Ischemic injury of the upper gastrointestinal tract after out-of-hospital cardiac arrest: a prospective, multicenter study.

BACKGROUND: The consequences of cardiac arrest (CA) on the gastro-intestinal tract are poorly understood. We measured the incidence of ischemic injury in the upper gastro-intestinal tract after Out-of-hospital CA (OHCA) and determined the risk factors for and consequences of gastrointestinal ischemic injury according to its severity. METHODS: Prospective, non-controlled, multicenter study in nine ICUs in France and Belgium conducted from November 1, 2014 to November 30, 2018. Included patients underwent an esophago-gastro-duodenoscopy 2 to 4 d after OHCA if still intubated and the presence of ischemic lesions of the upper gastro-intestinal tract was determined by a gastroenterologist. Lesions were a priori defined as severe if there was ulceration or necrosis and moderate if there was mucosal edema or erythema. We compared clinical and cardiac arrest characteristics of three groups of patients (no, moderate, and severe lesions) and identified variables associated with gastrointestinal ischemic injury using multivariate regression analysis. We also compared the outcomes (organ failure during ICU stay and neurological status at hospital discharge) of the three groups of patients. RESULTS: Among the 214 patients included in the analysis, 121 (57%, 95% CI 50-63%) had an upper gastrointestinal ischemic lesion, most frequently on the fundus. Ischemic lesions were severe in 55/121 (45%) patients. In multivariate regression, higher adrenaline dose during cardiopulmonary resuscitation (OR 1.25 per mg (1.08-1.46)) was independently associated with increased odds of severe upper gastrointestinal ischemic lesions; previous proton pump inhibitor use (OR 0.40 (0.14-1.00)) and serum bicarbonate on day 1 (OR 0.89 (0.81-0.97)) were associated with lower odds of ischemic lesions. Patients with severe lesions had a higher SOFA score during the ICU stay and worse neurological outcome at hospital discharge. CONCLUSIONS: More than half of the patients successfully resuscitated from OHCA had upper gastrointestinal tract ischemic injury. Presence of ischemic lesions was independently associated with the amount of adrenaline used during resuscitation. Patients with severe lesions had higher organ failure scores during the ICU stay and a worse prognosis. Clinical Trial Registration NCT02349074 .

Light Modulates Important Pathogenic Determinants and Virulence in ESKAPE Pathogens Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus.

Light sensing has been extensively characterized in the human pathogen Acinetobacter baumannii at environmental temperatures. However, the influence of light on the physiology and pathogenicity of human bacterial pathogens at temperatures found in warm-blooded hosts is still poorly understand. In this work, we show that Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa (ESKAPE) priority pathogens, which have been recognized by the WHO and the CDC as critical, can also sense and respond to light at temperatures found in human hosts. Most interestingly, in these pathogens, light modulates important pathogenicity determinants as well as virulence in an epithelial infection model, which could have implications in human infections. In fact, we found that alpha-toxin-dependent hemolysis, motility, and growth under iron-deprived conditions are modulated by light in S. aureus Light also regulates persistence, metabolism, and the ability to kill competitors in some of these microorganisms. Finally, light exerts a profound effect on the virulence of these pathogens in an epithelial infection model, although the response is not the same in the different species; virulence was enhanced by light in A. baumannii and S. aureus, while in A. nosocomialis and P. aeruginosa it was reduced. Neither the BlsA photoreceptor nor the type VI secretion system (T6SS) is involved in virulence modulation by light in A. baumannii Overall, this fundamental knowledge highlights the potential use of light to control pathogen virulence, either directly or by manipulating the light regulatory switch toward the lowest virulence/persistence configuration.IMPORTANCE Pathogenic bacteria are microorganisms capable of producing disease. Dangerous bacterial pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, are responsible for serious intrahospital and community infections in humans. Therapeutics is often complicated due to resistance to multiple antibiotics, rendering them ineffective. In this work, we show that these pathogens sense natural light and respond to it by modulating aspects related to their ability to cause disease; in the presence of light, some of them become more aggressive, while others show an opposite response. Overall, we provide new understanding on the behavior of these pathogens, which could contribute to the control of infections caused by them. Since the response is distributed in diverse pathogens, this notion could prove a general concept.

