PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR.

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.

Immunomodulatory roles of PARPs: Shaping the tumor microenvironment, one ADP-ribose at a time.

PARPs encompass a small yet pervasive group of 17 enzymes that catalyze a post-translational modification known as ADP-ribosylation. PARP1, the founding member, has received considerable focus; however, in recent years, the spotlight has shifted to other members within the PARP family. In this opinion piece, we first discuss surprising findings that some FDA-approved PARP1 inhibitors activate innate immune signaling in cancer cells that harbor mutations in the DNA repair pathway. We then discuss hot-off-the-press genetic and pharmacological studies that reveal roles for PARP7, PARP11, and PARP14 in immune signaling in both tumor cells and tumor-associated immune cells. We conclude with thoughts on tuning PARP1-inhibitor-mediated innate immune activation and explore the unrealized potential for small molecule modulators of other PARP family members as next-generation immuno-oncology drugs.

History of neurosurgery at Howard University: the nation's only historically black academic institution that practices neurological surgery.

Howard University Hospital has been a pillar for healthcare delivery in the Black community, an underserved sector of Washington, DC, since its founding in 1862. Neurological surgery, one of the many areas of service provided, was established by trailblazer Dr. Clarence Greene Sr., who was appointed the division's first chief in 1949. Because of the color of his skin, Dr. Greene had to complete his neurosurgical training at the Montreal Neurological Institute, as he was refused the opportunity to train in the United States. He went on to become the first African American to be board certified in neurological surgery in 1953. Drs. Jesse Barber, Gary Dennis, and Damirez Fossett, the subsequent division chiefs, have all continued Dr. Greene's legacy of providing academic enrichment and subserving a disparate population. Many patients who may not have received treatment otherwise have been able to receive exemplary neurosurgical care from them. Under their tutelage, numerous African American medical students have gone on to train in neurological surgery. Future directions include developing a residency program, collaborating with other neurosurgery programs in continental Africa and the Caribbean, and establishing a fellowship for training international students.

Utility of prolonged prophylactic systemic antibiotics for wound drains in posterior spine surgery: a systematic review and meta-analysis.

OBJECTIVE: Closed suction drains, often used after posterior spinal surgery, pose a potential risk of infection. To combat this risk, many surgeons opt for a prolonged prophylactic antibiotic regimen. Since 2015, several studies have shown that prolonged prophylactic systemic antibiotics (PPSA) for drains provides no additional benefit in reducing surgical site infection (SSI) rates. However, most of these studies lacked sufficient power to make reliable conclusions. To date, there has been no meta-analysis conducted to further investigate this issue. The aim of this study was to investigate whether a regimen of PPSA reduces the incidence of deep SSIs in adult patients with closed suction drains following posterior spinal surgeries. METHODS: The protocol of the current systematic review was registered with PROSPERO. A systematic review of the literature in PubMed (Medline), Europe PMC, Embase, and Cochrane Review databases was conducted for all relevant literature with the keywords "spine," "antibiotics," "surgical site infection," "prophylaxis," and "drain." Retrospective and prospective studies investigating the effectiveness of PPSA in patients 18 years or older who underwent posterior cervical or thoracolumbar surgery and had postoperative wound drains were included. The primary outcome was the odds ratio for deep SSI based on the intervention (PPSA vs non-PPSA). The secondary outcomes were the rates of superficial and overall SSIs. RESULTS: From a total of 2558 titles identified from the search, 7 studies were chosen for final analysis. Three were randomized controlled trials (RCTs), and 4 were retrospective reviews. A total of 2446 patients were analyzed; 1149 received a PPSA regimen and 1297 received a non-PPSA regimen. Deep SSIs occurred in 45 patients (3.9%) and 46 patients (3.5%) in the PPSA and non-PPSA groups, respectively. The odds ratio for deep SSIs in the PPSA group compared with the non-PPSA group was 1.10 (95% CI 0.69-1.74), which was not statistically significant. Additionally, there were no differences in the rates of superficial and overall SSIs. There was a trend toward increased infections with multidrug-resistant bacteria (Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus) in the PPSA group; however, it was not possible to perform a durable statistical analysis because of the small number of reported organisms in the selected publications. CONCLUSIONS: This meta-analysis demonstrates that there is no reduction in rate of deep, superficial, and overall SSIs with prolonged prophylactic antibiotics after posterior spinal surgery involving the use of closed suction drains.

Therapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction.

Myocardial infarction (MI) triggers an inflammatory response that transitions from pro-inflammatory to reparative over time. Restoring sympathetic nerves in the heart after MI prevents arrhythmias. This study investigated if reinnervation altered the immune response after MI. This study used quantitative multiplex immunohistochemistry to identify the immune cells present in the heart 2 weeks after ischemia-reperfusion. Two therapeutics stimulated reinnervation, preventing arrhythmias and shifting the immune response from inflammatory to reparative, with fewer pro-inflammatory macrophages and more regulatory T cells and reparative macrophages. Treatments did not alter macrophage phenotype in vitro, which suggested reinnervation contributed to the altered immune response.

B.2.16 is a non-lethal modifier of the Dark82 mosaic eye phenotype in Drosophila melanogaster.

Genetic screens have been used to identify genes involved in the regulation of different biological processes. We identified growth mutants in a Flp/FRT screen using the Drosophila melanogaster eye to identify conditional regulators of cell growth and cell division. One mutant identified from this screen, B.2.16, was mapped and characterized by researchers in undergraduate genetics labs as part of the Fly-CURE. We find that B.2.16 is a non-lethal genetic modifier of the Dark82 mosaic eye phenotype.

Evaluation of recombinant human SP-D in the rat premature lung model.

BACKGROUND: The lungs of premature and term babies are structurally different from the adult lungs. Preterm lungs are underdeveloped, non-compliant in terms of breathing, often need mechanical ventilation and these patients commonly develop syndromes as a consequence of their prematurity, such as bronchopulmonary dysplasia (BPD). Surfactant protein SP-D could be a therapy for BPD. However, there is a need for an animal model that resembles the structural characteristics of premature lungs to test SP-D and future molecules that will target the newborn population. The aim of this study was to develop and validate a pre-clinical model of early alveolarization and structurally premature lungs in 10-day-old rats, and establish the dose safety and distribution of rhSP-D administered intratracheally to premature lungs. METHODS: Ten-day-old Sprague Dawley rats were selected to develop the lung model. SP-D was administered intratracheally. Bronchoalveolar lavage fluid and lungs were collected to evaluate inflammation and SP-D distribution. RESULTS: The 10-day-old rat pup demonstrates early alveolarization features of premature lung development and it tolerates daily intratracheal injections for up to 14 days. The intratracheal administration of rhSP-D, at a dose of 8 mg/kg, does not induce an inflammatory response or histological signs of toxicity in the premature lung, even with a daily administration for 14 days. The pharmacokinetic distribution of rhSP-D in premature lungs has a half-life of ∼9 h, and the incorporation into blood is minimal. CONCLUSIONS: 10-day-old rats are a good pre-clinical animal model of premature lungs, and rhSP-D can be intratracheally administered at doses up to 8 mg/kg without expecting adverse reactions.

[Epidemiology, Diagnosis and Treatment of Adult Patients with Nosocomial Pneumonia - Update 2017 - S3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy, the German Radiological Society and the Society for Virology]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie ­ Update 2017.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However, infections on general wards are increasing. A central issue are infections with multidrug resistant (MDR) pathogens which are difficult to treat in the empirical setting potentially leading to inappropriate use of antimicrobial therapy.This guideline update was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and treatment of HAP on the basis of quality of evidence and benefit/risk ratio.This guideline has two parts. First an update on epidemiology, spectrum of pathogens and antimicrobials is provided. In the second part recommendations for the management of diagnosis and treatment are given. New recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia and prolonged infusion of antibacterial drugs have been added. The statements to risk factors for infections with MDR pathogens and recommendations for monotherapy vs combination therapy have been actualised. The importance of structured deescalation concepts and limitation of treatment duration is emphasized.

Perivascular tissue mediated relaxation - a novel player in human vascular tone regulation.

