Molecular Landscape of Pelvic Organ Prolapse Provides Insights into Disease Etiology.

Pelvic organ prolapse (POP) represents a major health care burden in women, but its underlying pathophysiological mechanisms have not been elucidated. We first used a case-control design to perform an exome chip study in 526 women with POP and 960 control women to identify single nucleotide variants (SNVs) associated with the disease. We then integrated the functional interactions between the POP candidate proteins derived from the exome chip study and other POP candidate molecules into a molecular landscape. We found significant associations between POP and SNVs in 54 genes. The proteins encoded by 26 of these genes fit into the molecular landscape, together with 43 other POP candidate molecules. The POP landscape is located in and around epithelial cells and fibroblasts of the urogenital tract and harbors four interacting biological processes-epithelial-mesenchymal transition, immune response, modulation of the extracellular matrix, and fibroblast function-that are regulated by sex hormones and TGFB1. Our findings were corroborated by enrichment analyses of differential gene expression data from an independent POP cohort. Lastly, based on the landscape and using vaginal fibroblasts from women with POP, we predicted and showed that metformin alters gene expression in these fibroblasts in a beneficial direction. In conclusion, our integrated molecular landscape of POP provides insights into the biological processes underlying the disease and clues towards novel treatments.

Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies.

Stress urinary incontinence (SUI) is a common and burdensome condition. Because of the large knowledge gap around the molecular processes involved in its pathophysiology, the aim of this review was to provide a systematic overview of genetic variants, gene and protein expression changes related to SUI in human and animal studies. On 5 January 2021, a systematic search was performed in Pubmed, Embase, Web of Science, and the Cochrane library. The screening process and quality assessment were performed in duplicate, using predefined inclusion criteria and different quality assessment tools for human and animal studies respectively. The extracted data were grouped in themes per outcome measure, according to their functions in cellular processes, and synthesized in a narrative review. Finally, 107 studies were included, of which 35 used animal models (rats and mice). Resulting from the most examined processes, the evidence suggests that SUI is associated with altered extracellular matrix metabolism, estrogen receptors, oxidative stress, apoptosis, inflammation, neurodegenerative processes, and muscle cell differentiation and contractility. Due to heterogeneity in the studies (e.g., in examined tissues), the precise contribution of the associated genes and proteins in relation to SUI pathophysiology remained unclear. Future research should focus on possible contributors to these alterations.

Bone conducted vibration is an effective stimulus for otolith testing in cochlear implant patients.

BACKGROUND: Treatment with a cochlear implant (CI) poses the risk of inducing a behaviorally unmeasurable air-bone gap leading to false negative absence of cervical and ocular vestibular evoked myogenic potentials (cVEMPs, oVEMPs) to air conducted sound (ACS). OBJECTIVE: To investigate VEMP response rates to ACS and bone conducted vibration (BCV) in CI patients and the applicability of the B81 transducer for BCV stimulation. METHODS: Prospective experimental study including unilateral CI patients, measuring cVEMPs and oVEMPs to ACS and to BCV, comparing response rates, signed asymmetry ratios, latencies, and amplitudes. RESULTS: Data of 13 CI patients (mean age 44±12 years) were analyzed. For the CI side, oVEMP and cVEMP response rates were significantly higher for BCV (77%cVEMP, 62%oVEMP) compared to ACS (23%cVEMP, 8%oVEMP). For the contralateral side, no difference between response rates to ACS (85%cVEMP, 69%oVEMP) and BCV (85%cVEMP, 77%oVEMP) was observed. Substantially higher asymmetries were observed for ACS (-88±23%for cVEMPs, -96±11%for oVEMPs) compared to BCV (-12±45%for cVEMPs, 4±74%for oVEMPs). CONCLUSIONS: BCV is an effective stimulus for VEMP testing in CI patients. The B81 is a feasible stimulator.

A hydrothermal apparatus for x-ray absorption spectroscopy of hydrothermal fluids at DESY.

