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في هذا الكتاب، يأخذنا أوفه كلوسمان في رحلة شاملة عبر تطور أجهزة الاستخبارات من بداياتها في العصور الوسطى إلى عصر \"الحرب الإلكترونية\"، مركزا على كيفية تطور دور العملاء والمخبرين عبر الزمن. يبدأ بسرد أنشطة التجسس كفن بدائي مرتبط بالحروب الرومانية والعصور الوسطى، ثم يتناول تشكل أجهزة علاقات المخابرات المنظمة في دول أوروبية حديثة وعصر النهضة، قبل أن يعرض لكيفية تحول السرية والبيروقراطية الاستخباراتية في العالم الحديث خاصة أثناء الحربين العالميتين والحرب الباردة. ويكشف أن استخدام التكنولوجيا (كالإنترنت وكشف الاتصالات المشفرة) قد منح أجهزة مثل CIA وNSA هيمنة غير مسبوقة، وجرى تجاوز مفاهيم الخصوصية والحريات الشخصية إذ باتت القدرة على المراقبة واسعة النطاق، كما رأينا في قضايا تسريبات سنودن، بعد أن توسع النفوذ الاستخباري ليشمل كل زاوية من شبكة الإنترنت العالمية.

A 51-year-old man presented with a 3-month history of weight loss, diarrhea, and fever. Transthoracic echocardiography showed vegetations on the aortic and mitral valves. A duodenal biopsy showed periodic acid–Schiff–positive macrophages.

During the early phase of the Covid-19 pandemic, reductions of hospital admissions with a focus on emergencies have been observed for several medical and surgical conditions, while trend data during later stages of the pandemic are scarce. Consequently, this study aims to provide up-to-date hospitalization trends for several conditions including cardiovascular, psychiatry, oncology and surgery cases in both the in- and outpatient setting. Using claims data of 86 Helios hospitals in Germany, consecutive cases with an in- or outpatient hospital admission between March 13, 2020 (the begin of the \"protection\" stage of the German pandemic plan) and December 10, 2020 (end of study period) were analyzed and compared to a corresponding period covering the same weeks in 2019. Cause-specific hospitalizations were defined based on the primary discharge diagnosis according to International Statistical Classification of Diseases and Related Health Problems (ICD-10) or German procedure classification codes for cardiovascular, oncology, psychiatry and surgery cases. Cumulative hospitalization deficit was computed as the difference between the expected and observed cumulative admission number for every week in the study period, expressed as a percentage of the cumulative expected number. The expected admission number was defined as the weekly average during the control period. A total of 1,493,915 hospital admissions (723,364 during the study and 770,551 during the control period) were included. At the end of the study period, total cumulative hospitalization deficit was -10% [95% confidence interval -10; -10] for cardiovascular and -9% [-10; -9] for surgical cases, higher than -4% [-4; -3] in psychiatry and 4% [4; 4] in oncology cases. The utilization of inpatient care and subsequent hospitalization deficit was similar in trend with some variation in magnitude between cardiovascular (-12% [-13; -12]), psychiatry (-18% [-19; -17]), oncology (-7% [-8; -7]) and surgery cases (-11% [-11; -11]). Similarly, cardiovascular and surgical outpatient cases had a deficit of -5% [-6; -5] and -3% [-4; -3], respectively. This was in contrast to psychiatry (2% [1; 2]) and oncology cases (21% [20; 21]) that had a surplus in the outpatient sector. While in-hospital mortality, was higher during the Covid-19 pandemic in cardiovascular (3.9 vs. 3.5%, OR 1.10 [95% CI 1.06-1.15], P<0.01) and in oncology cases (4.5 vs. 4.3%, OR 1.06 [95% CI 1.01-1.11], P<0.01), it was similar in surgical (0.9 vs. 0.8%, OR 1.06 [95% CI 1.00-1.13], P = 0.07) and in psychiatry cases (0.4 vs. 0.5%, OR 1.01 [95% CI 0.78-1.31], P<0.95). There have been varying changes in care pathways and in-hospital mortality in different disciplines during the Covid-19 pandemic in Germany. Despite all the inherent and well-known limitations of claims data use, this data may be used for health care surveillance as the pandemic continues worldwide. While this study provides an up-to-date analysis of utilization of hospital care in the largest German hospital network, short- and long-term consequences are unknown and deserve further studies.