Perivascular tissue (PVT) modulates vascular tone, releasing adventitia/adipocyte derived relaxing factor (ADRF). Its physiological role remains unclear. We studied isolated internal thoracic artery (ITA) segments obtained from 132 patients subjected to coronary artery bypass grafting. The vessels were skeletonized in vitro and the ITA rings and PVT were incubated in separate isolated organ baths. Skeletonized ITA segments were first precontracted with 10(-5.5)mol/L 5-hydroxytryptamine hydrochloride. The PVT was next transferred to the ITA tissue bath. This resulted in relaxation of ITA, presumably related to ADRF release from PVT which was floating freely in the tissue bath. The in-vitro relaxation responses were then correlated to patients' characteristics - including demographics, clinical and laboratory data, as well as therapy. Perivascular tissue transfer resulted in 49.7 ± 26.2% relaxation of precontracted ITA segments. In multiple linear regression modelling, the relaxation of ITAto PVT was negatively related to patient age (ß = -0.67; 95% CI -1.17 - -0.17; P = 0.009), symptoms of CCS class 4 angina (ß = -20.11; 95%CI -32.25 - -7.97; P = 0.001), and positively to body mass (ß = 0.37; 95%CI 0.08 - 0.67; P = 0.01) and lack of heart failure symptoms (NYHA class 1) (ß = 9.06; 95%CI 0.33 - 17.79; P = 0.04). The relaxation response to PVT was not related to patients' sex, diabetes, hypertension, lipid profile or therapy in both univariate and multivariate analysis. PVT might play an important role in regulating vascular tone in humans as exemplified by its changing physiological function with age and in atherosclerosis.

Long-term effect of computer-assisted decision support for antibiotic treatment in critically ill patients: a prospective 'before/after' cohort study.

OBJECTIVES: Antibiotic resistance has risen dramatically over the past years. For individual patients, adequate initial antibiotic therapy is essential for clinical outcome. Computer-assisted decision support systems (CDSSs) are advocated to support implementation of rational anti-infective treatment strategies based on guidelines. The aim of this study was to evaluate long-term effects after implementation of a CDSS. DESIGN: This prospective 'before/after' cohort study was conducted over four observation periods within 5 years. One preinterventional period (pre) was compared with three postinterventional periods: directly after intensive implementation efforts (post1), 2 years (post2) and 3 years (post3) after implementation. SETTING: Five anaesthesiological-managed intensive care units (ICU) (one cardiosurgical, one neurosurgical, two interdisciplinary and one intermediate care) at a university hospital. PARTICIPANTS: Adult patients with an ICU stay of >48 h were included in the analysis. 1316 patients were included in the analysis for a total of 12,965 ICU days. INTERVENTION: Implementation of a CDSS. OUTCOME MEASURES: The primary end point was percentage of days with guideline adherence during ICU treatment. Secondary end points were antibiotic-free days and all-cause mortality compared for patients with low versus high guideline adherence. MAIN RESULTS: Adherence to guidelines increased from 61% prior to implementation to 92% in post1, decreased in post2 to 76% and remained significantly higher compared with baseline in post3, with 71% (p=0.178). Additionally, antibiotic-free days increased over study periods. At all time periods, mortality for patients with low guideline adherence was higher with 12.3% versus 8% (p=0.014) and an adjusted OR of 1.56 (95% CI 1.05 to 2.31). CONCLUSIONS: Implementation of computerised regional adapted guidelines for antibiotic therapy is paralleled with improved adherence. Even without further measures, adherence stayed high for a longer period and was paralleled by reduced antibiotic exposure. Improved guideline adherence was associated with reduced ICU mortality. TRIAL REGISTRATION NUMBER: ISRCTN54598675.

Mechanisms of vasodilatatory effect of perivascular tissue of human internal thoracic artery.

