Left atrial appendage volume is an independent predictor of atrial arrhythmia recurrence following cryoballoon pulmonary vein isolation in persistent atrial fibrillation.

Purpose: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation in persistent AF (persAF), and cryoballoon PVI emerged as an initial ablation strategy. Symptomatic atrial arrhythmia recurrence following successful PVI in persAF is observed more frequently than in paroxysmal AF. Predictors for arrhythmia recurrence following cryoballoon PVI for persAF are not well described, and the role of left atrial appendage (LAA) anatomy is uncertain. Methods: Patients with symptomatic persAF and pre-procedural cardiac computed tomography angiography (CCTA) images undergoing initial second-generation cryoballoon (CBG2) were enrolled. Left atrial (LA), pulmonary vein (PV) and LAA anatomical data were assessed. Clinical outcome and predictors for atrial arrhythmia recurrence were evaluated by univariate and multivariate regression analysis. Results: From May 2012 to September 2016, 488 consecutive persAF patients underwent CBG2-PVI. CCTA with sufficient quality for measurements was available in 196 (60.4%) patients. Mean age was 65.7 ± 9.5 years. Freedom from arrhythmia was 58.2% after a median follow-up of 19 (13; 29) months. No major complications occurred. Independent predictors for arrhythmia recurrence were LAA volume (HR 1.082; 95% CI, 1.032 to 1.134; p = 0.001) and mitral regurgitation ≥ grade 2 (HR, 2.49; 95% CI 1.207 to 5.126; p = 0.013). LA volumes ≥110.35 ml [sensitivity: 0.81, specificity: 0.40, area under the curve (AUC) = 0.62] and LAA volumes ≥9.75 ml (sensitivity: 0.56, specificity 0.70, AUC = 0.64) were associated with recurrence. LAA-morphology, classified as chicken-wing (21.9%), windsock (52.6%), cactus (10.2%) and cauliflower (15.3%), did not predict outcome (log-rank, p = 0.832). Conclusion: LAA volume and mitral regurgitation were independent predictors for arrhythmia recurrence following cryoballoon ablation in persAF. LA volume was less predictive and correlated with LAA volume. LAA morphology did not predict the clinical outcome. To improve outcomes in persAF ablation, further studies should focus on treatment strategies for persAF patients with large LAA and mitral regurgitation.

Forest production efficiency increases with growth temperature.

Forest production efficiency (FPE) metric describes how efficiently the assimilated carbon is partitioned into plants organs (biomass production, BP) or-more generally-for the production of organic matter (net primary production, NPP). We present a global analysis of the relationship of FPE to stand-age and climate, based on a large compilation of data on gross primary production and either BP or NPP. FPE is important for both forest production and atmospheric carbon dioxide uptake. We find that FPE increases with absolute latitude, precipitation and (all else equal) with temperature. Earlier findings-FPE declining with age-are also supported by this analysis. However, the temperature effect is opposite to what would be expected based on the short-term physiological response of respiration rates to temperature, implying a top-down regulation of carbon loss, perhaps reflecting the higher carbon costs of nutrient acquisition in colder climates. Current ecosystem models do not reproduce this phenomenon. They consistently predict lower FPE in warmer climates, and are therefore likely to overestimate carbon losses in a warming climate.

Impacts of extreme summers on European ecosystems: a comparative analysis of 2003, 2010 and 2018.

In Europe, three widespread extreme summer drought and heat (DH) events have occurred in 2003, 2010 and 2018. These events were comparable in magnitude but varied in their geographical distribution and biomes affected. In this study, we perform a comparative analysis of the impact of the DH events on ecosystem CO2 fluxes over Europe based on an ensemble of 11 dynamic global vegetation models (DGVMs), and the observation-based FLUXCOM product. We find that all DH events were associated with decreases in net ecosystem productivity (NEP), but the gross summer flux anomalies differ between DGVMs and FLUXCOM. At the annual scale, FLUXCOM and DGVMs indicate close to neutral or above-average land CO2 uptake in DH2003 and DH2018, due to increased productivity in spring and reduced respiration in autumn and winter compensating for less photosynthetic uptake in summer. Most DGVMs estimate lower gross primary production (GPP) sensitivity to soil moisture during extreme summers than FLUXCOM. Finally, we show that the different impacts of the DH events at continental-scale GPP are in part related to differences in vegetation composition of the regions affected and to regional compensating or offsetting effects from climate anomalies beyond the DH centres. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.

