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Summary Evidence for an association between insulin‐like growth factors (IGF) and multiple myeloma (MM) is inconsistent. We examined total IGF‐I concentrations and risk of MM by combining baseline serological data among UK Biobank participants ( n = 444 187; 732 incident MM) with a two‐sample Mendelian randomisation (MR) analysis using identified genetic variants associated with circulating total IGF‐I and IGF‐binding protein 3 (IGFBP‐3) in the InterLymph consortium (2434 MM and their 2567 controls). Finally, additional lymphoid neoplasm (LN) subtypes were included for comparison with the main hypothesis. Circulating IGF‐I level was positively associated with MM risk Hazard ratio‐HR‐per one standard deviation‐SD‐increase (HR 1‐SD = 1.11, 95% confidence interval [CI]: 1.01–1.22; p ‐value = 0.03), especially closer to diagnosis. Genetically inferred IGF‐I levels were associated with increased MM risk (odds ratio [OR] = 1.27, 95% CI: 1.05–1.54) but not with any other LNs. Genetically inferred IGFBP‐3 levels showed no associations with any LN evaluated. Corroborating previous findings, in a secondary analysis, IGF‐I levels were associated with the risk of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) in males with higher body mass index (HR 1‐SD in obese male = 1.36, 95% CI: 1.14–1.61). Our serological and MR analyses suggest a contributing role of IGF‐I in the susceptibility of MM; the CLL/SLL findings warrant further investigation considering sex‐specific adiposity.

PURPOSE To compare mortality risk among long-term survivors of high-grade serous ovarian cancer (HGSOC) with that of the general US population and to examine how mortality and recurrence trends have evolved under changing treatment approaches. MATERIALS AND METHODS This is a retrospective cohort study including patients with histologically confirmed HGSOC treated at a single referral cancer center from 1991 to 2022. Mortality risk, expressed as standardized mortality ratios (SMRs, ratio of observed deaths in the study population to expected deaths in an age-matched US population), was assessed at diagnosis and yearly on patients without events (disease persistence, recurrence, or death from any cause). RESULTS A total of 2,074 consecutive patients were included. The median follow-up was 12.5 years (IQR, 11.7-13.8). Most patients were stage III (1,396, 69.2%), 1,299 (62.8%) underwent primary cytoreductive surgery, and 1,688 (87.4%) received platinum-taxane as first-line therapy. At diagnosis, the mortality rate was 7.40 times higher than that in the general population (95% CI, 7.04 to 7.77). By 7 event-free years, the 95% CI for the SMR included 1 for the first time, and at 10 years, the SMR was 1.05 (95% CI, 0.72 to 1.49), indicating no statistically significant excess mortality compared with the general population. In those event-free at 10 years, the 5-year cumulative incidence of ovarian cancer–related deaths (8.2% [95% CI, 4.2 to 16.0]) was comparable with that of non–ovarian cancer–related deaths (6.3% [95% CI, 2.9 to 13.8]). CONCLUSION In this cohort, mortality risk steadily declined for patients who remained event-free, approaching that of the general population by 7 years after diagnosis. These results emphasize the importance of individualized, long-term follow-up to address both recurrence risk and survivorship needs.

