Bone tunnel placement influences shear stresses at the coracoid process after coracoclavicular ligament reconstruction: a finite element study and radiological analysis.

INTRODUCTION: Coracoid fractures after arthroscopic treatment of acromioclavicular (AC) joint separations lead to poor clinical outcomes. In this study, different configurations of bone tunnels in the lateral clavicle and coracoid were examined concerning the amount of stress induced in the coracoid. METHODS: An authentic 3D finite element model of an ac joint was established. Three 2.4 mm bone tunnels were inserted in the lateral clavicle, which were situated above, medially and laterally of the coracoid. Then, two 2.4 mm bone tunnels were inserted in the latter, each simulating a proximal and a distal suture button position. Von Mises stress analyses were performed to evaluate the amount of stress caused in the coracoid process by the different configurations. Then, a clinical series of radiographs was examined, the placement of the clavicle drill hole was analyzed and the number of dangerous configurations was recorded. RESULTS: The safest configuration was a proximal tunnel in the coracoid combined with a lateral bone tunnel in the clavicle, leading to an oblique traction at the coracoid. A distal bone tunnel in the coracoid and perpendicular traction as well as a proximal tunnel in the coracoid with medial traction caused the highest stresses. Anatomical placement of the clavicle drill hole does lead to configurations with smaller stresses. CONCLUSION: The bone tunnel placement with the smallest amount of shear stresses was found when the traction of the suture button was directed slightly lateral, towards the AC joint. Anatomical placement of the clavicle drill hole alone was not sufficient in preventing dangerous configurations. LEVEL OF EVIDENCE: Controlled laboratory study.

A biomechanical comparison of steel screws versus PLLA and magnesium screws for the Latarjet procedure.

INTRODUCTION: The fixation of the coracoid process onto the glenoid is an important step of the Latarjet procedure, and implant-associated complications are a relevant and severe problem. This study compares the fixation strength and failure mode of two biodegradable materials with stainless-steel screws. METHODS: 24 Fresh-frozen cadaveric scapulae were divided into three groups of equal size and received a coracoid transfer. Cadavers were matched according to their bone mineral density (BMD). In group 1, small-fragment screws made of stainless steel were used. In the second group, magnesium screws were used, and in the third group, screws consisted of polylactic acid (PLLA). A continuously increasing sinusoidal cyclic compression force was applied until failure occurred, which was defined as graft displacement relative to its initial position of more than 5 mm. RESULTS: At 5-mm displacement, the axial force values showed a mean of 374 ± 92 N (range 219-479 N) in group 1 (steel). The force values in group 2 (magnesium) had a mean of 299 ± 57 N (range 190-357 N). In group 3 (PLLA), failure occurred at 231 ± 83 N (range 109-355 N). The difference between group 1 (steel) and group 2 (magnesium) was not statistically significant (P = 0.212), while the difference between group 1 (steel) and group 3 (PLLA) was significant (P = 0.005). CONCLUSION: Stainless-Steel screws showed the highest stability. However, all three screw types showed axial force values of more than 200 N. Stainless steel screws and PLLA screws showed screw cut-out as the most common failure mode, while magnesium screws showed screw breakage in the majority of cases. EVIDENCE: Controlled laboratory study.

Biofilm formation - what we can learn from recent developments.

Although biofilms have been observed early in the history of microbial research, their impact has only recently been fully recognized. Biofilm infections, which contribute to up to 80% of human microbial infections, are associated with common human disorders, such as diabetes mellitus and poor dental hygiene, but also with medical implants. The associated chronic infections such as wound infections, dental caries and periodontitis significantly enhance morbidity, affect quality of life and can aid development of follow-up diseases such as cancer. Biofilm infections remain challenging to treat and antibiotic monotherapy is often insufficient, although some rediscovered traditional compounds have shown surprising efficiency. Innovative anti-biofilm strategies include application of anti-biofilm small molecules, intrinsic or external stimulation of production of reactive molecules, utilization of materials with antimicrobial properties and dispersion of biofilms by digestion of the extracellular matrix, also in combination with physical biofilm breakdown. Although basic principles of biofilm formation have been deciphered, the molecular understanding of the formation and structural organization of various types of biofilms has just begun to emerge. Basic studies of biofilm physiology have also resulted in an unexpected discovery of cyclic dinucleotide second messengers that are involved in interkingdom crosstalk via specific mammalian receptors. These findings even open up new venues for exploring novel anti-biofilm strategies.

