SARS-CoV2 evokes structural brain changes resulting in declined executive function.

BACKGROUND: Several research has underlined the multi-system character of COVID-19. Though effects on the Central Nervous System are mainly discussed as disease-specific affections due to the virus' neurotropism, no comprehensive disease model of COVID-19 exists on a neurofunctional base by now. We aimed to investigate neuroplastic grey- and white matter changes related to COVID-19 and to link these changes to neurocognitive testings leading towards a multi-dimensional disease model. METHODS: Groups of acutely ill COVID-19 patients (n = 16), recovered COVID-19 patients (n = 21) and healthy controls (n = 13) were prospectively included into this study. MR-imaging included T1-weighted sequences for analysis of grey matter using voxel-based morphometry and diffusion-weighted sequences to investigate white matter tracts using probabilistic tractography. Comprehensive neurocognitive testing for verbal and non-verbal domains was performed. RESULTS: Alterations strongly focused on grey matter of the frontal-basal ganglia-thalamus network and temporal areas, as well as fiber tracts connecting these areas. In acute COVID-19 patients, a decline of grey matter volume was found with an accompanying diminution of white matter tracts. A decline in executive function and especially verbal fluency was found in acute patients, partially persisting in recovered. CONCLUSION: Changes in gray matter volume and white matter tracts included mainly areas involved in networks of executive control and language. Deeper understanding of these alterations is necessary especially with respect to long-term impairments, often referred to as 'Post-COVID'.

A multilocus genetic risk score for obesity: Association with BMI and metabolic alterations in a cohort with severe obesity.

Genome wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with obesity, yet effect sizes of individual SNPs are small. Therefore, the aim of our study was to investigate whether a genetic risk score (GRS) comprising risk alleles of SNPs identified in the GIANT consortium meta-analyses shows association with body mass index (BMI) and other BMI related metabolic alterations in a cohort with an extreme phenotype. Genotyping of 93 SNPs was performed in 314 obese individuals (mean BMI 40.5 ± 7.8 kg/m², aged 45 ± 12 years), participating in a standardized weight reduction program, and in 74 lean controls (mean BMI 24.6 ± 3.3 kg/m², aged 41.7 ± 13.4 years). Allele numbers of all 93 SNPs were added to a GRS. Anthropometric parameters, parameters of glucose/insulin and lipid metabolism were assessed standardized after a 12 hours fast. GRS was significantly different between controls and obese individuals (unweighted GRS: 86.6 vs 89.0, P = .002; weighted GRS: 84.9 vs 88.3, P = .005). Furthermore, linear regression analysis showed significant associations of GRS with BMI ( P < .0001), weight ( P = .0005), waist circumference ( P = .0039), fat mass ( P < .0001) and epicardial fat thickness ( P = .0032), yet with small effect sizes ( r ² < 0.06). In conclusion, in our study GRS could differentiate between extreme obese and lean individuals, and was associated with BMI and its related traits, yet with small effect sizes.

Improvement of obstructive sleep apnea does not rescue left atrial enlargement in obese participants of a multimodal weight reduction program.

The aim of our study was to investigate the effect of obstructive sleep apnea (OSA) and its weight loss related improvement on left atrial (LA) area in individuals with severe obesity participating in a multimodal weight reduction (WR) program. Participants with obesity (body mass index, BMI, 40.2 ± 7.3 kg/m2) underwent a 1-year WR program. Phenotyping was performed at baseline and after 12 months. Individuals were categorized according to their baseline apnea-hypopnea-index (AHI) into "no OSA" (AHI < 5) and "OSA" (AHI ≥ 5). From a total of 84 study participants, 69 completed the program. Average WR was 19.0 ± 15.7 kg after 12 months. Participants with obesity and OSA had a larger LA area at baseline as compared to participants with obesity but without OSA (22.4 ± 5.6 vs 18.8 ± 3.8 cm2; P = .008). Linear regression showed significant associations of AHI and BMI with LA area. In contrast, despite a significant decrease of AHI in participants with OSA as compared to those without OSA at 1 year follow up (ΔAHI was -12 ± 14) ΔLA area did not significantly differ between groups. Multivariable linear regression showed no significant association of ΔAHI or ΔBMI with ΔLA. In conclusion, the presence of obstructive sleep apnea contributes to LA enlargement on top of obesity in our study cohort. Yet, successful WR with subsequently improved OSA was not associated with an improvement of LA area.

TIMolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (TIM-HHT)-A Prospective, Randomized, Double-Blind, Controlled, Cross-Over Trial.

To date, there is no approved local therapeutic agent for the treatment of epistaxis due to hereditary hemorrhagic telangiectasia (HHT). Several case reports suggest the topical use of timolol. This monocentric, prospective, randomized, placebo-controlled, double-blinded, cross-over study investigated whether the effectiveness of the standard treatment with a pulsed diode laser can be increased by also using timolol nasal spray. The primary outcome was severity of epistaxis after three months, while the main secondary outcome was severity of epistaxis and subjective satisfaction after one month. Twenty patients were allocated and treated, of which 18 patients completed both 3-month treatment sequences. Timolol was well tolerated by all patients. Epistaxis Severity Score after three months, the primary outcome measure, showed a beneficial, but statistically nonsignificant (p = 0.084), effect of additional timolol application. Epistaxis Severity Score (p = 0.010) and patients' satisfaction with their nosebleeds after one month (p = 0.050) showed statistically significant benefits. This placebo-controlled, randomized trial provides some evidence that timolol nasal spray positively impacts epistaxis severity and subjective satisfaction in HHT patients when additively applied to standard laser therapy after one month. However, the effect of timolol was observed to diminish over time. Trials with larger sample sizes are warranted to confirm these findings.

Gender differences in cardiometabolic health and disease in a cross-sectional observational obesity study.

BACKGROUND: Beyond the degree of adiposity, the pattern of fat distribution has a profound influence on cardiometabolic risk. It is unclear if sex differences in body fat distribution can potentially explain any sex differences in the prevalence of the metabolic syndrome (MetS) and in individual cardiometabolic risk factors among obese men and women. METHODS: In this cross-sectional analysis, 432 persons from the ongoing Obesity Weight Reduction Study (n = 356 obese, ØBMI 41 ± 8 kg/m2, and 76 non-obese, ØBMI 25 ± 3 kg/m2), were included. The relations of sex to MetS prevalence and selected cardiometabolic risk factors were assessed using univariate and multivariate adjusted regression models. RESULTS: In crude analyses, %fat mass and the fat mass/lean mass ratio were significantly higher in women than in men, regardless of increasing obesity categories, from normal weight to grade-3-obesity. In contrast, markers of abdominal obesity, such as waist circumference and waist-to-hip ratio were higher in men than in women, despite similar BMI. The prevalence of the MetS was higher in obese men than in women (67.6 vs. 45.0%, p < 0.0001), particularly in younger individuals < 40 years (72.5 vs. 36.8%, p < 0.0001), but "metabolically healthy obesity" (BMI ≥ 30, no other NCEP ATPIII MetS component) was more common in women than in men (15.6 vs. 4.1%, p < 0.0001). After adjusting for age, %body fat and height, sex differences were observed for HDL-cholesterol (p < 0.001), triglycerides (p < 0.001), fasting glucose (p = 0.002), insulin and HOMA-IR levels (p < 0.001), ALAT (p < 0.001), adiponectin (p < 0.001), and sE-selectin (p = 0.005). In contrast, crude sex differences in other variables, such as leptin levels (68 ± 4 in obese women vs. 33 ± 2 µg/L in men, p < 0.0001), disappeared after accounting for differences in %body fat (least-squares means of leptin: 52 ± 4 vs. 55 ± 6 µg /L, p = 0.740). A logistic regression model adjusting for age and lifestyle factors revealed a lower risk of having MetS for women as compared to men (OR = 0.38[0.22-0.60]). That risk estimate did not materially alter after adding BMI to the model. In contrast, no statistically significant association between sex and MetS prevalence was observed after adding waist circumference and adiponectin to the model (OR = 1.41[0.59-3.36]). CONCLUSIONS: Different body fat distribution patterns, particularly abdominal adiposity, adiponectin, and related biomarkers, may contribute to sex differences in cardiometabolic risk factors and to the prevalence of the MetS.

