Citations

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vaginal Cancer outline the recommended diagnostic workup, staging considerations, and treatment options for this rare malignancy. Because vaginal cancer is uncommon and shares many biologic and clinical characteristics with cervical cancer, several management recommendations, particularly systemic therapy, are extrapolated from evidence and practices established for cervical cancer. This guideline excerpt summarizes key components of management, including diagnostic evaluation and workup, principles of staging, pathology considerations, radiation therapy principles, and primary treatment recommendations for both early-stage and advanced disease. It also details approaches to manage relapses, including locoregional recurrence and distant metastases, and provides an in-depth overview of systemic therapy recommendations for vaginal cancer.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate are intended to serve as a resource for health care providers to identify individuals who may benefit from cancer risk assessment and genetic counseling and testing; help guide decisions related to genetic testing; and facilitate a multidisciplinary approach in the comprehensive care of individuals at increased risk for hereditary breast, ovarian, pancreatic, and prostate cancer. The current guidelines focus primarily on assessment of pathogenic and likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants associated with increased risk of these cancers. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding screening for prostate cancer and pancreas cancer, as well as testing criteria for nonepithelial ovarian cancer.

GGGGCC (G 4 C 2 ) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Toxicity is thought to result from the accumulation of either repeat RNAs and/or dipeptide repeat proteins (DPRs) translated from repeat-containing transcripts through repeat-associated non-AUG (RAN) translation. To disentangle RNA from DPR toxicity, we mutated a CUG codon predominantly used to initiate DPR translation from all three reading frames. This mutation disrupted DPR synthesis while preserving the expression of repeat-containing RNAs. Despite the accumulation of RNA foci, behavioral deficits and pathological abnormalities, including p-TDP-43 inclusions, STING activation, motor neuron loss, neuroinflammation, and increased plasma neurofilament concentration, were alleviated in C9ORF72 mice. Base editing of the CUG codon also improved molecular phenotypes and survival in patient induced pluripotent stem cell–derived neurons, which highlights the potential of therapeutically targeting DPR production rather than repeat RNAs.

Alcohol use disorder (AUD) is a significant public health challenge, affecting multiple organs and organ systems, and fetal health. Additionally, AUD also significantly contributes to self-harm and road accidents. Beyond its health effects, AUD creates economic and political challenges, including escalating treatment costs and the complex alcohol regulation policies. Despite global impact, AUD remains under-addressed in countries like India due to cultural norms and limited resources. Early recognition of AUD is vital for better outcomes, relying on thorough clinical evaluation and patient history. However, denial, inebriation, or lack of awareness often delays diagnosis. Imaging techniques like ultrasound, CT, and MRI effectively depict AUD-related organ damage and aid in detecting chronic alcohol use. Radiologists play a crucial role in identifying these manifestations, contributing to its early detection and treatment. This review article highlights the imaging of alcohol use related disorders and diseases affecting different organs and organ systems at various stages. The review is presented in two parts: the first focuses on alcohol burden, alcohol metabolism and toxicity, and imaging findings of AUD-related abdominal diseases and disorders.

This cohort study evaluates the reduction in risk of high-grade serous carcinoma among women undergoing opportunistic bilateral salpingectomy in Canada.

Objective: To evaluate hearing outcomes after treatment with stereotactic radiosurgery (SRS) for sporadic vestibular schwannoma (VS) among patients with baseline 100% word recognition scores (WRS). Study design: Historical cohort. Setting: Tertiary academic medical center. Patients: Patients with 100% WRS on audiometric testing at initial treatment with SRS. Interventions: Gamma Knife SRS. Main outcome measures: Rate of maintaining serviceable hearing (SH), defined as American Academy of Otolaryngology-Head and Neck Surgery hearing class A or B. Results: In total, 125 patients had 100% WRS at SRS for sporadic VS. Median age at SRS was 56 years (IQR: 51 to 62) and median pure tone average (PTA) at SRS was 20 dB HL (IQR: 13 to 31). Sixty-eight patients progressed to non-SH at a median of 3.4 years after SRS (IQR: 1.0 to 8.6); the median duration of follow-up for the 57 patients who maintained SH was 5.1 years (IQR: 2.8 to 9.6). Rates of maintaining SH (95% CI, number still at risk) at 1, 3, 5, 7, and 10 years after SRS were 88% (82 to 94, 101), 75% (68 to 84, 81), 61% (53 to 71, 55), 58% (49 to 68, 43), and 44% (35 to 56, 26), respectively. Each 10-dB HL increase in PTA at SRS was associated with a 52% increased risk of progression to non-SH (hazard ratio: 1.52, 95% CI: 1.24-1.87, P <0.001). Conclusions: Despite having 100% pretreatment WRS, most patients with sporadic VS treated with SRS experienced clinically significant hearing decline over time. Even among this cohort of patients with excellent baseline hearing, at 10 years after treatment, only 44% of patients maintained SH.