Direct and seasonal legacy effects of the 2018 heat wave and drought on European ecosystem productivity.

In summer 2018, central and northern Europe were stricken by extreme drought and heat (DH2018). The DH2018 differed from previous events in being preceded by extreme spring warming and brightening, but moderate rainfall deficits, yet registering the fastest transition between wet winter conditions and extreme summer drought. Using 11 vegetation models, we show that spring conditions promoted increased vegetation growth, which, in turn, contributed to fast soil moisture depletion, amplifying the summer drought. We find regional asymmetries in summer ecosystem carbon fluxes: increased (reduced) sink in the northern (southern) areas affected by drought. These asymmetries can be explained by distinct legacy effects of spring growth and of water-use efficiency dynamics mediated by vegetation composition, rather than by distinct ecosystem responses to summer heat/drought. The asymmetries in carbon and water exchanges during spring and summer 2018 suggest that future land-management strategies could influence patterns of summer heat waves and droughts under long-term warming.

C-type natriuretic peptide and its receptors in atherosclerotic plaques of the carotid artery of clinically asymptomatic patients.

OBJECTIVES: C-type natriuretic peptide (CNP) has anti-inflammatory, anti-proliferative and anti-migratory properties. No data exist on the presence of CNP in human atherosclerotic plaques of the carotid artery. Therefore, this study aimed to analyse qualitatively the distribution pattern and characteristics of CNP and its receptors in both, early and advanced human carotid plaques, as well as in stable and unstable lesions. In addition, the aim of this study was to evaluate CNP and its receptors as possible biomarkers to predict plaque stability in advanced lesions. METHODS: Advanced carotid artery plaques of 40 asymptomatic patients (20 histologically stable and 20 histologically unstable) and early arteriosclerotic lesions of three patients were analysed. RESULTS: Serum level of CNP was similar in patients with stable and unstable plaques (196 ± 19 pg ml(-1) vs. 198 ± 25 pg ml(-1), p = 0.948). Expression level of natriuretic peptide receptor 3 (NPR3) was significantly higher in unstable plaques compared to stable plaques (5.6 ± 1.8% vs. 1.7 ± 0.5%, p = 0.045). Expression levels of CNP and NPR2 were higher in unstable plaques but the differences were not statistically significant. The distribution pattern of CNP, NPR2 and NPR3 varied qualitatively between early and advanced carotid plaques. No relevant histological differences were observed with respect to plaque stability. CONCLUSIONS: This study shows the presence of CNP and its receptors in atherosclerotic plaques of human carotid artery, with increased expression of NPR3 in histologically unstable plaques. In this study, serum CNP was not associated with histological plaque stability. In future, larger studies are required to further evaluate whether proteins of the CNP axis would be useful as biomarkers.

[Traumatic rupture of the aorta: origin, diagnosis, and therapy of a life-threatening aortic injury]. / Traumatische Aortenruptur. Pathomechanismus, Diagnostik und Therapie einer lebensbedrohlichen aortalen Verletzung.

In polytraumatized patients, traumatic rupture of the thoracic aorta is usually caused by blunt vascular injuries due to deceleration. The aortic injury is generally located distal to the left subclavian artery. Even without further thoracic lesions, a computer tomography should be performed in the emergency room, because a rupture can exist even in the absence of symptoms. The traditional therapeutic option is open, left thoracotomy followed by direct aortic reconstruction. Alternatively, endovascular implantation of a thoracic stent graft can be performed immediately in urgent situations or, with delayed priority, under systematically management of the blood pressure. In this article, not only the mechanisms of injury but also diagnostic and therapeutic options of traumatic rupture of the thoracic aorta are described. As depicted by two case histories, potential symptoms and prognosis of patients with this life-threatening vascular lesion depend on accompanying injuries. With rapid diagnosis and treatment, there is the possibility of good recovery from traumatic aortic rupture.