We present a new autoclave that enables in situ characterization of hydrothermal fluids at high pressures and high temperatures at synchrotron x-ray radiation sources. The autoclave has been specifically designed to enable x-ray absorption spectroscopy in fluids with applications to mineral solubility and element speciation analysis in hydrothermal fluids in complex compositions. However, other applications, such as Raman spectroscopy, in high-pressure fluids are also possible with the autoclave. First experiments were run at pressures between 100 and 600 bars and at temperatures between 25 °C and 550 °C, and preliminary results on scheelite dissolution in fluids of different compositions show that the autoclave is well suited to study the behavior of ore-forming metals at P-T conditions relevant to the Earth's crust.

Genome-Wide Association Study Identifies Two Novel Loci Associated with Female Stress and Urgency Urinary Incontinence.

PURPOSE: Genome-wide association studies have not identified replicable genetic risk loci for stress or urgency urinary incontinence. MATERIALS AND METHODS: We carried out a discovery stage, case control, genome-wide association study in 3 independent discovery cohorts of European women (8,979) for stress incontinence, urgency incontinence, and any incontinence phenotypes. We conducted replication in 6 additional studies of European ancestry (4,069). We collected bladder biopsies from women with incontinence (50) to further investigate bladder expression of implicated genes and pathways and used symptom questionnaires for phenotyping. We conducted meta-analyses using inverse variance fixed effects models and whole transcriptome analyses using Affymetrix® arrays with replication with TaqMan® polymerase chain reaction. RESULTS: In the discovery stage, we identified 16 single nucleotide polymorphisms genotyped or imputed at 5 loci that reached genome-wide significance (p <5×10-8). In replication, rs138724718 on chromosome 2 near the macrophage receptor with collagenous structure (MARCO) gene (replication p=0.003) was associated with stress incontinence. In addition, rs34998271 on chromosome 6 near the endothelin 1 (EDN1) gene (replication p=0.0008) was associated with urgency incontinence. In combined meta-analyses of discovery and replication cohorts, associations with genome-wide significance for these 2 single nucleotide polymorphisms were confirmed. Transcriptomics analyses showed differential expression of 7 of 19 genes in the endothelin pathway between stress and urgency incontinence (p <0.0001). CONCLUSIONS: We uncovered 2 new risk loci near the genes endothelin 1 (EDN1), associated with urgency incontinence, and macrophage receptor with collagenous structure (MARCO), associated with stress incontinence. These loci are biologically plausible given their roles in smooth muscle contraction and innate host defense, respectively.

Genetic variants and expression changes in urgency urinary incontinence: A systematic review.

AIM: To perform a systematic review summarizing the knowledge of genetic variants, gene, and protein expression changes in humans and animals associated with urgency urinary incontinence (UUI) and to provide an overview of the known molecular mechanisms related to UUI. METHODS: A systematic search was performed on March 2, 2020, in PubMed, Embase, Web of Science, and the Cochrane library. Retrieved studies were screened for eligibility. The risk of bias was assessed using the ROBINS-I (human) and SYRCLE (animal) tool. Data were presented in a structured manner and in the case of greater than five studies on a homogeneous outcome, a meta-analysis was performed. RESULTS: Altogether, a total of 10,785 records were screened of which 37 studies met the inclusion criteria. Notably, 24/37 studies scored medium-high to high on risk of bias, affecting the value of the included studies. The analysis of 70 unique genes and proteins and three genome-wide association studies showed that specific signal transduction pathways and inflammation are associated with UUI. A meta-analysis on the predictive value of urinary nerve growth factor (NGF) levels showed that increased urinary NGF levels correlate with UUI. CONCLUSION: The collective evidence showed the involvement of two molecular mechanisms (signal transduction and inflammation) and NGF in UUI, enhancing our understanding of the pathophysiology of UUI. Unfortunately, the risk of bias was medium-high to high for most studies and the value of many observations remains unclear. Future studies should focus on elucidating how deficits in the two identified molecular mechanisms contribute to UUI and should avoid bias.

[Early optimization of antibiotic therapy through rapid detection of pathogens and sensitivity : Health economic aspects]. / Frühe Optimierung der Antibiotikatherapie durch den schnellen Nachweis von Erregern und Empfindlichkeit : Gesundheitsökonomische Aspekte.

