017–2021). PATIENTS: A total of 126 patients with clinical stage II and III rectal adenocarcinoma who received neoadjuvant therapy and underwent curative-intent resection with coloanal anastomosis were included. INTERVENTION: Curative-intent resection with coloanal anastomosis. MAIN OUTCOME MEASURES: The primary outcome was stoma-free survival. Secondary analyses examined factors associated with permanent fecal diversion. RESULTS: The medical records of 126 patients were analyzed, comprising 62.5% men, with a mean age of 54 ± 10 years and a median BMI of 27.7 (interquartile range 24.5–31.4). At a median follow-up of 53.0 months, the 5-year stoma-free survival rate was 88.9%. Univariate Cox regression analysis showed that BMI ≥35 (HR 3.80; 95% CI, 1.04–13.91, p = 0.044) and handsewn coloanal anastomosis with mucosectomy compared to stapled coloanal anastomosis without mucosectomy (HR 5.58; 95% CI, 1.71–18.14, p = 0.004), as well as local recurrence (HR 6.51; 95% CI, 1.44–29.46), were associated with worse stoma-free survival. The 30-day major morbidity rate was 7.9% after the index surgery. Sixteen patients required permanent fecal diversion due to bowel dysfunction (n = 11), disease recurrence (n = 4), or bowel obstruction (n = 1). LIMITATIONS: Retrospective, single-institution design with limited generalizability. CONCLUSIONS: Coloanal anastomosis in the era of total neoadjuvant therapy resulted in favorable 5-year stoma-free survival. BMI ≥35, handsewn coloanal anastomosis with mucosectomy, and local recurrence were associated with worse stoma-free survival. See Video Abstract . SUPERVIVENCIA SIN ESTOMA TRAS UNA RESECCIÓN ANTERIOR BAJA CON ANASTOMOSIS COLOANAL PARA EL CÁNCER RECTAL EN ESTADIO II-III ANTECEDENTES: La supervivencia sin estoma representa un resultado clave para la calidad de vida tras la cirugía de cáncer rectal localmente avanzado. A pesar de los avances en el tratamiento neoadyuvante y quirúrgico, hasta un 30 % de los pacientes requieren finalmente una derivación fecal permanente. OBJETIVO: Evaluar la supervivencia sin estoma e identificar los factores asociados con la formación de un estoma permanente en pacientes con cáncer rectal localmente avanzado sometidos a anastomosis coloanal. DISEÑO: Estudio de cohorte retrospectivo. ENTORNO: Centro terciario de referencia único, 2017-2021. PACIENTES: Se incluyó a un total de 126 pacientes con adenocarcinoma rectal en estadio clínico II-III que recibieron terapia neoadyuvante y se sometieron a una resección con intención curativa con anastomosis coloanal. INTERVENCIÓN: Resección con intención curativa con anastomosis coloanal. PRINCIPALES MEDIDAS DE RESULTADO: El resultado principal fue la supervivencia sin estoma. Los análisis secundarios examinaron los factores asociados con la derivación fecal permanente. RESULTADOS: Se analizaron 126 pacientes, de los cuales el 62,5 % eran hombres, con una edad media de 54 ± 10 años y un índice de masa corporal medio de 27,7 kg/m 2 (rango intercuartílico: 24,5-31,4 kg/m 2 ). Con una mediana de seguimiento de 53,0 meses, la tasa de supervivencia sin estoma a 5 años fue del 88,9 %. El análisis de regresión de Cox univariante mostró que el índice de masa corporal ≥ 35 kg/m 2 (razón de riesgo = 3,80, intervalo de confianza del 95 %: 1,04-13,91, p = 0,044) y la anastomosis coloanal cosida a mano con mucosectomía, en comparación con la anastomosis coloanal grapada sin mucosectomía (razón de riesgo = 5,58, intervalo de confianza del 95 %: 1,71-18,14, p = 0,004), así como la recurrencia local (razón de riesgo = 6,51, intervalo de confianza del 95 %: 1,44-29,46) se asociaron con una peor supervivencia sin estoma. La tasa de morbilidad grave a los 30 días fue del 7,9 % tras la cirugía índice. Dieciséis pacientes requirieron una derivación fecal permanente debido a disfunción intestinal (n = 11), recurrencia de la enfermedad (n = 4) u obstrucción intestinal (n = 1). LIMITACIONES: Diseño retrospectivo, de una sola institución, con una generalización limitada. CONCLUSIONES: La anastomosis coloanal en la era de la terapia neoadyuvante total dio lugar a una supervivencia sin estoma favorable a los 5 años. El índice de masa corporal ≥ 35 kg/m2, la anastomosis coloanal cosida a mano con mucosectomía y la recurrencia local se asociaron con una peor supervivencia sin estoma. (AI-generated translation )