Background: ASCO recommends extended venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs) following cancer surgery. However, these recommendations were based on trials using routine venography, which detects asymptomatic VTEs, and real-life efficacy is not well studied. We aimed to assess the association of extended VTE prophylaxis with the incidence of clinically significant VTE after elective cancer surgery. Patients and Methods: In this retrospective, population-based cohort study, we identified patients who underwent surgical resection for lung, breast, esophageal, gastric, pancreas, and colon cancer from 2010 to 2017 using the SEER–Medicare linked dataset. Patients were divided into 1 of 2 main groups for comparative analyses: those who received extended VTE prophylaxis after cancer surgery and those who did not. Patients who received extended VTE prophylaxis after cancer surgery were identified as those prescribed prophylactic doses of LMWH or a DOAC within 7 days of discharge, as captured in Medicare Part D files. Results: A total of 113,739 Medicare beneficiaries were identified, of whom 1,570 (1.4%) received extended VTE prophylaxis. There was a year-over-year increase in the use of extended VTE prophylaxis during the study period, rising from 0.6% in 2010 to 3.3% in 2017. The overall incidence of VTE was 1.6% at 1 month, 4.3% at 6 months, 5.7% at 12 months, with significant differences observed across cancer types ( P <.001). However, patients who received extended VTE prophylaxis had a higher 1-year cumulative incidence of postoperative VTE compared with those who did not (11.4% vs 5.3%; P <.001), an association that was consistent across cancer sites. In adjusted analyses, extended VTE prophylaxis was independently associated with an increased risk of VTE (hazard ratio, 1.6; 95% CI, 1.3–2.0; P <.001). Extended prophylaxis was also associated with a higher 1-year incidence of bleeding events compared with patients who did not receive prophylaxis (12.0% vs 8.5%; P <.001). Conclusions: The utilization of extended VTE prophylaxis after cancer surgery remains low, although it has increased every year. Paradoxically, patients who received extended VTE prophylaxis had higher incidences of clinically significant VTE and bleeding compared with those who did not, likely reflecting patient selection and surveillance bias after surgery. In light of these findings, national guidelines recommending postoperative extended VTE prophylaxis, and its use as a surrogate for quality of care, should continue to be re-examined.

Abstract Neuromodulatory subcortical systems (NSSs) are uniquely susceptible to dementia‐related pathology, leading to frequent molecular and behavioral impairments associated with altered function of these nuclei. Some of these systems display clear sex‐specific cytoarchitecture and signaling leading to distinct physiology and behavioral outputs in males and females, while other regions display nominal sex differences. However, the relevance of sex differences in modulating dysfunction of NSSs in Alzheimer's disease (AD) and related dementias is not well understood. This review is a joint effort by the Neuromodulatory Subcortical Systems and Sex and Gender Differences in Alzheimer's Disease Professional Interest Areas of the Alzheimer's Association. We review sex differences in NSSs, both in non‐disease states and in AD models and patients. We highlight the possible role of NSSs in driving sex‐specific AD susceptibility and potential footholds for sex‐based interventions targeting these systems. We conclude by outlining immediate and long‐term actions to address the intersection of NSSs, sex, and AD.

Most palliative care (PC) physicians will change jobs over the course of their career, yet few supports exist to guide them through this often unfamiliar process. Job transitions frequently elicit stress and uncertainty, as individuals balance personal and professional priorities, navigate complex negotiations, and assume the inherent risks of pursuing new opportunities. Yet, when approached intentionally, a job transition can also be a transformative process that allows for self-discovery, cultivation of new skills and connections, and reshaping of one’s professional identity. This article, written by a team of PC physicians who have made job transitions themselves, offers 10 tips for navigating this professional step successfully. With emphases on authentic communication, skilled mentorship, relationship building, and exploration of local culture—the article offers practical advice to help PC physicians navigate a job transition confidently, while staying grounded in their personal values and the work they find most meaningful.

Background Difficulty tolerating the uncertainty of ambiguous or unpredictable situations may influence how patients with functional motor disorder (FMD) respond to treatment. However, only one study has examined the role of intolerance of uncertainty (IU) in FMD treatment. Objectives This study sought to expand on prior findings in a larger sample of patients with FMD who completed an intensive motor-retraining programme. Methods A consecutive cohort of 109 patients with FMD completed a 1-week intensive outpatient motor-retraining programme. Patients rated their IU using the Intolerance of Uncertainty Scale-12 and functional motor outcomes using three empirical measures before and after treatment. Univariate and multivariable analyses were conducted to (1) characterise the rate of elevated IU, (2) evaluate potential changes in IU across the programme, (3) examine whether changes in IU predict improvements in motor functioning and (4) determine if IU incrementally predicts functional improvements in patients with clinically elevated IU. Results Findings revealed that clinically elevated IU was common (yielding a base rate of 44%) and that the ‘prospective’ subtype of IU significantly decreased with 1 week of FMD treatment. Change in IU was not significantly associated with improved functional outcomes across the sample. However, change in prospective IU did predict patient-specific functional outcomes among those with clinically elevated IU ( R 2 =11%). Conclusions Findings support prior work suggesting that certain subtypes of IU are common, modifiable and related to treatment outcomes in FMD. The ‘prospective’ subtype of IU may represent an operative factor that can enhance the efficacy of existing FMD rehabilitation programmes.

