Nailing vs. plating in comminuted proximal ulna fractures : a biomechanical analysis

BACKGROUND Comminuted proximal ulna fractures are severe injuries with a high degree of instability. These injuries require surgical treatment, usually angular stable plating or double plating is performed. Nailing of proximal ulna fracture is described but not performed regularly. The aim of this study was to compare a newly developed, locked proximal ulna nail with an angular stable plate in an unstable fracture of the proximal ulna. We hypothesize, that locked nailing of the proximal ulna will provide non-inferior stability compared to locked plating. METHODS A defect fracture distal to the coronoid was simulated in 20 sawbones. After nailing or plate osteosynthesis the constructs were tested in a servo-pneumatic testing machine under physiological joint motion (0°-90°) and cyclic loading (30 N – 300 N). Intercyclic osteotomy gap motion and plastic deformation of the constructs were analyzed using micromotion video-analysis. RESULTS The locked nail showed lower osteotomy gap motion (0.50 ± 0.15 mm) compared to the angular stable plate (1.57 ± 0.37 mm, p < 0.001). At the anterior cortex the plastic deformation of the constructs was significantly lower for the locked nail (0.09 ± 0.17 mm vs. 0.39 ± 0.27 mm, p = 0.003). No statistically significant differences were observed at the posterior cortex for both parameters. CONCLUSIONS Nail osteosynthesis in comminuted proximal ulna fractures shows lower osteotomy gap motion and lower amount of plastic deformation compared to locking plate osteosynthesis under laboratory conditions

Comparison of Postoperative Coronal Leg Alignment in Customized Individually Made and Conventional Total Knee Arthroplasty

Neutral coronal leg alignment is known to be important for postoperative outcome in total knee arthroplasty (TKA). Customized individually made implants (CIM) instrumented with patient-specific cutting guides are an innovation aiming to increase the precision and reliability of implant positioning and reconstruction of leg alignment. We aimed to compare reconstruction of the hip–knee–ankle angle (HKA) of the novel CIM system iTotal™ CR G2 (ConforMIS Inc.) to a matched cohort of the off-the-shelf (OTS) knee replacement system Vanguard™ CR (Zimmer Biomet). Retrospective analysis of postoperative coronal full-leg weight-bearing radiographs of 562 TKA (283 CIM TKA, 279 OTS TKA) was conducted. Via a medical planning software, HKA and rotation of the leg were measured in postoperative radiographs. HKA was then adjusted for rotational error, and 180° ± 3° varus/valgus was defined as the target zone HKA. Corrected postoperative HKA in the CIM group was 179.0° ± 2.8° and 179.2° ± 3.1° in the OTS group (p = 0.34). The rate of outliers, outside of the ±3° target zone, was equal in both groups (32.9%). Our analysis showed that TKA using patient-specific cutting guides and implants and OTS TKA implanted with conventional instrumentation resulted in equally satisfying restoration of the coronal leg alignment with less scattering in the CIM group

The human brain is a detector of chemosensorily transmitted HLA-class I-similarity in same- and opposite-sex relations

Studies on subjective body odour ratings suggest that humans exhibit preferences for human leucocyte antigen (HLA)-dissimilar persons. However, with regard to the extreme polymorphism of the HLA gene loci, the behavioural impact of the proposed HLA-related attracting signals seems to be minimal. Furthermore, the role of HLA-related chemosignals in same- and opposite-sex relations in humans has not been specified so far. Here, we investigate subjective preferences and brain evoked responses to body odours in males and females as a function of HLA similarity between odour donor and smeller. We show that pre-attentive processing of body odours of HLA-similar donors is faster and that late evaluative processing of these chemosignals activates more neuronal resources than the processing of body odours of HLA-dissimilar donors. In same-sex smelling conditions, HLA-associated brain responses show a different local distribution in male (frontal) and female subjects (parietal). The electrophysiological results are supported by significant correlations between the odour ratings and the amplitudes of the brain potentials. We conclude that odours of HLA-similar persons function as important social warning signals in inter- and intrasexual human relations. Such HLA-related chemosignals may contribute to female and male mate choice as well as to male competitive behaviour

