Minimal invasive extracorporeal circulation should become the standard practice in coronary revascularization surgery†.

We read with great interest the large-scale network meta-analysis by Kowalewski et al. comparing clinical outcomes of patients undergoing coronary artery bypass grafting (CABG) operated on using minimal invasive extracorporeal circulation (MiECC) or off-pump (OPCAB) with those undergoing surgery on conventional cardiopulmonary bypass (CPB) [1]. The authors actually integrated into single study two recently published meta-analysis comparing MiECC and OPCAB with conventional CPB, respectively [2, 3] into a single study. According to the results of this study, MiECC and OPCAB are both strongly associated with improved perioperative outcomes following CABG when compared with CABG performed on conventional CPB. The authors conclude that MiECC may represent an attractive compromise between OPCAB and conventional CPB. After carefully reading the whole manuscript, it becomes evident that the role of MiECC is clearly undervalued. Detailed statistical analysis using the surface under the cumulative ranking probabilities indicated that MiECC represented the safer and more effective intervention regarding all-cause mortality and protection from myocardial infarction, cerebral stroke, postoperative atrial fibrillation and renal dysfunction when compared with OPCAB. Even though no significant statistical differences were demonstrated between MiECC and OPCAB, the superiority of MiECC is obvious by the hierarchy of treatments in the probability analysis, which ranked MiECC as the first treatment followed by OPCAB and conventional CPB. Thus, MiECC does not represent a compromise between OPCAB and conventional CPB, but an attractive dominant technique in CABG surgery. These results are consistent with the largest published meta-analysis by Anastasiadis et al. comparing MiECC versus conventional CPB including a total of 2770 patients. A significant decrease in mortality was observed when MiECC was used, which was also associated with reduced risk of postoperative myocardial infarction and neurological events [4]. Similarly, another recent meta-analysis by Benedetto et al. compared MiECC versus OPCAB and resulted in comparable outcomes between these two surgical techniques [5]. As stated in the text, superiority of MiECC observed in the current network meta-analysis, when compared with OPCAB, could be attributed to the fact that MiECC offers the potential for complete revascularization, whereas OPCAB poses a challenge for unexperienced surgeons; especially when distal marginal branches on the lateral and/or posterior wall of the heart need revascularization. This is reflected by a significantly lower number of distal anastomoses performed in OPCAB when compared with conventional CPB. Therefore, taking into consideration the literature published up to date, including the results of the current article, we advocate that MiECC should be integrated in the clinical practice guidelines as a state-of-the-art technique and become a standard practice for perfusion in coronary revascularization surgery.

Influence of unilateral maxillary first molar extraction treatment on second and third molar inclination in Class II subdivision patients.

OBJECTIVE To assess the maxillary second molar (M2) and third molar (M3) inclination following orthodontic treatment of Class II subdivision malocclusion with unilateral maxillary first molar (M1) extraction. MATERIALS AND METHODS Panoramic radiographs of 21 Class II subdivision adolescents (eight boys, 13 girls; mean age, 12.8 years; standard deviation, 1.7 years) before treatment, after treatment with extraction of one maxillary first molar and Begg appliances and after at least 1.8 years in retention were retrospectively collected from a private practice. M2 and M3 inclination angles (M2/ITP, M2/IOP, M3/ITP, M3/IOP), constructed by intertuberosity (ITP) and interorbital planes (IOP), were calculated for the extracted and nonextracted segments. Random effects regression analysis was performed to evaluate the effect on the molar angulation of extraction, time, and gender after adjusting for baseline measurements. RESULTS Time and extraction status were significant predictors for M2 angulation. M2/ITP and M2/IOP decreased by 4.04 (95% confidence interval [CI]: -6.93, 1.16; P  =  .001) and 3.67 (95% CI: -6.76, -0.58; P  =  .020) in the extraction group compared to the nonextraction group after adjusting for time and gender. The adjusted analysis showed that extraction was the only predictor for M3 angulation that reached statistical significance. M3 mesial inclination increased by 7.38° (95% CI: -11.2, -3.54; P < .001) and 7.33° (95% CI: -11.48, -3.19; P  =  .001). CONCLUSIONS M2 and M3 uprighting significantly improved in the extraction side after orthodontic treatment with unilateral maxillary M1 extraction. There was a significant increase in mesial tipping of maxillary second molar crowns over time.

Neurotoxicity of stem cell mobilization chemotherapy with vinorelbine in myeloma patients after bortezomib treatment.