INTRODUCTION: Severe infections require early optimization of antibiotic therapy. Since 2016, antibiotic susceptibility results with minimum inhibitory concentrations (MIC) direct from positive blood cultures are available in less than 8 h using a new diagnostic system. The aim of this study is to investigate the economic effects of a rapid availability of antibiotic susceptibility in Germany and to validate these theoretical results in a German hospital. MATERIALS AND METHODS: In the context of a literature search, the clinical and economic benefit of an adequate therapy as well as the rate of the initially inadequate antibiotic therapy (IIAT) were determined for sepsis and bloodstream infections. In addition to the weighted average of the pooled studies, the case numbers in Germany (data year 2015) of all DRGs for sepsis patients with coded pathogen and ICU stay were integrated into a theoretical economic model that was subsequently validated in a German hospital. RESULTS: The analysis of 14 studies with a total of 6408 patients showed an average weighted rate of 27.3% IIAT. From a total of 8 studies (n = 2988), an average weighted length of stay (LOS) saving of 4.7 days was determined with adequate initial therapy compared to an IIAT. In the theoretical model, an average of €â€¯1539 per case could be saved with a possible LOS reduction of 3.7 days. A conservative scenario with an IIAT of 20% and LOS reduction of 2.5 days still resulted in an average saving of € 201 per case. In the hospital-individual model, 68% of 146 cases had a positive blood culture. In 61% of the examined cases an adjustment of the therapy would have been necessary (35% IIAT, 26% de-escalation). After deducting the cost of the test for 60 patients, the total potential savings amounted to €â€¯122,112, which is over 2000 € per patient. CONCLUSION: A fast adequate antibiotic therapy was economically advantageous both in the economic model and in the real-life evaluation. The optimization of antibiotic therapy by early pathogen detection and MIC-based susceptibilities represents a possibility to achieve savings despite the high costs for diagnostics in the clinic. Particularly noteworthy is the optimization through de-escalation. The potential for each hospital should be identified through systematic case studies.

Coronary anatomy in Turner syndrome versus patients with isolated bicuspid aortic valves.

OBJECTIVE: Variations in coronary anatomy, like absent left main stem and left dominant coronary system, have been described in patients with Turner syndrome (TS) and in patients with bicuspid aortic valves (BAV). It is unknown whether coronary variations in TS are related to BAV and to specific BAV subtypes. AIM: To compare coronary anatomy in patients with TS with/without BAV versus isolated BAV and to study BAV morphology subtypes in these groups. METHODS: Coronary anatomy and BAV morphology were studied in 86 patients with TS (20 TS-BAV, 66 TS-tricuspid aortic valve) and 86 patients with isolated BAV (37±13 years vs 42±15 years, respectively) by CT. RESULTS: There was no significant difference in coronary dominance between patients with TS with and without BAV (25% vs 21%, p=0.933). BAVs with fusion of right and left coronary leaflets (RL BAV) without raphe showed a high prevalence of left coronary dominance in both TS-BAV and isolated BAV (both 38%). Absent left main stem was more often seen in TS-BAV as compared with isolated BAV (10% vs 0%). All patients with TS-BAV with absent left main stem had RL BAV without raphe. CONCLUSION: The equal distribution of left dominance in RL BAV without raphe in TS-BAV and isolated BAV suggests that presence of left dominance is a feature of BAVs without raphe, independent of TS. Both TS and RL BAV without raphe seem independently associated with absent left main stems. Awareness of the higher incidence of particularly absent left main stems is important to avoid complications during hypothermic perfusion.

Coding of coronary arterial origin and branching in congenital heart disease: The modified Leiden Convention.

OBJECTIVES: Variations in coronary anatomy are common and may relate to the position of the coronary ostium relative to the aortic sinus, the angle of coronary take-off, or the course of the coronary arterial branches. Several classification systems have been proposed. However, they all lack a simple rationale that is applicable irrespective of the relative position of the great arteries, as well as in bicuspid aortic valves. We present a modification of a relatively simple system introduced in the early 1980s, designated the "Leiden Convention." METHODS: The first step of the Leiden Convention is that the clinician takes position in the nonfacing sinus of the aorta looking toward the pulmonary orifice. The right-hand facing sinus is sinus 1, and the left-hand facing sinus is sinus 2. The coronary branches arising from sinus 1 are annotated proceeding in a counterclockwise fashion toward sinus 2. "Usual" (normal) coronary anatomy would be 1R-2LCx. Given their clinical relevance, single sinus coronary arteries are discussed separately. RESULTS: This system was originally designed and highly applicable in hearts with an altered great artery relationship, such as in the variable and complicated patterns seen in transposition of the great arteries and double outlet right ventricle. The modified system also can be used in cases with normally related great arteries, cases with single sinus coronary arteries, and cases with bicuspid aortic valves. CONCLUSIONS: The modified Leiden Convention is not a strict classification but a simple coronary coding system that is broadly applicable.

