A new medication-based prediction score for postoperative delirium in surgical patients: Development and proof of feasibility in a retrospective patient cohort.

Structured risk screening for postoperative delirium (POD) considering prehospital medication is not established. We aimed to develop a POD-risk prediction score based on known risk factors and delirium-risk increasing drugs to be used by pharmacists during medication reconciliation at hospital admission, and to test for feasibility in a retrospective cohort of surgical patients. Therefore, established POD-risk factors and drugs were extracted from the literature and a score was generated. Following this, the score was tested for feasibility in a retrospective 3-month-cohort of surgical patients. For patients with higher scores suggesting higher probability of POD, patient charts were screened for documentation of POD. For development of the score, the following POD-risk factors were defined and points assigned for score calculation: age (≥65 years=1 point/≥75 years=2), male sex (1), renal insufficiency (RI; 1), hepatic impairment (HI; Model-of-endstage-liver-disease (MELD) 10-14=1/≥15=2), delirium-risk increasing drugs (1 point per drug class), anticholinergic drug burden (ACB; ≥3=1). In the retrospective test cohort of 1174 surgical patients these factors concerned: age ≥65 years 567 patients (48%)/≥75 years 303 (26%), male 652 (55%), RI 238 (20%), MELD 10-14 106 (9%)/≥15 65 (5%), ≥ 1 delirium-risk increasing drug 418 (36%), ACB ≥3 106 (9%). The median POD-risk prediction score was 2 (range 0-9). Of 146 patients (12%) with a score ≥ 5, POD was documented for 43 (30%), no evidence for POD for 91 (62%) and data inconclusive for 12 (8%). For scores of ≥ 7, POD was documented for 50% of the patients with sufficient POD documentation. Overall, POD documentation was poor. To summarize, we developed and successfully tested the feasibility of a POD-prediction-score assessable by pharmacists at medication reconciliation at hospital admission.

Wearable blood pressure measurement devices and new approaches in hypertension management: the digital era.

Out-of-office blood pressure (BP) measurement is considered an integral component of the diagnostic algorithm and management of hypertension. In the era of digitalization, a great deal of wearable BP measuring devices has been developed. These digital blood pressure monitors allow frequent BP measurements with minimal annoyance to the patient while they do promise radical changes regarding the diagnostic accuracy, as the importance of making an accurate diagnosis of hypertension has become evident. By increasing the number of BP measurements in different conditions, these monitors allow accurate identification of different clinical phenotypes, such as masked hypertension and pathological BP variability, that seem to have a negative impact on cardiovascular prognosis. Frequent measurements of BP and the incorporation of new features in BP variability, both enable well-rounded interpretation of BP data in the context of real-life settings. This article is a review of all different technologies and wearable BP monitoring devices.

Adaptations to mentoring and peer mentor training at the medical faculty during the COVID-19 pandemic.

Objectives: The COVID-19 pandemic has led to major adjustments in health care systems and significantly affected medical education. Accordingly, our mentoring program MeCuM-Mentor had to expand its virtual elements, in order to continue to meet the needs for mentoring at the medical faculty of the Ludwig-Maximilians-University Munich. Methods: Here we report on our recently implemented online formats to facilitate training for currently coached peer mentors, as well as the introduction of an online consultation hour and a new social mentoring event called PubQuiz. Results: First results demonstrated feasibility of the above-mentioned virtual formats, which were positively rated by the participants in small voluntary evaluation questionnaires. Utilization rates indicate existing need for mentoring during the pandemic. In addition, the new event PubQuiz promotes social interaction among peers during isolation due to COVID-19. Conclusion: With the transition to online formats, mentoring at the Medical Faculty could be continued during COVID-19. The newly introduced mentoring event PubQuiz will be repeated. However, it remains unclear to what extent online formats can replace in-person one-to-one mentoring conversations or peer mentoring meetings.

Restructuring career counselling ventures of a mentoring program for medical students in the course of the COVID-19 pandemic.

