Weill Cornell Medicine

Differentiated thyroid carcinomas (DTC), including papillary thyroid carcinoma (PTC) and follicular carcinoma (FC), account for most thyroid malignancies and are generally associated with excellent prognosis. However, a subset of DTC demonstrate aggressive clinical behavior characterized by increased recurrence, distant metastasis (DM), radioactive iodine (RAI) resistance, and reduced survival. Identification of these tumors is critical for appropriate risk stratification and management. A number of pathologic features have been shown to predict aggressive behavior, including vascular invasion (VI), capsular invasion (CI), and extrathyroidal extension (ETE), as well as high-grade histologic features such as increased mitotic activity and tumor necrosis. In the 2022 World Health Organization (WHO) Classification for Endocrine and Neuroendocrine Tumours, high-grade features are acknowledged as prognostically significant, and DTC meeting these criteria are classified as high grade differentiated thyroid carcinoma (HGDTC), a category with a prognosis similar to PDTC. In addition, certain histologic subtypes of PTC, including the tall cell, hobnail, and columnar cell subtypes, have traditionally been associated with more aggressive clinical outcomes. However, the prognostic significance of histologic subtype alone remains debated, as tumor behavior is often influenced by the presence of invasive features and high-grade morphology. Recent advances in molecular profiling have further refined risk stratification. While the independent prognostic significance of the BRAFV600E mutation remains controversial, TERT promoter mutations have consistently been associated with aggressive tumor biology, including DM, RAI resistance, and decreased survival. Importantly, the coexistence of BRAFV600E and TERT promoter mutations identifies a subset of thyroid carcinomas with particularly poor outcomes. This review summarizes the key pathologic and molecular features associated with aggressive behavior in DTC, highlighting their diagnostic criteria, prognostic significance, and implications for clinical management. Comprehensive pathologic evaluation integrating morphologic and molecular findings remains essential for accurate risk stratification and multidisciplinary care of patients with thyroid carcinoma.

Importance:Individual breast cancer risk can guide screening initiation, frequency, use of supplemental imaging, and preventive measures to improve breast cancer screening by shifting resources from low-risk women to high-risk women. Objective:To determine whether risk-based breast cancer screening is a feasible alternative to annual mammography. Design, Setting, and Participants:Parallel-group, pragmatic, multicenter randomized clinical trial comparing risk-based (n = 14 212) with annual (n = 14 160) breast cancer screening. Women aged 40 to 74 years without prior diagnoses of breast cancer or ductal carcinoma in situ, or prophylactic bilateral mastectomy, were recruited from all 50 US states from September 2016 to February 2023, with follow-up through September 5, 2025 (median follow-up, 5.1 years). Statistical analysis was conducted between July and November 2025. All study procedures were conducted via an online platform. Women who declined randomization were enrolled in an observational cohort. Interventions:Risk assessment included sequencing of 9 susceptibility genes, polygenic risk score, and the Breast Cancer Surveillance Consortium version 2 model. The risk-based group received 1 of 4 recommendations: (1) highest risk (≥6% 5-year risk, high-penetrance pathogenic variant): alternating mammography and magnetic resonance imaging (MRI) every 6 months and counseling; (2) elevated risk (top 2.5 risk percentile by age): annual mammography and risk-reduction counseling; (3) average risk: biennial mammography; and (4) low risk (aged 40-49 years and <1.3% 5-year risk): no screening until risk is 1.3% or greater or age 50 years. Main Outcomes and Measures:The coprimary outcomes included noninferiority for stage ≥IIB cancers and superiority in reducing biopsy rates. Secondary outcomes included identification of stage ≥IIA cancers, mammogram rates, uptake of prevention strategies in higher risk cohorts, preference for screening group in the observational cohort, ductal carcinoma in situ, MRI, and stage-specific cancer rates. Results:A total of 28 372 women were randomized. The mean (SD) age was 54 (9.6) years and the majority were non-Hispanic White (77%). The rate of stage ≥IIB cancers was noninferior in the risk-based compared with the annual group (risk-based: 30.0 [95% CI, 16.3-43.8] vs annual: 48.0 [95% CI, 30.1-65.5] per 100 000 person-years; rate difference, -18.0 per 100 000 person-years [95% CI, -40.2 to 4.1]). The rate of breast biopsies was not lower in the risk-based group (rate difference, 98.7 per 100 000 person-years [95% CI, -17.9 to 215.3]) despite fewer mammograms (rate difference, -3835.9 [95% CI, -4516.8 to -3154.9]). The cumulative incidence of cancer, biopsy, mammogram, and MRI increased as risk category increased. In the observational cohort, 89% of participants (15 980/18 031) chose risk based. Conclusions:Risk-based breast cancer screening that includes population-based genetic testing safely stratified risk and screening intensity, but did not reduce biopsy rates. Trial Registration:ClinicalTrials.gov Identifier: NCT02620852.