[Avoidance-endurance fast screening (AE-FS) : Content and predictive validity of a 9­item screening instrument for patients with unspecific subacute low back pain]. / Avoidance-Endurance Fast-Screen (AE-FS) : Inhalts- und Vorhersagevalidität eines 9­Item-Screeninginstruments für Patienten mit unspezifischen subakuten Rückenschmerzen.

BACKGROUND: Among screening measures to assess psychosocial risk factors (yellow flags) for chronic low back pain (LBP) economic tools which address dysfunctional endurance pain responses besides emotional distress and fear-avoidance pain processing are rare. Targeting contrasting types of pain processing might improve stratified patient counselling. OBJECTIVE: The aim of the study was to develop a short screening method, based on the avoidance-endurance model of pain and to investigate the prognostic validity for pain intensity, disability and physical function. MATERIAL AND METHODS: A prospective observational study was carried out on 144 patients with subacute LBP (<3 months) from 7 general practitioners and 5 orthopedic practices. The 9­item avoidance-endurance fast screening (AE-FS) was derived from a previous 37-item screening using correlational and receiver operating curve (ROC) analyses and the agreement of subgrouping was calculated using Cohen's kappa. Primary outcomes were assessed after 6 months by mail in 124 patients (86%). Endpoints were pain intensity and disability. RESULTS: The classification of subgroups as high and low risk by both measures had considerable agreement with a value of 0.71 (Cohen's Kappa). The sensitivity to predict pain intensity >2 was high (82%) as was the positive predictive value (80%) but the negative predictive value was moderate (61%). The ROC (AUC) characteristics (95% confidence interval CI) were 0.70 (0.60-0.80) for pain intensity and for limitations in the pain disability index (PDI) 0.70 (0.55-0.87). DISCUSSION: The 9­item AE-FS displayed sufficient prognostic validity for all three outcomes in a sample of primary care patients with subacute LBP. The differentiation of the high-risk patients into fear-avoidance and endurance-related pain processing enables the physician to provide an individualized counselling with the aim of a healthy balance between stress and relaxation.

The relationship between global and specific components of quality of life, assessed with the EORTC QLQ-C30 in a sample of 2019 cancer patients.

Quality of life (QoL) is impaired in many cancer patients. The aim of this study was to test whether detriments in QoL were less pronounced in global assessments of QoL compared to more specific components. A total of 2059 cancer patients with mixed diagnoses were examined 6 months after discharge from a cancer rehabilitation clinic. QoL was measured with the EORTC QLQ-C30, which contains a global QoL scale, and 14 functioning and symptom scales and symptom items. A sample of the general population (n = 4476) served as controls. Regression analyses were performed to calculate expected mean scores for the patients, based on their age and gender distribution. Global QoL in the cancer sample (M = 69.3) was nearly equal to that of the general population, while the mean scores of all functioning scales, symptom scales and symptom items showed markedly worse QoL. This general relationship between global and specific QoL was found for seven of eight cancer types. The results indicate that global QoL is not the sum of its parts. This should be considered when treatment effects on QoL are examined. One alternative is to use higher order summarising functioning and symptom scales.

Aging with HIV-1 Infection: Motor Functions, Cognition, and Attention--A Comparison with Parkinson's Disease.

