Associations of carotid intima media thickness with gene expression in whole blood and genetically predicted gene expression across 48 tissues.

Carotid intima media thickness (cIMT) is a biomarker of subclinical atherosclerosis and a predictor of future cardiovascular events. Identifying associations between gene expression levels and cIMT may provide insight to atherosclerosis etiology. Here, we use two approaches to identify associations between mRNA levels and cIMT: differential gene expression analysis in whole blood and S-PrediXcan. We used microarrays to measure genome-wide whole blood mRNA levels of 5647 European individuals from four studies. We examined the association of mRNA levels with cIMT adjusted for various potential confounders. Significant associations were tested for replication in three studies totaling 3943 participants. Next, we applied S-PrediXcan to summary statistics from a cIMT genome-wide association study (GWAS) of 71 128 individuals to estimate the association between genetically determined mRNA levels and cIMT and replicated these analyses using S-PrediXcan on an independent GWAS on cIMT that included 22 179 individuals from the UK Biobank. mRNA levels of TNFAIP3, CEBPD and METRNL were inversely associated with cIMT, but these associations were not significant in the replication analysis. S-PrediXcan identified associations between cIMT and genetically determined mRNA levels for 36 genes, of which six were significant in the replication analysis, including TLN2, which had not been previously reported for cIMT. There was weak correlation between our results using differential gene expression analysis and S-PrediXcan. Differential expression analysis and S-PrediXcan represent complementary approaches for the discovery of associations between phenotypes and gene expression. Using these approaches, we prioritize TNFAIP3, CEBPD, METRNL and TLN2 as new candidate genes whose differential expression might modulate cIMT.

Upcycling of recycled minerals from sewage sludge through black soldier fly larvae (Hermetia illucens): Impact on growth and mineral accumulation.

Phosphorous (P) resources are finite. Sewage sludge recyclates (SSR) are not only of interest as plant fertilizer but also as potential source of minerals in animal nutrition. However, besides P and calcium (Ca), SSR contain heavy metals. Under EU legislation, the use of SSR derivatives in animal feed is not permitted, but given the need to improve nutrient recycling, it could be an environmentally sound future mineral source. Black soldier fly larvae (BSFL) convert low-grade biomass into valuable proteins and lipids, and accumulate minerals in their body. It was hypothesized that BSFL modify and increase their mineral content in response to feeding on SSR containing substrates. The objective was to evaluate the upcycling of minerals from SSR into agri-food nutrient cycles through BSFL. Growth, nutrient and mineral composition were compared in BSFL reared either on a modified Gainesville fly diet (FD) or on FD supplemented with either 4% of biochar (FD + BCH) or 3.6% of single-superphosphate (FD + SSP) recyclate (n = 6 BSFL rearing units/group). Larval mass, mineral and nutrient concentrations and yields were determined, and the bioaccumulation factor (BAF) was calculated. The FD + SSP substrate decreased specific growth rate and crude fat of BSFL (P < 0.05) compared to FD. The FD + SSP larvae had higher Ca and P contents and yields but the BAF for Ca was lowest. The FD + BCH larvae increased Ca, iron, cadmium and lead contents compared to FD. Larvae produced on FD + SSP showed lower lead and higher arsenic concentration than on FD + BCH. Frass of FD + BCH had higher heavy metal concentration than FD + SSP and FD (P < 0.05). Except for cadmium and manganese, the larval heavy metal concentration was below the legally permitted upper concentrations for feed. In conclusion, the SSR used could enrich BSFL with Ca and P but at the expense of growth. Due to the accumulation of Cd and Mn, BSFL or products thereof can only be a component of farmed animal feed whereas in BSFL frass heavy metal concentrations remained below the upper limit authorized by EU.

Effects of increasing dietary rye levels on physicochemical characteristics of digesta and its impact on stomach emptying as well as the formation of 'doughballs' in stomachs of young pigs.