Heart failure with recovered ejection fraction (HFrecEF): A new entity with improved cardiac outcome.

BACKGROUND: Aim of the study was a better characterization of heart failure (HF) with recovered ejection fraction (HFrecEF) and undulating EF (HFuEF) with regard to re-hospitalization due to congestive HF (CHF), adequate electric therapies (AETs) and mortality compared to HF with reduced EF (HFrEF), mid-range EF (HFmrEF) and preserved EF (pEF). METHODS: Retrospective study of 342 participants with an implantable cardioverter defibrillator (ICD) for primary or secondary prevention. Type of HF was classified according to left ventricular EF with 4.7 ± 3.1 investigations for each patient. RESULTS: Re-hospitalization due to CHF was similar in HFrecEF (7 (9.5%)), HFmrEF (2(9.0%)) and pEF (8(12.9%); p = n.s.) and significantly higher in HFrEF (62(38.0%)) and HFuEF (6(28.6%); p < .001 compared to HFrecEF and HFrEF). AETs were significantly lower in HFrecEF (13(17.6%)) compared to HFrEF (57(35.0%)), HFmrEF (7(31.8%)), pEF (18(29.0%)) and HFuEF (6(28.6%); each p < .01 compared to HFrecEF). Mortality was similar in HFrecEF (6(8.1%)) compared to HFuEF (0(0%)), pEF (4(6.5%)) and HFmrEF (2(9.0%), p = n.s.) and significantly lower compared to HFrEF (52(31.9%), p < .001). HFrEF was the strongest predictor for mortality besides age and chronic renal insufficiency according to Cox Regression (each p < .05) opposite to arterial hypertension, diabetes, type of cardiomyopathy and secondary prevention ICD indication (each p = n.s.). CONCLUSIONS: HFrecEF indicates as a new entity of HF with similar prognosis as pEF and HFmrEF with regard to re-hospitalization due to CHF and mortality and even better prognosis with regard to AETs. HFuEF showed similar rates of re-hospitalization due to CHF and AETs compared to HFrEF, but lower rates of mortality.

Successful weight loss reduces endothelial activation in individuals with severe obesity participating in a multimodal weight loss program.

INTRODUCTION: Endothelial dysfunction is a very common finding in obesity and metabolic syndrome. The aim of our study was to investigate if longterm weight reduction (WR) success may reverse endothelial activation in individuals with severe obesity participating in a multimodal WR program. METHODS: Participants with obesity (øBMI 40.3 ±7.5 kg/m2) underwent a standardized non-surgical 1-year WR program. Carotid artery studies and determination of endothelial function biomarkers were performed at baseline and after 1 year. Individuals were dichotomized in "successful WR" (% WR≥10% of initial body weight) and "failed WR" (% WR<10% of initial body weight). RESULTS: From 191 people with obesity, 115 achieved successful WR. Compared to controls without obesity (n=44) participants with obesity had higher carotid intima media thickness as well as higher sICAM-1, sE-selectin, MMP-9, hsCRP and IL-6 levels. After 12 months follow up delta values of inflammation and endothelial adhesion markers were significantly different between participants with obesity and successful WR and participants with obesity and failed WR, in favour of the successful WR group (mean ± standard deviation): ΔhsCRP (-5.2 mg/L ±7.8 vs. 1.1 mg/L ±5.1, P<0.001; Padj=0.009), ΔIL-6 (-1.0 pg/mL ±3.4 vs. 0.5 pg/mL ±2.6, P<0.001; Padj=0.057), ΔsE-selectin (-19.0 ng/mL ±24.4 vs. 39.2 ng/mL ±20.3, P<0.001; Padj<0.001), ΔsICAM-1 (-26.4 ng/mL ±68.8 vs. 10.6 ng/mL ±73.9, P=0.004; Padj=0.805) and ΔoxLDL (-4 mg/dL ±30 vs. 5 mg/dL ±25, P=0.004; Padj=0.473). In linear regression analysis reduction of BMI was significantly associated with improvement of several endothelial dysfunction biomarkers with the strongest effects for ΔsE-selectin and ΔhsCRP. CONCLUSION: Our data corroborate the finding that obesity leads to endothelial dysfunction. Furthermore, successful non-surgical WR may at least partially reverse endothelial activation implicating cardiovascular health benefits of WR in people with severe obesity.