Abstract Context Data on cognition in patients with primary aldosteronism (PA) are scarce. Mild autonomous cortisol secretion (MACS), defined based on post-dexamethasone cortisol &gt;1.8 mcg/dL, is diagnosed in up to 30% of patients with PA. Objectives (1) Assess cognition in patients with PA vs referent subjects with hypertension and (2) determine differences in cognition between patients with PA and those with MACS. Methods A prospective, cross-sectional study, 2019-2023. Cognition was assessed by National Institute of Health Toolbox Cognition Battery and reported as T-scores corrected for age, sex, race, and education. Only subjects with hypertension were included. Results Cognitive assessment was performed in 52 patients with PA (including 11 patients with both PA and MACS, median age of 51.0 years, 30 (57.7%) women), 47 patients with MACS (median age of 57.0 years, 31 (66.0%) women), and 52 referent subjects (median age of 66.1 years, 30 (57.7%) women). When compared to referents, and after adjusting for age, smoking, systolic blood pressure, and alcohol use, patients with PA had lower total cognition (β = −5.7, P = .023), notably fluid cognition (β = −6.8, P = .017), including attention and executive function (β = −5.6, P = .012) and cognitive flexibility and executive function (β = −8.2, P = .006). When compared to patients with MACS, patients with PA had a higher processing speed (β = 9.0, P = .003). No differences in cognition were found between patients with PA with and without MACS. Conclusion Patients with PA demonstrated lower cognition compared with referents and processing speed compared with MACS. Future studies should characterize the impact of MACS on the cognition of patients with PA.

PURPOSE For patients with advanced biliary tract cancer (BTC), cancer-related time spent in health care systems, time toxicity, represents a critical but understudied burden affecting quality of life. This study aimed to quantify time toxicity in patients receiving first-line systemic therapy and evaluate whether the addition of durvalumab to gemcitabine plus cisplatin (GC) increases health care contact time. METHODS This international, multicenter, retrospective cohort study included patients with advanced BTC seen between January 2019 and April 2024 at Mayo Clinic Enterprise (US), and between January 2021 and April 2024 at Kyorin University Hospital (Japan), and Hospital Israelita Albert Einstein (Brazil). Patients received GC plus durvalumab (GCD) or GC. Time toxicity was recorded from treatment initiation until discontinuation or last follow-up during first-line systemic therapy. Multiple regression analysis identified factors associated with high time toxicity. RESULTS Among 193 patients (102 GCD, 91 GC; median age 65 years; 50% male; 49% Eastern Cooperative Oncology Group performance status [PS] 0), median time on treatment (TOT) was 156 days (95% CI, 122 to 190). The median proportion of total time toxicity was 14.4% (IQR, 10.9-20.6). Planned visits accounted for 11.9%, while unplanned visits were infrequent (1.8%). Time toxicity strongly correlated with TOT ( r = 0.824) and progression-free survival ( r = 0.827). Despite longer treatment in the GCD group than the GC group (212 v 134 days; P = .027), total time toxicity was similar (27 v 18 days; P = .19). Younger age and poor PS were independent factors of higher time toxicity. CONCLUSION Time toxicity represents a meaningful metric that allows for more comprehensive integration of the net benefit in patients with advanced BTC with a limited lifespan.