Despite quite similar contents of starch and crude fibre of wheat and rye, the unique non-starch-polysaccharide fraction of rye (e.g. high levels of arabinoxylans and fructans) might have an impact on physicochemical properties of the digesta in pigs. Forty pigs (age: 46.8 ± 5.28 days; bodyweight: 16.1 ± 4.13 kg) were divided into four treatment groups. During four weeks, the pigs received diets consisting of wheat and/or rye, barley, soy, potato protein and a mineral supplement. The sum of wheat and rye was 69% in all diets, whereby the compound feed of each group was characterized by a different ratio (%) of wheat/rye (69/0; 46/23; 23/46; 0/69, respectively). In the stomach, 'doughballs' occurred more frequently with increasing dietary rye levels (9/10; 69% rye). With higher DM content and extract-viscosity of gastric digesta, the stomach emptying tended to be retarded in rye groups. Compared to the control group (69% wheat), maximum dietary rye levels (69%) resulted in significantly higher concentrations of lactic acid in digesta of the stomach and small intestine. With increasing lactic acid concentrations, the pH tended to be lower in small intestinal digesta. With an intensified formation of lactic acid, effects against Gram-negative bacteria, for example Salmonella, can be expected. Moreover, because of higher viscosity and the retarded stomach emptying, there could be advantages of including rye in compound feeds when a longer lasting satiety is intended, for example when feeding pregnant sows (regularly fed restrictively).

Effects of excessive or restricted phosphorus and calcium intake during early life on markers of bone architecture and composition in pigs.

Sufficient supply of pigs with calcium (Ca) and phosphorus (P) is essential for animal health and welfare during the growth period. However, the P content in animal manure is considered as a cause of massive environmental problems in soil and aquatic ecosystems. To complement previous findings, the objective of this study is the investigation of effects of a reduced and increased Ca and P supplementation on bone mineralization and bone structure compared with the current dietary recommendation. Another aim is to find possible serum markers that would allow the assessment of adequacy of P supply for bone health during growth. The result validated that the recommended Ca and P supply is sufficient, without the addition of microbial phytases. However, addition of P has no further beneficial effects on bone stability, while P supplementation below the recommended level affects bone development and growth performance. Reduced P levels have consequences for cancellous bone density and trabecular architecture. Further fine-tuning of the P supply in conjunction with an appropriate Ca supply will contribute to a reduction in P waste and associated environmental impact while maintaining animal health and welfare.

Reduced phosphorus intake throughout gestation and lactation of sows is mitigated by transcriptional adaptations in kidney and intestine.

BACKGROUND: The environmental impact of pig farming need to be reduced, with phosphorus (P) being of particular interest. Specified dietary regimens and management systems contribute to meet environmental concerns and reduce economic constrains. However, pregnant and lactating sows represent vulnerable individuals, whose reproductive potential and metabolic health status relies on adequate supply of macro- and micronutrients. The aim of this study was to investigate, whether sows fed with a dietary P content that is below or above current recommendations are capable to maintain mineral homeostasis during the reproduction cycle and which endogenous mechanisms are retrieved therefore in kidney and jejunum. Nulliparous gilts were fed iso-energetic diets with recommended (M), reduced (L), or high (H) amounts of mineral P supplements throughout gestation and lactation periods. Blood metabolites and hormones referring to the P homeostasis were retrieved prior to term (110 days of gestation) and at weaning (28 days of lactation). Transcriptional responses in kidney cortex and jejunal mucosa were analyzed using RNA sequencing. RESULTS: The variable dietary P content neither led to an aberration on fertility traits such as total weaned piglets nor to an effect on the weight pattern throughout gestation and lactation. Serum parameters revealed a maintained P homeostasis as reflected by unaltered inorganic P and calcium levels in L and H fed groups. The serum calcitriol levels were increased in lactating L sows. The endocrine responses to the dietary challenge were reflected at the transcriptional level. L diets led to an increase in CYP27B1 expression in the kidney compared to the H group and to an altered gene expression associated with lipid metabolism in the kidney and immune response in the jejunum. CONCLUSIONS: Our results suggest that current P requirements for gestating and lactating sows are sufficient and over supplementation of mineral P is not required. Shifts in renal and jejunal expression patterns between L and H groups indicate an affected intermediate metabolism, which long-term relevance needs to be further clarified.

DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis.

Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry-specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10-5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.

Effects of 2 colostrum and subsequent milk replacer feeding intensities on methane production, rumen development, and performance in young calves.

A growing need exists for the development of practical feeding strategies to mitigate methane (CH4) emissions from cattle. Therefore, the objective of this study was to evaluate the influence of milk replacer feeding intensity (MFI) in calves on CH4 emission, rumen development, and performance. Twenty-eight female newborn Holstein calves were randomly assigned to 2 feeding groups, offered daily either 10% of the body weight (BW) in colostrum and subsequently 10% of the BW in milk replacer (MR; 10%-MR), or 12% of the BW in colostrum followed by 20% of the BW in MR (20%-MR). In wk 3, half of each feeding group was equipped with a permanent rumen cannula. Both groups were weaned at the end of wk 12. Hay and calf starter (mixture of pelleted grains) were offered from d 1 until wk 14 and 16, respectively. A total mixed ration was offered from wk 11 onward. Feed intake was measured daily and BW, anatomical measures, and rumen size weekly. Methane production and gastrointestinal passage rate were measured pre-weaning in wk 6 and 9 and post-weaning in wk 14 and 22, with additional estimation of organic matter digestibility. Rumen fluid, collected in wk 1, 2, 3, 6, 9, 14, 18, and 22, was analyzed for volatile fatty acid concentrations. Although the experimental period ended in wk 23, rumen volume of 17 calves was determined after slaughter in wk 34. Data was analyzed using ANOVA for the effects of feeding group, cannulation, and time, if applicable. Dry matter intake (DMI) of solid feed (SF) in 20%-MR animals was lower pre-weaning in wk 6 to 10 but mostly higher post-weaning. From wk 6 onward, anatomical measures and BW were greater in 20%-MR animals, and only the differences in body condition score gradually ceased post-weaning. Following the amount of SF intake, 10%-MR calves emitted more CH4 pre-weaning in wk 9, whereas post-weaning the 20%-MR group tended to have higher levels. Methane emission intensity (CH4/BW) was lower pre-weaning in 20%-MR animals but was comparable to the 10%-MR group post-weaning. Methane yield (CH4/DMI of SF) and estimated post-weaning organic matter digestibility were not affected by MFI. Rumen size normalized to heart girth was greater in 10%-MR calves from wk 5 to 10, but differences did not persist thereafter. In wk 34, rumen volume was higher in 20%-MR calves, but normalization to BW revealed no difference between feeding groups. In conclusion, high MFI reduces CH4 emission from calves pre-weaning, although this effect ceases post-weaning.

Tissue-Wide Gene Expression Analysis of Sodium/Phosphate Co-Transporters in Pigs.

Sodium/phosphate co-transporters are considered to be important mediators of phosphorus (P) homeostasis. The expression of specific sodium/phosphate co-transporters is routinely used as an immediate response to dietary interventions in different species. However, a general understanding of their tissue-specificity is required to elucidate their particular contribution to P homeostasis. In this study, the tissue-wide gene expression status of all currently annotated sodium/phosphate co-transporters were investigated in two pig trials focusing on a standard commercial diet (trial 1) or divergent P-containing diets (trial 2). A wide range of tissues including the gastrointestinal tract (stomach, duodenum, jejunum, ileum, caecum, and colon), kidney, liver, bone, muscle, lung, and aorta were analyzed. Both trials showed consistent patterns in the overall tissue-specific expression of P transporters. While SLC34A2 was considered as the most important intestinal P transporter in other species including humans, SLC34A3 appeared to be the most prominent intestinal P transporter in pigs. In addition, the P transporters of the SLC17 family showed basal expression in the pig intestine and might have a contribution to P homeostasis. The expression patterns observed in the distal colon provide evidence that the large intestine may also be relevant for intestinal P absorption. A low dietary P supply induced higher expressions of SLC20A1, SLC20A2, SLC34A1, and SLC34A3 in the kidney cortex. The results suggest that the expression of genes encoding transcellular P transporters is tissue-specific and responsive to dietary P supply, while underlying regulatory mechanisms require further analyses.

