Citations

The NCCN Clinical Practice Guidelines (NCCN Guidelines) for Wilms Tumor (WT; nephroblastoma) cover strategies for the screening, diagnosis, and treatment of WT, which is the most frequent primary kidney tumor in children. WT can generally be separated into 2 histology types: favorable histology WT and anaplastic WT. Five-year survival is high for children with favorable histology WT who receive appropriate treatment; however, survival rates are much lower for patients who present with higher stage diffuse anaplastic WT. Treatment of WT can range from surgery alone to surgery plus intensive chemotherapy and radiation depending on whether the tumor is unilateral or bilateral, histology, and local stage. The goal of therapy is to maximize cure while minimizing long-term toxicities. The content featured in this issue covers the NCCN panel’s recommendations for overall management of both favorable histology WT and anaplastic WT.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer and uterine sarcoma. The NCCN Cervical Uterine Panel meets at least annually to review comments from reviewers within their institutions; examine relevant new data from publications, abstracts, and recent FDA approvals; and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel’s deliberations on the new FIGO 2023 staging system and updates on the new systemic therapy recommendations for the management of endometrial cancer.

Objective: To determine the impact of modifiable surgical factors on ossiculoplasty outcomes after controlling for ear environment risk. Study Design: Multi-institutional retrospective review. Setting: Six tertiary care centers from 2011 to 2019. Patients Adults and children. Interventions: Ossiculoplasty, including synthetic ossicular replacement prosthesis, autograft interposition, bone cement repair, and mobilization. Main Outcome Measure: Correlation between modifiable surgical factors and pure-tone average air-bone gap (ABG) at most recent audiogram after controlling for preoperative risk using the statistically validated Ear Environment Risk (EER) score. Results: A total of 1,679 cases were included with a median follow-up time of 20 months (IQR, 5–51). After controlling for EER score, malleus engagement of prosthesis yielded favorable ABG versus direct contact to tympanic membrane without malleus engagement (beta = −2.4 dB [−3.8, −1.1], p < 0.001). For total ossicular replacement prostheses (TORP), use of a footplate prosthesis yielded favorable ABG as compared with no footplate prosthesis (−3.6 dB [−6.1, −1.1], p = 0.005). For synthetic prostheses, polyethylene prostheses had a less favorable ABG compared with full titanium or titanium with hydroxyapatite prostheses ( p < 0.05). In cases where the malleus was not engaged in reconstruction, amputation of the malleus head yielded worse ABG (+3.9 dB [1.2, 6.7], p = 0.005). There was no significant difference ( p > 0.05) in ABG for single-stage versus multistaged approach, use of a cartilage cap over the prosthesis versus no cartilage, use of bone cement to secure a PORP to the stapes versus no cement, mastoid cavity obliteration versus no obliteration, and incudostapedial joint reconstruction with joint prosthesis/bone cement versus synthetic PORP. Conclusions: With statistical correction for ear environment risk, several modifiable surgical factors are noted to impact ossiculoplasty hearing outcomes. Level of Evidence: 4.

Abstract Background & Aims Pregnancy can be a complex and risk-filled event for women with inflammatory bowel disease (IBD). High-quality studies in this population are lacking, with limited data on medications approved to treat IBD during pregnancy. For patients, limited knowledge surrounding pregnancy impacts pregnancy rates, medication adherence, and outcomes. Limited provider knowledge leads to highly varied practices in care affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus. The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike. The Global Consensus Consortium is a group of 39 IBD and content experts and 7 patient advocates from 6 continents who convened to review and assess current data and come to an agreement on best practices based on these data. Methods The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process was used when sufficient published data were available and the RAND (Research and Development) process in those instances where expert opinion was needed to guide consistent practice. Recommendations were informed by the guiding principle that maternal health best supports infant health. Results The topics were divided into ten categories with 34 GRADE recommendations and 35 consensus statements. Conclusions Overall, the goal of the group was to provide data-driven and practical guidance to improve the care of women with IBD around the globe based on the best available research.

The NCCN Guidelines for Thyroid Carcinoma address the management of different types of thyroid carcinoma, including papillary, follicular, oncocytic, medullary, and anaplastic carcinoma. The NCCN Thyroid Carcinoma Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on the panel’s most recent recommendations regarding systemic therapies for thyroid carcinoma as well as the supporting clinical data.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain provide recommendations for the comprehensive management of pain in patients with cancer. This article will focus on methods for screening for pain, safe and appropriate prescription of opioid and miscellaneous analgesics, and the optimization of nonpharmacologic interventions including integrative and interventional strategies for treatment of cancer-related pain. Additionally, the NCCN Guidelines discuss methods for the safe reduction of opioids when appropriate, as well as techniques for encouraging the judicious use of opioids. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional issues that are not covered here, including management of pain during a pain crisis, management of procedure-related pain and anxiety, pain management for cancer survivors, and the use of nonopioid and adjuvant analgesics for cancer-related pain.