Chest CTs done for unrelated reasons have the potential to reveal unsuspected abnormalities and provide complementary information to help direct appropriate management. By thoroughly understanding the diagnostic role and limitations of CT in assessing ventricular size and morphology as well as myocardial attenuation, enhancement, and thickness, radiologists will be better equipped to differentiate between normal and abnormal findings and provide precise, clinically appropriate recommendations.

OBJECTIVE Chordomas are rare, locally aggressive primary neoplasms. Resection with negative margins is the primary recommended therapeutic approach, while adjuvant radiotherapy and chemotherapy can also play a role in their treatment in certain situations, including lesions with positive margins or those that are poorly differentiated or dedifferentiated. Cervical spine chordomas pose significant surgical challenges given their proximity to critical anatomical structures and the mechanical constraints of the cervical spine. In the current case series, authors aimed to explore the clinical and patient-reported outcomes (PROs) of the surgical treatment of cervical chordomas in a large multicenter cohort. METHODS This multicenter case series analysis utilized data from the prospectively collected Primary Tumor Research and Outcomes Network (PTRON) registry, from its inception (May 16, 2016) to data extraction (February 29, 2024). The study population was restricted to patients with histologically confirmed cervical chordomas involving levels C0–7, who underwent surgical treatment at one of the participating centers, and for whom both the initially planned and postoperatively pathologically confirmed surgical margins were documented. Patient demographics, tumor characteristics, surgical and adjuvant treatments, local recurrence–free survival (LRFS), overall survival (OS), and perioperative adverse events were retrieved. PROs included the Spine Oncology Study Group Outcomes Questionnaire version 2.0 (SOSGOQ2.0), EQ-5D, and SF-36 version 2.0 (SF-36v2). RESULTS Thirty-eight patients were identified, 12 of whom underwent true en bloc resection (EBR), 18 of whom underwent deliberate intralesional resection, and 8 of whom underwent EBR after intralesional surgery or in whom EBR failed. True EBR led to better LRFS (92% vs 83% vs 63%, respectively) and OS (83% vs 39% vs 50%, respectively). Surgical adverse events within 1 year were more frequent with true EBR (100% vs 39% vs 75%, respectively). EQ-5D, SOSGOQ2.0, and SF-36v2 showed improvement with true EBR, whereas the trends for PROs from the other groups were more variable. CONCLUSIONS This multicenter case series analysis provides critical insights into the clinical outcomes and PROs in the largest cohort of surgically treated cervical spine chordomas described to date. It underscores the importance and challenges of wide resection for oncological control. It establishes the associated morbidity and provides an overview of PROs following surgery. These findings contribute valuable evidence to inform shared decision-making and optimize patient care.