Objectives: Due to the COVID-19 pandemic, medical curricula face major challenges. This also applies to mentoring programs, where face-to-face meetings are considered essential. Methods: The LMU Munich medical faculty mentoring program (MeCuM-Mentor) adapted to counteract the unforeseen pause of conventional course formats and associated uncertainty of many students. We here present an approach to transform the established large scale or group mentoring events of our program into online formats. Three projects are presented as examples: 1. HowTo Klink (HK), mainly informative in nature and with peer-mentoring character, 2. FacharztDuell (FAD) and 3. "Auf ein Gespräch mit... (AEGM)", both with a focus on career counseling. Results: Initial evaluations show a similarly high participation rate and a high level of satisfaction among the participating students. Students' evaluation of whether the projects presented should take place in presence or in online format has so far shown no clear trend. Conclusion: Prospective studies are necessary to investigate the effectiveness of these online formats and analyse differences in participant behaviour. The extent to which online mentoring can replace classic mentoring functions has to be discussed anew.

Low rate of intracerebral hemorrhage after cardiac catheterization in patients with acute ischemic stroke in a large case series.

BACKGROUND AND AIMS: Myocardial infarction complicating acute ischemic stroke (IS) is associated with high mortality, but evidence guiding the acute management is scarce. In particular, data on the risk of intracerebral hemorrhage (ICH) due to early cardiac catheterization including the peri-procedural application of antithrombotic drugs in patients with acute ischemic stroke are limited. Here, we aimed to evaluate the incidence and patient characteristics of ICH after cardiac catheterization in acute stroke patients to help to govern the risk of intracranial bleeding versus the benefits of myocardial reperfusion via cardiac catheterization. METHODS: We screened a consecutive cohort of n = 126 patients with acute ischemic stroke (IS) who underwent cardiac catheterization during the same hospital stay at a large German neurovascular center (LMU Munich). Eventually, we identified n = 42 patients with cardiac catheterization after acute stroke. N = 22/42 patients did not receive neuroimaging post cardiac catheterization and were discharged without any new neurological deficits, n = 20/42 had neuroimaging after cardiac catheterization and were included for final analysis. RESULTS: Cardiac catheterization was performed within a median of 3,6 days after ischemic stroke (No-ICH 7,3 days (IQR, 3,8-16,2) vs. ICH 1,1 days (IQR, 0,8-74,6), p = 0,40), One patient showed new neurological deficits after cardiac procedures (n = 1/42, 2,4 %). New or progressive ICH was ultimately found in 15 % (3/20) of cases. They were classified as HT1, PH1 and PH2 according to ECASS II criteria, respectively. With regards to the coronary catheterization, 85 % of all patients undergoing catheterization ultimately received percutaneous cardiac intervention. ICH was not significantly associated with any of the independent variables. Intrahospital death due to either ischemic stroke, ICH or cardiovascular events did not occur. CONCLUSION: The incidence of ICH in ischemic stroke followed by early cardiac catheterization and application of antithrombotic drugs was comparable to studies reporting on the incidence of ICH in ischemic stroke patients without catheterization. This study's results strengthen the hypothesis that in presence of both, acute myocardial infarction and acute ischemic stroke, the general risk for ICH is not prohibitive of cardiac catheterization.

Aortic Stenosis, Aortic Regurgitation and Arterial Hypertension.

BACKGROUND: Hypertension (HT) is an important risk factor for cardiovascular disease and might precipitate pathology of the aortic valve. OBJECTIVE: To investigate the association of HT with aortic dysfunction (including both aortic regurgitation and stenosis) and the impact of antihypertensive treatment on the natural course of underlying aortic disease. METHODS: We performed a systematic review of the literature for all relevant articles assessing the correlation between HT and phenotype of aortic disease. RESULTS: Co-existence of HT with aortic stenosis and aortic regurgitation is highly prevalent in hypertensive patients and predicts a worse prognosis. Certain antihypertensive agents may improve haemodynamic parameters (aortic jet velocity, aortic regurgitation volume) and remodeling of the left ventricle, but there is no strong evidence of benefit regarding clinical outcomes. Renin-angiotensin system inhibitors, among other vasodilators, are well-tolerated in aortic stenosis. CONCLUSION: Several lines of evidence support a detrimental association between HT and aortic valve disease. Therefore, HT should be promptly treated in aortic valvulopathy. Despite conventional wisdom, specific vasodilators can be used with caution in aortic stenosis.

Blood pressure response to catheter-based renal sympathetic denervation in severe resistant hypertension: data from the Greek Renal Denervation Registry.

