The joint impact of donor and recipient parameters on the outcome of heart transplantation in Germany after graft allocation

Organ shortage in heart transplantation (HTx) results in increased use of grafts from donors with substantial risk factors. It is discussed controversially which donor characteristics may be detrimental. Therefore, we evaluated the joint impact of donor‐ and patient‐related risk factors in HTx on patient survival by multiple analysis in a nationwide multicentre study after donor selection was carried out. The research database consists of data concerning hearts donated and transplanted in Germany between 2006 and 2008 as provided by Deutsche Stiftung Organtransplantation and the BQS Institute. Multiple Cox regression (significance level 5%, hazard ratio [95% CI]) was conducted (n = 774, recipient age ≥ 18 years). Survival was significantly decreased by donor age (1.021 [1.008–1.035] per year), nontraumatic cause of death (1.481 [1.079–2.034]), troponin >0.1 ng/ml (2.075 [1.473–2.921]), ischaemia time (1.197 [1.041–1.373] per hour), recipient age (1.017 [1.002–1.031] per year) and in recipients with pulmonary vascular resistance ≥320 dyn*s*cm^?5 (1.761 [1.115–2.781]), with ventilator dependency (3.174 [2.211–6.340]) or complex previous heart surgery (1.763 [1.270–2.449]). After donor selection had been conducted, multiple Cox regression revealed donor age, nontraumatic cause of death, troponin and ischaemia time as well as recipient age, pulmonary hypertension, ventilator dependency and previous complex heart surgery as limiting risk factors concerning patient survival.     

Clinical,angiographic and cardiovascular magnetic resonance findings in consecutive patients with Takotsubo cardiomyopathy

BACKGROUND: The aim was to assess clinical, angiographic and cardiovascular magnetic resonance (CMR) findings in patients with Takotsubo cardiomyopathy. METHODS: Between 2003 and 2007, 20 consecutive patients admitted to our hospital with suspected acute myocardial infarction and presenting with apical ballooning in the left ventricular (LV) angiogram in the absence of a significant coronary artery disease, were included in the study. Echocardiography and CMR was performed in all patients. RESULTS: The mean age of patients with Takotsubo cardiomyopathy was 62 +/- 8 years (range 43-78 years). Eighteen (90%) were female. Clinical presentations included chest pain (95%) and cardiogenic shock (5%). The mean angiographic LV ejection fraction on admission was 45% +/- 9% (range 26%-60%) and resolved rapidly in all cases. Mean time delay between presentation CMR was 2 +/- 1 days (range 1-6 days). Mean ejection fraction was 51% +/- 15% (range 25%-81%). While 19 (95%) patients showed no evidence of late enhancement or signs of myocarditis in the CMR, 1 (5%) patient who was resuscitated showed hyperenhancement confined to the apex. CONCLUSION: In patients showing the clinical picture of an acute myocardial syndrome and angiographic picture of a TakoTsubo cardiomyopathy, CMR might be helpful in confirming the diagnosis through the exclusion of other causes for the acute LV dysfunction.     

Facial deformation following treatment for pediatric head and neck rhabdomyosarcoma; the difference between treatment modalities. Results of a trans-Atlantic,multicenter cross-sectional cohort study

Background

The four different local therapy strategies used for head and neck rhabdomyosarcoma (HNRMS) include proton therapy (PT), photon therapy (RT), surgery with radiotherapy (Paris-method), and surgery with brachytherapy (AMORE). Local control and survival is comparable; however, the impact of these different treatments on facial deformation is still poorly understood. This study aims to quantify facial deformation and investigates the differences in facial deformation between treatment modalities.

Methods

Across four European and North American institutions, HNRMS survivors treated between 1990 and 2017, more than 2 years post treatment, had a 3D photograph taken. Using dense surface modeling, we computed facial signatures for each survivor to show facial deformation relative to 35 age–sex–ethnicity-matched controls. Additionally, we computed individual facial asymmetry.

Findings

A total of 173 HNRMS survivors were included, survivors showed significantly reduced facial growth (p < .001) compared to healthy controls. Partitioned by tumor site, there was reduced facial growth in survivors with nonparameningeal primaries (p = .002), and parameningeal primaries (p ≤.001), but not for orbital primaries (p = .080) All patients were significantly more asymmetric than healthy controls, independent of treatment modality (p ≤ .001). There was significantly more facial deformation in orbital patients when comparing RT to AMORE (p = .046). In survivors with a parameningeal tumor, there was significantly less facial deformation in PT when compared to RT (p = .009) and Paris-method (p = .007).