Lowered dietary phosphorus affects intestinal and renal gene expression to maintain mineral homeostasis with immunomodulatory implications in weaned piglets.

BACKGROUND: In monogastric animals, phosphorus (P) homeostasis is maintained by regulating intestinal absorption, bone mobilization, and renal excretion. Since P is a non-renewable resource, a shortage is imminent due to widespread over-usage in the farming and animal husbandry industries. As a consequence, P efficiency should be improved in pig production. We sought to characterize the transcriptional response in re-/absorbing and excreting tissues in pigs to diets varying in calcium: phosphorus ratios. Weaned piglets were assigned to one of three groups fed diets varying in digestible P content for a period of five weeks. Gene expression profiles were analyzed in jejunum, colon, and kidney. RESULTS: Transcriptome analysis revealed that reduced dietary P intake affects gene expression in jejunum and kidney, but not in colon. The regulation of mineral homeostasis was reflected via altered mRNA abundances of CYP24A1, CYP27A1, TRPM6, SPP1, and VDR in jejunum and kidney. Moreover, lowered abundances of transcripts associated with the classical complement system pathway were observed in the jejunum. In kidney, shifted transcripts were involved in phospholipase C, calcium signaling, and NFAT signaling, which may have immunomodulatory implications. CONCLUSIONS: Our results revealed local transcriptional consequences of variable P intake in intestinal and renal tissues. The adaptive responses are the result of organismal efforts to maintain systemic mineral homeostasis while modulating immune features at local tissue sites. Therefore, the deviation from the currently recommended dietary P supply must be carefully considered, as the endogenous mechanisms that respond to low P diets may impact important adaptive immune responses.

Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration.

Thioredoxin 2 (TXN2; also known as Trx2) is a small mitochondrial redox protein essential for the control of mitochondrial reactive oxygen species homeostasis, apoptosis regulation and cell viability. Exome sequencing in a 16-year-old adolescent suffering from an infantile-onset neurodegenerative disorder with severe cerebellar atrophy, epilepsy, dystonia, optic atrophy, and peripheral neuropathy, uncovered a homozygous stop mutation in TXN2. Analysis of patient-derived fibroblasts demonstrated absence of TXN2 protein, increased reactive oxygen species levels, impaired oxidative stress defence and oxidative phosphorylation dysfunction. Reconstitution of TXN2 expression restored all these parameters, indicating the causal role of TXN2 mutation in disease development. Supplementation with antioxidants effectively suppressed cellular reactive oxygen species production, improved cell viability and mitigated clinical symptoms during short-term follow-up. In conclusion, our report on a patient with TXN2 deficiency suggests an important role of reactive oxygen species homeostasis for human neuronal maintenance and energy metabolism.

Toward improved phosphorus efficiency in monogastrics-interplay of serum, minerals, bone, and immune system after divergent dietary phosphorus supply in swine.

Phosphorus (P) is of vital importance for many aspects of metabolism, including bone mineralization, blood buffering, and energy utilization. In order to identify molecular routes affecting intrinsic P utilization, we address processes covering P intake, uptake, metabolism, and excretion. In particular, the interrelation of bone tissue and immune features is of interest to approximate P intake to animal's physiology and health status. German Landrace piglets received different levels of digestible phosphorus: recommended, higher, or lower amounts. At multiple time points, relevant serum parameters were analyzed and radiologic studies on bone characteristics were performed. Peripheral blood mononuclear cells were collected to assess differential gene expression. Dietary differences were reflected by serum phosphorus, calcium, parathyroid hormone, and vitamin D. Bone reorganization was persistently affected as shown by microstructural parameters, cathepsin K levels, and transcripts associated with bone formation. Moreover, blood expression patterns revealed a link to immune response, highlighting bidirectional loops comprising bone formation and immune features, where the receptor-activator of NF-κB ligand/receptor-activator of NF-κB kinase system may play a prominent role. The modulated P supplementation provoked considerable organismal plasticity. Genes found to be differentially expressed due to variable P supply are involved in pathways relevant to P utilization and are potential candidate genes for improved P efficiency.