BACKGROUND/INTRODUCTION: The efficacy of catheter-based renal sympathetic denervation (RDN) in terms of blood pressure (BP) reduction has been questioned, while "real-world" data from registries are needed. In this study, we report the complete set of 12-month data on office and ambulatory BP changes as well as the predictors for BP response to RDN from a national registry. METHODS: In 4 Greek hospital centers, 79 patients with severe drug-resistant hypertension (age 59 ± 10 years, 53 males, body mass index 33 ± 5 kg/m2; office BP and 24-h ambulatory BP were 176 ± 15/95 ± 13 and 155 ± 14/90 ± 12 mmHg, respectively, 4.4 ± 0.9 antihypertensive drugs) underwent RDN and were followed-up for 12 months in the Greek Renal Denervation Registry. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. RESULTS: Reduction in office systolic/diastolic BP at 6 and 12 months from baseline was -30/-12 and -29/-12 mmHg, while the reduction in 24-h ambulatory BP was -16/-9 and -15/-9 mmHg, respectively (p < 0.05 for all). Patients that were RDN responders (85%, n = 58), defined as an at least 10-mmHg decrease in office systolic BP at 12 months, compared to non-responders were younger (57 ± 9 vs 65 ± 8 years, p < 0.05), had higher baseline office systolic BP (176 ± 17 vs 160 ± 11 mmHg, p < 0.05) and 24-h systolic BP (159 ± 13 vs 149 ± 11 mmHg, p < 0.05). Stepwise logistic regression analysis revealed that age, obesity parameters, and baseline office BP were independent predictors of RDN response (p < 0.05 for both), but not the type of RDN catheter or the use of aldosterone antagonists. At 12 months, there were no significant changes in renal function and any new serious device or procedure-related adverse events. CONCLUSIONS: In our "real-world" multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is confirmed during a 12-month follow-up. Moreover, younger age, obesity, and higher levels of baseline systolic BP are independently related to better BP response to RDN.

Long-term effects of multielectrode renal denervation on cardiac adaptations in resistant hypertensive patients with left ventricular hypertrophy.

Left ventricular (LV) hypertrophy and diastolic dysfunction predict long-term cardiovascular events. We evaluated whether multielectrode renal denervation (RDN) can provide beneficial cardiac adaptations in patients with resistant hypertension and LV hypertrophy long term at 24 months. Seventeen patients with true drug-resistant hypertension (age: 57±9 years, 11 men, body mass index: 33.79±5.49 kg m-2, office blood pressure (BP): 183±20/97±18 mm Hg and ambulatory BP: 152±16/86±15 mm Hg receiving 4.5 anti-hypertensive drugs per day) and LV hypertrophy underwent multielectrode RDN (EnligHTNTM, St Jude Medical). At baseline, LV mass index averaged 141.1±16.8 g m-2 (58.4±7.8 g m-2.7) and mitral lateral E/E' 14.7±6.2. At 6, 12 and 24 months after RDN, the LV mass/body surface area (LV mass per height2.7) reduced significantly by 9.1% (8.8%), 11.3% (10.5%) and 15.5% (14.1%), respectively; and the mitral lateral E/E' reduced significantly by 14.0%, 15.3% and 29.7%, respectively. At 24 months after RDN, majority (70.6%) of the patients showed regression of LV hypertrophy of at least one level; the proportion of patients with concentric LV hypertrophy had dropped by 47.1% from baseline; and the proportion of patients with office systolic BP level of ⩾160 mm Hg had dropped by 76.5% from baseline. No statistically significant association was observed between the changes in office BP and the changes in LV mass index or diastolic function. In patients with drug-resistant hypertension and LV hypertrophy, multielectrode RDN can contribute to significant and sustained improvements of diastolic dysfunction and attenuation of LV mass indices long term at 24 months.

Drug-resistant hypertensive patients responding to multielectrode renal denervation exhibit improved heart rate dynamics and reduced arrhythmia burden.

