Citations

Abstract Background: There is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects. Methods: This analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. The prediagnosis inflammation-related exposures of interest included alcohol use; aspirin use; other nonsteroidal anti-inflammatory drug use; body mass index; environmental tobacco smoke exposure; history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis; menopausal hormone therapy use; physical inactivity; smoking status; and talc use. Using Cox proportional hazards models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed, and its association with survival was assessed using Cox proportional hazards models in the remaining 50% of the data. Results: There was a statistically significant trend of increasing risk of death per quartile of the IRRS [HR = 1.09; 95% confidence interval (CI), 1.03–1.14]. Women in the upper quartile of the IRRS had a 31% higher death rate compared with the lowest quartile (95% CI, 1.11–1.54). Conclusions: A higher prediagnosis IRRS was associated with an increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether postdiagnosis exposures are also associated with survival. Impact: Given that pre- and postdiagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among patients with ovarian cancer.

Uterine fibroids are noncancerous tumors associated with significant morbidity among symptomatic patients. While medical and surgical treatments have expanded, hysterectomy remains common. We interviewed women diagnosed with uterine fibroids ( n = 47) to explore their experiences and recommendations for shared decision-making. A majority were non-Hispanic Black, highly educated (51.1%), and had graduate degrees (40.4%). Participants with both positive and negative provider experiences expressed a desire for a more proactive therapeutic approach, including a presentation by their provider of the spectrum of medical and surgical treatment options, and greater provider recognition of the impact of symptoms on quality of life. Women advocated for expanded shared decision-making that acknowledged their contribution to their own treatment plan and felt early screening and improved patient/provider education of uterine fibroid symptoms would facilitate greater congruence between treatment approaches and patient goals. Perceptions of insufficient input into their treatment plans frequently served as a barrier to care-seeking and treatment acceptance among women with uterine fibroid symptoms. Improved discussion of treatment options in the context of the unique symptom burden and values of the patient may facilitate greater provider trust and acceptance of uterine fibroid treatment.

Abstract The American Thoracic Society Sleep Core Curriculum updates clinicians on important sleep topics, presented during the annual meeting, and appearing in summary here. This year’s sleep core theme is sleep-disordered breathing and its management. Topics range from pathophysiological mechanisms for the association of obstructive sleep apnea (OSA) and metabolic syndrome, surgical modalities of OSA treatment, comorbid insomnia and OSA, central sleep apnea, and sleep practices during a pandemic. OSA has been associated with metabolic syndrome, independent of the role of obesity, and the pathophysiology suggests a role for sleep fragmentation and intermittent hypoxia in observed metabolic outcomes. In specific patient populations, surgical treatment modalities for OSA have demonstrated large reductions in objective disease severity compared with no treatment and may facilitate adherence to positive airway pressure treatment. Patient-centered approaches to comorbid insomnia and sleep apnea include evaluating for both OSA and insomnia simultaneously and using shared-decision making to determine the order and timing of positive airway pressure therapy and cognitive behavioral therapy for insomnia. The pathophysiology of central sleep apnea is complex and may be due to the loss of drive to breathe or instability in the regulatory pathways that control ventilation. Pandemic-era sleep practices have evolved rapidly to balance safety and sustainability of care for patients with sleep-disordered breathing.

AbstractIntroductionEfforts to model the cost‐effectiveness of managing/modifying cognitive impairment lack reliable, objective, baseline medical, and nursing‐home (NH) costs.MethodsA stratified‐random sample of Olmsted County, MN, residents ages 70–89 years (N = 3545), well‐characterized as cognitively unimpaired, mild cognitive impairment (MCI), or dementia, were followed forward ≤1 year in provider‐linked billing data and the Centers for Medicare & Medicaid Services NH assessments. Direct medical/nursing home/medical + NH costs were estimated. Costs were stratified by vital status and NH‐use intensity (NH days/follow‐up days [0%, 1% to 24%, 25% to 99%, and 100%]). Between‐category mean‐annual cost differences were adjusted for patient characteristics and follow‐up days.ResultsCosts/follow‐up day distributions differed significantly across cognitive categories. Mean costs/follow‐up days were 2.5 to 18 times higher for decedents versus survivors. Among all persons with MCI, <9% with any NH use accounted for 18% of all total annual medical + NH costs. Adjusted‐between‐category comparisons revealed significantly higher medical and medical + NH costs for MCI versus cognitively unimpaired.DiscussionCost‐effectiveness for managing/modifying both MCI and dementia should consider end‐of‐life costs and NH‐use intensity. Results can help inform cost‐effectiveness models, predict future‐care needs, and aid decision‐making by individuals/providers/payers/policymakers.

4-Aminopyridine is a potential therapeutic option for a subgroup of patients with KCNA2 -encephalopathy and gain-of-function variants.

Background: Chronic kidney disease (CKD), a growing public health issue in the elderly, is associated with increased risk of cognitive impairment. Objective: To investigate the mechanisms through which CKD impacts brain health using longitudinal imaging. Methods: We identified 97 participants (74 CKD and 23 non-CKD) from the BRINK (BRain IN Kidney Disease), a longitudinal study of CKD with two MRI scans (baseline and 3-year follow-up). We measured the associations between baseline and change in kidney disease biomarkers of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR), considered a measure of microvascular inflammation, and imaging outcomes of cortical thickness and ventricular volume from structural MRI, white matter hyperintensities (WMH) volume from FLAIR images, and fractional anisotropy of the corpus callosum (FACC). Results: There were white matter-specific changes as observed by increased WMH volume and decreased FACC in CKD participants, as well as ventricular volume increase in both CKD and non-CKD groups reflective of aging-related changes. Decline in eGFR was associated with decrease in the FACC, suggesting that subtle early white matter changes due to kidney disease can be captured using DTI. An increase in UACR was associated with increase in ventricular volume. Conclusion: Our results support the role of eGFR as a measure of kidney microvascular disease which is associated with concurrent white matter damage in CKD. Future work is needed to investigate the possible link between endothelial microvascular inflammation (as measured by an increased UACR) and ventricular volume increase.

Abstract Background: Many loci have been found to be associated with risk of epithelial ovarian cancer (EOC). However, although there is considerable variation in progression-free survival (PFS), no loci have been found to be associated with outcome at genome-wide levels of significance. Methods: We carried out a genome-wide association study (GWAS) of PFS in 2,352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy. Results: We found seven SNPs at 12q24.33 associated with PFS (P &lt; 5 × 10–8), the top SNP being rs10794418 (HR = 1.24; 95% CI, 1.15–1.34; P = 1.47 × 10–8). High expression of a nearby gene, ULK1, is associated with shorter PFS in EOC, and with poor prognosis in other cancers. SNP rs10794418 is also associated with expression of ULK1 in ovarian tumors, with the allele associated with shorter PFS being associated with higher expression, and chromatin interactions were detected between the ULK1 promoter and associated SNPs in serous and endometrioid EOC cell lines. ULK1 knockout ovarian cancer cell lines showed significantly increased sensitivity to carboplatin in vitro. Conclusions: The locus at 12q24.33 represents one of the first genome-wide significant loci for survival for any cancer. ULK1 is a plausible candidate for the target of this association. Impact: This finding provides insight into genetic markers associated with EOC outcome and potential treatment options. See related commentary by Peres and Monteiro, p. 1604