Procalcitonin ratio and on-demand relaparotomy for septic peritonitis: validation of the focus index (FI).

PURPOSE: Secondary peritonitis remains challenging to manage and some recent evidence suggests that on-demand relaparotomy is more appropriate than planned relaparotomy. This study was designed to validate the predictive power of postoperative procalcitonin (PCT) changes in relation to elimination of the septic abdominal focus. METHODS: In this prospective trial, postoperative PCT serum levels were monitored in 234 surgical patients with secondary peritonitis. The PCT ratio on postoperative days (PODs) 1 and 2 (focus index; FI) was calculated and correlated with the success of the operation. RESULTS: A cutoff value of 1.1 was calculated for the FI. Values below 1.1 indicated insufficient elimination of the focus and values above 1.1 correlated with effective treatment. The optimal time for first PCT sampling was found to be 12-24 h after the index operation. After the respective data cleanup, successful elimination of the intraabdominal focus could be confirmed, with a sensitivity of 93 % and a specificity of 71 %. CONCLUSIONS: The FI is a single parameter-based reliable predictor of successful surgical eradication and strengthens the on-demand relaparotomy concept as the method of choice to treat secondary peritonitis.

Clinical prognosticators of survival in patients with urothelial carcinoma of the bladder and lymph node metastases after cystectomy with curative intent.

INTRODUCTION: Patients with lymph node-positive urothelial carcinoma of the bladder generally have a poor prognosis. Nevertheless, long-term survival in up to 30% of patients is reported. In the absence of established prognostic molecular markers, an assessment of the prognosis with clinical parameters is mandatory. PATIENTS AND METHODS: All patients from one high-volume center with a curatively intended cystectomy for lymph node-positive urothelial carcinoma were evaluated. Patients' overall and cancer-specific survival were correlated with clinicopathological parameters. Pathological lymph node staging was performed with both the 2002 and 2010 TNM classification of the AJCC. RESULTS: Lack of a perioperative chemotherapy (p < 0.001), higher numbers of positive nodes (p = 0.002), a higher lymph node density (p = 0.003), a higher pathological T stage (p = 0.006) and urinary diversion with an ileal conduit compared to an ileal neobladder (p = 0.023) were prognostic of a shorter overall survival while the number of removed lymph nodes showed no significant association with survival. Both with the 2002 and 2010 TNM classifications patients staged pN1 had a longer overall survival and time to cancer-specific death in comparison to patients with more extensive lymph node disease. According to the 2002 classification, there was a significant survival difference between patients with lymph node metastases in regional and distant lymph nodes. DISCUSSION: Patients with a low lymph node density and an early pT stage present with the best prognosis among LN positive patients. The value of perioperative chemotherapy is emphasized. Which lymph node metastases are to be considered regional or distant remains a matter of debate.

Dynamic quantification of tibio-femoral rotation in postero-lateral bundle insufficiency of the anterior cruciate ligament: a cadaver study.