Abstract Background Myocardial feature-tracking (FT) strain from cardiovascular magnetic resonance (CMR) has incremental prognostic value beyond traditional imaging biomarkers. Clinical use is limited by the absence of population-specific healthy reference ranges. This study provides age-, sex-, and ethnicity-specific reference ranges for CMR-derived FT strain from the Healthy Hearts Consortium (HHC). Methods The HHC is an international collaboration comprising CMR scans from 9,088 verified healthy adults across six centres, covering the entire adult age spectrum and with diverse ethnic background. Standardised CMR acquisition protocols were used. Image analysis was performed by two experienced readers following pre-specified standard operating procedures and using two commercially available software platforms (cvi42®, Circle Cardiovascular Imaging Inc.; suiteHEART®, Neosoft LLC). The following metrics were extracted: i) global FT strain metrics from both ventricles (longitudinal, circumferential, and radial) and both atria (longitudinal); ii) strain rate; iii) Mitral/Tricuspid annular plane systolic excursion (MAPSE, TAPSE); iv) rapid strain (long-axis, junctional strain) from the left ventricle and both atria. Quality control included visual inspection of all images and the removal of biologically non-sensical values and extreme statistical outliers. Reference ranges were calculated by age group (deciles: 20-80 years), sex (male/female), and ethnicity (White, Black, Chinese, South Asian, Mixed/Other) using the 95% prediction interval method. Technical variations due to scanner vendor, software platform, and field strength (1.5T vs. 3.0T), were analysed. Results The study included 4,452 men (49%) and 4,636 women (51%). Ages ranged from 18 to 83 (mean 61±13) years. The sample included diverse ethnic backgrounds [White (81.7%), South Asian (5.6%), Mixed/Other (5.3%), Black (3.7%), and Chinese (3.7%)]. Women demonstrated significantly higher absolute strain values than men across. Absolute myocardial strain values were higher in younger age groups and lower in older age groups, most notably in left global circumferential and longitudinal strain. Ethnic differences in strain were most pronounced between White and Black as well as between White and Chinese individuals regarding left and right ventricular strain values, while left and right atrial strain values as well as rapid strain values, were similar across ethnic groups. Conclusion This study provides comprehensive, population-specific reference ranges for FT-CMR-derived myocardial strain, addressing a clinical knowledge gap. These findings inform clinical interpretation, improving diagnostic accuracy and risk stratification in different populations. This work represents a significant step towards a broader clinical implementation of myocardial strain analysis in routine cardiovascular care, ensuring more accurate classification of findings across varying demographic groups.

BACKGROUND AND OBJECTIVES: Myelomeningocele is defined by the presence of a fluid-filled sac that contains the neural placode and cerebrospinal fluid (CSF) at the level of the spinal defect. Alternatively, the term myeloschisis is used when the neural placode is not contained within a CSF-filled sac. While both are eligible for prenatal closure, few studies have characterized the impact of the type of lesion on postnatal outcomes. This study compares the outcomes of these 2 types of open spinal dysraphism using data from the Fetal Myelomeningocele Consortium registry sponsored by the North American Fetal Therapy Network. METHODS: The prospective observational Fetal Myelomeningocele Consortium registry was used to extract deidentified data corresponding to patients who underwent fetal closure of myelomeningocele vs myeloschisis. Demographics, operative characteristics, perioperative complications, and postnatal outcomes were collected. RESULTS: A total of 1327 patients were identified, including 991 (74.7%) with myelomeningocele and 336 (25.3%) with myeloschisis. Compared with myelomeningocele, myeloschisis was associated with lower rates of prenatal talipes (11% vs 24%, P < .001) and higher rates of favorable prenatal movement (94% vs 86%, P < .001). Postnatally, myeloschisis conferred higher rates of leg movement (97% vs 90%, P = .002) and an increased likelihood of ambulation in the household (10.4% vs 4.1%, P = .009) and outside (7.2% vs 1.9%, P = .004) at 1 year. However, myeloschisis was also linked to greater use of skin patches during closure (49% vs 27%, P < .001), higher CSF leak rates among those with wound dehiscence (26% vs 8%, P = .014), and more frequent CSF diversion and tethered cord surgeries at follow-up. CONCLUSION: Myeloschisis and myelomeningocele demonstrate distinct clinical profiles. Although patients with myeloschisis may have favorable motor outcomes, they are also characterized by higher rates of CSF leakage, CSF diversion, and tethered cord surgery. These findings highlight the need for lesion-specific prognostication and may inform surgical planning and parental counseling in the context of prenatal spina bifida closure.