Recent advances in highly active anti-retroviral therapy (HAART) in their various combinations have dramatically increased the life expectancies of HIV-infected persons. People diagnosed with HIV are living beyond the age of 50 but are experiencing the cumulative effects of HIV infection and aging on brain function. In HIV-infected aging individuals, the potential synergy between immunosenescence and HIV viral loads increases susceptibility to HIV-related brain injury and functional brain network degradation similar to that seen in Parkinson's disease (PD), the second most common neurodegenerative disorder in the aging population. Although there are clear diagnostic differences in the primary pathology of both diseases, i.e., death of dopamine-generating cells in the substantia nigra in PD and neuroinflammation in HIV, neurotoxicity to dopaminergic terminals in the basal ganglia (BG) has been implied in the pathogenesis of HIV and neuroinflammation in the pathogenesis of PD. Similar to PD, HIV infection affects structures of the BG, which are part of interconnected circuits including mesocorticolimbic pathways linking brainstem nuclei to BG and cortices subserving attention, cognitive control, and motor functions. The present review discusses the combined effects of aging and neuroinflammation in HIV individuals on cognition and motor function in comparison with age-related neurodegenerative processes in PD. Despite the many challenges, some HIV patients manage to age successfully, most likely by redistribution of neural network resources to enhance function, as occurs in healthy elderly; such compensation could be curtailed by emerging PD.

Computer-assisted abdominal surgery: new technologies.

BACKGROUND: Computer-assisted surgery is a wide field of technologies with the potential to enable the surgeon to improve efficiency and efficacy of diagnosis, treatment, and clinical management. PURPOSE: This review provides an overview of the most important new technologies and their applications. METHODS: A MEDLINE database search was performed revealing a total of 1702 references. All references were considered for information on six main topics, namely image guidance and navigation, robot-assisted surgery, human-machine interface, surgical processes and clinical pathways, computer-assisted surgical training, and clinical decision support. Further references were obtained through cross-referencing the bibliography cited in each work. Based on their respective field of expertise, the authors chose 64 publications relevant for the purpose of this review. CONCLUSION: Computer-assisted systems are increasingly used not only in experimental studies but also in clinical studies. Although computer-assisted abdominal surgery is still in its infancy, the number of studies is constantly increasing, and clinical studies start showing the benefits of computers used not only as tools of documentation and accounting but also for directly assisting surgeons during diagnosis and treatment of patients. Further developments in the field of clinical decision support even have the potential of causing a paradigm shift in how patients are diagnosed and treated.

Quality of life in patients with muscle invasive and non-muscle invasive bladder cancer.

PURPOSE: Compared to the literature on other malignancies, data on quality of life (QoL) in bladder cancer are sparse. This study sought answers to the following questions: In what QoL domains do patients with bladder cancer differ from the general population? Do patients with radical cystectomy differ in QoL compared to those who received conservative treatment? Do patients with neobladder generally have better QoL compared to patients with other diversion methods? METHODS: At the beginning of inpatient rehabilitation, N = 823 patients with bladder cancer were assessed. Data of a representative community sample (N = 2037) were used for comparison. The questionnaire EORTC QLQ-C30 was used to measure QoL. Multivariate linear regression models were computed to investigate differences between groups. RESULTS: Patients with both non-muscle invasive and muscle invasive bladder cancer reported significantly more problems and worse functioning than the general population. Radiotherapy is associated with clinically relevant more pain, dyspnoea, constipation, appetite loss and decreased social functioning while chemotherapy is associated more with dyspnoea. Cystectomy patients reported more fatigue, appetite loss and decreased role functioning. Male patients ≥70 years with conduit experienced more sleep and emotional problems. These effects of urinary diversion were not observed in women and younger patients. CONCLUSIONS: Patients with bladder cancer experience various QoL concerns at the beginning of inpatient rehabilitation. These problems can partly be explained by the type of treatment the patients receive. Type of urinary diversion is relevant for QoL in subgroups of patients.

Molecular characterization and functional analysis of murine interleukin 4 receptor allotypes.