Background: In younger patients (<60 years) with cryptogenic stroke presumed to be patent foramen ovale (PFO)-related, the standard approach involves transcatheter PFO closure combined with antithrombotic therapy (ATA). However, due to their exclusion from randomized clinical trials, no formal recommendations exist for patients ≥60 years. This study investigates whether PFO closure benefits patients ≥60 years with prior cryptogenic stroke or if ATA remains the preferred option. Methods: We searched the PubMed, Embase, Web of Science, and ScienceDirect databases to obtain articles in all languages from January 2004 until July 2025. The primary outcome was a risk of recurrent stroke during follow-up and secondary outcomes were risk of new-onset atrial fibrillation (AF), all-cause mortality and in-hospital complications. PROSPERO registration ID: CRD420250652870. Results: One post hoc evaluation of the DEFENSE-PFO trial and eleven observational studies were included. Compared to ATA, PFO closure was associated with a reduced risk of recurrent stroke (HR=0.60; 95% CI: 0.45 to 0.80, p<.001) and mortality (HR=0.41; 95% CI: 0.19 to 0.90, p=.02; I2 = 43.8%) with no difference in risk of new-onset AF (HR=1.13, 95%CI: 0.53 to 2.44, p=.74). When compared with patients <60 years, individuals ≥60 years had a higher risk of recurrent stroke (HR = 2.68; 95% CI 1.40–5.13; p=.002), new-onset AF (HR = 4.12; 95% CI 1.90–8.95; p<0.001) and mortality during follow-up (HR = 8.24; 95% CI 3.49–19.46; p<.0001). In-hospital complications after PFO closure were comparable between two age groups. Conclusion: While PFO closure may reduce ischemic stroke risk in older patients with cryptogenic stroke, this benefit is offset by higher absolute risks for recurrent stroke, new-onset AF, and mortality. Therefore, highly individualized patient selection and age-specific risk tools are crucial. Further long-term randomized trials are essential to optimize PFO closure in this population.

Background: Periodontitis is a potential modifiable factor influencing dementia risk. We examined whether improving periodontal health via regular flossing is associated with lower dementia risk. Methods: A total of 9,766 Atherosclerosis Risk in Communities (ARIC) study participants with teeth were followed from visit 4 (1996-1998) through 2021. Cox proportional hazards regression was used to estimate associations between regular dental flossing (≥1/week) and incident dementia. Covariates included age, race, gender, hypertension, diabetes, alcohol use, smoking status, obesity, physical activity, education level, income, insurance status, brushing frequency, regular dental care use and apolipoprotein E4 (APOE4) allele status . Cumulative incidence functions were estimated using death as a competing event. Results: Participants had mean age 62.6 years (SD = 5.6), 56% female, 79% white, 21% black, 63% reported regular flossing and 29.2% participants carry at least one APOE4 allele. The cumulative incidence of dementia was 52.6 % overall over 25 years. Regular flossing was independently and significantly associated with a lower hazard of developing dementia (HR = 0.90, 95% CI: 0.82–0.98, p = 0.02) after adjustment for all the covariates. In contrast, tooth brushing frequency (p=0.55) and regular dental care visit (p=0.22) were not significantly associated with dementia risk. By 25 years of follow-up, the cumulative incidence of dementia was 50% among flossers compared with 57% among non-flossers (Gray’s test p<0.0001, Figure). This translated to an Absolute Risk Reduction of 7%, Relative Risk Reduction of 12%, Number Needed to Floss 14. Conclusion: Flossing, but not tooth brushing or regular dental care, is independently associated with a reduced hazard of incident dementia. Dental flossing may be an additional strategy to reduce dementia risk. For every 14 individuals who floss ≥1/week, one fewer person will develop dementia.