Conventional surgical aortic valve replacement (AVR) is the ‘gold standard’ for treatment of severe or symptomatic aortic valve stenosis. The increasing age of patients and increasing comorbidities has led to the development of procedures to minimise operative time and reduce risks of surgery. One method of reducing operative times is the use of sutureless aortic valves (SU-AVR). We examine the current literature surrounding the use of SU-AVR. Alternatives to AVR are SU-AVR, sometimes referred to as rapid deployment valves, or transcatheter aortic valve implantation (TAVI). TAVI has been demonstrated to be superior over medical therapy in patients deemed inoperable and non-inferior in high and intermediate-risk patients compared with surgical AVR. However, the lack of excision of the calcified aortic valve and annulus raises concerns regarding long-term durability and possibly thromboembolic complications. TAVI patients have increased rates of paravalvular leaks, major vascular complications and pacemaker implantation when compared with conventional AVR. SU-AVR minimises the need for suturing, leading to reduced operative times, while enabling complete removal of the calcified valve. The increase in use of SU-AVR has been mostly driven by minimally invasive surgery. Other indications include patients with a small and/or calcified aortic root, as well as patients requiring AVR and concomitant surgery. SU-AVR is associated with decreased operative times and possibly improved haemodynamics when compared with conventional AVR. However, this has to be weighed against the increased risk of paravalvular leak and pacemaker implantation when deciding which prosthesis to use for AVR.

Asymptomatic severe aortic stenosis (AS) poses a clinical challenge with variations in recommendations for management. We sought to compare contemporary guidelines focusing on asymptomatic AS management and present a summary of contemporary studies on early intervention in these patients. Systematic search of electronic databases was conducted with guidelines analyzed using a comparative matrix. A pooled random-effects meta-analysis of randomized controlled trial (RCT) data comparing intervention versus clinical surveillance in asymptomatic severe AS was also performed. Four guidelines from ACC/AHA, ESC/EACTS, JCS/JSCS/JATS/JSVS, and NICE were included encompassing 108 recommendations. Consensus was found for intervention thresholds including left ventricular dysfunction and very severe AS while discrepancies existed in the utility of biomarkers, myocardial fibrosis, exercise stress testing and choice of intervention. Despite variation in study inclusion criteria, current RCTs on the management of asymptomatic AS indicated a significant reduction in rates of major adverse cardiovascular events when comparing early intervention to clinical surveillance (hazard ratio [HR] 0.52 [0.42, 0.63]), driven primarily by reductions in unplanned hospitalizations (HR 0.41 [0.32, 0.52]). While there is broad consensus on classic indicators of severity such as left ventricular dysfunction as indication for intervention, guidelines diverge on other high-risk features warranting intervention. Early studies indicate the overall safety of early intervention, although further work is needed to identify whether it can reduce the risk of hard clinical endpoints. This underscores the need for further research and updated guidelines to clarify the optimal thresholds for intervention and harmonize treatment pathways for the growing number of patients with asymptomatic AS.