Vinorelbine chemotherapy with G-CSF stimulation is the standard mobilization regimen in Switzerland for multiple myeloma patients. However, with the increasing use of bortezomib during induction treatment, adding the neurotoxic compound vinorelbine for mobilization may aggravate bortezomib-induced polyneuropathy. In this retrospective single-center study, we aimed to explore vinorelbine mediated neuropathy in 106 consecutive bortezomib pretreated myeloma patients. We confirmed that vinorelbine with G-CSF represents a reliable and effective regimen for mobilization of autologous stem cells. However, the single administration of 35 mg/m(2) vinorelbine added significant neurotoxicity. We found that 24 patients (24%) reported vinorelbine mediated neurotoxicity: Aggravation of bortezomib-induced neuropathy was observed in 17 patients (17%), and vinorelbine mobilization induced first occurrence of polyneuropathy in additional 7 patients (7%). We observed that development of polyneuropathy was not associated with differing survival rates. Finally, affected patients reported polyneuropathy associated disease burden as "very high" in 13% and "high" in 50%. Our data indicate that a single administration of vinorelbine to mobilize autologous stem cells is associated with significant additional polyneuropathy in bortezomib pretreated myeloma patients. The efficacy of vinorelbine mobilization should be balanced against its neurotoxic potential.

[Diagnosis and Treatment of Spondylodiscitis/Spondylitis in Clinical Practice].

BACKGROUND The clinical presentation of spondylsodiscitis/spondylitis are manifold. This commonly leads to a period of several months from initial symptoms to final diagnosis. A standardised treatment is difficult. The purpose of this study is to investigate the treatment carried out for patients with spondylodiscitis or spondylitis to develop an individualised standard care for better treatment. PATIENTS AND METHODS Data of 90 patients were retrospective analysed. In particular documented data of the initial examination and the following treatments concerning identification of causes and systematically control of pathogens were examined. RESULTS In 91 % of patients a diagnostically conclusive MRI was conducted. The degree of spondylidiscitis/spondylitis was mainly ASA criteria I or II (86 %). In 96 % of patients different diagnostic methods for identification of pathogens were conducted and documented. RESULTS confirmed the most common pathogens mentioned in the literature. 75 % of patients were treated by surgery. In 93 % of patients an antibiotic treatment was documented. 50 patients (81 %) were successfully healed. CONCLUSION It is important to identify and treat spondylodiscitis/spondylitis as early as possible. Diagnosis by means of blood culture and MRI and treatment of the infection with antibiotics and possibly surgical interventions seem be very suitable, but need to be individualised to each and every patient.

Computer Assisted Diagnosis and Treatment Planning of Femoroacetabular Impingement (FAI)

Femoroacetabular impingement (FAI) is a dynamic conflict of the hip defined by a pathological, early abutment of the proximal femur onto the acetabulum or pelvis. In the past two decades, FAI has received increasing focus in both research and clinical practice as a cause of hip pain and prearthrotic deformity. Anatomical abnormalities such as an aspherical femoral head (cam-type FAI), a focal or general overgrowth of the acetabulum (pincer-type FAI), a high riding greater or lesser trochanter (extra-articular FAI), or abnormal torsion of the femur have been identified as underlying pathomorphologies. Open and arthroscopic treatment options are available to correct the deformity and to allow impingement-free range of motion. In routine practice, diagnosis and treatment planning of FAI is based on clinical examination and conventional imaging modalities such as standard radiography, magnetic resonance arthrography (MRA), and computed tomography (CT). Modern software tools allow three-dimensional analysis of the hip joint by extracting pelvic landmarks from two-dimensional antero-posterior pelvic radiographs. An object-oriented cross-platform program (Hip2Norm) has been developed and validated to standardize pelvic rotation and tilt on conventional AP pelvis radiographs. It has been shown that Hip2Norm is an accurate, consistent, reliable and reproducible tool for the correction of selected hip parameters on conventional radiographs. In contrast to conventional imaging modalities, which provide only static visualization, novel computer assisted tools have been developed to allow the dynamic analysis of FAI pathomechanics. In this context, a validated, CT-based software package (HipMotion) has been introduced. HipMotion is based on polygonal three-dimensional models of the patient’s pelvis and femur. The software includes simulation methods for range of motion, collision detection and accurate mapping of impingement areas. A preoperative treatment plan can be created by performing a virtual resection of any mapped impingement zones both on the femoral head-neck junction, as well as the acetabular rim using the same three-dimensional models. The following book chapter provides a summarized description of current computer-assisted tools for the diagnosis and treatment planning of FAI highlighting the possibility for both static and dynamic evaluation, reliability and reproducibility, and its applicability to routine clinical use.