Nailing vs. plating in comminuted proximal ulna fractures – a biomechanical analysis

Background!#!Comminuted proximal ulna fractures are severe injuries with a high degree of instability. These injuries require surgical treatment, usually angular stable plating or double plating is performed. Nailing of proximal ulna fracture is described but not performed regularly. The aim of this study was to compare a newly developed, locked proximal ulna nail with an angular stable plate in an unstable fracture of the proximal ulna. We hypothesize, that locked nailing of the proximal ulna will provide non-inferior stability compared to locked plating.!##!Methods!#!A defect fracture distal to the coronoid was simulated in 20 sawbones. After nailing or plate osteosynthesis the constructs were tested in a servo-pneumatic testing machine under physiological joint motion (0°-90°) and cyclic loading (30 N - 300 N). Intercyclic osteotomy gap motion and plastic deformation of the constructs were analyzed using micromotion video-analysis.!##!Results!#!The locked nail showed lower osteotomy gap motion (0.50 ± 0.15 mm) compared to the angular stable plate (1.57 ± 0.37 mm, p &amp;lt; 0.001). At the anterior cortex the plastic deformation of the constructs was significantly lower for the locked nail (0.09 ± 0.17 mm vs. 0.39 ± 0.27 mm, p = 0.003). No statistically significant differences were observed at the posterior cortex for both parameters.!##!Conclusions!#!Nail osteosynthesis in comminuted proximal ulna fractures shows lower osteotomy gap motion and lower amount of plastic deformation compared to locking plate osteosynthesis under laboratory conditions

Generation and Characterization of dickkopf3 Mutant Mice

dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice. dkk3-deficient mice are viable and fertile. Phenotypic analysis shows no major alterations in organ morphology, physiology, and most clinical chemistry parameters. Since Dkk3 was proposed to function as thyroid hormone binding protein, we have analyzed deiodinase activities, as well as thyroid hormone levels. Mutant mice are euthyroid, and the data do not support a relationship of dkk3 with thyroid hormone metabolism. Altered phenotypes in dkk3 mutant mice were observed in the frequency of NK cells, immunoglobulin M, hemoglobin, and hematocrit levels, as well as lung ventilation. Furthermore, dkk3-deficient mice display hyperactivity

The multicentre, double-blinded, placebo-controlled clinical-trial (Pre-GvHD) for prediction and pre-emptive treatment of acute GvHD [Abstract]