To analyze outcomes in patients with normal preoperative left ventricular ejection fraction (LVEF) undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy due to postcardiotomy cardiogenic shock (PCCS) related to coronary malperfusion. Retrospective single-center analysis in patients with normal preoperative LVEF treated with VA-ECMO for coronary malperfusion-related PCCS between May 1998 and May 2018. The primary outcome was 30-day mortality, which was compared using the Kaplan-Meier method and the log-rank test. Multivariable logistic regression was performed to identify predictors of mortality. During the study period, a total of 62,125 patients underwent cardiac surgery at our institution. Amongst them, 59 patients (0.1%) with normal preoperative LVEF required VA-ECMO support due to coronary malperfusion-related PCCS. The mean duration of VA-ECMO support was 6 days (interquartile range 4-7 days). The 30-day mortality was 50.8%. Under VA-ECMO therapy, a complication composite outcome of bleeding, re-exploration for bleeding, acute renal failure, acute liver failure, and sepsis occurred in 51 (86.4%) patients. Independent predictors of 30-day mortality were lactate levels > 9.9 mmol/l before VA-ECMO implantation (odds ratio [OR]: 3.3; 95% confidence interval [CI] 1.5-7.0; p = 0.002), delay until revascularization > 278 minutes (OR: 2.9; 95% CI 1.3-6.4; p = 0.008) and peripheral arterial artery disease (OR: 3.3; 95% 1.6-7.5; p = 0.001). Mortality rates are high in patients with normal preoperative LVEF who develop PCCS due to coronary malperfusion. The early implantation of VA-ECMO before the development of profound tissue hypoxia and early coronary revascularization increases the likelihood of survival. Lactate levels are useful to define optimal timing for the VA-ECMO initiation.

The role of continued versus interrupted oral anticoagulation (OAC) in patients with atrial fibrillation (AF) who underwent transfemoral transcatheter aortic valve implantation (TF-TAVI) for severe aortic stenosis is uncertain. The aim of this retrospective investigation was to evaluate the impact (1) of continued versus interrupted OAC on early safety and (2) of postoperative anticoagulant management on the 1-year mortality in patients with AF who underwent TF-TAVI. Consecutive patients with AF and on OAC at admission (n = 598) were stratified according to interrupted (iVKA) versus continued vitamin K antagonist (cVKA) versus continued direct oral anticoagulants (DOAC) at the time of TF-TAVI. Valve Academic Research Consortium-2 early safety was the primary outcome measure. Patients with iVKA (n = 299), cVKA (n = 117), and DOAC (n = 182) had comparable baseline characteristics including age (p = 0.25), gender (p = 0.33), and STS-Score (p = 0.072). The proportion of patients having a CHA2DS2-VASc-Score ≥3 (p = 0.791) and HAS-BLED-Score ≥3 (p = 0.185) was not different between groups. The rate of early safety events (with lower values indicating superior safety) was lowest in DOAC (13.2%) and not increased in cVKA (19.7%) compared to iVKA (23.1%) (p = 0.029). Valve Academic Research Consortium-2 defined stroke (p = 0.527) and bleeding (p = 0.097) did not differ between groups. Renal failure occurred more often in iVKA compared to cVKA and DOAC (p = 0.02). All-cause 1-year mortality was 20.1% in iVKA, 13.7% in cVKA, and 8.8% in DOAC (p = 0.015). Multivariate analysis revealed DOAC to be associated with reduced all-cause 1-year mortality (HR 0.56 (95%-CI 0.32 to 0.99), p = 0.047) whereas cVKA was comparable to iVKA (HR 0.75 (95%-CI 0.43 to 1.31), p = 0.307). In conclusion, cVKA did not increase the rate for the composite end point of early safety at 30 days in this cohort of patients. Treatment with a DOAC was associated with a significantly reduced rate of early safety end points at 30 days and lower 1-year mortality.