PURPOSE: Anterior cruciate ligament (ACL) injury represents one of the most common diagnoses in orthopaedic sports medicine. In the past, anatomic knowledge about the different bundles within the cruciate ligaments triggered new treatment concepts, such as double-bundle ACL reconstruction. Recently, besides complete tearing, partial ACL ruptures and bundle augmentation became a focus. However, only little is known regarding rotational stability of the knee with an isolated torn postero-lateral (PL) bundle. Therefore, the aim of the present study was the torsiometric analysis of tibio-femoral restraint patterns of the PL-insufficient knee joint. METHODS: Fresh human whole body cadavers were enrolled. After diagnostic arthroscopy to ensure the structural integrity of the cruciate ligaments, knee joints underwent torsiometry at 0°, 30°, and 90° degree flexion. Then stepwise the PL bundle and the anteromedial (AM) bundle were arthroscopically resected, while torsiometry of the PL- as well as of the ACL-deficient knee joints was repeated. An area under the curve (AUC) was calculated. All statistical analyses were conducted using a p-value of 0.05 as level of significance. RESULTS: The comparison of charged and equilibrated curves during internal rotation revealed significant results at low flexion (30° flexion) angles between the ACL intact versus PL absent conditions (p = 0.04). In addition, charged and equilibrated curves during external rotation at 90° flexion, thus high angles, resulted in a significant difference when comparing the ACL-intact with the PL-deficient condition (p = 0.01). CONCLUSIONS: In the present cadaver study using the Torsiometer tool we found a distinct destabilization of the rotational restraints in full knee extension only after total ACL resection. In contrast, no significant findings resulted after an isolated dissection of the PL bundle during internal deflection. Nevertheless, a significant loss of stability was found during unstressed external deflection after isolated PL bundle dissection. Therefore patients, undergoing PL augmentation might benefit regarding rotational instability patterns.

Three-dimensional echocardiographic optimization improves outcome in cardiac resynchronization therapy compared to ECG optimization: a randomized comparison.

AIMS: There is little consensus on optimal atrioventricular (AV) and ventricular-to-ventricular (VV) intervals in cardiac resynchronization therapy (CRT). The aim of this study was to examine a novel combination of Doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized AV- and VV-interval optimization compared to conventional electrocardiogram (ECG) optimization. METHODS: In this double-blind, randomized controlled trial, 77 patients (male: 57, age: 68 ± 10 years) with severely reduced ejection fraction (EF), New York Heart Association (NYHA) class III or IV, and wide QRS complex (>120 ms) have been included. Patients were randomized to either AV- and VV-interval optimization using DE and 3DE (group 1, n = 39) or ECG (group 2, n = 38). 3DE was performed in all patients for the evaluation of left ventricular (LV) dimensions, EF and systolic dyssynchrony index (SDI), and NYHA class obtained before CRT and after 3 months. Primary endpoint of the study was clinical response to CRT, defined as a reduction of NYHA class by ≥1 score. Secondary endpoints were change of EF, LV volumes, and SDI. RESULTS: There were significantly more responders in group 1 (82%) than in group 2 (58%, P = 0.021). Similarly, group 1 showed a larger increase in EF (7.0 ± 6.0% vs 3.4 ± 5.6%, P = 0.015) and a more pronounced reduction of SDI (-4.5 ± 5.9% vs -1.5 ± 5.6%, P = 0.039) than group 2. CONCLUSION: Compared with conventional ECG optimization, this novel echocardiographic optimization protocol resulted in a significantly higher response rate, improved LV systolic function, and may be used to select the optimal AV and VV intervals in CRT.

Solo-surgical laparoscopic cholecystectomy with a joystick-guided camera device: a case-control study.