Allogeneic stem cell transplantation (HSCT) is a curative treatment for adult patients with hematologic malignancies, but is limited by severe, life-threatening complications such as acute graft-versus-host disease (aGvHD). We have developed a proteomic urine pattern “aGvHD_MS17”, consisting of 17 differentially excreted peptides, capable to predict aGvHD grade II or more (1, 2). In 2008, a multicenter, randomized, placebo-controlled, double blind clinical trial (Pre-GvHD) was initiated testing aGvHD_MS17 for prediction of aGvHD and to initiate pre-emptive therapy using prednisolone 2-2.5mg/kg. Patients and Methods: Eleven German transplant-centres contributed 267 patients. Urine was collected weekly from day +7 to +35 and on days +50 and +80 (all +/-3 days) frozen, shipped to Hannover and analyzed using capillary electrophoresis coupled on-line to mass spectrometry (CE-MS) within 72h as described (1). aGvHD_MS17 was considered positive, when the dimensionless classification factor (CF) was +0.1 or more. Eight patients were excluded from analyses, either due to no medication (n=5) or protocol violations (n=3) and 92 were randomized according to the positivity of aGvHD-MS17 to receive either prednisolone (2-2.5mg/kg, n=44) or placebo (n=48) for 5 days followed by a taper for 19 days, if no aGvHD occurred. The remaining 167 patients formed the observation group according to pattern negativity. About half of the patients had acute leukemia (placebo group: n=24/48 (50%), prednisolone group: n=21/44 (50%); observation group: n= 91/167 (54%)) and were in complete remission/chronic phase (CR/CP) (placebo n=23/48 (47%), prednisolone n=27/44 (61%) and observation n=68/167 (41%). The majority was transplanted from matched donors (placebo: n=42/48 (87%); prednisolone: n=37/44 (84%); observation: 146/167 (87%), using reduced intensity conditioning regimens (RIC; 64%), and a calcineurin-inhibitor based GvHD-prophylaxis with MTX or MMF). Results: Prospective and blinded evaluation of aGvHD_MS17 revealed that the first analysis time point (day +7; range: 2-17) most accurately predicted aGvHD grade II or more with a sensitivity of 87% and a specificity of 81% prior to clinical signs with a CF of +0.1 (2). Patients with samples positive for aGvHD_MS17 in the early analyses time points had a 21-fold higher risk to develop aGvHD grade II or more ((p<0.0001), Figure 1). By day +28 the predictive value of aGvHD_MS17 was lost. Confounding factors were conditioning with RIC-protocols and early death after HSCT. Patients with one sample positive for aGvHD_MS17 had a 3-fold higher risk to die, 35% of those died prior to day +500, compared to only 10% of the patients with negative samples. Analysis of pre-emptive therapy using prednisolone revealed that the incidence and severity of acute GvHD was not significantly different between the placebo and prednisolone arm suggesting that prednisolone 2-2.5mg/kg was insufficient to prevent aGvHD in this setting. Further analyses of aGvHD according to organ manifestation are ongoing. The occurrence of aGvHD after a positive proteomic pattern test in the placebo group of this trial was lower than in the previous pilot study. Possible reasons include different patient populations (pilot study: 18% of patients transplanted in relapse; current trial: only 4% transplanted in relapse, increasing the risk to develop aGvHD), different intestinal decontamination and GvHD prophylaxis protocols. The frequency of adverse and serious adverse events was not higher in the prednisolone arm than the placebo arm. No specific safety risk of the pre-emptive therapy with prednisolone was identified. Conclusions: Taken together our results indicate that pre-emptive treatment of imminent aGvHD based on proteomic-pattern-diagnostic with prednisolone 2-2.5mg/kg appears to be safe, but did not influence severity or incidence of aGvHD grade II or more. The prospective evaluation of aGvHD_MS17 confirms the highly reproducible results in the early analysis time points (day +7 to +21) for prediction of aGvHD (day +7; range 2-17). Patients with aGvHD_MS17 positive samples have a 21-fold risk to develop severe GvHD (grade II-IV). Moreover, patients with one sample positive for aGvHD_MS17have a 3-fold increased risk of death by day +500 after HSCT

Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy

Clinical presentation of congenital heart disease is heterogeneous, making identification of the disease-causing genes and their genetic pathways and mechanisms of action challenging. By using in vivo electrocardiography, transthoracic echocardiography and microcomputed tomography imaging to screen 3,894 single-gene-null mouse lines for structural and functional cardiac abnormalities, here we identify 705 lines with cardiac arrhythmia, myocardial hypertrophy and/or ventricular dilation. Among these 705 genes, 486 have not been previously associated with cardiac dysfunction in humans, and some of them represent variants of unknown relevance (VUR). Mice with mutations in Casz1, Dnajc18, Pde4dip, Rnf38 or Tmem161b genes show developmental cardiac structural abnormalities, with their human orthologs being categorized as VUR. Using UK Biobank data, we validate the importance of the DNAJC18 gene for cardiac homeostasis by showing that its loss of function is associated with altered left ventricular systolic function. Our results identify hundreds of previously unappreciated genes with potential function in congenital heart disease and suggest causal function of five VUR in congenital heart disease