Transluminal renal sympathetic denervation (RDN) reduces blood pressure (BP) in patients with drug-resistant uncontrolled hypertension. We assessed the effect of RDN on heart rate, supraventricular and ventricular ectopic activity and indexes of heart rate variability in 14 patients with drug-resistant uncontrolled hypertension who were all responders to RDN (defined as a reduction in office systolic BP ⩾ 10 mm Hg) at baseline and at 1 and 6 months after the procedure using the multielectrode EnligHTN ablation catheter (St Jude Medical). Office and 24-h systolic and diastolic BP were significantly reduced both at 1 and 6 months after RDN and all patients were office BP responders. There was a trend toward office heart rate reduction (by 6.9 b.p.m., P=0.064) at 1 month and a significant reduction by 10 b.p.m. (P=0.004) at 6 months. Mean 24-h Holter monitoring heart rate was reduced by 6.7 b.p.m. (P=0.022) at 1 month and by 5.3 b.p.m. (P=0.010) at 6 months after RDN. The total number of premature supraventricular and ventricular contractions was significantly decreased and time- and frequency- domain indexes were increased both at 1 and at 6 months after RDN (P<0.05 for both cases). Apart from the substantial BP lowering, RDN results in significant reduction of mean heart rate and arrhythmia burden, restoring autonomic balance in responder patients with drug-resistant uncontrolled hypertension.

Soluble receptor for advanced glycation end-product levels are related to albuminuria and arterial stiffness in essential hypertension.

BACKGROUND AND AIMS: Emerging evidence suggests that the soluble receptor for advanced glycation end-products (sRAGE) is implicated in the development of vascular disease. We investigated the interrelationships of sRAGE with albumin to creatinine ratio (ACR) and arterial stiffness in essential hypertension. METHODS AND RESULTS: In 309 untreated non-diabetic hypertensives, ACR values were determined as the mean of three non-consecutive morning spot urine samples and aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (c-f PWV). In all subjects, venous blood sampling was performed for the estimation of sRAGE levels. Patients with low (n = 155) compared to those with high sRAGE values (n = 154) had greater 24-h systolic BP (140 ± 8 vs. 134 ± 7 mmHg, p < 0.0001), exhibited higher ACR (36.3 ± 51.6 vs. 17.2 ± 1.2 mg g(-1), p < 0.0001) and c-f PWV (8.3 ± 1.5 vs. 7.8 ± 1.1 m s(-1), p = 0.003), independently of confounding factors. Multiple regression analyses revealed that age, male sex, 24-h systolic BP and sRAGE were the 'independent correlates' of ACR (R(2) = 0.493, p < 0.0001), while age, 24-h systolic BP and sRAGE were the 'independent correlates' of c-f PWV (R(2) = 0.428, p < 0.0001). CONCLUSION: In hypertensives, decreased sRAGE levels are accompanied by pronounced albuminuria and arterial stiffening. The association of sRAGE with ACR and c-f PWV suggests involvement of sRAGE in the progression of hypertensive vascular damage.

Subendocardial viability ratio as an index of impaired coronary flow reserve in hypertensives without significant coronary artery stenoses.

Subendocardial viability ratio (SEVR), calculated through pulse wave analysis, is an index of myocardial oxygen supply and demand. Our aim was to evaluate the relationship between coronary flow reserve (CFR) and SEVR in 36 consecutive untreated hypertensives (aged 57.9 years, 12 males, all Caucasian) with indications of myocardial ischaemia and normal coronary arteries in coronary angiography. CFR was calculated by a 0.014-inch Doppler guidewire (Flowire, Volcano, San Diego, CA, USA) in response to bolus intracoronary administration of adenosine (30-60 µg). SEVR was calculated by radial applanation tonometry, while diastolic function was evaluated by means of transmitral flow and tissue Doppler imaging. Hypertensive patients with low CFR (n=24) compared with those with normal CFR (n=12) exhibited significantly decreased SEVR by 24.5% (P=0.002). In hypertensives with low CFR, CFR was correlated with SEVR (r=0.651, P=0.001). After applying multivariate linear regression analysis, age, left ventricular mass index, Em/Am, 24-h diastolic blood pressure (BP) and SEVR turned out to be the only independent predictors of CFR (adjusted R(2)=0.718). Estimation of SEVR by using applanation tonometry may provide a reliable tool for the assessment of coronary microcirculation in essential hypertensives with indications of myocardial ischaemia and normal coronary arteries.