Physical and ecological effects of rehabilitating the geothermally influenced Waikite Wetland, New Zealand.

Pressure to optimise land use and to maximise the economic viability of land has had a detrimental impact on wetlands worldwide. Rehabilitating wetlands has been identified by resource managers as increasingly important to enhance environmental values and restore ecosystem functions that may have been lost through developments effecting wetlands. This paper investigates rehabilitating a geothermally influenced wetland that had been drained and used for grazing stock. The Waikite Wetland (New Zealand) is a relatively unique wetland because the primary water source to the wetland has a significant geothermal water component. This results in the area hosting populations of rare flora and fauna that are significant to New Zealand. A range of management actions that included diverting a geothermal stream back into the wetland, blocking drains, pest control, weed control, native plantings, fencing and building a weir to increase water levels were used to rehabilitate the wetland. This was done to promote thermotolerant vegetation growth, restore wetland water levels and minimise pest plant species re-establishing while minimising the effects on geothermal surface features and allowing indigenous wetland vegetation to re-establish. Physical, chemical and vegetation monitoring show that management actions have increased thermotolerant vegetation growth in the wetland while having a small potential impact on geothermal discharges into the wetland. Increasing the water level in the wetland appears to be helping control plant pest species close to the weir, but has also made sensitive vegetation growing close to the waterways more susceptible to flooding caused by high-intensity rainfall events.

Does vaginal breech delivery have a future despite low volumes for training? Results of a questionnaire.

OBJECTIVE: Since publication of the Term Breech Trial in 2000 only 15% of term breech presentations is delivered vaginally in the Netherlands. This declined exposure to vaginal breech deliveries (VBD) is a problem for those who still need to be trained. The aim of this study was to evaluate the level of training of the Dutch gynecological residents, and their intentions on guiding VBDs during their careers. STUDY DESIGN: Via an online questionnaire Dutch residents and starting gynecologists, were asked about their training, exposure and confidence in guiding VBDs during their residency. MAIN OUTCOME MEASURES: Number of VBDs performed, level of entrustment of independent practice in guiding VBDs, courses in guiding VBDs, confidence in guiding VBDs after finishing their residency. RESULTS: The response rate was 64% (N = 294). Thirteen per cent performed less than three VBDs, 15% more than 15. Of sixth year residents 65% has not yet obtained entrustment for personally guiding VBDs. The residents are trained in VBDs at least once during a national mandatory course. Further training is strongly dependent on local hospital policy: 34% are trained every quarter versus 29% who never receive a local training. CONCLUSION: Our survey showed that more than half of the respondents judge the current residency program to be insufficient for guiding VBDs. This seems to be related to the low overall exposure to VBDs and the lack of quantity and quality of attended courses.

Pulmonary Valve Morphology in Patients with Bicuspid Aortic Valves.

The aortic and pulmonary valve share a common developmental origin from the embryonic arterial trunk. Bicuspid aortic valve is the most common congenital anomaly and can occur isolated as well as in association with other congenital heart disease (CHD). Data on pulmonary valve morphology in these cases are scarce. In this study, we aimed to determine pulmonary valve morphology in hearts with BAV associated with CHD. In 83 post-mortem heart specimens with BAV and associated CHD, pulmonary valve morphology was studied and related to BAV morphology. In 14/83 (17%) hearts, the pulmonary valve was affected, bicuspid in 8/83 (10%), dome-shaped in 3/83 (4%) and atretic in 3/83 (4%). In specimens with a bicuspid pulmonary valve, 5/8 (63%) had a strictly bicuspid aortic valve (without raphe), 2/3 hearts (67%) with dome-shaped pulmonary valves and 2/3 hearts (67%) with atretic pulmonary valves had BAV without raphe. Six out of eight (75%) specimens with a bicuspid pulmonary valve had a perimembranous ventricular septal defect (VSD). 4/8 (50%) specimens with a bicuspid pulmonary valve were associated with chromosomal abnormalities: 3 (38%) had trisomy 18 and 1 (13%) had trisomy 13. In BAV with associated CHD, abnormal pulmonary valve morphology was observed in 17% of the hearts. The majority of hearts with abnormal pulmonary valve morphology had a Type B bicuspid aortic valve (without raphe). Bilateral semilunar valvular disease is associated with Type B BAVs and in many cases related to chromosomal abnormalities. As this study was performed in post-mortem specimens with high frequency of associated CHD, caution is warranted with application of these results to the general BAV population.