Patients with interstitial lung disease (ILD) are at elevated risk of postoperative pulmonary complications (PPCs), including acute exacerbation, which carry high mortality. Surgical decision-making in this population requires careful preoperative risk stratification, medical optimization, and tailored intra- and postoperative management. This review summarizes current evidence to guide perioperative care for patients with ILD. The ARISCAT (Assess Respiratory Risk in Surgical Patients in Catalonia) risk index is widely used for PPC prediction but likely underestimates risk in ILD. Recent studies highlight the high prevalence of comorbid obstructive sleep apnea in ILD, supporting the need for routine screening. Updated American College of Rheumatology guidelines inform perioperative antirheumatic drug management, while International Society for Heart and Lung Transplantation consensus recommendations guide care of patients with pulmonary hypertension and right heart failure, a common comorbid condition. Emerging evidence suggests that perioperative antifibrotic therapy is safe and may reduce the risk of acute exacerbation, although further investigation is needed. Regional anesthesia can be a feasible alternative to general anesthesia when possible, for further risk mitigation in this patient population. Intraoperative lung-protective ventilation and use of the lowest oxygen concentration that maintains safe oxygen saturation remain critical, while judicious fluid management, postoperative extubation to high-flow nasal cannula or noninvasive ventilation, early mobilization, and multimodal analgesia may further reduce PPC risk. Perioperative management of ILD patients is complex due to heightened vulnerability to PPCs. Current evidence supports adapting general perioperative strategies while incorporating disease-specific considerations. As therapeutic advances extend survival, further prospective studies are needed to establish evidence-based perioperative guidelines for this high-risk group.

Social support may improve clinician well-being and teamwork in primary care, yet evidence remains limited on how social support affects job outcomes, such as job satisfaction, burnout, and turnover intention among all members of primary care teams, including clinicians and staff. To investigate the relationship between social support network characteristics in primary care teams and their impact on job satisfaction, burnout, and turnover intention among clinicians and staff. A cross-sectional study using a sociometric network survey design. 652 primary care clinicians and staff in 23 primary care practices in New York (14) and Pennsylvania (9), which had implemented team-based primary care models. Social support network measures were calculated at two-levels. At the participant-level, these included in-degree (incoming connections), out-degree (outgoing connections), and betweenness (frequency of appearing on the shortest path between other member pairs) centrality. At the practice-level, measures included density (observed ties as a proportion of all possible ties) and transitivity (number of closed triads). Job outcome measures included job satisfaction, burnout, and intent to leave the job. Participants with higher out-degree centrality—indicating that they identified more team members who supported them—were less likely to intend to leave their jobs (OR = 0.77; CI 0.65–0.90; p < .001). Similarly, those in practices with greater support network density, indicating a heightened level of interaction among team members for support, were also less likely to express intentions to leave their job (OR = 0.63; CI 0.40–0.97; p < .05). Betweenness centrality was not significantly associated with the outcome variables. Social support within primary care teams can potentially reduce turnover among primary care clinicians and staff. A better understanding of social support in primary care teams can lay a foundation for network-based interventions. Future research should test the impact of support networks on patient outcomes.

Previous reports have suggested concurrence of cervical dystonia (CD) and chronic migraine (CM); however, the extent of the burden is unclear. This analysis estimated the prevalence of comorbid CD and CM (CD + CM) and described patient characteristics and health care costs among real-world patients with CD + CM. This retrospective cohort study used administrative claims data from the Merative MarketScan (January 1, 2017–December 31, 2021) and Optum® Market Clarity databases (January 1, 2017–September 30, 2021). Adults with CD and/or CM were identified using ICD-10-CM diagnosis codes. Outcomes were summarized descriptively and included prevalence of CD, CM, and CD + CM; relative risk of comorbid CD + CM; patient characteristics stratified by cohort and botulinum neurotoxin (BoNT) exposure status; and health care costs for CD + CM. In 2017–2021, numbers of patients identified as above annually ranged from 10.5 million to 16.3 million. The relative risk of CM among patients with CD, and of CD among patients with CM, was 31.8 and 39.5, respectively. Among patients with CD, the overall prevalence of CD + CM from 2017 to 2021 was 12.6