Gender variation of exercise-induced anti-arrhythmic protection: the Ikaria Study.

BACKGROUND: Regular physical activity (PA) has shown substantial cardiac benefits. We sought to investigate whether habitual PA is associated with changes of the electrical action potential duration, as it is represented by the QT duration on a rest ECG, in a population based sample of middle-aged and elderly individuals of Ikaria island. METHODS: In a cross-sectional survey 1071 inhabitants of Ikaria Island (65 ± 13 years, 47% males) were enrolled. PA was estimated by means of IPAQ classifying the participants into low, moderate and vigorous group. QT duration was measured from a surface electrocardiogram; while using Bazett's formula the heart-rate-corrected QT (QTc) was calculated. RESULTS: Among participants, 85% reported at least moderate PA levels. Women in the 'vigorous' and 'moderate' PA level compared to those in the 'low' PA level had significantly shorter QTc (408 ± 2 ms vs. 411 ± 1 ms vs. 419 ± 2 ms, P = 0.001, respectively). In contrast, no significant difference in QTc according to PA levels was observed in men (P = 0.053). Linear regression analysis revealed that PA level was significantly associated with shorter QTc in women after adjustment for established confounders; while no such association was evident in men. Furthermore, compared to the 'low' PA group, women in the 'vigorous' PA group were 5.5-times less likely to have QTc interval above 450 ms (P = 0.031). CONCLUSION: Increased PA is associated with shorter QTc interval only in middle-aged and elderly women of Ikaria Island irrespectively of participant's habits or medical conditions, illustrating gender differences in the cardioprotective effect of habitual exercise.

[The motivation to become a medical doctor - doctoral students in a formal academic study program compared with those pursuing their doctorate independently]. / Die Motivation zu promovieren. Ein Vergleich von medizinischen Doktoranden in einem Promotionsstudiengang mit individuell promovierenden Doktoranden.

BACKGROUND AND OBJECTIVE: Weight and quality of medical doctoral theses have been discussed in Germany for years. Doctoral study programs in various graduate schools offer opportunities to improve quality of medical doctoral theses. The purpose of this study was to demonstrate distinctions and differences concerning motivation, choice of subject and the dissertation process between doctoral candidates completing the doctoral seminar for doctoral students in the Ludwig-Maximilians-University (LMU) Munich and doctoral candidates doing their doctorate individually. METHODS: All 4000 medical students of the LMU obtained an online-questionnaire which was completed by 767 students (19 % response rate). The theoretical framework of this study was based upon the Self-Determination-Theory by Deci and Ryan. RESULTS: Doctoral candidates completing the doctoral study program were more intrinsically motivated than doctoral candidates doing their doctorate individually; no difference was found in their extrinsic motivation. In regard to choice of subject and dissertation process the doctoral students in the seminar were distinguished from the individual group by having chosen a more challenging project. They anticipated a demanding dissertation process including conference participation, publishing of papers, etc. Intrinsic motivation correlates positively with choosing a challenging project and a demanding dissertation process. CONCLUSION: High intrinsic motivation seems to be very important for autonomous scholarly practice. Our results suggest that doctoral study programs have a positive impact on intrinsic motivation and interest in research.

Adherence to the Mediterranean diet and albuminuria levels in Greek adolescents: data from the Leontio Lyceum ALbuminuria (3L study).

BACKGROUND/OBJECTIVES: Mediterranean diet has favorable effects on the cardiovascular system, whereas albuminuria is associated with atherosclerosis progression. The aim of the study was to assess the relationships of adherence rates to the Mediterranean diet with albumin to creatinine ratio (ACR), in a cohort of Greek adolescents who participated in the Leontio Lyceum ALbuminuria (3L) study. SUBJECTS/METHODS: In a total of 365 adolescents 12-17 years of age included in 3L study, ACR values were determined in a morning-spot urine. RESULTS: The Mediterranean diet Quality Index for children and adolescents (KIDMED) was estimated and accordingly subjects were divided into those with high (≥ 8), average (4-7) and low (≤ 3) score. Adolescents with low (n=153, 42%) compared with those with average (n=187, 51.2%) and high (n=25, 6.8%) KIDMED score were characterized by greater ACR values (22.4 vs 13.4 vs 12.1 mg/g, P<0.05) even after adjustment for confounders. In the total population, KIDMED score was related to body mass index (r=0.122, P=0.02), waist circumference (r=0.118, P=0.02), systolic blood pressure (BP) (r=0.119, P=0.023), whereas it was negatively associated with ACR (r=-0.111, P=0.041). Regarding ACR, it was associated with age (r=-0.11, P=0.044), male sex (r=0.16, P=0.003), body mass index (r=-0.131, P=0.016) and systolic BP (r=-0.144, P=0.008). CONCLUSIONS: Adolescents who adhere to the Mediterranean diet exhibit lower levels of albuminuria, independently of demographic and hemodynamic confounders. The inverse relation of KIDMED index with ACR suggests a close link of accelerated vascular damage reflected by albuminuria with low adherence to this favorable diet of the Mediterranean basin.

