Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Arterial stiffness is an independent risk factor for cognitive impairment in the elderly: a pilot study

BACKGROUND: Loss of cognitive function is a common condition in the elderly population. Cognitive impairment is defined as the transitional stage of cognitive decline, between normal aging and early dementia. We tested whether arterial stiffness, evaluated as pulse wave velocity (PWV), is associated with cognitive impairment in older subjects, and whether PWV is increased at a comparable extent in older subjects with cortical or subcortical cerebral lesions when compared with age-matched controls referred for memory deficits. SUBJECTS AND METHODS: Eighty-four subjects (78 +/- 5 years, 30 men and 54 women) referred for memory deficit with no history of stroke or atrial fibrillation were studied. Carotid-femoral PWV was determined non-invasively with Complior. The Mini Mental State Examination was assessed as a measure of global cognitive function. The sum of the score on the Activities of Daily Living and Instrumental Activities of Daily Living scales was used as a measure of personal independency. Based upon brain imaging, subjects were classified as referred for memory deficits with normal brain imaging, or control, with subcortical microvascular lesions or with cortical atrophy. RESULTS: PWV, normalized for mean blood pressure, was inversely correlated with the Mini Mental State Examination (r = -0.26, P < 0.05), even after controlling for education, prevalent cardiovascular (CV) disease, CV risk factors, and medication use (beta coefficient = -0.28, P < 0.01). PWV was also inversely correlated with personal independency (r = -0.36, P < 0.01; beta coefficient = -0.38, P < 0.01, after multiple adjustment). In the presence of no significant differences in age, education, traditional CV risk factor levels, carotid plaques, or prevalence of CV disease, higher PWV values were more frequent in subjects with cortical atrophy than in patients with subcortical microvascular lesions or controls (P < 0.05). CONCLUSIONS: PWV was associated with cognitive impairment and with a greater personal dependency, independently of major modifiable CV risk factors

Depression treatment selectively modifies arterial stiffness in older participants

Background.Depression is emerging as an independent cardiovascular disease risk factor. We investigated whether treating depression in older participants impacted on arterial stiffness, a known cardiovascular disease risk factor and a clinical marker of arterial aging.Methods.Seventy-five participants with pulse wave velocity (PWV), the gold standard measure for arterial stiffness, at baseline and at 12-month follow-up were included. Depressed patients were randomized to escitalopram (10mg/d) or to duloxetine (60mg/d). In patients without depression, no antidepressant therapy was started. The psychologist and the doctor measuring PWV were both unaware of antidepressant treatment.Results.At study entry, no difference in PWV were observable in the three groups of participants. A significant time à drug interaction term (p &lt;. 05) was observed for the impact of antidepressant therapy on PWV by analysis of covariance analysis. After 12 months of therapy, duloxetine treatment resulted in a significant (+21%) and escitalopram treatment in a not significant (6%) PWV increase. These changes in PWV were accompanied by a similar increase in blood pressure and LDL cholesterol in the two treated groups. However, duloxetine resulted in a significant 10% greater heart rate after 12 months that was not observable in participants treated with escitalopram nor in not-depressed older participants. Multiple regression models revealed that a drug-specific effect on PWV persisted after controlling for cardiovascular risk factor levels.Conclusion.Duloxetine but not escitalopram significantly increased PWV in older depressed participants after 12 months of treatment. The effect was not fully explained by concomitant changes in traditional cardiovascular risk factors known to significantly impact arterial stiffness

Decreased nocturnal systolic blood pressure fall in older subjects with depression

Depressed subjects have a two-fold increased risk of CV events than non-depressed ones. Altered blood pressure (BP) circadian profile may be one mechanism underlying this association. We studied 135 elderly subjects (mean age 78±6 yrs, range 69-93; 30 M, 87 F). On the basis of the 15-items Geriatric Depression Scale (GDS), score&gt;5 identified subjects with depressive symptoms. Based upon 24-h Ambulatory BP Monitoring (Spacelabs 90207®), the following BP circadian profile measures were examined: SD of 24-h, day, and night SBP, DBP, MBP; 24-h, day, and night SBP and DBP load; night SBP and DBP decline; dipping status for SBP and DBP. Compared with non-depressed subjects (n=61), depressed subjects (n=74) were similar in age and more likely to be women. No significant differences in traditional CV risk factors or in medication use were observed between the two groups. After controlling for age, sex, and traditional CV risk factors, subjects with depressive symptoms presented a significantly lower night-time SBP fall than non-depressed ones (average, -4.4 mmHg for SBP) with a significantly higher occurrence of non-dipper status. The GDS score was an independent significant inverse determinant of 24-h SD of SBP. Depressive symptoms in older subjects are accompanied by lower nocturnal BP fall and are significant independent determinants of SBP variability

Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study

Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy.Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of >= 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site.Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of >= 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P = 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH).Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes