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Fracture repair is initiated by a multitude of immune cells and induction of an inflammatory cascade. Alterations in the early healing response due to an aged adaptive immune system leads to impaired bone repair, delayed healing or even formation of non-union. However, immuno-senescence is not limited to the adaptive immunity, but is also described for macrophages, main effector cells from the innate immune system. Beside regulation of pro- and anti-inflammatory signaling, macrophages contribute to angiogenesis and granulation tissue maturation. Thus, it seems likely that an altered macrophage function due to aging may affect bone repair at various stages and contribute to age related deficiencies in bone regeneration. To prove this hypothesis, we analyzed the expression of macrophage markers and angiogenic factors in the early bone hematoma derived from young and aged osteotomized Spraque Dawley rats. We detected an overall reduced expression of the monocyte/pan-macrophage markers CD14 and CD68 in aged rats. Furthermore, the analysis revealed an impaired expression of anti-inflammatory M2 macrophage markers in hematoma from aged animals that was connected to a diminished revascularization of the bone callus. To verify that the age related disturbed bone regeneration was due to a compromised macrophage function, CD14+ macrophage precursors were transplanted locally into the osteotomy gap of aged rats. Transplantation rescued bone regeneration partially after 6 weeks, demonstrated by a significantly induced deposition of new bone tissue, reduced fibrosis and significantly improved callus vascularization.

Within the BUSTER trial, we analyzed the surgeon’s amount of experience and other parameters associated with URS procedures regarding the stone-free rate, complication rate, and operative time. Patient characteristics and surgical details on 307 URS procedures were prospectively documented according to a standardized study protocol at 14 German centers 01–04/2015. Surgeon’s experience was correlated to clinical characteristics, and its impact on the stone-free rate, complication rate, and operative time subjected to multivariate analysis. 76 (25%), 66 (21%) and 165 (54%) of 307 URS procedures were carried out by residents, young specialists, and experienced specialists (> 5 years after board certification), respectively. Median stone size was 6 mm, median operative time 35 min. A ureteral stent was placed at the end of 82% of procedures. Stone-free rate and stone-free rate including minimal residual stone fragments (adequate for spontaneous clearance) following URS were 69 and 91%, respectively. No complications were documented during the hospital stays of 89% of patients (Clavien–Dindo grade 0). According to multivariate analysis, experienced specialists achieved a 2.2-fold higher stone-free rate compared to residents (p = 0.038), but used post-URS stenting 2.6-fold more frequently (p = 0.023). Surgeon’s experience had no significant impact on the complication rate. We observed no differences in this study’s main endpoints, namely the stone-free and complication rates, between residents and young specialists, but experienced specialists’ stone-free rate was significantly higher. During this cross-sectional study, 75% of URS procedures were performed by specialists. The experienced specialists’ more than two-fold higher stone-free rate compared to residents’ justifies ongoing efforts to establish structured URS training programs.

SummaryBackgroundDespite the high utilisation of ureterorenoscopy (URS) in interventional stone treatment, there is little evidence of any link between annual hospital volume and outcome.MethodsFrom January to April 2015, data from 307 URS patients were prospectively recorded in the multicentre observational BUSTER-Trial (Benchmarks of ureterorenoscopic stone treatment-results in terms of complications, quality of life, and stone-free rates). The best threshold value for annual hospital volume with an independent effect on the outcome (measured on stone-free and complication rates) of our study group was established with logistic regression.ResultsIn 38.4% of cases of renal and 61.6% of ureteral stones, median stone size was 6 mm with an interquartile range (IQR) of 4–8 mm. The annual URS rate in the 14 participating hospitals ranged from 77 to 333 (median 144; IQR 109–208). The binary endpoint as a combination of completely stone-free or residual fragments small enough to pass spontaneously and a maximum complication severity of Clavien–Dindo grade 1 was attained in 234/252 (92.9%) cases with a hospital volume of ≥ 99 URS compared with 43/55 (78.2%) in < 99 URS (p = 0.002). Adjusted for patient-, stone- and physician-related factors, an annual hospital URS volume of ≥ 99 increases the chance of an optimum outcome (OR = 3.92; 95% CI 1.46–10.51; p = 0.007).ConclusionsAn independent effect of URS hospital volume on outcome quality in the 14 participating hospitals was demonstrated. Threshold values for annual case numbers should be scientifically established irrespective of the considered procedure.

HintergrundDie „Post-Ureteroscopic Lesion Scale“ (PULS) wurde als eine Klassifikation zur Standardisierung der iatrogenen Harnleiterläsionen während der Ureterorenoskopie (URS) vorgestellt. Mit der vorliegenden Studie sollen die praktische Anwendung und der mögliche klinische Nutzen des PULS-Scores an einem repräsentativen Patientenkollektiv überprüft werden.Material und MethodeIm Rahmen der prospektiven BUSTER-Studie (Bewertung der ureterorenoskopischen Steintherapie – Ergebnisse hinsichtlich Komplikationen, Lebensqualität und Steinfreiheitsrate) konnten Daten von 307 Patienten aus 14 deutschen Kliniken aufgezeichnet werden. Für die hier vorgestellte Arbeit wurden drei Studienhypothesen (H) überprüft: Es besteht eine hohe Übereinstimmung der unabhängig zu einander erfolgten PULS-Graduierungen von Operateur und Pflegeassistenzpersonal (H1), es gibt eine positive Korrelation der PULS-Grade mit der postoperativen Komplikationsdichte während des stationären Aufenthalts (H2), es liegt eine signifikante Übereinstimmung des postinterventionellen Harnleiterstentings mit den verursachten PULS-Graden vor (H3).ErgebnisseDas mediane Alter der Studienpatienten lag bei 54,4 („interquartile range“ [IQR] 44,4–65,84) Jahren; 65,5 % der Patienten waren männlichen Geschlechts. Die mediane Steingröße des Indexkonkrements betrug 6 (IQR, 4–8) mm, wobei 117 (38,4 %) und 188 (61,6 %) der Indexkonkremente in der Niere bzw. im Harnleiter lagen. 70 und 82,4 % erhielten ein präoperatives bzw. postoperatives Harnleiterstenting. 68,7 % der Studienpatienten waren nach einer URS komplett steinfrei, die Komplikationsrate betrug 10,8 % (dominant Grad 1 oder 2 nach Clavien-Dindo). Die PULS-Grade 0, 1, 2 und 3 nach Einschätzung des Operateurs lagen bei 40 %, 52,1 %, 6,9 % bzw. 1 %. Es bestand eine hohe Interobserver-Übereinstimmung der erfolgten Pulsgraduierungen zwischen Operateur und Pflegeassistenzpersonal (κ = 0,883, p < 0,001; H1+). Eine signifikante Korrelation zwischen dem PULS-Grad und den aufgezeichneten Komplikationen konnte nicht gefunden werden (ρ = 0,09, p = 0,881; H2−). Es bestand hingegen eine signifikante positive Korrelation zwischen dem PULS-Grad und der postoperativen Einlage eines Harnleiterstents (ρ = 0,287, p < 0,001; H3+), wobei hier beispielsweise ein PULS-Grad 1 (im Vergleich zu PULS-Grad 0) die Wahrscheinlichkeit um den Faktor 3,24 erhöhte (95 %-Konfidenzintervall 1,43–7,34, p = 0,005).SchlussfolgerungDie URS ist in der täglichen Routine ein sicheres und effektives Verfahren zur Behandlung von Konkrementen des oberen Harntrakts. Die vorliegenden „Real-world-Daten“ bestätigen die hohe Interrater-Reliabilität des PULS-Scores und dessen potentiellen Anwendernutzen hinsichtlich der Indikationsstellung zur postoperativen Harnleiterschienung. Auf der Basis des PULS-Scores sollte jetzt eine prospektiv-randomisierte Studie prüfen, inwieweit die Standardisierung einer postoperativen Harnleiterstenteinlage erfolgen kann.

Autochthonous carbon fixation by algae and subsequent deposition of particulate organic matter can have significant effects on redox conditions and elimination of trace organic chemicals (TOrCs) in managed aquifer recharge (MAR). This study investigated the impacts of different algae loadings (0–160 g/m 2 ) and infiltration rates (0.06–0.37 m/d) on overall oxygen consumption and elimination of selected TOrCs (diclofenac, formylaminoantipyrine, gabapentin, and sulfamethoxazole) in adapted laboratory sand columns. An infiltration rate of 0.37 m/d in conjunction with an algae load of 80 g/m 2 (dry weight) sustained oxic conditions in the sand bed and did not affect the degradation of TOrCs. Thus, the availability of easily degradable organic carbon from algae did not influence the removal of TOrCs at an influent concentration of 1 µg/L. In contrast, a lower infiltration rate of 0.20 m/d in combination with a higher algae loading of 160 g/m 2 caused anoxic conditions for 30 days and significantly impeded the degradation of formylaminoantipyrine, gabapentin, sulfamethoxazole, and diclofenac. Especially the elimination of gabapentin did not fully recover within 130 days after pulsed algae deposition. Hence, measures like micro-sieving or nutrient control are required at bank filtration or soil aquifer treatment sites with low infiltration rates.

High nitrate concentrations in wastewater treatment plant effluents and aquifers can challenge sequential biofiltration systems in preventing nitrite and gas formation in the sand bed, as well as to achieve the regulated limit value for nitrate in potable water reuse applications. This study investigates the introduction of electron donors in the form of organic fixed bed materials as an in-situ anoxic zone into sequential biofiltration systems. Laboratory batch and column tests with straw, soft wood, peat, polylactic acid (PLA), and polycaprolacton (PCL) revealed incomplete denitrification with a hydraulic retention time below 10 h, high organic carbon leaching, especially during the first three months, and gas accumulation within the filter bed. Therefore, ex-situ denitrification prior to oxic biofilters or in a defined side-stream treatment is recommended. No enhanced transformation of trace organic chemicals was observed under nitrate reducing conditions. Peat revealed a sorption potential for 5-methyl-benzotriazole, carbamazepine, benzotriazole, and metoprolol.

Bank filtration (BF) and soil aquifer treatment (SAT) are efficient natural technologies in potable water reuse systems. The removal of many organic micro-pollutants (OMPs) depends on redox-conditions in the subsoil, especially on the availability of molecular oxygen. Due to microbial transformation of particulate and dissolved organic constituents, oxygen can be consumed within short flow distances and induce anoxic and anaerobic conditions. The effect of accumulated particulate organic carbon (POC) on the fate of OMPs in BF and SAT systems is not fully understood. Long-term column experiments with natural sediment cores from the bank of Lake Tegel and from a SAT basin were conducted to investigate the impact of accumulated POC on dissolved organic carbon (DOC) release, on oxygen consumption, on mobilization of iron and manganese, and on the elimination of the organic indicator OMPs. The cores were fed with aerated tap water spiked with OMPs to exclude external POC inputs. Complete oxygen consumption within the first infiltration decimeter in lake sediments caused mobilization of iron, manganese, and DOC. Redox-sensitive OMPs like diclofenac, sulfamethoxazole, formylaminoantipyrine, and gabapentin were eliminated by more than 50% in all sediment cores, but slightly higher residual concentrations were measured in effluents from lake sediments, indicating a negative impact of a high oxygen consumption on OMP removal.

Background Although antimicrobial resistance and persistence of resistant bacteria in humans and animals are major health concerns worldwide, the impact of antimicrobial resistance on bacterial intestinal colonization in healthy domestic animals has only been rarely studied. We carried out a retrospective analysis of the antimicrobial susceptibility status and the presence of resistance genes in intestinal commensal E. coli clones from clinically healthy pigs from one production unit with particular focus on effects of pheno- and/or genotypic resistance on different nominal and numerical intestinal colonization parameters. In addition, we compared the occurrence of antimicrobial resistance phenotypes and genotypes with the occurrence of virulence associated genes typical for extraintestinal pathogenic E. coli . Results In general, up to 72.1% of all E. coli clones were resistant to ampicillin, chloramphenicol, kanamycin, streptomycin, sulfamethoxazole or tetracycline with a variety of different resistance genes involved. There was no significant correlation between one of the nominal or numerical colonization parameters and the absence or presence of antimicrobial resistance properties or resistance genes. However, there were several statistically significant associations between the occurrence of single resistance genes and single virulence associated genes. Conclusion The demonstrated resistance to the tested antibiotics might not play a dominant role for an intestinal colonization success in pigs in the absence of antimicrobial drugs, or cross-selection of other colonization factors e.g. virulence associated genes might compensate \"the cost of antibiotic resistance\". Nevertheless, resistant strains are not outcompeted by susceptible bacteria in the porcine intestine. Trial Registration The study was approved by the local animal welfare committee of the \"Landesamt für Arbeitsschutz, Gesundheitsschutz und technische Sicherheit\" Berlin, Germany (No. G0037/02).