BACKGROUND: This study aimed to evaluate the implementation of a joystick-controlled camera holder (Soloassist; Actormed, Barbing, Germany) in laparoscopic cholecystectomy as so-called solo-surgery compared with the standard operation. METHODS: Of the 123 patients included in this study, 63 underwent laparoscopic cholecystectomy using the Soloassist system and were compared with 60 patients who underwent laparoscopic cholecystectomy with human assistance. The two groups did not differ significantly in terms of age, sex, body mass index, or American Society of Anesthesiology classification. The surgeons were divided into those highly experienced and those experienced with the new camera holder. The operation times were measured, including setup and dismantling of the system. The assessment also included complications, postoperative hospital stay, measurement of human resources in terms of personnel/minutes/operation, and subjective evaluation of the camera-guiding device by the surgeons. RESULTS: The hospital stay and operation-related complications were not enhanced in the Soloassist group. The differences in core operation time (p = 0.008) and total operating time (p = 0.001) significantly favored the human assistant. Whereas the absolute duration of surgery was longer, the relative operating time (in personnel/minutes/operation) was significantly shorter (p < 0.001). In 4.8 % of the cases, the operation could not be performed completely with the camera-holding device. Clinically relevant postoperative complications did not occur. The experience of the surgeons did not differ significantly. The subjective evaluation regarding handling, image quality, effort, and satisfaction demonstrated high acceptance of the Soloassist system. CONCLUSIONS: The camera-guiding device can be implemented without increased complications. The Soloassist system is safe and can be operated even by colleagues without system experience. All the surgeons rated their satisfaction with the system as very good to excellent. Although the operating times were longer than with the standard camera guidance, the absolute overall staff time was reduced.

Osteoarthritis of the knee or hip significantly impairs driving ability (cross-sectional survey).

BACKGROUND: Advising patients about when they can drive after surgery is common practice after arthroplasty of the knee or hip. In the literature, the preoperative braking performance values of the patients are frequently taken as the "safe" landmark. We hypothesised that osteoarthritis (OA), the most frequent reason for arthroplasty, already compromises the ability to perform an emergency stop. We expected that both Reaction Time (RT) and Movement Time (MT) as components of the Total Brake Response Time (TBRT), would be prolonged in patients with OA of the knee or hip in comparison with healthy subjects. We also expected maximum pressure levels on the brake pedal to be reduced in such cases. METHODS: A real car cabin was equipped with pressure sensors on the accelerator and brake pedals to measure RT, MT, TBRT and maximum Brake Force (BF) under realistic spatial constraints. Patients with OA of the knee (right n = 18, left n = 15) or hip (right n = 20, left n = 19) were compared with a healthy control group (n = 21). RESULTS: All measured values for TBRT in the control group remained below 600 ms. OA of the right hip or knee significantly prolonged the braking performance (right hip: TBRT p = 0.025, right knee: TBRT p < 0.001), whereas OA of the left hip did not impair driving ability (TBRT p = 0.228). Intriguingly, OA of the left knee prolonged RT and MT to the same degree as OA on the contralateral side (RT p = 0.001, MT p < 0.001). CONCLUSIONS: This study demonstrates that depending on the localisation of OA, driving capability can be impaired; OA can significantly increase the total braking distance. To ensure safe traffic participation the safety margin for TBRT should be strictly set, under our experimental conditions, at around 600 ms. Moreover, therapeutic approaches to OA, such as physiotherapy, and patients receiving surgery of the left knee should take into account that left knee OA can also impair driving ability. CLINICAL TRIAL REGISTRATION NUMBER: Project number of the ethics committee of the University of Tübingen: 268/2009BO2; 267/2009BO2.

Respiratory rate predicts outcome after acute myocardial infarction: a prospective cohort study.

AIMS: Risk stratification after acute myocardial infarction (MI) remains imperfect and new indices are sought that might improve the post-MI risk assessment. In a contemporarily-treated cohort of acute MI patients, we tested whether the respiratory rate provides prognostic information and how this information compares to that of established risk assessment. METHODS AND RESULTS: A total of 941 consecutive patients (mean age 61 years, 19% female) presenting with acute MI were enrolled between May 2000 and March 2005. The last follow-up was performed May 2010. Main outcome measure was total mortality during a follow-up period of 5 years. Patients underwent 10-min resting recordings of the respiratory rate within 2 weeks after MI in addition to the measurement of the left ventricular ejection fraction (LVEF) and standard clinical assessment including the GRACE score. During the follow-up, 72 patients died. The respiratory rate was a significant predictor of death in univariable analysis (hazard ratio 1.19 per 1/min, 95% confidence interval: 1.12-1.27) as was the GRACE score [1.04 (1.03-1.05) per point], LVEF [0.96 (0.94-0.97) per 1%], and the diagnosis of diabetes mellitus [2.78 (1.73-4.47)], all P < 0.0001. On multivariate analysis, the GRACE score (P < 0.0001), respiratory rate (P < 0.0001), LVEF (P = 0.013), and diabetes (P = 0.016) were independent prognostic markers. CONCLUSION: The respiratory rate provides powerful prognostic information which is independent and complementary to that of existing risk assessment. Simple and inexpensive assessment of the respiratory rate should be considered a complementary variable for the assessment of risk after acute MI.