The murine interleukin 4 receptor (IL-4R) exists as a transmembrane protein transducing pleiotropic IL-4 functions, or as soluble (s)IL-4-binding molecule with potent immunoregulatory effects. In this study we identified and characterized a murine IL-4R allotype. Sequence analysis of the IL-4R cDNA of BALB/c mice revealed 18 base substitutions leading to three extracellular and five cytoplasmic amino acid changes when compared with the published IL-4R sequence of C57BL/6 mice. Analyses with allotype-specific mAbs revealed that AKR/J and SJL/J mice possess the newly identified BALB/c IL-4R allotype whereas the IL-4Rs of C3H, CBA, DBA-2, and FVB/N mice are identical to that of the C57BL/6 mouse. The extracellular Thr49 to Ile substitution abrogates one N-glycosylation site in the naturally occurring BALB/c IL-4R as well as in the experimentally point mutated C57BL/6-T49I sIL-4R, and both molecules display a nearly threefold reduction in IL-4-neutralizing activity compared to the C57BL/6 sIL-4R. In line with this, a significantly enhanced dissociation rate of IL-4 was detected for the BALB/c IL-4R allotype by surface plasmon resonance and in radioligand binding studies with IL-4R-transfected cell lines. These findings suggest that the altered ligand binding behavior of the newly described IL-4R allotype may influence the IL-4 responsiveness, thus contributing to the diverse phenotypes of inbred mouse strains in IL-4-dependent diseases.

Drainage of esophageal leakage using endoscopic vacuum therapy: a prospective pilot study.

BACKGROUND AND STUDY AIMS: Major leakage from an esophageal anastomosis is a life-threatening surgical complication. Endoscopically guided endoluminal vacuum therapy using polyurethane sponges is a new method for treating such leakage. PATIENTS AND METHODS: Between June 2007 and June 2009, five patients (mean age 68 years) who developed anastomotic leakage after esophageal surgery were prospectively evaluated. After endoscopic diagnosis of a major leakage, polyurethane sponges were endoscopically positioned in the wound cavity of the anastomosis. Continuous suction was applied via drainage tubes fixed to the sponges. Initially sponges were endoscopically changed three times per week. RESULTS: In all five patients treatment was successful. Median time to reduce levels of inflammation markers by 50 % was 10 days for white blood cell (WBC) count and 7 days for C-reactive protein (CRP). The smallest initial wound cavity size was 42 cm (3) and the largest was 157 cm (3). The median duration of drainage was 28 days, with a median of 9 sponge changes and a median time to total cavity closure of 42 days. Two patients needed anastomotic dilation by Savary-Miller bougienage due to stenosis found on further follow-up. One of these patients died of acute severe hemorrhage from an aortoanastomotic fistula after the dilation procedure. CONCLUSIONS: Endoscopically assisted vacuum therapy is a well-tolerated and effective therapeutic option for treatment of major esophageal leaks after surgery. Additional surgery was avoided in all cases. However, the occurrence of a delayed aortoesophageal fistula calls for careful further investigation of this new technique.

[Pedicle screw augmentation from a biomechanical perspective]. / Pedikelschraubenaugmentation aus biomechanischer Sicht.

Severe osteoporosis is a serious problem in the instrumentation during spine surgery. Besides kyphosis, adjacent vertebral fractures and of course pedicle screw loosening and implant pullout are frequent challenges in instrumentation of the osteoporotic spine. In addition to screw diameter and length, bone mineral density has the most important impact on the stability of a pedicle screw. In cases of severe osteoporosis cement augmentation increases the stability of a pedicle screw. Pullout force can be increased with augmentation by 96-278%. Nowadays, there are two different procedures for augmentation: cement augmentation of the vertebra before inserting the screw into the soft, fresh cement or augmentation via a perforated screw that has already been inserted.The main problem in augmentation techniques are cement leakages. In both techniques leakages may occur. The problem of leakages seems to be less severe in the augmentation technique via the perforated screw, because cement application can be stopped immediately if the onset of leakage is noticed. Even surgical revision of cement augmented screws is not a major clinical problem based on recent biomechanical studies. The revision screw can be chosen 1 mm thicker and can be cement augmented again without technical problems.

[Posterior operative correction of idiopathic scoliosis. Value of pedicle screws versus hooks]. / Dorsale operative Korrektur der idiopathischen Skoliose. Stellenwert von Pedikelschrauben vs. Haken.