It has beed showed that perivascular adipose tissue (PVAT) of human internal thoracic artery (ITA) releases adventitia/adipocyte-derived relaxing factor (ADRF). The precise mechanism of vasodilatatory effect of ADRF is still unknown. It was suggested that various potassium channels may be involved in the action of ADRF. The aim of this study was to assess the involvment of potassium channels in the vasorelaxing properties of ADRF in human internal thoracic artery. Human ITA rings were studied in vitro. First the ability of perivascular tissue of human ITA to release ADRF to the bath was checked. In subsequent experiments two fragments of skeletonised ITA were used to assess the involvement of various potassium channels in vasorelaxing action of PVAT. Segment of ITA, precontracted with serotonin (10(-5.5)M), was relaxed by adding PVAT to tissue bath, first without and then in the presence of appropriate potassium channel blocker. Second segment served as a control (no addition of PVAT). The magnitude of relaxation was measured and compared between preparations. This protocol was used to analyze the influence of iberiotoxin (100 nM), apamin (1 uM), 4-aminopyridine (1 mM, 5 mM), BaCl2 (100 uM) and glibenclamide (10 uM). The addition of PVAT to precontracted skeletonized ITA caused significant vasorelaxation (54.6±8.03 mN versus 33.7±6.58 mN p=0.03). Similar effect was seen when 5 ml of aliquot from separate incubation of PVAT was added (36.3±5.45 mN versus 20.7±3.02 mN; p<0.001). PVAT dependent relaxation was blocked in the presence of Ca⁺² dependent potassium channel blocker iberiotoxin (47.4±16.67 mN versus 43.3±14.54 mN; p=0.36) and 4-aminopyridine (5 mM) (59.3±3.54 mN versus 51.6±4.77 mN; p=0.12). We conclude that perivascular adipose tissue of human ITA releases relaxing factor that seems to act with the involvement of Ca⁺² dependent potassium channels.

[Epidemiology, diagnosis and treatment of adult patients with nosocomial pneumonia. S-3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie. S-3 Leitlinie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V., der Deutschen Gesellschaft für Infektiologie e.V., der Deutschen Gesellschaft für Hygiene und Mikrobiologie e.V., der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. und der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However infections on general wards are also increasing. A central issue are infections with multi drug resistant (MDR) pathogens which are difficult to treat particularly in the empirical setting potentially leading to inappropriate use of antimicrobial therapy. This guideline was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and therapy of HAP on the basis of quality of evidence and benefit/risk ratio. The guideline has two parts. First an update on epidemiology, spectrum of pathogens and antiinfectives is provided. In the second part recommendations for the management of diagnosis and treatment are given. Proper microbiologic work up is emphasized for knowledge of the local patterns of microbiology and drug susceptibility. Moreover this is the optimal basis for deescalation in the individual patient. The intensity of antimicrobial therapy is guided by the risk of infections with MDR. Structured deescalation concepts and strict limitation of treatment duration should lead to reduced selection pressure.

[Coincidence of traumatic tracheal rupture accompanied by ARDS. Illustrated by the example of a 17-year-old patient with multiple injuries]. / Koinzidenz der traumatischen Trachealruptur mit begleitendem ARDS. Beispiel anhand eines 17-jährigen polytraumatisierten Patienten.

Treatment and diagnosis of a traumatic tracheal rupture is a challenge. Due to the rarity of such injuries and the subtle and delayed clinical presentation it is difficult to diagnose. We present for the first time the successful management of a 17-year-old multiply injured patient with coincidental tracheal rupture and ARDS (acute respiratory distress syndrome) after a fall. Besides the case report and pathogenesis the essential diagnostic and therapeutic measures are mentioned and discussed. The circumstances surrounding the accident have to be balanced with the severity of the trauma to also exclude rare injuries with certainty. Finally level 1 trauma centers specialized in ARDS provide the best clinical setting for successful treatment of these life-threatening injuries.

Central area for induction of anesthesia and job satisfaction.

A central area for induction of anesthesia (CAIA) is supposed to optimize processes of preoperative patient preparation for anesthesia. The purpose of this study was to assess whether the separation of the anesthesia process into anesthesia induction and anesthesia maintenance is associated with residents' job satisfaction. The central area for induction of anesthesia model (CAIA model) was prospectively compared to the conventional model of anesthesia being induced, maintained and ended by the same anesthetist. Quality of senior staff supervision for each day as well as workday satisfaction was additionally graded by a Likert-scale. More than 80% of residents considered their workday as satisfying or very satisfying, regardless of the model applied. Furthermore, work day satisfaction was significantly associated with the quality of supervision provided by the teaching staff. It was concluded that time and attention provided by the teaching staff rather than the anesthesia organisational model were the major determinants of workday satisfaction.

Strategies for diagnosis and treatment of iatrogenic tracheal ruptures.