The diverse associations of uric acid with low-grade inflammation, adiponectin and arterial stiffness in never-treated hypertensives.

The data regarding the role of serum uric acid (SUA) along with subclinical inflammation in the context of hypertensive vascular damage are rather scarce and controversial. Towards this end, we assess the links between SUA, high-sensitivity CRP (hs-CRP), adiponectin and carotid to femoral pulse wave velocity (c-f PWV) in 292 subjects with never-treated stage I-II essential hypertension. On the basis of the median SUA levels (0.31 mmol l(-1)), the study population was divided into subjects with low (n=149) and high (n=143) SUA values. By multiple regression analysis, it was revealed that SUA was independently associated with log hs-CRP (R(2)=0.098; P=0.02), log adiponectin (R(2)=0.102; P=0.03), waist circumference (R(2)=0.049; P=0.04), 24-h systolic blood pressure (SBP) (R(2)=0.179; P=0.001) and estimated glomerular filtration rate (R(2)=0.156; ß (s.e.)=-0.169 (0.023); P=0.02). In addition, c-f PWV was independently associated with age (R(2)=0.116; P<0.0001), waist circumference (R(2)=0.088; P<0.0001), 24-h SBP (R(2)=0.167; P=0.001), log adiponectin (R(2)=0.07; P=0.006) and log hs-CRP (R(2)=0.06; P=0.034). In conclusion, SUA levels are independently associated with hs-CRP and adiponectin levels but not with c-f PWV in essential hypertensive patients. Increased SUA levels are accompanied by a state of pronounced inflammatory activation and hypoadiponectinemia that significantly impairs the arterial stiffness accelerating the vascular ageing process in this setting.

Independent association of circulating resistin with glomerular filtration rate in the early stages of essential hypertension.

Resistin, a newly discovered protein, promotes endothelial dysfunction and proinflammatory activation, contributing to subclinical atherosclerosis in different clinical settings. In this study we sought to investigate the relationship of increased resistin levels with estimated glomerular filtration rate (eGFR), the most established marker of kidney impairment, in hypertensive subjects. Our population consisted of 132 untreated non-diabetic subjects with stage I-II essential hypertension (49 males, mean age=54 years, office blood pressure (BP)=159/100 mm Hg). In all patients eGFR was assessed by the Modification in Renal Disease equation and venous blood sampling was performed for estimation of resistin concentrations. The distribution of resistin was split by the median (4.63 ng ml(-1)) and accordingly subjects were stratified into those with high and low values. Hypertensive patients with high (n=66) compared to those with low resistin (n=66) exhibited lower eGFR values (77.1+/-9.4 vs 89.1+/-12.2 ml min(-1) per 1.73m(2), P<0.0001), even after adjustment for established confounders. In the total population, resistin was associated with 24-h systolic BP (r=0.244, P<0.05), serum creatinine (r=0.311, P=0.007) and eGFR (r=-0.519, P<0.0001). Multiple regression analysis revealed that age (b=0.379, P=0.01), body mass index (b=0.158, P=0.022), 24-h systolic BP (b=0.284, P=0.006) and resistin (b=0.429, P<0.0001) were independent predictors of eGFR (R(2)=0.436, P<0.0001). In essential hypertensive subjects, higher resistin levels are associated with renal function impairment, as reflected by decreased eGFR. Moreover, the independent association of resistin with eGFR suggests involvement of resistin in the progression of kidney damage in the early stages of hypertension.