[Frequency and causes of vascular complications requiring surgery in patients without primary vascular disease]. / Häufigkeit und Ursachen operationsbedürftiger vaskulärer Komplikationen bei nicht gefäßchirurgischen Patienten.

Arterial and venous vascular injuries are known but rare complications of severe multiple traumatised patients but are meanwhile more frequently induced iatrogenically. However there are only few reports about incidence, causes, surgical techniques and prognosis of these vascular emergencies. We have therefore analysed the causes, type of therapy, localisation of injury, primary dis-ease, morbidity and mortality of all vascular emergencies in patients without preexisting vascular disease. 2.9 % of all vascular repairs in our unit had to be performed for cases of iatrogenic (87 %) and non-iatrogenic (13 %) vascular complications. The overall mortality and major complication rate of these intrahospital iatrogenically aquired lesions were 4.8 % and 5 %, respectively, which are clearly below those of extrahospital vascular injuries. Thereby the observed increase of iatrogenic vascular injuries seems to be due to the increase in complex and even catheter-based techniques in modern therapy. The iliacofemoral region was affected in 45 % of the cases, in 50 % complex reconstructions and specific surgical skills were needed for the repair. This article on the incidence of and reasons for vascular iatrogenic lesions shows the importance of a planned management for the prognosis of these injuries.

A comparison of diameter, wall stress, and rupture potential index for abdominal aortic aneurysm rupture risk prediction.

An abdominal aortic aneurysm (AAA) is a balloon-like dilation of the aorta, which is potentially fatal in case of rupture. Computational finite element (FE) analysis is a promising approach to a more accurate and patient-specific rupture risk prediction. AAA wall strength and rupture potential index (RPI) calculation are implemented in our FE software. Static structural FE simulations are performed on n = 30 non-ruptured asymptomatic, n = 9 non-ruptured symptomatic, and n = 14 ruptured AAAs. We calculate maximum values for diameter, wall displacement, strain, stress, and RPI as well as minimum wall strength for every AAA. All investigated quantities, except minimum strength, show statistically significant differences between non-ruptured asymptomatic and symptomatic/ruptured AAAs. Maximum wall stress and especially the RPI are notably increased for symptomatic and ruptured AAAs. The biggest difference is found to be the RPI (Δ = 44.9%, p = 8.0e-5). Lowest RPI obtained for symptomatic or ruptured AAAs is 0.3. The RPI of more than 55% of the investigated asymptomatic AAAs falls below this value. Maximum wall stress and maximum RPI criteria enable a reliable rupture risk evaluation for AAAs. Especially in the diameter range where surgical indication is not obvious, the RPI holds great potential for improvement of clinical decisions.

Young girl presenting with heart failure 5 years after laparoscopic appendectomy. Case report of an ilio-iliac AV fistula.

INTRODUCTION: Secondary arteriovenous (AV) fistulae following appendectomy are very rare. REPORT: We report the case of a 15-year-old girl suffering from progressive heart failure and sub-acute abdominal pain caused by an ilio-iliac AV fistula 5 years after a complicated appendectomy. The vessel-wall defects were closed by open surgery and the aneurysmatic iliac vein was gathered. DISCUSSION: Open fistula repair should be recommended to healthy and/or young patients, especially when they are not fully-grown. Endovascular treatment should be the therapy of choice in high-risk patients or patients with local contraindications against open surgery.

Dissection of biochemical borderline phenotypes in carriers and genetic variants of medium-chain acyl-CoA dehyrogenase deficiency: implications for newborn screening [corrected].

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid beta-oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut-off policies, false-positive and negative rates. In a retrospective case-control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false-positives, and 34 patients. c.985A>G was more frequently identified in the study group and false-positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false-positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false-negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C(8)) and three secondary markers in the initial and follow-up sample. The new approach allowed a reduction of false-positives (by defining high cut-offs: 1.4 micromol/l for C(8); 7 for C(8)/C(12)) and false-negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42-->88%) and to target NBS to MCADD-subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS-based NBS.

CpG island clones for chromosome 11p--a resource for mapping and gene identification.