Patients with inflammatory bowel disease (IBD) often consider their gastroenterologist to be the primary provider of care. To improve the care delivered to patients with IBD, health maintenance issues need to be addressed by the gastroenterology team. In particular, documentation and recommendation for vaccinations are crucial because more than 70% of patients with IBD will at some time be on immune-modifying therapies that may increase the risk for infections, many of which are preventable with vaccinations. Health maintenance recommendations addressed in this guideline include the safety and appropriate timing of vaccinations, screening for osteoporosis, cervical cancer, melanoma and non-melanoma skin cancer and screening for depression, anxiety, and need for smoking cessation. To accomplish these health maintenance goals, coordination among the primary care provider, gastroenterology team, and other specialists is necessary.

INTRODUCTION: Many patients with chronic pouchitis and Crohn's-like disease of the pouch (CLDP) are treated with biologics; however, the comparative effectiveness of advanced therapies in this population has not been systematically evaluated. We sought to compare the effectiveness of antitumor necrosis factor α (anti-TNF) therapies and ustekinumab in patients with chronic inflammatory conditions of the pouch. METHODS: We conducted a prospective, multicenter, cohort study. We included patients with chronic pouchitis and CLDP initiating treatment with anti-TNF therapies or ustekinumab. The primary outcome was clinical remission at 6 months after induction. We also evaluated clinical remission at 6 months among patients with chronic pouchitis and CLDP separately. RESULTS: Among 132 patients, 106 (80%) had a diagnosis of CLDP and 82 (62%) initiated therapy with ustekinumab. A significantly higher proportion of patients with CLDP treated with ustekinumab were in clinical remission at 6 months as compared with patients treated with anti-TNF therapy (62% vs 40%, P = 0.027); however, there was no significant difference among patients with chronic pouchitis ( P = 0.946). There was no independent statistical significance in the odds of remission at 6 months among patients with CLDP among patients receiving ustekinumab compared with anti-TNF therapy (adjusted odds ratio 1.91, 95% confidence interval 0.69–5.30) after adjusting for presence of a fistula, number of preoperative advanced therapies, and number of advanced therapies after IPAA. DISCUSSION: These data suggest the potential benefit of ustekinumab in patients with CLDP and should prompt future novel effectiveness evaluations in this population.

Dynamic cerebral autoregulation (CA) refers to the brain's ability to maintain stable cerebral blood flow despite fluctuations in blood pressure (BP). Impaired CA has been associated with cardiovascular disease severity and cognitive decline. On the other hand, enhanced cardiorespiratory fitness appears to be protective against both cerebrovascular dysregulation and cognitive decline, with an unclear link between the two. However, among individuals with cardiovascular disease, the impact of exercise-based cardiac rehabilitation (CR) on CA remains unclear. Therefore, the aim of this study was to test the hypothesis that a 12-week CR program would improve dynamic CA in adults with CVD. To address this question, data were collected from 14 patients enrolled in the Mayo Clinic CR program following a cardiac-related hospital admission (age: 43-70 yrs; n=3 females), which included moderate-high intensity aerobic exercise 3 times/week for 12-weeks. Continuous measures of middle cerebral artery velocity (MCAv; transcranial doppler) and finger BP (photoplethysmography) were obtained during 3-minutes of rest and a 3-minute sit-to-stand protocol (0.025Hz frequency) pre- and post the CR program. Transfer function analyses were used to provide an index of dynamic CA. BP-MCAv coherence in the low frequency (LF) and very low frequency (vLF) domains at rest were not different pre- and post- CR (LF: 0.48±0.19 vs 0.43±0.16; P=0.54; vLF: 0.51±0.12 vs 0.47±0.16; P=0.14). Similarly, gain and phase values at rest were not different pre- and post- CR (gain LF: 0.66±0.37 vs 0.58±0.33; P=0.16; vLF: 0.87±0.53 vs 0.74±0.43; P=0.21; phase LF: 0.41±0.30 vs 0.43±0.26; P=0.64; vLF: 0.72±0.53 vs 0.66±0.16; P=0.18). In contrast, during the sit-to-stand protocol, coherence was lower following CR (pre vs post LF: 0.81±0.13 vs 0.79±0.16; p<0.01; vLF: 0.80±0.09 vs 0.79±0.14; p<0.01). In addition, gain was reduced post CR (pre vs post LF: 0.59±0.35 vs 0.55±0.31; P=0.02; vLF: 0.76±0.33 vs 0.61±0.37; p<0.01), suggesting CR-induced improvements in CA efficiency. However, phase remained unchanged pre- and post- CR during the sit-to-stand protocol (LF: 1.01±0.71 vs 0.84±0.58; P=0.17; vLF: 1.16±0.69 vs 1.08±0.60; P=0.19). Taken together, these findings demonstrate that a 12-week exercise-based CR program improves dynamic CA efficiency after a cardiac event. These novel results highlight the potential role of exercise training in improving cerebrovascular regulation. Funding: NIH AG073726 and Mayo Clinic This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.