Interpretation

When selecting optimal treatment, musculoskeletal facial outcomes are an expected difference between treatment options. These anticipated differences are currently based on clinicians’ bias, expertise, and experience. These data supplement clinician judgment with an objective analysis highlighting the impact of patient age and tumor site between existing treatment options.     

PNPLA3 genetic variation in alcoholic steatosis and liver disease progression

Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations. Although carriership of one or both mutated PNPLA3 alleles does not explain the entire liver phenotypic variability in drinkers, it clearly represents one of the strongest single genetic modulators in a complex trait such as ALD. As more genetic data supporting its important role aggregates, novel insight as to PNPLA3’s function and that of its genetic variation in liver injury is unveiled pointing to an important novel pathway in alcohol-mediated hepatic lipid turnover with strong implications on inflammation, extra cellular matrix remodelling, and hepatocarcinogenesis. Future study shall decipher whether the gathered knowledge can be translated into therapeutic benefits of patients.     

Ultrasound point shear wave elastography of the pancreas: comparison of patients with type 1 diabetes and healthy volunteers – results from a pilot study

Background

The aims of this study were to establish shear wave elastography of the pancreas by comparing measurements in patients with type 1 diabetes (T1D) and healthy volunteers and to consider whether this method could contribute to the screening or prevention of T1D.

Methods

This pilot study included 15 patients with T1D (10 men, 5 women) and 15 healthy volunteers (10 men, 5 women) as controls. Measurements were performed with a Siemens Acuson S3000 (Siemens Healthcare, Erlangen, Germany) using a 6C1 convex transducer and the Virtual Touch? tissue quantification (VTQ) method.

Results

The mean shear wave velocity of the head of the pancreas was 1.0?±?0.2?m/s (median: 1.1?m/s) for the study group and likewise 1.0?±?0.2?m/s (median: 0.9?m/s) for the control group. Velocities of 1.2?±?0.2?m/s (median: 1.2?m/s) were measured in the body of the pancreas in both groups. There was a significant difference between the values obtained in the tail of the pancreas: patients 1.1?±?0.1?m/s (median: 1.0?m/s) versus controls 0.9?±?0.1?m/s (median: 0.8?m/s) (p?=?0.0474). The mean value in the whole pancreas of the study group was not significantly above that of the control group: 1.1?±?0.1?m/s (median: 1.0?m/s) versus 1.0?±?0.1?m/s (median: 1.0?m/s) (p?=?0.2453).

Conclusions

Sonoelastography of the pancreas revealed no overall difference between patients with T1D and healthy volunteers. Patients with T1D showed higher values only in the tail segment. Future studies need to determine whether specific regional differences can be found in a larger study population.

     