OBJECTIVE The minimal important difference (MID) and minimal important change (MIC) are two metrics that bridge the gap between statistical significance and clinical relevance and are critical to managing clinical decisions and conducting clinical research. The objective of this study was to define MIDs to evaluate cross-sectional differences among groups and to define MICs to evaluate longitudinal within-patient changes for the Mayo Clinic Vestibular Schwannoma Quality of Life (VSQOL) Index. METHODS Anchor-based methods were used to define MIDs and MICs for the VSQOL Index domain scores, which range from 0 to 100 points, for a national cohort of 1050 patients with sporadic vestibular schwannoma, 644 of whom completed the VSQOL Index twice approximately 1 year apart. RESULTS The median of the MID estimates for the VSQOL Index domains were: hearing problems (17, IQR 12.5–21); dizziness and imbalance (21, IQR 18–23); pain, discomfort, and tinnitus (19.5, IQR 15–23.5); problems with face or eyes (18, IQR 17–28); impact on physical, emotional, and social well-being (19.5, IQR 14.5–23.5); difficulty with thinking and memory (23.5, IQR 18.5–28.5); global quality of life (12, IQR 8–16); and satisfaction or regret (13.5, IQR 7–17). MIC estimates for the hearing problems and satisfaction and regret domains were not obtained because the correlations between these domain scores and their associated anchors were not sufficiently strong. The MIC estimates (minimum and maximum) for the remaining domains were: dizziness and imbalance (7.2 and 8.3); pain, discomfort, and tinnitus (8.3 and 8.5); problems with face or eyes (7.0 and 7.4); impact on physical, emotional, and social well-being (2.1 and 8.0); and difficulty with thinking and memory (12.9 and 15.0). The median of the MIC estimates for global quality of life was 5.2 (IQR 3.7–5.6). CONCLUSIONS The MIDs and MICs reported herein provide a framework to interpret quality-of-life benefit or harm cross-sectionally among groups and longitudinally within patients. Moving forward, these values should be considered when interpreting studies using the VSQOL Index to assess disease-specific quality of life in patients with sporadic vestibular schwannoma.

OBJECTIVE The objective of this study was to describe the long-term efficacy of single-fraction stereotactic radiosurgery (SRS) for the primary treatment of sporadic vestibular schwannoma. METHODS Adult (≥ 18 years of age) patients with sporadic vestibular schwannoma who underwent SRS from 2000 through 2022 were included. RESULTS A total of 749 patients met inclusion criteria, the majority (n = 566, 76%) of whom had tumors extending into the cerebellopontine angle at SRS. The median patient age at SRS was 62 years, half (50%) of the patients were women, and 744 (99%) exhibited House-Brackmann grade I facial nerve function at SRS. A total of 42 patients experienced radiosurgical failure and underwent salvage treatment; the median duration of follow-up for the patients who did not undergo salvage treatment was 7.0 years. Overall tumor control rates (95% CI, number still at risk) at 1, 3, 5, 10, and 15 years after SRS were 100% (100%–100%, 718), 98% (97%–99%, 589), 96% (94%–97%, 464), 92% (90%–95%, 258), and 91% (89%–94%, 125), respectively. Patient age (hazard ratio [HR] for a 10-year increase of 0.92, 95% CI 0.71–1.19; p = 0.5), presence of a macrocystic tumor (HR 0.59, 95% CI 0.14–2.46; p = 0.5), and treated tumor volume (HR for a 1-cm 3 increase of 1.02, 95% CI 0.88–1.18; p = 0.8) were not significantly associated with the risk of salvage. Three distinct post-SRS tumor behavior patterns were observed, with 13% of patients demonstrating tumor pseudoprogression, all but 4 of whom demonstrated pseudoprogression by year 5 post-SRS. CONCLUSIONS SRS demonstrates durable tumor control through 15 years of follow-up in most patients (91%); however, a minority are found to still experience SRS failure even beyond 10 years of surveillance. Although occurring in only a minority of patients, tumor pseudoprogression can be evident out to 5 years or longer post-SRS.