[The Respiratory Syncytial Virus (RSV) in Adults]. / Das Respiratorische Synzytial-Virus beim Erwachsenen.

RSV induces an acute viral disease with involvement of the respiratory tract. It can be notably life-threatening for infants but also for older adults. New RSV-subtypes are constantly evolving globally. The knowledge about epidemiology, hygiene measures, diagnostics and clinical feature is essential not only for the paediatrician. Vaccines or specific therapeutics are still missing. This article gives an overview with focus on RSV in adults. In addition, molecular pathological characteristics of the virus are explained, research approaches concerning vaccines and therapeutics are mentioned and current problems in management are discussed.

Analysis of Direct Effects of the CB1 Receptor Antagonist Rimonabant on Fatty Acid Oxidation and Glycogenolysis in Liver and Muscle Cells in vitro.

Recent pharmacological findings regarding rimonabant, an anorectic and cannabinoid type 1 receptor (CB1R) antagonist, strongly suggest that some of its effects on the metabolic parameters and energy balance in rats are not related to the centrally mediated reduction in caloric intake. Instead, they may be associated with acute induction of glycogenolysis in the liver, in combination with transient increase in glucose oxidation and persistent increase in fat oxidation. It is possible that rimonabant produced direct short- or long-term stimulatory effect on these processes in primary and cultured rat cells. Rimonabant slightly stimulated ß-oxidation of long-chain fatty acids in cultured rat myocytes overexpressing glucose transporter isoform 4, as well as activated phosphorylation of adenosine monophosphate-dependent protein kinase (AMPK) in primary rat hepatocytes upon long-term incubation. However, short-term action of rimonabant failed to stimulate ß-oxidation in myocytes, myotubes, and hepatocytes, as well as to upregulate AMPK phosphorylation, glycogenolysis, and cAMP levels in hepatocytes. As a consequence, the acute effects of rimonabant on hepatic glycogen content (reduction) and total energy expenditure (increase) in rats fed with a standard diet cannot be explained by direct stimulation of glycogenolysis and fatty acid oxidation in muscles and liver. Rather, these effects seem to be centrally mediated.

BOPHYs versus BODIPYs: A comparison of their performance as effective multi-function organic dyes.

The computationally-aided photophysical and lasing properties of a selected battery of BOPHYs are described and compared to those of related BODIPY counterparts. The present joined theoretical-experimental study helps to put into context the weaknesses and strengths of both dye families under different irradiation conditions. The chemical versatility of the BOPHY scaffold has been also comparatively explored to modulate key photonic properties towards the development of red-emitting dyes, chiroptical dyes and singlet oxygen photosensitizers. Thus, BOPHY BINOLation by fluorine substitution with enantiopure BINOLs endows the BOPHY chromophore with chiroptical activity, as supporting by the simulated circular dichroism, decreasing deeply its fluorescent response due to the promotion of fluorescence-quenching intramolecular charge transfer (ICT). Interestingly, the sole alkylation of the BOPHY core strongly modulates the promotion of ICT, allowing the generation of highly bright BINOL-based BOPHY dyes. Moreover, 3,3'-dibromoBINOLating BOPHYs can easily achieve singlet-oxygen photogeneration, owing to spin-orbit coupling mediated by heavy-atom effect feasible in view of the theoretically predicted disposition of the bromines surrounding the chromophore. From this background, we have established the master guidelines to design bright fluorophores and laser dyes, photosensitizers for singlet oxygen production and chiroptical dyes based on BOPHYs. The possibility to finely mix and balance such properties in a given molecular scaffold outstands BOPHYs as promising dyes competing with the well-settled BODIPY dyes.

[What influence do increased physical performance, age, sex and training frequency have on the effectiveness of back training?] / Welche Bedeutung haben physische Leistungssteigerungen, Alter, Geschlecht und Trainingsumfang für die Wirksamkeit eines Rückentrainings?

BACKGROUND: Active exercising can effectively reduce low back pain but the mechanisms of action are still unclear. OBJECTIVE: What are the influences of training frequency, increased physical performance, age and gender on the effectiveness of a multimodal back training? MATERIAL AND METHODS: A total of 1395 persons with back pain (mean age 46.9 ± 12.3 years, 65% female) took part in a multimodal back training over 24 months in the context of a multicenter study (39 locations). Back pain, physical capacity of strength, mobility and bilateral strength ratio of the spine stabilizing muscles were measured at the beginning of the training and after 6, 12 and 18 months. RESULTS AND DISCUSSION: The participants trained on average for 41.0 (SD ± 17.8) 60-min training units. This resulted in an increase of strength (28.1%), mobility (14.7%) and strength ratio (6.5%) compared to an age and gender-matched cohort without back pain. Back pain was reduced by 37.5%. The reduction in back pain can be ascribed to the training frequency by 70% and to increased physical performance by 30%. Age only marginally influenced the effect of training, while gender had no significant effect. CONCLUSION: Increases in physical performance have positive effects on the reduction of back pain but the number of training sessions was shown to be more relevant in the reduction of low back pain.

Gastrointestinal helminths of wolves (Canis lupus Linnaeus, 1758) in Piedmont, north-western Italy.

Free-ranging grey wolves (Canis lupus), which are presently recolonizing Italy, can be parasitized by a diversity of helminths, but have rarely been subject to studies of their parasites. Therefore, this study aims to determine the prevalence of gastrointestinal helminths of road-killed grey wolves from the Piedmont region of Italy. Forty-two wolves were collected and examined for the presence of helminths. We recorded 12 helminth species: nine Nematoda and three Cestoda. The nematodes were: Ancylostoma caninum (7.1%), Capillaria sp. (2.4%), Molineus sp. (2.4%), Pterygodermatites affinis (11.9%), Physaloptera sibirica (9.5%), Toxocara canis (9.5%), Toxascaris leonina (2.4%) and Uncinaria stenocephala (26.2%); the cestodes were: Dipylidium caninum (4.8%), Mesocestoides sp. (4.8%) and Taenia multiceps (76.2%). Physaloptera sibirica had the highest mean intensity and T. multiceps had the highest prevalence. Based on age and sex, no differences in the intensity or prevalence of helminth species were found among the hosts. Molineus sp. was recorded for the first time in wolves from the Palearctic region; P. affinis and P. sibirica are respectively reported for the first time in wolves from Europe and Italy.

Rituximab in routine care of severe active rheumatoid arthritis : A prospective, non-interventional study in Germany.

OBJECTIVE: To assess safety, effectiveness and onset of effect of rituximab (RTX) in routine clinical treatment of severe, active rheumatoid arthritis (RA). METHODS: Prospective, multi-centre, non-interventional study in rheumatological outpatient clinics or private practices in Germany. RTX-naïve adult patients were to receive RTX according to marketing authorisation and at their physician's discretion. Also according to their physician's discretion, patients could receive a second cycle of RTX (re-treatment = treatment continuation). Major outcome was the change in Disease Activity Score based on 28-joints count and erythrocyte sedimentation rate (DAS28-ESR) over 24 weeks and during 6 months of re-treatment. RESULTS: Overall, 1653 patients received at least one cycle RTX; 99.2% of these had received disease-modifying antirheumatic drugs (DMARD) pre-treatment and 75.5% anti-tumor necrosis factor(TNF)­α pre-treatment. After a mean interval of 8.0 months, 820 patients received RTX re-treatment. Mean DAS28-ESR decreased from 5.3 at baseline to 3.8 after 24 weeks (-1.5 [95% confidence interval, CI: -1.6; -1.4]), and from 4.1 at start of cycle 2 to 3.5 at study end (change from baseline: -1.8 [95% CI: -2.0; -1.7]). Improvements in DAS28-ESR and Health Assessment Questionnaire (HAQ) score occurred mainly during the first 12 weeks of RTX treatment, with further DAS28-ESR improvement until week 24 or month 6 of re-treatment. Improvements in DAS28-ESR and EULAR responses were more pronounced in seropositive patients. RF was a predictor of DAS28-ESR change to study end. Safety analysis showed the established profile of RTX. CONCLUSION: RTX was safe and effective in a real-life setting with rapid and sustained improvement in RA signs and symptoms.

Autophagy activation in circulating proangiogenic cells aggravates AKI in type I diabetes mellitus.