Acute kidney injury (AKI) is a serious complication following on-pump cardiac surgery. Choosing the cardioplegic solution with the most appropriate myocardial protection and lowest grade of AKI could improve patient outcome. We compared the crystalloid histidine-tryptophan-ketoglutarate (HTK) solution and a Jonosteril -based DelNido blood cardioplegic solution regarding AKI in a porcine model. Therefore, German landrace pigs (50-60kg) underwent median sternotomy, cardiopulmonary bypass at 34 °C and 90 min of cardiac arrest. Animals were randomized to single-shot cardioplegia of HTK (  = 9) or DelNido (  = 9) cardioplegic solution followed by 120 min of reperfusion. This study demonstrated that DelNido cardioplegia induced less hemoglobin (  < 0.01) and electrolyte imbalances of blood sodium, chloride, and calcium levels (all  < 0.01) after aortic cross-clamp than HTK cardioplegia. Renal biopsy analysis after 120 min of reperfusion revealed that histomorphological changes, oxidative and nitrosative stress as well as the cytosolic release of pro-apoptotic molecules in different nephron structures were comparable in HTK and DelNido cardioplegia. The comparability of both cardioplegic solutions was supported by measurements of the urine AKI biomarkers of L-type fatty acid-binding protein 1 (  = 0.38), neutrophil gelatinase-associated lipocalin (  = 0.34), and cystatin C (  = 0.46), which could not detect any differences between the groups. This large animal study demonstrated superiority of the DelNido solution regarding hemoglobin and blood electrolyte concentrations, but comparability of the HTK and DelNido blood cardioplegic solution regarding AKI for surgical interventions requiring cardiac arrest of 90 min. Patients with a higher risk for adverse events, due to either complex, prolonged surgery or a multitude of comorbidities, could especially benefit from the more physiological arrest conditions with DelNido cardioplegia.

Atrioventricular septal defect (AVSD) in association with tetralogy of Fallot (TOF) is a rare and complex congenital cardiac malformation. We report our institutional experience and outcomes following surgical correction over a 20-year period. Patients who underwent combined surgical AVSD and TOF correction between October 2001 and February 2020 were included for analysis. All patients underwent primary repair. The study data were prospectively collected and retrospectively analyzed. Primary outcomes were in-hospital mortality and long-term freedom from reoperation. During the study period, a total of 10 consecutive patients underwent combined surgical AVSD and TOF correction. Median age at operation was 307 days (IQR 228–457) and median weight was 7.7 kg (IQR 6.7–9.5). Down Syndrome was present in six of the patients . In-hospital mortality was 0%. One patient required re-exploration due to bleeding. Median follow-up was 11 years (IQR 11 months -16 years). There was one case of reoperation due to significant residual ventricular septal defect after 2 months. None of the patients died during follow-up. Combined primary AVSD and TOF repair can be performed with low early mortality and morbidity, as well as a high long-term freedom from reoperation.

Male sex and aging are risk factors for fibro-calcific aortic valve disease (FCAVD), indicating an understudied influence of sex hormones. Valvular interstitial cells (VICs) from female and male donors were isolated and exposed to pro-calcifying medium (PM), and the expression of matrix gla protein (MGP), fibronectin (FN1) and bone morphogenic protein 2 (BMP2) was analyzed. The effect of sex hormones on hydroxyapatite (HA) deposition by VICs was also analyzed. Exposure to PM increased MGP gene expression in male (n = 5, +5.8-fold, p = 0.031), and female VICs (n = 6, +4.9-fold, p = 0.004). In female VICs a +3.5-fold MGP increase accompanied the transition from the fibrotic to the calcific phase (p = 0.022 vs. males) while in male VICs the increase was delayed to the calcific phase. Female VICs upregulated FN1 (+1.8-fold, p = 0.003), while male VICs upregulated BMP2 (+3.7-fold, p = 0.05). 5α-dihydrotestosterone increased HA deposition +6.3-fold in male and +5.2-fold in female VICs (p ≤ 0.001 and p < 0.04, respectively). It further decreased BMP2 (p < 0.001) in male VICs and increased MGP in female VICs (p = 0.087). Female VICs decreased HA deposition when exposed to progesterone (−2.4-fold, p = 0.037 vs. PM) and estrogen (−2.0-fold, p = 0.072). In summary, VICs show donor-sex-specific gene expression which is modifiable by 5α-dihydrotestosterone. This needs to be considered when designing in vitro regulatory studies.