Case report: Recovery after large intramyocardial dissecting haematoma of the ventricular septum-a rare complication of myocardial infarction.

BACKGROUND: Intramyocardial dissecting haematoma is a rare and potentially life-threatening complication of myocardial infarction (MI). Only a few isolated cases have been reported so far. CASE SUMMARY: We report the case of a patient with a large, obstructing intramyocardial haematoma of the ventricular septum following MI due to plaque rupture of the right coronary artery (RCA) and following successful coronary intervention. The clinically inapparent haematoma was discovered during routine echocardiography and confirmed by both computed tomography (CT) and magnetic resonance imaging (MRI). With non-surgical treatment, the patient remained clinically stable. Repeated echocardiography showed gradual regression of the haematoma. Follow-up echocardiography 3 months after the initial diagnosis demonstrated no evidence of septal haematoma. DISCUSSION: This report suggests that even large intramyocardial haematoma may recede without operative intervention. Echocardiography, CT, and MRI are all helpful in quantifying the size of the haematoma. The appropriate management should be patient-oriented, depending on clinical stability and progression of the haematoma. Conservative treatment in clinically stable patients suffering from septal haematoma following MI and coronary intervention can be a feasible option.

The adipo-fibrokine activin A is associated with metabolic abnormalities and left ventricular diastolic dysfunction in obese patients.

AIMS: Left ventricular diastolic dysfunction (LVDD) is common in obese subjects, and a relationship between epicardial adipose tissue (EAT), increased adipocytokines, and cardiovascular diseases has been reported. This study sought to examine as to whether the adipo-fibrokine activin A is a link between increased EAT, the metabolic syndrome (MetS), and LVDD in severely obese subjects. METHODS AND RESULTS: In 236 obese subjects (ø body mass index 39.8 ± 7.9 kg/m2 ) with a variable degree of the MetS and in 60 healthy non-obese controls (ø body mass index 24.8 ± 3.4 kg/m2 ), serum activin A levels were measured and correlated with parameters of the MetS, epicardial fat thickness (EFT), and echocardiographic parameters of LVDD. Activin A levels were higher in obese than in non-obese subjects (362 ± 124 vs. 301 ± 94 pg/mL, P = 0.0004), increased with the number of MetS components (from 285 ± 82 with no MetS component, 323 ± 94 with one or two MetS components, to 403 ± 131 pg/mL with ≥3 MetS components, P < 0.0001) and correlated with EFT (r = 0.41, P < 0.001). Furthermore, activin A levels were related to several parameters of LVDD [e.g. left atrial size (382 ± 117 vs. 352 125 pg/mL, P = 0.024), E/e' (394 ± 108 vs. 356 ± 127 pg/mL, P = 0.005)]. LVDD was highest in MetS obese subjects with high EFT (44.3%) compared with MetS obese subjects with low EFT (27.0%), non-MetS obese subjects with high EFT (24.2%), and non-MetS obese subjects with low EFT (10.6%, P < 0.0001). CONCLUSIONS: In severe obesity, activin A was significantly related to EFT, MetS, and LVDD, implicating MetS-related alterations in the secretory profile of EAT in the pathogenesis of obesity-related heart disease.