Acute kidney injury (AKI) occurs frequently in hospitals worldwide, but the therapeutic options are limited. Diabetes mellitus (DM) affects more and more people around the globe. The disease worsens the prognosis of AKI even further. In recent years, cell-based therapies have increasingly been applied in experimental AKI. The aim of the study was to utilize two established autophagy inducers for pharmacological preconditioning of so-called proangiogenic cells (PACs) in PAC treatment of diabetic AKI. Insulin-dependent DM was induced in male C57/Bl6N mice by intraperitoneal injections of streptozotocine. Six weeks later, animals underwent bilateral renal ischemia for 45 min, followed by intravenous injections of either native or zVAD (benzyloxycarbonyl-Val-Ala-Asp-fluoro-methylketone)- or Z-Leu-Leu-Leu-al (MG132)-pretreated syngeneic murine PACs. Mice were analyzed 48 h (short term) and 6 wk (long term) later, respectively. DM worsened postischemic AKI, and PAC preconditioning with zVAD and MG132 resulted in a further decline of excretory kidney function. Injection of native PACs reduced fibrosis in nondiabetic mice, but cell preconditioning promoted interstitial matrix accumulation significantly. Both substances aggravated endothelial-to-mesenchymal transition (EndoMT) under diabetic conditions; these effects occurred either exclusively in the short (zVAD) or in the short and long term (MG132). Preconditioned cells stimulated the autophagocytic flux in intrarenal endothelial cells, and all experimental groups displayed increased endothelial abundances of senescence-associated ß-galactosidase, a marker of premature cell senescence. Pharmacological autophagy activation may not serve as an effective strategy for improving PAC competence in diabetic AKI in general. On the contrary, several outcome parameters (excretory function, fibrosis, EndoMT) may even be worsened.

Therapeutic response to glucocorticoids, anticoagulation and plasma exchange in a patient with primary antiphospholipid syndrome presenting with purpura fulminans.

We report the case of a 25-year-old female patient who presented with purpura fulminans as a manifestation of primary antiphospholipid syndrome. Purpura fulminans is considered a rare cutaneous manifestation of antiphospholipid syndrome. Most frequently, it occurs in the context of catastrophic antiphospholipid syndrome and is associated with significant morbidity and mortality, either due to loss of affected extremities or thromboembolic damage to internal organs. After insufficient efficacy of parenteral anticoagulation and oral glucocorticosteroid treatment, we escalated treatment to high-dose intravenous glucocorticosteroid and five consecutive sessions of plasma exchange with good and sustained clinical response. At follow-up six months after admission, skin manifestations had healed with scarring, and no additional thrombotic events had occurred. Plasma exchange may hold promise as a therapeutic option in refractory or severe cases of antiphospholipid syndrome-related purpura fulminans with extensive cutaneous necrosis, although evidence is limited.

Age, burnout and physical and psychological work ability among nurses.

Background: The ageing of the US labour force highlights the need to examine older adults' physical and psychological ability to work, under varying levels of occupational burnout. Aims: To examine how age and burnout interact in predicting physical and psychological work ability. Methods: Using a cohort of actively working nurses, we assessed factors on the Work Ability Index at 12-month follow-up and determined how these were related to age and exhaustion-related burnout at baseline. Results: The study group consisted of 402 nurses aged 25-67 (mean = 41.7). Results indicated age by burnout interactions in which decrements in physical work ability with greater age were observed at all but the lowest level of burnout (1.5 SD below mean: ß = -0.14, 95% CI -0.36, 0.07; 1 SD below: ß = -0.23, 95% CI -0.39, -0.06; mean: ß = -0.39, 95% CI -0.50, -0.29; 1 SD above: ß = -0.56, 95% CI -0.70, -0.42; 1.5 SD above: ß = -0.64, 95% CI -0.83, -0.46). In contrast, we observed decrements in psychological work ability with age at higher levels of burnout only (1 SD above: ß = -0.20, 95% CI -0.35, -0.05; 1.5 SD above: ß = -0.30, 95% CI -0.49, -0.11); at lower levels of burnout, older age was associated with improvements in this (1 SD below: ß = 0.19, 95% CI 0.03, 0.35; 1.5 SD below: ß = 0.29, 95% CI 0.08, 0.50). Conclusions: Findings indicated physical and psychological dimensions of work ability that differed by age and occupational burnout. This emphasizes the need for interventions to reduce burnout and to address age-related strengths and vulnerabilities relating to physical and psychological work ability.

Dialysis vintage time has the strongest correlation to psychosocial pattern of oral health-related quality of life - a multicentre cross-sectional study.

BACKGROUND: Aim of this cross-sectional, multicentre study was to investigate associations of dialysis vintage time in haemodialysis (CKD5D) patients with oral health-related quality of life (OHRQoL) and dental and periodontal treatment need. MATERIAL AND METHODS: CKD5D patients were divided into subgroups according to dialysis vintage time in different dialysis centres in Germany. OHRQoL was assessed with oral health impact profile (OHIP-G14). Dental treatment need was classified as presence of carious lesions. Periodontal treatment need was defined as periodontal screening index score (PSI) 3-4. RESULTS: In total, 190 participants were divided into the subgroups according to the time on CKD5D: 0 - 2 (n = 29), 3 - 5 (n = 35), 6 - 8 (n = 34), 9 - 12 (n = 29), 13 - 20 (n = 34) and >20 years (n = 29). The overall treatment need in the total cohort was 92% (dental 56%, periodontal 88%) with a total OHIP-G14 sum score of 4.17 [2; 0-5] without a significant correlation. Time on CKD5D was inversely correlated with the OHIP G14 score (p<0.01, R = -0.201). The pattern psychosocial impact was significantly associated with the dialysis duration (p<0.01) and showed a negative correlation to the OHIP-G14 (R = -0.283, Spearman's rho test p<0.01). For oral function also a negative correlation with OHIP-G14 was detected (Spearman's rho: -0.183). CONCLUSIONS: Patients with a prolonged dialysis vintage time show an improved OHRQoL, which might be mainly caused by the positive development of psychosocial pattern of OHRQoL. The oral health situation of HD patients seems unsatisfying, independently of dialysis vintage time and OHRQoL. Accordingly, an improvement in oral health situation of CKD5D patients is mandatory necessary. Thereby, consideration of psychosocial aspects especially at the beginning of CKD5D therapy and a sensitization regarding oral health issues with increasing vintage time might be recommendable.

Altered white matter integrity in adults with autism spectrum disorder and an IQ >100: a diffusion tensor imaging study.

OBJECTIVE: White matter (WM) alterations have been reported in children and adults with autism spectrum disorder (ASD). In particular, impaired connectivity of limbic structures may be related to social deficits. Heterogeneous findings could be explained in terms of differences in sample characteristics and methodology. In this context, non-syndromic forms might differ substantially in WM structure from secondary ASD forms. METHOD: In an attempt to recruit a homogeneous study sample, we included adults with high-functioning ASD and an IQ > 100 to decrease the influence of syndromic forms being often associated with cognitive deficits. Diffusion tensor imaging (DTI) was performed in 30 participants with ASD and 30 pairwise-matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) as surrogate imaging markers for WM integrity were calculated. RESULTS: We found a significant FA decrease in the ASD group in the genu and body of the corpus callosum (CC). Increased MD was detected in the subgenual anterior cingulate cortex (sACC). CONCLUSION: The finding of decreased WM integrity in the genu of the CC is in line with earlier studies reporting a decreased number of interhemispheric fibers in the frontal lobe of ASD. Alterations in the sACC might be associated with 'Theory of mind' deficits.

Prognostic significance of central venous-to-arterial carbon dioxide difference during the first 24 hours of septic shock in patients with and without impaired cardiac function.

OBJECTIVE: To investigate the prognostic significance of central venous-to-arterial carbon dioxide difference (cv-art CO 2 gap) during septic shock in patients with and without impaired cardiac function. METHODS: We performed a prospective cohort study in 10 French intensive care units. Patients suffering from septic shock were assigned to the impaired cardiac function group ('cardiac group', n =123) if they had atrial fibrillation (AF) and/or left ventricular ejection fraction (LVEF) <50% at study entry and to the non-cardiac group ( n =240) otherwise. RESULTS: Central venous and arterial blood gases were sampled every 6 h during the first 24 h to calculate cv-art CO 2 gap. Patients in the cardiac group had a higher cv-art CO 2 gap [at study entry and 6 and 12 h (all P <0.02)] than the non-cardiac group. Patients in the cardiac group with a cv-art CO 2 gap >0.9 kPa at 12 h had a higher risk of day 28 mortality (hazard ratio=3.18; P =0.0049). Among the 59 patients in the cardiac group with mean arterial pressure (MAP) ≥65 mm Hg, central venous pressure (CVP) ≥8 mm Hg and central venous oxygen saturation (ScvO 2 ) ≥70% at 12 h, those with a high cv-art CO 2 gap (>0.9 kPa; n =19) had a higher day 28 mortality (37% vs. 13%; P =0.042). In the non-cardiac group, a high cv-art CO 2 gap was not linked to a higher risk of day 28 death, whatever the threshold value of the cv-art CO 2 gap. CONCLUSION: Patients with septic shock and with AF and/or low LVEF were more prone to a persistent high cv-art CO 2 gap, even when initial resuscitation succeeded in normalizing MAP, CVP, and ScvO 2 . In these patients, a persistent high cv-art CO 2 gap at 12 h was significantly associated with higher day 28 mortality.