Neural coding underlying the cue preference for celestial orientation

Diurnal and nocturnal African dung beetles use celestial cues, such as the sun, the moon, and the polarization pattern, to roll dung balls along straight paths across the savanna. Although nocturnal beetles move in the same manner through the same environment as their diurnal relatives, they do so when light conditions are at least 1 million-fold dimmer. Here, we show, for the first time to our knowledge, that the celestial cue preference differs between nocturnal and diurnal beetles in a manner that reflects their contrasting visual ecologies. We also demonstrate how these cue preferences are reflected in the activity of compass neurons in the brain. At night, polarized skylight is the dominant orientation cue for nocturnal beetles. However, if we coerce them to roll during the day, they instead use a celestial body (the sun) as their primary orientation cue. Diurnal beetles, however, persist in using a celestial body for their compass, day or night. Compass neurons in the central complex of diurnal beetles are tuned only to the sun, whereas the same neurons in the nocturnal species switch exclusively to polarized light at lunar light intensities. Thus, these neurons encode the preferences for particular celestial cues and alter their weighting according to ambient light conditions. This flexible encoding of celestial cue preferences relative to the prevailing visual scenery provides a simple, yet effective, mechanism for enabling visual orientation at any light intensity.The blue sky is a rich source of visual cues that are used by many animals during orientation or navigation (1, 2). Besides the sun, celestial phenomena, such as the skylight intensity gradient or the more complex polarization pattern, can serve as references for spatial orientation (3–5). Polarized skylight is generated by scattered sunlight in the atmosphere, and to a terrestrial observer, the resulting alignment of the electric field vectors extends across the entire sky, forming concentric circles around the position of the sun (Fig. 1A). A similar distribution of brightness and polarization pattern is also created around the moon (6). Although this nocturnal pattern is 1 million-fold dimmer than the daylight pattern (6), some animals, such as South African ball-rolling dung beetles, can use this lunar polarization pattern for orientation (7). To avoid competition for food at the dung pile, these beetles detach a piece of dung, shape it into a ball, and roll it away along a straight-line path. For this type of straight-line orientation, nocturnal beetles seem to rely exclusively on celestial cues (8), such as the moon or polarized light.Open in a separate windowFig. 1.Celestial cue preference in dung beetles under a natural sky. (A) Schematic illustration of the polarization pattern around a celestial body (sun or moon). Change of direction in diurnal (D, Left) and nocturnal (N, Right) beetles rolling under a sun-lit (B) or moon-lit (C) sky. The change of direction was calculated as the angular difference between two consecutive rolls, either without manipulation (control, ●) or when the sun or moon was reflected to the opposite sky hemisphere between the two rolls (test, ○). The mean directions (μ) are indicated by black (control) or red (test) lines, and error bars indicate circular SDs. (B) Without manipulation, both species kept the direction [P < 0.001 by V test; μ_diurnal (±SD) = 2.6° ± 17.98°, n = 20; μ_nocturnal = −8.7° ± 38.34°, n = 20). When the sun was reflected to the opposite sky hemisphere (and the real sun was shaded), both species responded to this change (P < 0.001 by V-test; μ_diurnal = 178.9° ± 54.6°, n = 20; μ_nocturnal = 163.8° ± 46.58°, n = 20). (C) Under the moon in the control experiments, both species showed a constant rolling direction (P < 0.001 by V test; μ_diurnal = 3.1° ± 35.39°, n = 20; μ_nocturnal = −3.3° ± 37.87°, n = 20). When the moon was reflected to the opposite sky hemisphere, the diurnal species followed the position change of the moon (P = 0.002 by V test; μ = 179.5° ± 72.37°, n = 20), whereas the nocturnal species continued rolling in the original rolling direction (P < 0.001 by V test; μ = −13.4° ± 74.27°, n = 20).As with all nocturnal animals, night-active beetles have to overcome a major challenge: They need to maintain high orientation precision even under extremely dim light conditions. Indeed, recent experiments have shown that nocturnal dung beetles orient at night with the same precision as their diurnal relatives during the day (9), an ability partly due to the fact that their eyes are considerably more sensitive than the eyes of species that are active at brighter light levels (10–12). Nonetheless, for each species, orientation precision relies on being tuned to the most reliable celestial compass cue that is available during the animal’s normal activity window. How salient are these cues for nocturnal and diurnal species? Do diurnal species have a different celestial cue preference than nocturnal species? If so, how are these preferences represented neurally in the brain?In this study, we present a detailed picture of how the orientation systems of two closely related nocturnal and diurnal animals have been adapted to the ambient light conditions, combining behavioral experiments from the field with electrophysiological investigations of the underlying neural networks. Using behavioral experiments, we show that nocturnal dung beetles switch from a compass that uses a discrete celestial body (the sun) during the day to a celestial polarization compass for dim light orientation at night, whereas diurnal beetles use a celestial body (the sun or moon) for orientation at all light levels. In a second step, we simulated these skylight cues (the sun or moon and the polarization pattern) while electrophysiologically recording responses from neurons in the dung beetle’s central complex, a brain area that has been suggested to house the internal compass for celestial orientation (13, 14). These neural data precisely matched the cue preferences observed in behavioral field trials and show how an animal’s visual ecology influences the neural activity of its sky compass neurons. Our results also reveal, for the first time to our knowledge, how a weighting of celestial orientation cues could be neurally encoded in an animal brain.     

Implementing an Innovative Cardiac Assist System in a Nonuniversity Hospital—Feasibility,Complications, and First Results

To evaluate the feasibility of implementing a cardiac assist system in a nonuniversity hospital we analyzed 18 consecutive patients treated with venoarterial membrane oxygenation. The system was used electively in 5/18 (27.8%) patients during high‐risk interventions. Thirteen patients (72.2%) were treated in emergency situations. The extracorporal system could be initiated successfully in all patients. Periprocedural complications were hemolysis in 3/18 (16.7%), disseminated intravascular coagulation in 2/18 (11.1%), cerebral ischemia in 1/18 (5.6%), and local infection in 2/18 (11.1%) patients. None of these led to a discontinuation of the therapy. All electively treated patients were successfully weaned from the extracorporeal system. In 9/13 (69.2%) emergency patients the system was removed successfully. The 60‐day survival rate of the emergency patients was 53.8% (7/13). Our experience confirms that an innovative extracorporeal circulatory support system can be implemented in a nonuniversity hospital at a tolerable risk and a low complication and high procedural success rate.