[Procalcitonin as a tool for the assessment of successful therapy of severe sepsis : An analysis using clinical routine data]. / Procalcitonin als Instrument zur Erfolgsmessung der Therapie einer schweren Sepsis : Eine Untersuchung mit klinischen Routinedaten.

INTRODUCTION: Procalcitonin (PCT) is a well-evaluated biomarker for the detection of severe bacterial infections and monitoring effectiveness of antibiotic therapy. This study aims to evaluate the usefulness of PCT in a clinical routine setting. MATERIALS AND METHODS: Of 358,763 clinical cases from 7 German hospitals in 2012 and 2013, 3854 cases had an ICD-10 code representing sepsis. A total of 1778 cases had pathologic PCT and one episode of infection. Of those, 671 showed a series of measures that was suitable to assess treatment success using PCT reduction. Propensity score matching was used to create two comparable groups with 211 patients in each group. RESULTS: The group with PCT reduction within 12 days showed a highly significant better proportion of survival (146/211 vs. 17/211; p < 0.0001). The odds ratio for death according to PCT reduction vs. nonreduction is 25.64 (p < 0.0001; 95 % CI: 14.49-45.45). PCT was normalized after an average of 6.2 days. DISCUSSION: The difference in survival implicates that PCT reduction is a suitable surrogate parameter to indicate successful antimicrobial therapy. Successful antibiotic therapy is a proven predictor for survival in sepsis. This study also showed concordant results in the group of patients with sepsis after abdominal surgery. Results from subgroup analyses confirm the initial findings. PCT reduction was used as surrogate for therapy success, as the antimicrobial therapy was not electronically available. CONCLUSION: PCT reduction is a strong predictor for survival. However, the data show that overall use of PCT to monitor sepsis therapy is not yet routinely established. Hospitals should establish algorithms for sepsis treatment that include PCT for the assessment of adequacy and the monitoring of success of the antimicrobial therapy.

Coronary anatomy in children with bicuspid aortic valves and associated congenital heart disease.

OBJECTIVE: In patients with bicuspid aortic valve (BAV), coronary anatomy is variable. High take-off coronary arteries have been described, but data are scarce, especially when associated with complex congenital heart disease (CHD). The purpose of this study was to describe coronary patterns in these patients. METHODS: In 84 postmortem heart specimens with BAV and associated CHD, position and height of the coronary ostia were studied and related to BAV morphology. RESULTS: High take-off right (RCA) and left coronary arteries (LCA) were observed in 23% and 37% of hearts, respectively, most frequently in hearts with hypoplastic left ventricle (HLV) and outflow tract anomalies. In HLV, high take-off was observed in 18/40 (45%) more frequently of LCA (n=14) than RCA (n=6). In hearts with aortic hypoplasia, 8/13 (62%) had high take-off LCA and 6/13 (46%) high take-off RCA. High take-off was seen 19 times in 22 specimens with perimembranous ventricular septal defect (RCA 8, LCA 11). High take-off was associated with type 1A BAV (raphe between right and left coronary leaflets), more outspoken for the RCA. Separate ostia of left anterior descending coronary artery and left circumflex coronary artery were seen in four hearts (5%), not related to specific BAV morphology. CONCLUSION: High take-off coronary arteries, especially the LCA, occur more frequently in BAV with associated CHD than reported in normal hearts and isolated BAV. Outflow tract defects and HLV are associated with type 1A BAV and high take-off coronary arteries. Although it is unclear whether these findings in infants with detrimental outcome can be related to surviving adults, clinical awareness of variations in coronary anatomy is warranted.

