Management after acute injury of the anterior cruciate ligament (ACL). Part 3: Recommendation on surgical treatment.

PURPOSE: The aim of this consensus project was to give recommendations regarding surgical treatment of the anterior cruciate ligament (ACL) injured patient. METHODS: For this consensus process, an expert, steering and rating group was formed. In an initial online meeting, the steering group, together with the expert group, formed various key topic complexes for which multiple questions were formulated. For each key topic, a structured literature search was performed by the steering group. The results of the literature review were sent to the rating group with the option to give anonymous comments until a final consensus voting was performed. Sufficient consensus was defined as 80% agreement. RESULTS: During this consensus process, 30 topics regarding the surgical management and technique of ACL reconstruction were identified. The literature search for each key question resulted in 30 final statements. Of these 30 final statements, all achieved consensus. CONCLUSIONS: This consensus process has shown that surgical treatment of ACL injury is a complex process. Various surgical factors influence patient outcomes. The proposed treatment algorithm can be used as a decision aid for the surgeon. LEVEL OF EVIDENCE: Level V.

Structural and functional consequences of the H180A mutation of the light-driven sodium pump KR2.

Krokinobacter eikastus rhodopsin 2 (KR2) is a light-driven pentameric sodium pump. Its ability to translocate cations other than protons and to create an electrochemical potential makes it an attractive optogenetic tool. Tailoring its ion-pumping characteristics by mutations is therefore of great interest. In addition, understanding the functional and structural consequences of certain mutations helps to derive a functional mechanism of ion selectivity and transfer of KR2. Based on solid-state NMR spectroscopy, we report an extensive chemical shift resonance assignment of KR2 within lipid bilayers. This data set was then used to probe site-resolved allosteric effects of sodium binding, which revealed multiple responsive sites including the Schiff base nitrogen and the NDQ motif. Based on this data set, the consequences of the H180A mutation are probed. The mutant is silenced in the presence of sodium while in its absence proton pumping is observed. Our data reveal specific long-range effects along the sodium transfer pathway. These experiments are complemented by time-resolved optical spectroscopy. Our data suggest a model in which sodium uptake by the mutant can still take place, while sodium release and backflow control are disturbed.

Impact of surgical site infection on patients' outcome after fixation of tibial plateau fractures: a retrospective multicenter study.

BACKGROUND: Surgical site infection (SSI) occurs in 3-10 % of patients with surgically treated tibial plateau fractures. This study aimed to evaluate the impact of SSI on patients' outcome after fixation of tibial plateau fractures. METHODS: We conducted a retrospective multicenter study in seven participating level I trauma centers between January 2005 and December 2014. All participating centers followed up with patients with SSI. In addition, three centers followed up with patients without SSI as a reference group. Descriptive data and follow-up data with patient-reported outcome scores (Knee Injury and Osteoarthritis Outcome Score [KOOS] and Lysholm knee scoring scale score) were evaluated. RESULTS: In summary, 287 patients (41 with SSI and 246 without SSI; average 50.7 years) with an average follow-up of 75.9 ± 35.9 months were included in this study. Patients with SSI had a significantly poorer overall KOOS (KOOS5) (48.7 ± 23.2 versus [vs.] 71.5 ± 23.5; p < 0.001) and Lysholm knee scoring scale score (51.4 ± 24.0 vs. 71.4 ± 23.5; p < 0.001) than patients without SSI. This significant difference was also evident in the KOOS subscores for pain, symptoms, activities of daily living (ADL), and quality of life (QoL). SSI remained an important factor in multivariable models after adjusting for potential confounders. Clinically relevant differences in the KOOS5 and KOOS subscores for symptoms, pain, and ADL were found between those with SSI and without SSI even after adjustment. Furthermore, the number of previous diseases, Arbeitsgemeinschaft für Osteosynthesefragen Foundation (AO) C fractures, and compartment syndrome were found to be additional factors related to poor outcome. CONCLUSIONS: Compared to previous studies, validated patient-reported outcome scores demonstrated that the impact of SSI in patients with surgically treated tibial plateau fractures is dramatic, in terms of not only pain and symptoms but also in ADL and QoL, compared to that in patients without SSI.

