Longitudinal growth on an everolimus‐ versus an MMF‐based steroid‐free immunosuppressive regimen in paediatric renal transplant recipients

Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case‐control study on longitudinal growth over 2 years in steroid‐free pediatric renal transplant recipients. Fourteen patients on a steroid‐free maintenance immunosuppressive regimen consisting of low‐dose everolimus (EVR) in conjunction with low‐dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid‐free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch‐up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid‐free pediatric patients on low‐dose EVR and CsA is not different to that of a matched steroid‐free control group on an immunosuppressive regimen with standard‐dose CNI and MMF. Hence, low‐dose EVR does not appear to negatively impact short‐term growth in pediatric renal transplant recipients.     

Diffusion tensor imaging in brainstem tuberculoma

Integrity of descending white matter tracts can be evaluated by diffusion tensor imaging. In rim-enhancing intraparenchymal lesions, this technique can assist in the differentiation of demyelinating disease from tumor or abscess. Diffusion tensor imaging characteristics of tuberculoma have not been previously reported to our knowledge. A patient with headaches, dizziness, and mild left-sided weakness underwent MRI with diffusion tensor imaging. A large, rim-enhancing lesion within the pons was discovered, which subsequently was diagnosed as tuberculoma. Tractography maps prepared from diffusion tensor imaging data revealed predominantly displaced descending fiber tracts in the region of the rim-enhancing lesion. A few tracts adjacent to the lesion appeared truncated, and this abnormal finding correlated to the patient’s clinical deficit. The tractography characteristics of diffusion tensor imaging in this patient potentially are distinct from those seen with demyelinating lesions, which may show more extensive tract truncation. Together with the consonance of exam findings and tract truncation seen in this patient, tractography may prove useful in the diagnosis of suspected tuberculoma.     

25 Jahre Notfall+Rettungsmedizin – reine Männersache?

Notfall + Rettungsmedizin -     

Comparison of Risk Factors for Unplanned Conversion from Laparoscopic and Robotic to Open Colorectal Surgery Using the Michigan Surgical Quality Collaborative (MSQC) Database

Robotic colorectal surgery has been shown to have lower rates of unplanned conversion to open surgery when compared to laparoscopic surgery. Risk factors associated with conversion from robotic to open colectomy and comparisons of the risk factors between robotic and laparoscopic approaches have not been previously reported. Patients who underwent elective laparoscopic and robotic colorectal surgeries between July 1, 2012 and April 28, 2015, were identified in the Michigan Surgical Quality Collaborative registry. Candidate covariates were identified, and hierarchical logistic regression models were used to identify risk factors for conversion. There were 4796 cases that met study inclusion criteria. Conversion was required in 18.2 % of laparoscopic and 7.7 % of robotic cases (p?<?0.0001). Risk factors for conversion in the laparoscopic group included the following: moderate/severe adhesions, obesity, colorectal cancer, hypertension, rectal operations, urgent priority, and tobacco use. Risk factors for conversion in the robotic group included the following: severe adhesions, bleeding disorder, presence of cancer, cirrhosis, and use of statins. Higher surgeon volume was protective in both groups. Conversion rates are lower for robotic than for laparoscopic colorectal surgery with fewer predictors of conversion. Recognition of factors predicting conversion may allow surgeons to choose an operative approach that optimizes the benefits of the available technologies.     

Effects of endogenous D-alanine synthesis and autoinhibition of Bacillus anthracis germination on in vitro and in vivo infections

Bacillus anthracis transitions from a dormant spore to a vegetative bacillus through a series of structural and biochemical changes collectively referred to as germination. The timing of germination is important during early steps in infection and may determine if B. anthracis survives or succumbs to responsive macrophages. In the current study experiments determined the contribution of endogenous D-alanine production to the efficiency and timing of B. anthracis spore germination under in vitro and in vivo conditions. Racemase-mediated production of endogenous D-alanine by B. anthracis altered the kinetics for initiation of germination over a range of spore densities and exhibited a threshold effect wherein small changes in spore number resulted in major changes in germination efficiency. This threshold effect correlated with D-alanine production, was prevented by an alanine racemase inhibitor, and required L-alanine. Interestingly, endogenous production of inhibitory levels of D-alanine was detected under experimental conditions that did not support germination and in a germination-deficient mutant of B. anthracis. Racemase-dependent production of D-alanine enhanced survival of B. anthracis during interaction with murine macrophages, suggesting a role for inhibition of germination during interaction with these cells. Finally, in vivo experiments revealed an approximately twofold decrease in the 50% lethal dose of B. anthracis spores administered in the presence of D-alanine, indicating that rates of germination may be directly influenced by the levels of this amino acid during early stages of disease.     

Protective and immunochemical activities of monoclonal antibodies reactive with the Bacillus anthracis polypeptide capsule

Bacillus anthracis is surrounded by a polypeptide capsule composed of poly-gamma-d-glutamic acid (gammaDPGA). In a previous study, we reported that a monoclonal antibody (MAb F26G3) reactive with the capsular polypeptide is protective in a murine model of pulmonary anthrax. The present study examined a library of six MAbs generated from mice immunized with gammaDPGA. Evaluation of MAb binding to the capsule by a capsular "quellung" type reaction showed a striking diversity in capsular effects. Most MAbs produced a rim type reaction that was characterized by a sharp increase followed directly by a decrease in refractive index at the capsular edge. Some MAbs produced a second capsular reaction well beneath the capsular edge, suggesting complexity in capsular architecture. Binding of MAbs to soluble gammaDPGA was assessed by a fluorescence perturbation assay in which a change in the MAb intrinsic fluorescence produced by ligand binding was used as a reporter for antigen-antibody interaction. The MAbs differed considerably in the complexity of the binding curves. MAbs producing rim type capsule reactions typically produced the more complex binding isotherms. Finally, the protective activity of the MAbs was compared in a murine model of pulmonary anthrax. One MAb was markedly less protective than the remaining five MAbs. Characteristics of the more protective MAbs included a relatively high affinity, an immunoglobulin G3 isotype, and a complex binding isotherm in the fluorescence perturbation assay. Given the relatively monotonous structure of gammaDPGA, the results demonstrate a striking diversity in the antigen binding behavior of gammaDPGA antibodies.