Nanoantenna arrays combining enhancement and beam control for fluorescence-based sensing applications.

This paper presents measured fluorescence enhancement results for ∼250×250 element aluminum nanoantenna arrays fabricated using electron beam lithography. The arrays have been designed to use diffractive coupling to enhance and control the direction of fluorescent emission. Highly directional emission is obtained at the designed angles with beam widths simulated to be in the range of 4-6°. Angle-resolved spectroscopy measurements of dye-coated nanoantenna arrays were in good agreement with finite difference time domain modeling. Critically, these results were obtained for near UV wavelengths (∼360 nm), which is relevant to a number of biosensing applications.

Endothelial Colony Forming Cells (ECFCs) in murine AKI - implications for future cell-based therapies.

BACKGROUND: In recent years, early Endothelial Progenitor Cells (eEPCs) have been proven as effective tool in murine ischemic AKI and in diabetic nephropathy. The mechanisms of eEPC-mediated vasoprotection have been elucidated in detail. Besides producing a diverse range of humoral factors, the cells also act by secreting vasomodulatory microvesicles. Only few data in contrast have been published about the role of so-called Endothelial Colony Forming Cells (ECFCs - late EPCs) in ischemic AKI. We thus aimed to investigate ECFC effects on postischemic kidney function over several weeks. Our special interest focused on endothelial-to-mesenchymal transition (EndoMT), peritubular capillary density (PTCD), endothelial alpha-Tubulin (aT - cytoskeletal integrity), and endothelial p62 (marker of autophagocytic flux). METHODS: Eight to twelve weeks old male C57Bl/6 N mice were subjected to bilateral renal pedicle clamping for 35 or 45 min, respectively. Donor-derived syngeneic ECFCs (0.5 × 106) were i.v. injected at the end of ischemia. Animals were analyzed 1, 4 and 6 weeks later. RESULTS: Cell therapy improved kidney function exclusively at week 1 (35 and 45 min). Ischemia-induced fibrosis was diminished in all experimental groups by ECFCs, while PTCD loss remained unaffected. Significant EndoMT was detected in only two of 6 groups (35 min, week 4 and 45 min, week 6), ECFCs reduced EndoMT only in the latter. Endothelial aT declined under almost all experimental conditions and these effects were further aggravated by ECFCs. p62 was elevated in endothelial cells, more so after 45 than after 35 min of ischemia. Cell therapy did not modulate p62 abundances at any time point. CONCLUSION: A single dose of ECFCs administered shortly post-ischemia is capable to reduce interstitial fibrosis in the mid- to long-term whereas excretory dysfunction is improved only in a transient manner. There are certain differences in renal outcome parameters between eEPCs and ECFC. The latter do not prevent animals from peritubular capillary loss and they also do not further elevate endothelial p62. We conclude that differences between eEPCs and ECFCs result from certain mechanisms by which the cells act around and within vessels. Overall, ECFC treatment was not as efficient as eEPC therapy in preventing mice from ischemia-induced mid- to long-term damage.

[Outcome Quality in Medical Rehabilitation: Relationship Between "Patient-Reported Outcomes" (PROs) and Social Security Contributions]. / Ergebnisqualität medizinischer Rehabilitation: Zum Zusammenhang zwischen "Patient Reported Outcomes" (PROs) und geleisteten Sozialversicherungsbeiträgen.

