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- Tristao-Pereira, C., et al.
(författare)
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Longitudinal interplay between subclinical atherosclerosis, cardiovascular risk factors, and cerebral glucose metabolism in midlife: results from the PESA prospective cohort study
- 2023
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Ingår i: Lancet Healthy Longevity. - 2666-7568. ; 4:9, s. E487-E498
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Tidskriftsartikel (refereegranskat)abstract
- Background Cardiovascular disease and dementia often coexist at advanced stages. Yet, longitudinal studies examining the interplay between atherosclerosis and its risk factors on brain health in midlife are scarce. We aimed to characterise the longitudinal associations between cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in middle-aged asymptomatic individuals. Methods The Progression of Early Subclinical Atherosclerosis (PESA) study is a Spanish longitudinal observational cohort study of 4184 asymptomatic individuals aged 40-54 years (NCT01410318). Participants with subclinical atherosclerosis underwent longitudinal cerebral [18F]fluorodeoxyglucose ([18F]FDG)-PET, and annual percentage change in [18F]FDG uptake was assessed (primary outcome). Cardiovascular risk was quantified with SCORE2 and subclinical atherosclerosis with three-dimensional vascular ultrasound (exposures). Multivariate regression and linear mixed effects models were used to assess associations between outcomes and exposures. Additionally, blood based biomarkers of neuropathology were quantified and mediation analyses were performed. Secondary analyses were corrected for multiple comparisons using the false discovery rate (FDR) approach. Findings This longitudinal study included a PESA subcohort of 370 participants (median age at baseline 49 & BULL;8 years [IQR 46 & BULL;1-52 & BULL;2]; 309 [84%] men, 61 [16%] women; median follow-up 4 & BULL;7 years [IQR 4 & BULL;2-5 & BULL;2]). Baseline scans took place between March 6, 2013, and Jan 21, 2015, and follow-up scans between Nov 24, 2017, and Aug 7, 2019. Persistent high risk of cardiovascular disease was associated with an accelerated decline of cortical [18F]FDG uptake compared with low risk (& beta;=-0 & BULL;008 [95% CI -0 & BULL;013 to -0 & BULL;002]; pFDR=0 & BULL;040), with plasma neurofilament light chain, a marker of neurodegeneration, mediating this association by 20% (& beta;=0 & BULL;198 [0 & BULL;008 to 0 & BULL;740]; pFDR=0 & BULL;050). Moreover, progression of subclinical carotid atherosclerosis was associated with an additional decline in [18F]FDG uptake in Alzheimer's disease brain regions, not explained by cardiovascular risk (& beta;=-0 & BULL;269 [95% CI -0 & BULL;509 to -0 & BULL;027]; p=0 & BULL;029). Interpretation Middle-aged asymptomatic individuals with persistent high risk of cardiovascular disease and subclinical carotid atherosclerosis already present brain metabolic decline, suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life.
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- Cibula, D., et al.
(författare)
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Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement : ABRAX international retrospective cohort study
- 2021
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 143, s. 88-100
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Tidskriftsartikel (refereegranskat)abstract
- Background: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. Patients and methods: We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA–IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. Results: The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799–1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458–1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690–1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. Conclusion: We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. Clinical trials identifier: NCT04037124.
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