BACKGROUND: Management of tracheal ruptures in critically ill patients is challenging. Conservative treatment has been described, but in mechanically ventilated patients with distal tracheal ruptures surgical repair might be inevitable. Strategies for diagnosis and treatment of tracheal ruptures and handling of mechanical ventilation remain to be clarified. Our aim was to comprise a structured diagnostic and treatment protocol for patients suspicious of tracheal injury, including detailed principles of mechanical ventilation and specific indications for conservative or surgical treatment. METHODS: Patients with tracheal ruptures were compared in accordance to the need of mechanical ventilation and to indication for surgical repair. In patients suffering from tracheal ruptures affecting the whole tracheal wall and with protrusion of mediastinal structures into the lumen surgery was indicated. We compared ventilatory, hemodynamic and clinical parameters between the different patient groups. We report our structured approach in diagnostics and treatment of tracheal ruptures and place special emphasis on respiratory management. RESULTS: Seventeen patients with tracheal rupture were identified. In 8 patients surgical repair was performed 1.8±1.5 days after diagnosis. Previous to surgery, ventilation parameters improved significantly: plateau pressure decreased, percentage of assisted spontaneous breathing increased and compliance improved. Conservative treatment was successful in long-term ventilated patients (13.7±8 days) even when suffering from distal lesions. CONCLUSION: Invasiveness of mechanical ventilation and obstruction of tracheal lumen might indicate conservative or surgical treatment strategies in long-term ventilated patients suffering from iatrogenic tracheal rupture. Indications for surgical repair remain to be further clarified.

Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia.

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation>48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence>10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50-4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14-0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence>10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0-6.1) and colistin (OR 115.7, 95% CI 6.9-1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p=0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6-12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence>10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Ventilator-associated pneumonia in trauma patients is associated with lower mortality: results from EU-VAP study.

BACKGROUND: Differences in trauma patients developing ventilator-associated pneumonia (VAP) are described regarding etiology and risk factors associated. We aim to describe the differences in outcomes in trauma and nontrauma patients with VAP. METHODS: A prospective, observational study conducted in 27 intensive care units from nine European countries. We included patients requiring invasive mechanical ventilation for >48 hours who developed VAP. Logistic regression model was used to assess the factors independently associated with mortality in trauma patients with VAP. RESULTS: A total of 2,436 patients were evaluated; 465 developed VAP and of these 128 (27.5%) were trauma patients. Trauma patients were younger than nontrauma (45.3 ± 19.4 vs. 61.1 ± 16.7, p < 0.0001). Nontrauma had higher simplified acute physiology score II compared with trauma patients (45.5 ± 16.3 vs. 41.1 ± 15.2, p = 0.009). Most prevalent pathogens in trauma patients with early VAP were Enterobacteriaceae spp. (46.9% vs. 27.8%, p = 0.06) followed by methicillin-susceptible Staphylococcus aureus (30.6% vs. 13%, p = 0.03) and then Haemophilus influenzae (14.3% vs. 1.9%, p = 0.02), and the most prevalent pathogen in late VAP was Acinetobacter baumannii (12.2% vs. 44.4%, p < 0.0001). Mortality was higher in nontrauma patients than in trauma patients (42.6% vs. 17.2%, p < 0.001, odds ratio [OR] = 3.55, 95%CI = 2.14-5.88). A logistic regression model adjusted for sex, age, severity of illness at intensive care unit admission, and sepsis-related organ failure assessment score at the day of VAP diagnosis confirmed that trauma was associated with a lower mortality compared with nontrauma patients (odds ratio [OR] = 0.37, 95%CI = 0.21-0.65). CONCLUSIONS: Trauma patients developing VAP had different demographic characteristics and episodes of etiology. After adjustment for potential confounders, VAP episodes in trauma patients are associated with lower mortality when compared with nontrauma patients.

[Correction of angular deformity of the knee in growing children by temporary hemiepiphyseodesis using the eight-plate]. / Die kniegelenksnahe Achskorrektur im Wachstumsalter durch temporäre Hemiepiphyseodese mit der eight-Plate.