The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter.

Creatine transport has been assigned to creatine transporter 1 (CRT1), encoded by mental retardation associated SLC6A8. Here, we identified a second creatine transporter (CRT2) known as monocarboxylate transporter 12 (MCT12), encoded by the cataract and glucosuria associated gene SLC16A12. A non-synonymous alteration in MCT12 (p.G407S) found in a patient with age-related cataract (ARC) leads to a significant reduction of creatine transport. Furthermore, Slc16a12 knockout (KO) rats have elevated creatine levels in urine. Transport activity and expression characteristics of the two creatine transporters are distinct. CRT2 (MCT12)-mediated uptake of creatine was not sensitive to sodium and chloride ions or creatine biosynthesis precursors, breakdown product creatinine or creatine phosphate. Increasing pH correlated with increased creatine uptake. Michaelis-Menten kinetics yielded a Vmax of 838.8 pmol/h/oocyte and a Km of 567.4 µm. Relative expression in various human tissues supports the distinct mutation-associated phenotypes of the two transporters. SLC6A8 was predominantly found in brain, heart and muscle, while SLC16A12 was more abundant in kidney and retina. In the lens, the two transcripts were found at comparable levels. We discuss the distinct, but possibly synergistic functions of the two creatine transporters. Our findings infer potential preventive power of creatine supplementation against the most prominent age-related vision impaired condition.

Assessment of Complication Risk in the Treatment of Proximal Humerus Fractures: A Retrospective Analysis of 4019 Patients.

(1) Background: The treatment of proximal humeral fractures (PHFs) is debated controversially. Current clinical knowledge is mainly based on small single-center cohorts. The goal of this study was to evaluate the predictability of risk factors for complications after the treatment of a PHF in a large clinical cohort in a multicentric setting. (2) Methods: Clinical data of 4019 patients with PHFs were retrospectively collected from 9 participating hospitals. Risk factors for local complications of the affected shoulder were assessed using bi- and multivariate analyses. (3) Results: Fracture complexity with n = 3 or more fragments, cigarette smoking, age over 65 years, and female sex were identified as predictable individual risk factors for local complications after surgical therapy as well as the combination of female sex and smoking and the combination of age 65 years or older and ASA class 2 or higher. (4) Conclusion: Humeral head preserving reconstructive surgical therapy should critically be evaluated for patients with the risk factors abovementioned.

Expression of interleukin-4 and interleukin-13 and their receptors in colorectal cancer.

PURPOSE: Interleukin-4 (IL-4) and interleukin-13 (IL-13) are anti-inflammatory and immunomodulatory cytokines which can influence cancer-directed immunosurveillance. Nothing is presently known about expression of these cytokines and their receptors (IL-4R and IL-13R) in colorectal cancer. The aim of this study was to characterize their expression in primary colorectal cancer specimens and to evaluate possible functions for this disease. METHODS: Expression of IL-4, IL-13, IL-4R, and IL-13R protein was characterized by immunohistochemistry in 359 patients with Union for International Cancer Control stage I-III colorectal cancer and evaluated by uni- and multivariate analysis for their prognostic relevance. RESULTS: All four proteins were expressed in colorectal cancer specimens. In the cancer cells, high IL-4, IL-13, IL-4R, and IL-13R immunoreactivity were present in 33 % (118/359), 50 % (181/359), 36 % (129/359), and 42 % (152/359), respectively. Patients with high expression of IL-4, IL-4R, and IL-13R had a lower frequency of lymph node metastases. Expression of IL-13 did not influence the frequency of lymph node metastases. However, high IL-13-immunoreactivity was associated with a better overall survival (p = 0.041). Expression of IL-4, IL-4R, or IL-13R did not influence survival. Multivariate analysis revealed that besides pT classification and tumor recurrence, IL-13 expression was an independent prognostic factor for overall survival. CONCLUSIONS: Expression of IL-4, IL-4R, and IL-13R are involved in the process of local metastases in colorectal cancer, while IL-13 expression has an impact on survival. These interleukins and their receptors may become attractive targets for the treatment of colorectal cancer.