Exploration of the phase diagram of liquid water in the low-temperature metastable region using synthetic fluid inclusions.

We present new experimental data of the low-temperature metastable region of liquid water derived from high-density synthetic fluid inclusions (996-916 kg m-3) in quartz. Microthermometric measurements include: (i) prograde (upon heating) and retrograde (upon cooling) liquid-vapour homogenisation. We used single ultrashort laser pulses to stimulate vapour bubble nucleation in initially monophase liquid inclusions. Water densities were calculated based on prograde homogenisation temperatures using the IAPWS-95 formulation. We found retrograde liquid-vapour homogenisation temperatures in excellent agreement with IAPWS-95. (ii) Retrograde ice nucleation. Raman spectroscopy was used to determine the nucleation of ice in the absence of the vapour bubble. Our ice nucleation data in the doubly metastable region are inconsistent with the low-temperature trend of the spinodal predicted by IAPWS-95, as liquid water with a density of 921 kg m-3 remains in a homogeneous state during cooling down to a temperature of -30.5 °C, where it is transformed into ice whose density corresponds to zero pressure. (iii) Ice melting. Ice melting temperatures of up to 6.8 °C were measured in the absence of the vapour bubble, i.e. in the negative pressure region. (iv) Spontaneous retrograde and, for the first time, prograde vapour bubble nucleation. Prograde bubble nucleation occurred upon heating at temperatures above ice melting. The occurrence of prograde and retrograde vapour bubble nucleation in the same inclusions indicates a maximum of the bubble nucleation curve in the ϱ-T plane at around 40 °C. The new experimental data represent valuable benchmarks to evaluate and further improve theoretical models describing the p-V-T properties of metastable water in the low-temperature region.

[Endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) in neoplastic Barrett's esophagus or Barrett early cancer is also economically superior to sole radical endoscopic resection]. / Endoskopische Mukosaresektion (EMR) mit nachfolgender Radiofrequenzablation (RFA) bei neoplastischem Barrett-Ösophagus bzw. Barrett-Frühkarzinom ist der alleinigen radikalen endoskopischen Resektion auch ökonomisch überlegen.

INTRODUCTION: Neoplastic changes (mild or high grade intraepithelial neoplasia (L- or HGIEN) or early cancer) in Barrett esophagus are treated with various methods. This study compares clinical-economical aspects of sole stepwise radical endoscopic resection (SRER) against combination treatment with EMR (Endoscopic mucosal resection) and RFA (radiofrequency ablation). MATERIAL AND METHODS: Based on clinical data from a randomized controlled trial 1 we developed an economic model for costs of treatment according to the German Hospital Remuneration System (G-DRG). Our calculating incorporated initial treatment costs and the cost of treating complications (both paid via G-DRG). RESULTS: Medical and economically, the treatment with EMR + RFA advantages over sole SRER treatment 1. The successful complete resection or destruction of neoplastic intestinal metaplastic tissue is similar in both procedures. Acute complications (24 vs. 13 % in SRER EMR + RFA) and late complications (88 vs. 13 % in SRER EMR + RFA) are significantly more likely in sole SRER than in the EMR + RFA. DISCUSSION: While SRER initially appears more cost-effective as a sole therapy, cost levels move significantly above EMR+RFA due to higher complication rates and following procedures costs. Overall, the costs of treatment was €â€Š13 272.11 in the SRER group and €â€Š11 389.33 in the EMR + RFA group. The EMR + RFA group thus achieved a cost advantage of €â€Š1882.78. The study shows that the treatment of neoplastic Barrett esophagus with EMR + RFA is also appropriate in economic terms.

Coronary anatomy as related to bicuspid aortic valve morphology.