A NotI end fragment library has been constructed for human Chromosome (Chr) 11p. Seventy-two clones were mapped to chromosomal subregions by use of somatic cell hybrids. The clones detect 44 different CpG islands, and we have isolated cosmid contigs for 36 of them. Extrapolation from the known 11p13 NotI restriction map suggests that every second CpG island from 11p containing a Not site is already represented in the clone collection. By sequence analysis all of the 11p13 clones exhibit typical features of CpG islands, and cross-species hybridization has been detected with at least one fragment in most cases. The cosmids serve as valuable linking clones for long-range restriction mapping. They also provide excellent starting material for transcript isolation procedures to identify genes on chromosome 11p associated with developmental anomalies and various tumor types. Several transcribed sequences have already been isolated with some of these clones.

An ordered NotI fragment map of human chromosome band 11p15.

An ordered NotI fragment map containing over 60 loci and encompassing approximately 17 Mb has been constructed for human chromosome band 11p15. Forty-two probes, including 11 NotI-linking cosmids, were subregionally mapped to 11p15 using a subset of the J1-deletion hybrids. These and 23 other probes defining loci previously mapped to 11p15 were hybridized to genomic DNA digested with NotI and 5 other infrequently cleaving restriction enzymes and separated by pulsed-field gel electrophoresis. Thirty-nine distinct NotI fragments were detected encompassing approximately 85% of the estimated length of 11p15. The predicted order of the gene loci used is cen-MYOD1-PTH-CALCA-ST5-RBTN1-HPX-HBB-RRM1 -TH/INS/IGF2-H19-CTSD-MUC2-DRD4-HRAS - RNH-tel. This map will allow higher resolution mapping of new 11p15 markers, facilitate positional cloning of disease genes, and provide a framework for the physical mapping of 11p15 in clone contigs.

No evidence of linkage between the locus for autosomal dominant retinitis pigmentosa and D3S47 (C17) in three Australian families.

A linkage analysis has been performed on three Australian families segregating for autosomal dominant retinitis pigmentosa (ADRP). No evidence of linkage has been found in any of the pedigrees studied between the locus D3S47 and the gene for ADRP. The D3S47 locus was found to show very close linkage with the ADRP gene in a large Irish pedigree. Our study together with a similar report on a British family indicates that there is genetic heterogeneity in this disease.

Gene of type II autosomal dominant retinitis pigmentosa maps on the long arm of chromosome 3.

Linkage analysis has been performed on a large Australian family segregating for the autosomal dominant form of retinitis pigmentosa (ADRP). The majority of patients had no subjective symptoms of night blindness until their second decade and good visual acuity until late in life. The disease in this family has been classified as Type II ADRP according to the subdivisions provided by both Massof and Finkelstein and Fishman and colleagues. Linkage (Omax:0.08 at Zmax:4.78) is here demonstrated between the disease locus and D3S47 (a marker locus on the long arm of chromosome 3), which showed in an earlier study very close linkage without recombination to the disease locus in an Irish pedigree with a clinically more severe and early onset (Type I) ADRP.

[Leading symptom: vertebral pain - a psychosomatic study]. / Leitsymptom: Wirbelsäulenschmerzen - Eine psychosomatische Studie.

Two different groups of patients (n about 40 each) having vertebral column pain as a common indicating symptom were studied using the Giessen-Test. The answers were interpreted on the basis of standard scales and single items. The findings were: The statements obtained from both groups suggest a basic disturbance in the area of being loved--not being loved, as well as conflicts in connection with aging or maturing. Spinal column patients from my practice must deal predominantly with feelings of inadequacy, whereas, in the patients from a sanatorium, these feelings became evident only indirectly in their overcompensation. These patients exhibit an image of themselves that can only be interpreted as an "ideal self-image". Accordingly, practice patients are perceptively more depressive in their fundamental disposition than the sanatorium patients. It seems as though the outbreak of vertebral column syndrome occurs when--as is often the case in threshold situations--feelings of inadequacy, especially those linked with losses of objects and love, can no longer be warded off by delusions of grandeur or their projections. On the other hand, the "sanatorium effect" seems to have an influence upon the stabilization of this defence mechanism.