Coil Efficiency for Inductive Peripheral Nerve Stimulation.

Magnetic stimulation of peripheral nerves is evoked by electric field gradients caused by high-intensity, pulsed magnetic fields created from a coil. Currents required for stimulation are very high, therefore devices are large, expensive, and often too complex for many applications like rehabilitation therapy. For repetitive stimulation, coil heating due to power loss poses a further limitation. The geometry of the magnetic coil determines field depth and focality, making it the most important factor that determines the current required for neuronal excitation. However, the comparison between different coil geometries is difficult and depends on the specific application. Especially the distance between nerve and coil plays a crucial role. In this investigation, the electric field distribution of 14 different coil geometries was calculated for a typical peripheral nerve stimulation with a 27 mm distance between axon and coil. Coil parameters like field strength and focality were determined with electromagnetic field simulations. In a second analysis, the activating function along the axon was calculated, which quantifies the efficiency of neuronal stimulation. Moreover, coil designs were evaluated concerning power efficacy based on ohmic losses. Our results indicate that power efficacy of magnetic neurostimulation can be improved significantly by up to 40% with optimized coil designs.

Risk Factors for Deep Surgical Site Infection in Patients With Operatively Treated Tibial Plateau Fractures: A Retrospective Multicenter Study.

OBJECTIVES: To identify the potential controllable risk factors for surgical site infection (SSI). DESIGN: A retrospective cohort study. SETTING: Seven Level-I trauma centers. PATIENTS/PARTICIPANTS: Patients with OTA/AO 41 B or C tibial plateau fractures (n = 2106). INTERVENTION: Various surgical treatments for tibial plateau fractures. MAIN OUTCOME MEASUREMENTS: The primary outcome was SSI after the index operation. The secondary outcomes were the risk factors for SSI, identified using backward stepwise generalized multiple regression analysis. RESULTS: Of the 2106 enrolled patients, 94 had deep SSIs. The average SSI rate was 4.5%. Fracture morphology revealed type B injuries in 57.5% and type C in 42.5% of the patients. Univariate regression analysis revealed that several factors, namely, number of comorbidities [>6 vs. none; odds ratio (OR) 8.01, 95% confidence interval (CI) 2.8-22.8, P < 0.001], diabetes mellitus (OR 3.5, 95% CI 2.0-6.3, P < 0.001), high body mass index (OR 1.3, 95% CI 1.1-1.6, P = 0.001), OTA/AO fracture type C (OR 5.6, 95% CI 3.3-9.5, P < 0.001), compartment syndrome (OR 9.1, 95% CI 5.7-14.8, P < 0.001), and open fracture (OR 6.6, 95% CI 3.7-11.7, P < 0.001), were associated with a significantly higher SSI risk. Analysis of microbial sensitivity tests revealed that 55.1% of the pathogens were resistant to perioperative antibiotic prophylaxis. CONCLUSIONS: Most of the identified risk factors cannot be controlled or are subject to other factors that are difficult to control. However, our data suggest that the choice of perioperative antibiotic prophylaxis may influence the rate of SSI. This possibility should be investigated in a prospective randomized controlled trial. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Effect of fracturoscopy on the incidence of surgical site infections post tibial plateau fracture surgery.

PURPOSE: Surgical treatment of tibial plateau fracture (TPF) is common. Surgical site infections (SSI) are among the most serious complications of TPF. This multicentre study aimed to evaluate the effect of fracturoscopy on the incidence of surgical site infections in patients with TPF. METHODS: We performed a retrospective multicentre study. All patients with an AO/OTA 41 B and C TPF from January 2005 to December 2014 were included. Patients were divided into three groups: those who underwent arthroscopic reduction and internal fixation (ARIF), and those who underwent open reduction and internal fixation (ORIF) with fracturoscopy, and those treated with ORIF without fracturoscopy. The groups were compared to assess the effect of fracturoscopy. We characterised our cohort and the subgroups using descriptive statistics. Furthermore, we fitted a logistic regression model which was reduced and simplified by a selection procedure (both directions) using the Akaike information criterion (AIC). From the final model, odds ratios and inclusive 95% confidence intervals were calculated. RESULTS: Overall, 52 patients who underwent fracturoscopy, 48 patients who underwent ARIF, and 2000 patients treated with ORIF were identified. The rate of SSI was 0% (0/48) in the ARIF group and 1.9% (1/52) in the fracturoscopy group compared to 4.7% (93/2000) in the ORIF group (OR = 0.40, p = 0.37). Regression analyses indicated a potential positive effect of fracturoscopy (OR, 0.65; 95% CI, 0.07-5.68; p = 0.69). CONCLUSION: Our study shows that fracturoscopy is associated with reduced rates of SSI. Further studies with larger cohorts are needed to investigate this. LEVEL OF EVIDENCE: Level III.