Abstract Introduction Cardiovascular magnetic resonance (CMR) imaging enables precise, non-invasive assessment of cardiac structure and function, yet the clinical utility of CMR metrics is limited by the lack of comprehensive, population-specific reference values. By directly reanalyzing data from a large, multi-ethnic cohort rather than relying solely on pooled literature, could enable the establishment of standardized reference ranges and severity grading thresholds. Aim To provide comprehensive, age-, sex-, and ethnicity-stratified CMR reference ranges and severity grading thresholds for key ventricular and atrial parameters. Methods We analyzed over 9,000 CMR scans from the Healthy Hearts Consortium (HHC), comprising six international cohorts. All individuals were free from overt cardiovascular disease and major comorbidities, ensuring a verified healthy sample. Two automated segmentation software solutions—cvi42 (Circle Cardiovascular Imaging) and suiteHEART (Neosoft)—were used to quantify left and right ventricular volumes, myocardial mass, and atrial volumes in standard cine stacks. All endorsed segmentation modes were applied. Quality control protocol combined expert visual review and statistical outlier analysis. We derived 95% prediction intervals (PI) to define the normal range, with additional severity thresholds for mild (95–99.73% PI), moderate (99.73–99.99% PI), and severe (&gt;99.99% PI) deviation from the reference range. Results The final dataset comprised of 9,059 verified healthy adults aged 18–83 years (mean 61 ± 13 years), with a near-equal sex distribution (51% women). Demographics included White (81.6%), South Asian (5.6%), Mixed/Other (5.3%), Black (3.8%), and Chinese (3.7%) participants. Results demonstrated that sex, age, and ethnicity strongly influenced cardiac indices. Men had higher indexed LV and RV volumes and greater myocardial mass than women. Black participants presented the highest indexed LV myocardial mass across age groups, whereas Chinese participants had comparatively lower myocardial mass values (Figure 1). In contrast, atrial volumes remained relatively stable across age categories. Comparative analysis showed minor differences between the two software tools, particularly for atrial parameters; however, derived ejection fractions remained consistent. We established age-, sex-, and ethnicity-stratified reference ranges for key CMR parameters. To facilitate clinical interpretation, we defined severity thresholds corresponding to mild, moderate, and severe abnormalities. Conclusion This large-scale, international effort addresses prior limitations in CMR interpretation by offering robust, contemporary reference ranges and severity grading applicable to diverse populations and imaging protocols. Our severity grading thresholds support consistency in clinical reporting and decision-making, enabling clearer identification of early subclinical changes and more accurate monitoring of disease progression.Subset of CMR value ranges in females

This pilot, randomized, double-blind trial in a relatively small sample of patients with IBS-related pain shows rimegepant significantly reduced sensations of gas, urgency, and pain during rectal distention and decreased rectal compliance. Decrease in compliance implies that changes in physical properties or distensibility of rectum did not contribute to alterations in rectal sensation. Same dose of rimegepant did not significantly impact daily abdominal pain, BM frequency, or colonic transit. There were no serious adverse events.

Objective: Orthobiologics are increasingly sought-after interventions in sports medicine for treatment of musculoskeletal injuries and conditions. Despite this trend, differences exist across sports medicine fellowship programs regarding foundational knowledge, educational curricula, and practical experience with orthobiologic therapies (eg, platelet-rich plasma, bone marrow aspirate concentrate, microfragmented adipose tissue). This represents an important educational gap for those training in sports medicine fellowships. To address this gap, an educational toolkit was envisioned with the sports medicine fellowship director and trainee in mind. Data Sources: Collective observations from physician experts in sports medicine education established the variations in curricula and expertise of graduating fellows. A literature review was conducted to source English-language peer reviewed articles from the online PubMed database. The scope of this project did not include an independent systematic analysis or statistical assessments. Main Results: An educational toolkit consisting of 12 adaptable modules was developed, each with a suggested reading list from the published literature. The modules may be rearranged to support each program's learning schedule. The information and lessons contained herein may be valuable to all healthcare providers interested in the evidence-based application of orthobiologics and insightful interpretation of related research. Conclusions: By implementing an educational toolkit, sports medicine fellowships may improve the quality of education on orthobiologics. This is intended to improve the knowledge and skill set of fellowship graduates, thus promoting the scientific, responsible use of orthobiologic interventions.