Relation Between Obesity, Metabolic Syndrome, Successful Long-Term Weight Reduction, and Right Ventricular Function.

This study sought to examine the relationships between right ventricular (RV) function and geometry, morbid obesity with and without the metabolic syndrome, and the effect of long-term weight loss. Obese (n = 153, BMI 41.2 ± 8.7 kg/m(2)) and healthy non-obese control subjects (n = 38, BMI 25.5 ± 3.3 kg/m(2)) of similar age and gender distribution were prospectively studied during the course of a 1-year weight reduction program with echocardiography at baseline and after one year of follow up. Function and geometry of the right heart were evaluated by tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TDI S'), RV myocardial performance index (TEI), RV end-diastolic (RVEDD) and end-systolic diameter (RVESD), area of the right atrium (RAA), and systolic pulmonary artery pressure (PAP). Whereas parameters of systolic and diastolic LV function were significantly worse in the obese subjects than those in the non-obese subjects (EF 66 ± 6 versus 69 ± 6%, P = 0.004; E/E' 7.4 ± 2.5 versus 6.3 ± 2.6, P = 0.010), parameters of RV function (TAPSE 25.6 ± 4.5 versus 25.1 ± 3.5 mm, P = 0.528; TDI S' 13.5 ± 2.9 versus 13.8 ± 2.9 mm/second, P = 0.553; TEI 0.25 ± 0.13 versus 0.28 ± 0.09, P = 0.283) as well as geometry measurements were comparable between the obese and non-obese participants and also in obese subjects with full blown metabolic syndrome. Additionally, successful weight reduction did not alter the RV parameters. Nevertheless, in the few obese subjects with RV dysfunction (n = 7), metabolic syndrome parameters were more pronounced than in obese with normal RV function.Morbid obesity with and without the metabolic syndrome is accompanied by an impaired LV systolic and diastolic function. In contrast, RV function appears to be less affected by obesity independent of the presence of the metabolic syndrome.

Multimodal recanalization therapy in acute basilar artery occlusion: long-term functional outcome and quality of life.

BACKGROUND AND PURPOSE: Multimodal recanalization therapy in patients with acute basilar artery occlusion provides high recanalization rates. A substantial subset of treated patients survives with only minor or moderate functional handicap. However, long-term functional outcome and quality of life in these patients have rarely been systematically analyzed. METHODS: In this monocentric retrospective study, we analyzed mortality, long-term functional outcome (modified Rankin Scale), and quality of life (36-Item Short-Form Health Survey questionnaire) in all consecutive patients who had been treated for acute basilar artery occlusion in our institution between December 2002 and December 2009. RESULTS: Ninety-one patients (57 male; median age, 65 years; range, 20-89 years) were treated by multimodal recanalization therapy. This included intravenous thrombolysis (n=32) with consecutive on-demand intra-arterial therapy (n=23) or intra-arterial therapy alone (n=59). The overall recanalization rate was 89%. After a median observation time of 4.2 years (range, 0.5-7.4 years), the mortality rate was 59%. Among the 35 survivors, 26 patients (74%) had a good or moderate long-term functional outcome (modified Rankin Scale ≤3). Health-related quality of life was better than that of unselected patients with stroke. Backward stepwise logistic regression identified intravenous thrombolysis (P=0.002) and female sex (P=0.001) as predictors of favorable functional long-term outcome (modified Rankin Scale ≤3). Coma at admission (Glasgow Coma Scale ≤8) was associated with poor outcome (modified Rankin Scale ≥4; P=0.036). CONCLUSIONS: Long-term survival is achieved in approximately 40% of patients with basilar artery occlusion treated with multimodal recanalization therapy. Approximately 75% of the survivors have a favorable functional long-term outcome with an acceptable quality of life.