Causes of mortality among adults with Down syndrome before and after the COVID-19 pandemic in Spain.

BACKGROUND: The life expectancy of people with Down syndrome (DS) is limited by Alzheimer's disease (AD)-related deaths, mainly due to respiratory infections. The emergence of the COVID-19 pandemic could have changed known, past trends in mortality in this population. We analysed the differences in causes of mortality between individuals with DS deceased before and after the onset of the pandemic. METHOD: This is a cross-sectional study of adults with DS recruited at a tertiary, university outpatient clinic in Madrid, Spain. Demographic and clinical data were retrospectively collected from their medical records, including information on their deaths, if any. RESULTS: Five hundred seventy-two adults were included in the study, and 67 (11.7%) died. The main cause of death was respiratory infections, which occurred in 36 participants [9 (45.0%) before, and 27 (58.7%) after the appearance of COVID-19]. No significant differences were found in the determinants of pre-pandemic and post-pandemic death after adjusting for age and AD, except for an association between the use of psychotropic medication and death in the post-pandemic period (odds ratio: 2.24; 95% confidence interval: 1.04-4.82). Vaccination against COVID-19 showed a marked protective effect against mortality (odds ratio: 0.0002; 95% confidence interval: 6.7e10-6 to 0.004). CONCLUSIONS: The appearance of COVID-19 has not impacted the overall trend of increase in mean age of death of adults with DS in our milieu, probably thanks to the very important protective effect of vaccination, which supports prioritising people with DS in future immunisation campaigns. The association between psychotropic medication use and mortality requires further exploration.

Voxel-based dysconnectomic brain morphometry with computed tomography in Down syndrome.

OBJECTIVE: Alzheimer's disease (AD) is a major health concern for aging adults with Down syndrome (DS), but conventional diagnostic techniques are less reliable in those with severe baseline disability. Likewise, acquisition of magnetic resonance imaging to evaluate cerebral atrophy is not straightforward, as prolonged scanning times are less tolerated in this population. Computed tomography (CT) scans can be obtained faster, but poor contrast resolution limits its function for morphometric analysis. We implemented an automated analysis of CT scans to characterize differences across dementia stages in a cross-sectional study of an adult DS cohort. METHODS: CT scans of 98 individuals were analyzed using an automatic algorithm. Voxel-based correlations with clinical dementia stages and AD plasma biomarkers (phosphorylated tau-181 and neurofilament light chain) were identified, and their dysconnectomic patterns delineated. RESULTS: Dementia severity was negatively correlated with gray (GM) and white matter (WM) volumes in temporal lobe regions, including parahippocampal gyri. Dysconnectome analysis revealed an association between WM loss and temporal lobe GM volume reduction. AD biomarkers were negatively associated with GM volume in hippocampal and cingulate gyri. INTERPRETATION: Our automated algorithm and novel dysconnectomic analysis of CT scans successfully described brain morphometric differences related to AD in adults with DS, providing a new avenue for neuroimaging analysis in populations for whom magnetic resonance imaging is difficult to obtain.

Previous use of statins does not improve the outcome of bloodstream infection after kidney transplantation.

Previous studies have suggested that exposure to statins confers a protective effect in bloodstream infection (BSI) due to the anti-inflammatory and immunomodulatory properties attributed to these lipid-lowering drugs. Scarce evidence is available for the solid organ transplant population. Therefore, we compared the time to clinical cure (primary outcome) and the time to fever resolution, new requirement of intensive care unit admission or renal replacement therapy, and 30-day all-cause mortality (secondary outcomes) between kidney transplant (KT) recipients with post-transplant BSI that were receiving or not statin therapy for at least the previous 30 days. We included 80 KT recipients that developed 109 BSI episodes (43 [39.4%] and 66 [60.6%] episodes within the statin and non-statin groups, respectively). The median interval since the initial prescription to BSI was 512 days (interquartile range [IQR]: 172-1388). Most episodes were of urinary source and due to Enterobacterales. There were no differences in the median time to clinical cure in the statin and non-statin groups (3.4 [IQR: 3-6.8] versus 4 [IQR: 2-6] days; p-value = .112). The lack of effect was confirmed by multiple linear regression analysis adjusted for confounding factors (standardized ß coefficient = 0.040; p-value = .709). No significant differences were observed for any of the secondary outcomes either. Vital signs and laboratory values at BSI onset and after 72-96 h were similar in both groups. In conclusion, previous statin therapy had no apparent protective effect on the outcome of post-transplant BSI among KT recipients.

Sporadic, non-functional, gastrin-producing duodenal neuroendocrine tumors: A retrospective study of an infrequent disease.

OBJECTIVES: Non-functioning gastrin-producing neuroendocrine neoplasms (NEN) of the duodenum are rare gastrointestinal tumors without a clinical syndrome due to gastrin production. Their incidence has significantly increased as an incidental finding during endoscopic studies. The aim of this study was to describe the characteristics and prognostic factors of this emergent and infrequent neoplasm. METHODS: We performed a retrospective observational study based on the duodenal NENs samples with positive staining for gastrin at the Department of Pathology, University Hospital 12-de-Octubre (Madrid, Spain) between 2000 and 2017. Patients with clinically functional tumors ([Zollinger-Ellison syndrome] or gastrin >1000 pg/mL), with previously diagnosed multiple endocrine neoplasia (MEN) syndrome or synchronous neoplasia were excluded. Clinicopathological and therapeutic variables, follow-up, recurrence, and mortality data were collected. RESULTS: In all, 21 patients were included. Most of the tumors were diagnosed incidentally as a single small polypoid lesion limited to mucosa/submucosa and with a low histological grade. Four (19.0%) patients presented with metastatic involvement at diagnosis (lymphatic and/or hepatic). These four patients also had a high or intermediate mitotic grade and infiltration further than submucosa. Local resection was applied in most cases as curative treatment. There were two cases of tumor recurrence and two tumor-related deaths with a 5-year disease-free survival of 81.0%. CONCLUSIONS: The majority of these tumors were diagnosed at a localized stage and had a good prognosis with treatment. Nevertheless, given the potential metastatic risk, a close follow-up is necessary, especially in those with aggressive pathological factors such as deep infiltration or high histological grade.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19.

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality). We evaluated both outcomes in patients whose treatment with ACEI/ARB was continued or withdrawn. Between February and June 2020, 11,205 patients were included, mean age 67 years (SD = 16.3) and 43.1% female; 2162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed lower all-cause mortality (p < 0.0001). Hypertensive patients in the ACEI/ARB group had better results in IMV, ICU admission, and the composite outcome of prognosis (p < 0.0001 for all). No differences were found in the incidence of major adverse cardiovascular events. Patients previously treated with ACEI/ARB continuing treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB was associated with better survival than ACEI (HR 0.77, 95%CI 0.62-0.96). ACEI/ARB treatment during COVID-19 hospitalization was associated with protection on mortality. The benefits were greater in hypertensive, those who continued treatment, and those taking ARB.