Posterior correction and fusion of scoliosis with multisegmental instrumentation systems was developed by Cotrel-Dubousset in the 1980s. Initially correction and instrumentation was performed using hooks only. Later pedicle screws were implemented first for the lumbar and then for the thoracic spine. Nowadays instrumentation based on pedicle screws only is well established for posterior scoliosis surgery. Biomechanical studies demonstrated higher pull-out forces for pedicle than for hook constructs.In clinical studies several authors reported better Cobb angle correction of the primary and the secondary curves and less loss of correction in pedicle screw versus hook instrumentations. Furthermore, pedicle screw instrumentation allows fewer segments to be fused, especially caudally, and thus saving mobile segments. In most of these publications there were no differences in operation time, blood loss and complication rates. In summary, there is better curve correction without an increased risk using multisegmental pedicle screw instrumentation in modern posterior scoliosis surgery.

Increased risk of myeloid leukaemia in patients with ankylosing spondylitis following treatment with radium-224.

OBJECTIVE: To investigate long-term health effects in AS patients treated with (224)Ra. METHODS: A prospective epidemiological study has been carried out on 1471 AS patients treated with repeated intravenous injections of (224)Ra between 1948 and 1975. These patients have been followed together with a control group of 1324 AS patients not treated with radioactive drugs and/or X-rays. Numbers of malignancies expected in a normal population were computed from German and Danish cancer registry data. RESULTS: After a mean follow-up time of 26 yrs in the exposed group or 25 yrs in the control group, causes of death have been ascertained for 1006 exposed patients and 1072 controls. In particular, 19 cases of leukaemia were observed in the exposure group (vs 6.8 cases expected, P < 0.001) compared to 12 cases of leukaemia in the control group (vs 7.5 cases expected). Further subclassification of the leukaemia cases demonstrated a high increase of myeloid leukaemia in the exposure group (11 cases observed vs 2.9 cases expected, P < 0.001), especially a high excess of acute myeloid leukaemias (7 cases observed vs 1.8 cases expected, P = 0.003), whereas in the controls the observed cases are within the expected range (4 myeloid leukaemias vs 3.1 cases expected). CONCLUSIONS: The enhanced leukaemia incidence in the exposed group is in line with results from experiments in mice injected with varying amounts of the bone-seeking alpha-emitter (224)Ra. In these studies, in animals exposed to lower doses of (224)Ra, i.e. at doses lower than those found to induce osteosarcomas, an increased risk of leukaemia was observed.

Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway.

The serine/threonine kinase Raf-1 functions downstream of Rats in a signal transduction cascade which transmits mitogenic stimuli from the plasma membrane to the nucleus. Raf-1 integrates signals coming from extracellular factors and, in turn, activates its substrate, MEK kinase. MEK activates mitogen-activated protein kinase (MAPK), which phosphorylates other kinases as well as transcription factors. Raf-1 exists in a complex with HSP90 and other proteins. The benzoquinone ansamycin geldanamycin (GA) binds to HSP90 and disrupts the Raf-1-HSP90 multimolecular complex, leading to destabilization of Raf-1. In this study, we examined whether Raf-1 destabilization is sufficient to block the Raf-1-MEK-MAPK signalling pathway and whether GA specifically inactivates the Raf-1 component of this pathway. Using the model system of NIH 3T3 cells stimulated with phorbol 12-myristate 13-acetate (PMA), we show that GA does not affect the ability of protein kinase C alpha to be activated by phorbol esters, but it does block activation of MEK and MAPK. Further, GA does not decrease the activity of constitutively active MEK in transiently transfected cells. Finally, disruption of the Raf-1-MEK-MAPK signalling pathway by GA prevents both the PMA-induced proliferative response and PMA-induced activation of a MAPK-sensitive nuclear transcription factor. Thus, we demonstrate that interaction between HSP90 and Raf-1 is a sine qua non for Raf stability and function as a signal transducer and that the effects observed cannot be attributed to a general impairment of protein kinase function.

[Mass of the pelvis minor--the coloproctological point of view]. / Raumforderung im kleinen Becken--Sicht des Coloproktologen.