OBJECTIVE: Variable coronary anatomy has been described in patients with bicuspid aortic valves (BAVs). This was never specified to BAV morphology, and prognostic relevance of coronary vessel dominance in this patient group is unclear. The purpose of this study was to evaluate valve morphology in relation to coronary artery anatomy and outcome in patients with isolated BAV and with associated aortic coarctation (CoA). METHODS: Coronary anatomy was evaluated in 186 patients with BAV (141 men (79%), 51±14 years) by CT and invasive coronary angiography. Correlation of coronary anatomy was made with BAV morphology and coronary events. RESULTS: Strictly bicuspid valves (without raphe) with left-right cusp fusion (type 1B) had more left dominant coronary systems compared with BAVs with left-right cusp fusion with a raphe (type 1A) (48% vs. 26%, p=0.047) and showed more separate ostia (28% vs. 9%, p=0.016). Type 1B BAVs had more coronary artery disease than patients with type 1A BAV (36% vs. 19%, p=0.047). More left dominance was seen in BAV patients with CoA than in patients without (65% vs. 24%, p<0.05). CONCLUSIONS: The incidence of a left dominant coronary artery system and separate ostia was significantly related to BAVs with left-right fusion without a raphe (type 1B). These patients more often had significant coronary artery disease. In patients with BAV and CoA, left dominancy is more common.

A rabbit humerus model of plating and nailing osteosynthesis with and without Staphylococcus aureus osteomyelitis.

The local mechanical environment at a fracture is known to influence biological factors such as callus formation, immune cell recruitment and susceptibility to infection. Infection models incorporating a fracture are therefore required to evaluate prevention and treatment of infection after osteosynthesis. The aim of this study was to create humane, standardised and repeatable preclinical models of implant-related bone infection after osteosynthesis in the rabbit humerus. Custom-designed interlocked intramedullary nails and commercially available locking plates were subjected to biomechanical evaluation in cadaveric rabbit humeri; a 10-week in vivo healing study; a dose response study with Staphylococcus aureus over 4 weeks; and finally, a long-term infection of 10 weeks in the plate model.Outcome measures included biomechanical testing, radiography, histology, haematology and quantitative bacteriology. Both implants offered similar biomechanical stability in cadaveric bones, and when applied in the in vivo study, resulted in complete radiographic and histological healing and osteotomy closure within 10-weeks. As expected in the infection study, higher bacterial doses led to an increasing infection rate. In both infected groups, there was a complete lack of osteotomy closure at 4 weeks. C-reactive protein (CRP), lymphocyte: granulocyte ratio and weight loss were increased in infected animals receiving IM nails in comparison with non-inoculated equivalents, although this was less evident in the plate group. In the 10-week infection group, healing does not occur in the plated rabbits. We have successfully developed a rabbit model that is suitable for further studies, particularly those looking into preventative strategies for post-traumatic implant-related osteomyelitis.

[Economic burden of Clostridium difficile enterocolitis in German hospitals based on routine DRG data]. / Ökonomische Auswirkungen einer Clostridium-difficile-Enterokolitis in deutschen Krankenhäusern auf der Basis von DRG-Kostendaten.

BACKGROUND: Clostridium difficile associated diarrhea (CDAD) is not only a increasing medical but also economical problem. METHODS: Data from the DRG project group of the German society for digestive and metabolic diseases (DGVS) were analyzed for CDAD. Out of 430,875 cases from 37 German hospitals 2,767 cases were grouped by having CDAD either as primary (PD) or secondary diagnosis (SD; likely to be from a hospital source) in an initial or recurring hospital stay (RD). For comparison non-CDAD cases from the same hospitals from that year where matched using propensity score matching. As endpoints we defined LOS (length of stay), difference of LOS to national average LOS, total costs per case and difference between costs and revenue for all three groups. RESULTS: Patients from the PD group (n = 817) showed a mean LOS of 11.2 days compared to 8.5 days for the control group, 4,132 € mean cost per case (536 € more than control) and a mean loss of -1,064 € per case compared to -636 €. In the SD group (n = 1,840) patients stayed in the hospital for 28.8 days (control: 18.1 days), had costs of 19,381 € (control: 13,082 €) and a loss of -3,442 € compared to -849 € in the control group. Recurring cases (RD; n = 110) showed a LOS of 37.3 days (control: 21.3 days), had even higher costs (20.755 € vs. 13,101 €) and higher losses (-4,196 € vs. -1,109 €). CONCLUSION: By extrapolating these findings CDAD not only harms patients but generates a yearly cost burden of 464 million € for the German healthcare system including a loss of 197 million € for German hospitals. To the authors' opinion sufficient measures against CDAD should include pre hospital risk reduction programs, introduction of effective therapeutic and hygienic strategies in hospitals as well as improvements in documentation for these cases to support further developments of the German DRG system.