Aim of the Study The outcome quality of medical rehabilitation is evaluated often by "Patient Reported Outcomes" (PROs). It is examined to what extent these PROs are corresponding with "hard" or "objective" outcomes such as payments of contributions to social insurance. Methods The "rehabilitation QM outcome study" includes self-reports of patients as well as data from the Rehabilitation Statistics Database (RSD) of the German pension insurance Baden-Wurttemberg. The sample for the question posed includes N=2 947 insured who were treated in 2011 in 21 clinics of the "health quality network" and who were either employed or unemployed at the time of the rehabilitation application (e. g. the workforce or labour force group, response rate: 55%). The sample turned out widely representative for the population of the insured persons. Results PROs and payment of contributions to pension insurance clearly correspond. In the year after the rehabilitation improved vs. not improved rehabilitees differed clearly with regard to their payments of contributions. Conclusions The results support the validity of PROs. For a comprehensive depiction of the outcome quality of rehabilitation PROs and payments of contributions should be considered supplementary.

Postischemic microvasculopathy and endothelial progenitor cell-based therapy in ischemic AKI: update and perspectives.

Acute kidney injury (AKI) dramatically increases mortality of hospitalized patients. Incidences have been increased in recent years. The most frequent cause is transient renal hypoperfusion or ischemia which induces significant tubular cell dysfunction/damage. In addition, two further events take place: interstitial inflammation and microvasculopathy (MV). The latter evolves within minutes to hours postischemia and may result in permanent deterioration of the peritubular capillary network, ultimately increasing the risk for chronic kidney disease (CKD) in the long term. In recent years, our understanding of the molecular/cellular processes responsible for acute and sustained microvasculopathy has increasingly been expanded. The methodical approaches for visualizing impaired peritubular blood flow and increased vascular permeability have been optimized, even allowing the depiction of tissue abnormalities in a three-dimensional manner. In addition, endothelial dysfunction, a hallmark of MV, has increasingly been recognized as an inductor of both vascular malfunction and interstitial inflammation. In this regard, so-called regulated necrosis of the endothelium could potentially play a role in postischemic inflammation. Endothelial progenitor cells (EPCs), represented by at least two major subpopulations, have been shown to promote vascular repair in experimental AKI, not only in the short but also in the long term. The discussion about the true biology of the cells continues. It has been proposed that early EPCs are most likely myelomonocytic in nature, and thus they may simply be termed proangiogenic cells (PACs). Nevertheless, they reliably protect certain types of tissues/organs from ischemia-induced damage, mostly by modulating the perivascular microenvironment in an indirect manner. The aim of the present review is to summarize the current knowledge on postischemic MV and EPC-mediated renal repair.

The endothelial-to-mesenchymal transition and endothelial cilia in EPC-mediated postischemic kidney protection.

Renal ischemia induces peritubular capillary rarefication and fibrosis, with the latter partly resulting from the endothelial-to-mesenchymal transition (EndoMT). Endothelial cilia transmit blood flow-associated forces into the cell. Early endothelial progenitor cells (eEPCs) have been shown to protect mice from acute kidney injury in the short term. The aim of the present study was to analyze midterm consequences of eEPC treatment in the context of endothelial cilia and the EndoMT. Male C57/Bl6N mice were subjected to unilateral renal ischemia postuninephrectomy. Syngeneic murine eEPCs were systemically injected at the time of reperfusion. Animals were investigated 1, 4, and 6 wk later. Cultured mature endothelial cells were exposed to a variable flow with versus without eEPC supernatant incubation. Systemically injected eEPCs reduced serum creatinine levels at week 1 (35 and 45 min) and week 4 (45 min). Interstitial fibrosis was significantly diminished by cell treatment at all time points as well. The EndoMT was less pronounced at week 4 (35 min) and week 6 (45 min). eEPC supernatant reduced α-smooth muscle actin expression and α-tubulin abundance in flow-treated cultured mature endothelial cells, and percentages of cilium-positive cells increased. The loss of peritubular capillaries was prevented by eEPCs. Intrarenal endothelial α-tubulin decreased postischemia and was further reduced by eEPC administration. We conclude that eEPCs are capable of reorganizing the endothelial cytoskeleton in an indirect manner, ultimately resulting in stabilization of the endothelial ciliome. The investigation indicates an antimesenchymal role of endothelial cilia in the process of postischemic tissue fibrosis/EndoMT.