The pelvis minor is cranial defined by the promontory and caudal by the pelvic diaphragm. It contains the pelvic organs like the inner genital organs of women, the urinary bladder the rectum and parts of the anus. The rectum is the origin of benign and malign tumors. Most frequently you find under these tumors the benign adenoma and hamartoma and the malign like the rectal and anal cancer. The further diagnostic work up and following therapy relates to the histology and the anatomical location of the tumor.

The neural correlates of priming emotion and reward systems for conflict processing in alcoholics.

Emotional dysregulation in alcoholism (ALC) may result from disturbed inhibitory mechanisms. We therefore tested emotion and alcohol cue reactivity and inhibitory processes using negative priming. To test the neural correlates of cue reactivity and negative priming, 26 ALC and 26 age-matched controls underwent functional MRI performing a Stroop color match-to-sample task. In cue reactivity trials, task-irrelevant emotion and alcohol-related pictures were interspersed between color samples and color words. In negative priming trials, pictures primed the semantic content of an alcohol or emotion Stroop word. Behaviorally, both groups showed response facilitation to picture cue trials and response inhibition to primed trials. For cue reactivity to emotion and alcohol pictures, ALC showed midbrain-limbic activation. By contrast, controls activated frontoparietal executive control regions. Greater midbrain-hippocampal activation in ALC correlated with higher amounts of lifetime alcohol consumption and higher anxiety. With negative priming, ALC exhibited frontal cortical but not midbrain-hippocampal activation, similar to the pattern observed in controls. Higher frontal activation to alcohol-priming correlated with less craving and to emotion-priming with fewer depressive symptoms. The findings suggest that neurofunctional systems in ALC can be primed to deal with upcoming emotion- and alcohol-related conflict and can overcome the prepotent midbrain-limbic cue reactivity response.

Induction of immediate early gene expression by high-frequency stimulation of the subthalamic nucleus in rats.

Deep brain stimulation is associated with delayed improvement of parkinsonian symptoms, such as hypokinesia with subthalamic nucleus stimulation, or dystonia with globus pallidus internus stimulation. The latency observed is better explained by molecular alterations than immediate electrophysiological processes, and clinical improvement may involve adaptive gene expression. Here, we have studied immediate early gene expression as fast molecular response to subthalamic nucleus stimulation. Bipolar electrodes were implanted bilaterally into the subthalamic nucleus of anesthetized male Wistar rats. High-frequency stimulation (130 Hz or 80 Hz, 60 micros, 300 microA) or low-frequency stimulation (5 Hz, 60 micros, 300 microA) was performed with the right electrode for 15, 60, 120, and 240 min whereas the silent left electrode served as negative control. Brains were fixed by transcardial perfusion and frozen sections were stained with polyclonal antibodies directed against three immediate early gene-encoded proteins, c-Fos, c-Jun, and Krox-24 (NGFI-A, Egr-1, Zif268, Tis8, Zenk). After 120 and 240 h, c-Fos immunoreactivity was strongly upregulated in subthalamic nucleus neurons on the stimulated site. In contrast, no c-Fos immunoreactivity was detected on the non-stimulated site except for single positive cells located in close proximity to the electrode tracks. Furthermore, c-Fos immunoreactivity was induced in subthalamic nucleus projection areas, such as primary and secondary motor cortex, primary somatosensory and insular cortex, lateral and medial globus pallidus, suprageniculate thalamic nucleus, pontine nuclei, medial geniculate nucleus, and substantia nigra. Similarly, c-Jun and Krox-24 were induced at the site of stimulation and in projection areas following high-frequency subthalamic nucleus stimulation. Whereas high frequency stimulation with 80 Hz was similarly effective none of the three immediate early gene-encoded proteins was induced with low-frequency stimulation (5 Hz) for 4 h. This is in accordance with the therapeutic effects of deep brain stimulation which are only elicited with high frequency stimulation. Our data provide evidence that immediate early gene expression in the subthalamic nucleus is rapidly and substantially induced by high-frequency stimulation. The induction of immediate early genes in projection sites suggests ipsilateral transsynaptic modulation of neuronal activity.