Differences in the accumulation of phosphorus between vegetative cells and heterocysts in the cyanobacterium Nodularia spumigena.

The cyanobacterium Nodularia spumigena is a species that frequently forms blooms in the Baltic Sea. Accumulation of the vital nutrient phosphorus (P) apparently plays an important role in the ability of this and other cyanobacteria to grow even when dissolved inorganic phosphorus is depleted. However, until now, this has not been studied in N. spumigena at the cellular level. Therefore, in this study, phosphorus incorporation and distribution in cyanobacterial filaments over time was examined by scanning electron microscopy in combination with energy dispersive X-ray analysis (SEM/EDX) and nanoscale secondary ion mass spectrometry (NanoSIMS). Immediately after phosphate addition to a phosphorus-depleted population, the phosphate concentration decreased in the water while intracellular polyphosphate accumulated. Microscopically, phosphorus in form of polyphosphate granules was stored preferentially in vegetative cells, whereas heterocysts remained low in intracellular phosphorus. This information is an essential step towards understanding the phosphorus dynamics of this species and demonstrates that the division of tasks between vegetative cells and heterocysts is not restricted to nitrogen fixation.

The impact of pH inhomogeneities on CHO cell physiology and fed-batch process performance - two-compartment scale-down modelling and intracellular pH excursion.

Due to high mixing times and base addition from top of the vessel, pH inhomogeneities are most likely to occur during large-scale mammalian processes. The goal of this study was to set-up a scale-down model of a 10-12 m3 stirred tank bioreactor and to investigate the effect of pH perturbations on CHO cell physiology and process performance. Short-term changes in extracellular pH are hypothesized to affect intracellular pH and thus cell physiology. Therefore, batch fermentations, including pH shifts to 9.0 and 7.8, in regular one-compartment systems are conducted. The short-term adaption of the cells intracellular pH are showed an immediate increase due to elevated extracellular pH. With this basis of fundamental knowledge, a two-compartment system is established which is capable of simulating defined pH inhomogeneities. In contrast to state-of-the-art literature, the scale-down model is included parameters (e.g. volume of the inhomogeneous zone) as they might occur during large-scale processes. pH inhomogeneity studies in the two-compartment system are performed with simulation of temporary pH zones of pH 9.0. The specific growth rate especially during the exponential growth phase is strongly affected resulting in a decreased maximum viable cell density and final product titer. The gathered results indicate that even short-term exposure of cells to elevated pH values during large-scale processes can affect cell physiology and overall process performance. In particular, it could be shown for the first time that pH perturbations, which might occur during the early process phase, have to be considered in scale-down models of mammalian processes.

[Effects of psychotherapeutic interventions on length of stay in cardiology inpatients]. / Der Einfluss eines psychosomatischen Liaisondienstes auf die stationäre Verweildauer von Patienten in der Kardiologie.

OBJECTIVES: Mental comorbidities as recorded in the DRG system by the Patient Comorbidity and Complication Level (PCCL) cause extended length of stay in cardiology with resultant higher costs. Studies analyzing the influence of a psychiatric consultation and liaison service on the length of stay and the costs incurred thereby have generated inconsistent results. The present prospective study examines the effects of the psychotherapeutic liaison service on the length of stay. METHODS: In the course of 6 months, two cardiology wards were alternately provided traditional psychotherapeutic consultation and psychotherapeutic liaison service based on a Cross-Over-Design (A-B-A). Inclusion criteria for patients was the presence of one of the four most common cardiological diagnoses (ischemic heart diseases, heart valve defects, cardiomyopathies, arrhythmias). After the exclusion of patients with a length of less than five days, the random sampling comprised n = 317 patients. RESULTS: The study showed no direct correlation between the intensified care system of the liaison service and a reduction in the length of stay. The results obtained remained consistent even after controlling for age, sex, and case complexity. Recommendations for further investigations are discussed.