A 2-year multicentre, open-label, randomized, controlled study of growth hormone (Genotropin(®) ) treatment in very young children born small for gestational age: Early Growth and Neurodevelopment (EGN) Study

OBJECTIVE In Europe, growth hormone (GH) treatment for children born small for gestational age (SGA) can only be initiated after 4 years of age. However, younger age at treatment initiation is a predictor of favourable response. To assess the effect of GH treatment on early growth and cognitive functioning in very young (<30 months), short-stature children born SGA. DESIGN A 2-year, randomized controlled, multicentre study (NCT00627523; EGN study), in which patients received either GH treatment or no treatment for 24 months. PATIENTS Children aged 19-29 months diagnosed as SGA at birth, and for whom sufficient early growth data were available, were eligible. Patients were randomized (1:1) to GH treatment (Genotropin(®) , Pfizer Inc.) at a dose of 0·035 mg/kg/day by subcutaneous injection, or no treatment. MEASUREMENTS The primary objective was to assess the change from baseline in height standard deviation score (SDS) after 24 months of GH treatment. RESULTS Change from baseline in height SDS was significantly greater in the GH treatment vs control group at both month 12 (1·03 vs 0·14) and month 24 (1·63 vs 0·43; both P < 0·001). Growth velocity SDS was significantly higher in the GH treatment vs control group at 12 months (P < 0·001), but not at 24 months. There was no significant difference in mental or psychomotor development indices between the two groups. CONCLUSIONS GH treatment for 24 months in very young short-stature children born SGA resulted in a significant increase in height SDS compared with no treatment.

Feasibility of stereotactic MRI-based image guidance for the treatment of vascular malformations: a phantom study.

PURPOSE Treatment of vascular malformations requires the placement of a needle within vessels which may be as small as 1 mm, with the current state of the art relying exclusively on two-dimensional fluoroscopy images for guidance. We hypothesize that the combination of stereotactic image guidance with existing targeting methods will result in faster and more reproducible needle placements, as well as reduced radiationexposure, when compared to standard methods based on fluoroscopy alone. METHODS The proposed navigation approach was evaluated in a phantom experiment designed to allow direct comparison with the conventional method. An anatomical phantom of the left forearm was constructed, including an independent control mechanism to indicate the attainment of the target position. Three interventionalists (one inexperienced, two of them frequently practice the conventional fluoroscopic technique) performed 45 targeting attempts utilizing the combined and 45 targeting attempts utilizing the standard approaches. RESULTS In all 45 attempts, the users were able to reach the target when utilizing the combined approach. In two cases, targeting was stopped after 15 min without reaching the target when utilizing only the C-arm. The inexperienced user was faster when utilizing the combined approach and applied significantly less radiation than when utilizing the conventional approach. Conversely, both experienced users were faster when using the conventional approach, in one case significantly so, with no significant difference in radiation dose when compared to the combined approach. CONCLUSIONS This work presents an initial evaluation of a combined navigation fluoroscopy targeting technique in a phantom study. The results suggest that, especially for inexperienced interventionalists, navigation may help to reduce the time and the radiation dose. Future work will focus on the improvement and clinical evaluation of the proposed method.

New insights into the pharmacokinetics and pharmacodynamics of natalizumab treatment for patients with multiple sclerosis, obtained from clinical and in vitro studies.

BACKGROUND The monoclonal antibody natalizumab (NAT) inhibits the migration of lymphocytes throughout the blood-brain barrier by blocking very late antigen (VLA)-4 interactions, thereby reducing inflammatory central nervous system (CNS) activity in patients with multiple sclerosis (MS). We evaluated the effects of different NAT treatment regimens. METHODS We developed and optimised a NAT assay to measure free NAT, cell-bound NAT and VLA-4 expression levels in blood and cerebrospinal fluid (CSF) of patients using standard and prolonged treatment intervals and after the cessation of therapy. RESULTS In paired CSF and blood samples of NAT-treated MS patients, NAT concentrations in CSF were approximately 100-fold lower than those in serum. Cell-bound NAT and mean VLA-4 expression levels in CSF were comparable with those in blood. After the cessation of therapy, the kinetics of free NAT, cell-bound NAT and VLA-4 expression levels differed. Prolonged intervals greater than 4 weeks between infusions caused a gradual reduction of free and cell-bound NAT concentrations. Sera from patients with and without NAT-neutralising antibodies could be identified in a blinded assessment. The NAT-neutralising antibodies removed NAT from the cell surface in vivo and in vitro. Intercellular NAT exchange was detected in vitro. CONCLUSIONS Incorporating assays to measure free and cell-bound NAT into clinical practice can help to determine the optimal individual NAT dosing regimen for patients with MS.