AIM: Angular deformities of the lower extremity are considered as prearthrotic factors. Osteotomy is regarded as a way of corrective treatment. But this intervention is considered as complex and requires a special after-treatment. During childhood and with remaining growth, guided growth offers an elegant solution for this problem. Resulting in a temporary hemiepiphyseodesis, the eight-Plate offers an alternative technique besides the Blount staples and the definitive epiphyseodesis. We evaluated the effect of this device on the correction of angular deformities in children with different diagnoses and at different ages. METHOD: Since 04/2006 22 patients with angular deformities of the lower extremities due to different diagnoses were treated at our department with the eight-Plate (42 eight-Plates). In this study we evaluated the outcome of 13 patients (26 eight-Plates) until the completed angular correction and removal of the eight-Plate. A special treatment after plate removal was not applied. RESULTS: All patients improved their mechanical leg axis. The average age at implantation was 9.4 years (2.3-13.7 years). The average time until plate removal was 10.7 months (6-34 months). No hardware failures, extrusions, growth arrests, wound infections or other complications were observed. Two patients did not achieve the desired axis correction because of insufficient remaining growth potential. An additional surgical intervention was realised. The average correction of the study group regarding the mechanical axis deviation (MAD) was 22 mm (6-43 mm) and 10.6 degrees (5-27 degrees) regarding the angular correction of the mechanical lateral distal femoral angle (mLDFW). The mechanical medial proximal tibial angle (mMPTW) changed by 8.0 degrees (3-15 degrees). CONCLUSION: In our opinion the eight-Plate seems to be a safe and reliable device for guided growth of angular deformities around the knee. The technique is easy to learn and the complication rate low compared to the staple technique. A special after-treatment is not needed and there is only minor operative trauma. At present there are only few data on long-term follow-up after plate removal until skeletal maturity. The definition of the ideal point in time for plate removal is still open.

Computer-assisted decision support for changing practice in severe sepsis and septic shock.

Computer-assisted decision support systems (CDSS) are designed to improve infection management. The aim of this prospective, clinical pre- and post-intervention study was to investigate the influence of CDSS on infection management of severe sepsis and septic shock in intensive care units (ICUs). Data were collected for a total of 180 days during two study periods in 2006 and 2007. Of the 186 patients with severe sepsis or septic shock, 62 were stratified into a low adherence to infection management standards group (LAG) and 124 were stratified into a high adherence group (HAG). ICU mortality was significantly increased in LAG versus HAG patients (Kaplan-Meier analysis). Following CDSS implementation, adherence to standards increased significantly by 35%, paralleled with improved diagnostics, more antibiotic-free days and a shortened time until antibiotics were administered. In conclusion, adherence to infection standards is beneficial for patients with severe sepsis or septic shock and CDSS is a useful tool to aid adherence.

[Partial physeal growth arrest with increasing genu varum deformity caused by a cortical enchondroma--a case report]. / Partielle epiphyseale Brückenbildung mit zunehmendem Genu varum bei kortikalem Enchondrom--ein Fallbericht.

INTRODUCTION: Trauma or infectious diseases can cause destruction of the epiphyseal region of the knee with premature partial bridging of the physis and deviation of length and axis. There is only little information about tumorous lesions as pathogenetic factor for these deviations. We have been searching for an approach to take advantage of the particular growth potential in order to avoid further complex procedures. METHOD: We report the case of a 6-year-old girl with progredient varus deformity of the left knee and reduction of walking distance. The X-ray and MRI investigations have shown a benign lesion like osteofibroma of the mediodistal femur with an affection of the medial physis. Because of the early and rapidly progredient deformity we planned an operative intervention, including the following two steps: 1) resection of the benign lesion and arthroscopically assisted resection of the bony bar with fat-patch interposition; 2) lateral hemiepiphyseodesis with an eight-plate. The histological examination revealed a cortical enchondroma, which had caused the above-mentioned growth disturbance. During follow-up (clinical and radiological examinations every 3 months) we saw a nearly normal growth of the mediodistal femoral physis with consecutive correction of the axial deviation. RESULTS: With surgical intervention (resection and temporary lateral hemiepiphyseodesis) we achieved a complete deformity correction in reference to the opposite side within one year post operation. Removal of the eight-plate has already been accomplished. Follow-up will be continued until completion of growth. CONCLUSION: In cases of rare partial bridging of the physis induced by a benign bone tumour one can achieve early correction of axial deviation during growth with resection, interposition of a fat patch and temporary hemiepiphyseodesis. With the help of such a procedure it is possible to prevent further progression of a pre-existing deformity and later aggressive surgical intervention.