Comparative analyses of olfactory systems in terrestrial crabs (Brachyura): evidence for aerial olfaction?

Adaptations to a terrestrial lifestyle occurred convergently multiple times during the evolution of the arthropods. This holds also true for the "true crabs" (Brachyura), a taxon that includes several lineages that invaded land independently. During an evolutionary transition from sea to land, animals have to develop a variety of physiological and anatomical adaptations to a terrestrial life style related to respiration, reproduction, development, circulation, ion and water balance. In addition, sensory systems that function in air instead of in water are essential for an animal's life on land. Besides vision and mechanosensory systems, on land, the chemical senses have to be modified substantially in comparison to their function in water. Among arthropods, insects are the most successful ones to evolve aerial olfaction. Various aspects of terrestrial adaptation have also been analyzed in those crustacean lineages that evolved terrestrial representatives including the taxa Anomala, Brachyura, Amphipoda, and Isopoda. We are interested in how the chemical senses of terrestrial crustaceans are modified to function in air. Therefore, in this study, we analyzed the brains and more specifically the structure of the olfactory system of representatives of brachyuran crabs that display different degrees of terrestriality, from exclusively marine to mainly terrestrial. The methods we used included immunohistochemistry, detection of autofluorescence- and confocal microscopy, as well as three-dimensional reconstruction and morphometry. Our comparative approach shows that both the peripheral and central olfactory pathways are reduced in terrestrial members in comparison to their marine relatives, suggesting a limited function of their olfactory system on land. We conclude that for arthropod lineages that invaded land, evolving aerial olfaction is no trivial task.

Clusterin protects the lung from leukocyte-induced injury.

Clusterin (CLU) is a multifunctional 75- to 80-kDa glycoprotein that is upregulated during cellular stress and might represent a defense mechanism during local cellular damage. Mechanisms discussed are antiapoptotic, antioxidative, and anticomplement properties as well as chaperone-like features protecting stressed proteins. The aim of this study was to investigate potential protective effects of CLU on pulmonary vasculature after in situ PMN activation in isolated rabbit lungs. The experiments were performed on 24 isolated and ventilated rabbit lungs that were perfused with 200 mL of Krebs-Henseleit-10% blood buffer with a constant flow of 150 mL/min in a recirculating system. It was tested whether pretreatment with CLU (2.5 microg/ml; n = 8) or catalase (CAT, 5000 U/ml; n = 8) before N-formyl-Met-Leu-Phe (fMLP; 10(-8) M) injection influenced pulmonary artery pressure (PAP) peak airway pressures (PAW) and edema formation as compared with controls (n = 8). Baseline values of PAP were 9-11 mmHg and PAW 11-13 cm H2O. Application of fMLP resulted in an acute significant (P < 0.01) increase of PAP (48 +/- 29 mmHg) within 2 min in the control group and PAW increased to 35 +/- 7 cm H2O within 30 min. Pretreatment with CLU completely suppressed the PAP and PAW response as a result of the fMLP challenge (P < 0.001), whereas a transient PAW increase up to 27 +/- 15 mmHg was observed after CAT. Complement factor C3a release was suppressed by CAT, whereas CLU blocked the complement cascade at the level of C5b-9 formation. Moreover, generation of thromboxane A(2) was reduced after CLU and CAT. Lung edema occurred in the fMLP group but was absent (P < 0.001) after CLU and CAT treatment. Both CLU and CAT prevented fMLP-induced lung injury. Stabilizing effects of CLU, point towards complement regulating features at the level of the terminal complement sequence. Elevated levels of CLU during inflammation could reflect a compensatory organ protective mechanism. Further studies are required to elucidate the clinical impact of the observed organ-protective properties of CLU.