The functional outcome of forty-nine single-incision suture anchor repairs for distal biceps tendon ruptures at the elbow.

PURPOSE: The objective of this retrospective study was to evaluate the functional results of distal biceps tendon repair using suture anchors via a single-incision approach. METHODS: Forty-nine patients were re-examined at a mean follow-up of 44.2 ± 32.1 months (range, 12-119 months). Subjective and objective criteria included patient's satisfaction, active range of motion (ROM), maximum isometric strength in flexion (at 45° and 90°), and supination of both arms. Functional scoring included the Morrey elbow score (MES) and the QuickDASH. Furthermore, follow-up radiographs were performed. RESULTS: Eighty-six percent of patients were highly satisfied or satisfied with their outcome. Compared to contralateral, the active ROM of elbow flexion, extension, and pronation was not affected; however, supination was decreased by 3° (P < 0.001). The isometric maximum strengths showed significant deficits in all tested scenarios (at 45°, P = 0.002; at 90°, P < 0.001; for supination, P < 0.001). The MES and the QuickDASH were 97.2 ± 4.9 and 7.9 ± 13.9, respectively. Heterotopic ossifications (HO) were found in 39% of patients; however, with respect to scores and strength, no significant differences were seen compared to patients without HO. Moreover, four anchor failures were detected. CONCLUSIONS: Single-incision suture anchor repair provides high patient's satisfaction and good results with respect to ROM and functional scoring. Nevertheless, based on presented data, the patient has to be informed of postoperative HO and especially for supination strength weakness after surgery. Distal biceps tendon repair should be reserved for experienced upper extremity surgeons to avoid procedure-related complications.

Antitumor T cell responses in bladder cancer are directed against a limited set of antigens and are modulated by regulatory T cells and routine treatment approaches.

Regulatory T cells (Tregs) play a key role in cancer immune escape. We identified target antigens of spontaneous tumor-specific T cell responses in urothelial carcinoma (UC) and evaluated their modulation by treatment and Treg. We determined Treg target antigens in UC. Fifty-six UC and 13 control patients were prospectively enrolled. Blood was drawn before and after routine treatment. Changes in Treg frequency were measured by fluorescence cytometry and the T effector cell (Teff) response against a set of nine tumor-associated antigens (TAAs) was monitored with an interferon-gamma ELISpot. Antigen specificity of Treg was determined by their increased capacity to inhibit after TAA-specific activation the proliferation of an autologous T cell population. The highest difference in the overall response rate for the total T cell population was observed for epidermal growth factor receptor (EGFR) (UC: 23% and controls: 0%). After depleting Treg, also new york esophageal (NYES)O1 (19 and 0%) and MUC20 (27 and 0%) were more frequently recognized in UC patients. In metastasized patients, the TAA-directed T cell response was augmented by Treg depletion. Tumor resection seemed to diminish Treg suppression of TAA-specific immunity, whereas chemotherapy had no effect. We demonstrated the existence of TAA-specific Treg in UC, which share antigen specificities with Teff. The coexistence of TAA-specific Treg and Teff was very rare. Treg frequencies in the peripheral blood were not changed by therapy. In summary, we identified potentially immunologically relevant TAA in UC. TAA-specific T cell responses against these antigens are suppressed by Treg. We identified TAA-specific Treg in UC patients, which do not cooccur with TAA-specific Teff.