A biomechanical rationale for C1-ring osteosynthesis as treatment for displaced Jefferson burst fractures with incompetency of the transverse atlantal ligament

Nonsurgical treatment of Jefferson burst fractures (JBF) confers increased rates of C1–2 malunion with potential for cranial settling and neurologic sequels. Hence, fusion C1–2 was recognized as the superior treatment for displaced JBF, but sacrifies C1–2 motion. Ruf et al. introduced the C1-ring osteosynthesis (C1–RO). First results were favorable, but C1–RO was not without criticism due to the lack of clinical and biomechanical data serving evidence that C1–RO is safe in displaced JBF with proven rupture of the transverse atlantal ligament (TAL). Therefore, our objectives were to perform a biomechanical analysis of C1–RO for the treatment of displaced Jefferson burst fractures (JBF) with incompetency of the TAL. Five specimens C0–2 were subjected to loading with posteroanterior force transmission in an electromechanical testing machine (ETM). With the TAL left intact, loads were applied posteriorly via the C1–RO ramping from 10 to 100 N. Atlantoaxial subluxation was measured radiographically in terms of the anterior antlantodental interval (AADI) with an image intensifier placed surrounding the ETM. Load–displacement data were also recorded by the ETM. After testing the TAL-intact state, the atlas was osteotomized yielding for a JBF, the TAL and left lateral joint capsule were cut and the C1–RO was accomplished. The C1–RO was subjected to cyclic loading, ramping from 20 to 100 N to simulate post-surgery in vivo loading. Afterwards incremental loading (10–100 N) was repeated with subsequent increase in loads until failure occurred. Small differences (1–1.5 mm) existed between the radiographic AADI under incremental loading (10–100 N) with the TAL-intact as compared to the TAL-disrupted state. Significant differences existed for the beginning of loading (10 N, P = 0.02). Under physiological loads, the increase in the AADI within the incremental steps (10–100 N) was not significantly different between TAL-disrupted and TAL-intact state. Analysis of failure load (FL) testing showed no significant differences among the radiologically assessed displacement data (AADI) and that of the ETM (P = 0.5). FL was Ø297.5 ± 108.5 N (range 158.8–449.0 N). The related displacement assessed by the ETM was Ø5.8 ± 2.8 mm (range 2.3–7.9). All specimens succeeded a FL >150 N, four of them >250 N and three of them >300 N. In the TAL-disrupted state loads up to 100 N were transferred to C1, but the radiographic AADI did not exceed 5 mm in any specimen. In conclusion, reconstruction after displaced JBF with TAL and one capsule disrupted using a C1–RO involves imparting an axial tensile force to lift C0 into proper alignment to the C1–2 complex. Simultaneous compressive forces on the C1-lateral masses and occipital condyles allow for the recreation of the functional C0–2 ligamentous tension band and height. We demonstrated that under physiological loads, the C1–RO restores sufficient stability at C1–2 preventing significant translation. C1–RO might be a valid alternative for the treatment of displaced JBF in comparison to fusion of C1–2.     

Angiotensin II receptor expression and relation to <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-infection in the stomach of the Mongolian gerbil

Background  

The role of the renin-angiotensin system in gastric physiology and disease has as yet been sparsely explored. The first aim of the study was to investigate the baseline presence and location of angiotensin II receptors (AT1R and AT2R) in the stomach of the Mongolian gerbil. A second aim was to elucidate whether the presence of H. pylori infection is associated with changes in the expression of these receptors.     

Under-documentation of chronic kidney disease in the electronic health record in outpatients

Objective

To ascertain if outpatients with moderate chronic kidney disease (CKD) had their condition documented in their notes in the electronic health record (EHR).

Design

Outpatients with CKD were selected based on a reduced estimated glomerular filtration rate and their notes extracted from the Columbia University data warehouse. Two lexical-based classification tools (classifier and word-counter) were developed to identify documentation of CKD in electronic notes.

Measurements

The tools categorized patients'' individual notes on the basis of the presence of CKD-related terms. Patients were categorized as appropriately documented if their notes contained reference to CKD when CKD was present.

Results

The sensitivities of the classifier and word-count methods were 95.4% and 99.8%, respectively. The specificity of both was 99.8%. Categorization of individual patients as appropriately documented was 96.9% accurate. Of 107 patients with manually verified moderate CKD, 32 (22%) lacked appropriate documentation. Patients whose CKD had not been appropriately documented were significantly less likely to be on renin-angiotensin system inhibitors or have urine protein quantified, and had the illness for half as long (15.1 vs 30.7 months; p<0.01) compared to patients with documentation.

Conclusion

Our studies show that lexical-based classification tools can accurately ascertain if appropriate documentation of CKD is present in a EHR. Using this method, we demonstrated under-documentation of patients with moderate CKD. Under-documented patients were less likely to receive CKD guideline recommended care. A tool that prompts providers to document CKD might shorten the time to implementing guideline-based recommendations.     

Phosphorothioate Oligonucleotide Quantification by μ-Liquid Chromatography-Mass Spectrometry

Phosporothioate oligonucleotides represent an important class of therapeutic oligonucleotides, in which none-bridging oxygen atoms of the phosphate groups are replaced by sulfur. These oligonucleotides are designed to treat disease by modulating gene expression of an affected individual. As the development and application of these therapeutical oligonucleotides require analytical support, the development, validation, and application of an assay for the quantitative analysis of a phosporothioate oligonucleotide in rat plasma is described. The method employs ion-pair reversed-phase chromatography on a monolithic capillary column with acetonitrile gradients in cyclohexyldimethylammonium acetate for separation and high-resolution tandem mass spectrometry for detection of nucleic acids. Chromatographic parameters (i.e. column temperature, mobile phase composition) as well as mass spectrometric parameters (i.e. spray voltage, gas flow, and capillary position, scan mode) have been optimized for sensitive oligonucleotide quantification. Furthermore, a solid-phase extraction method was developed which enabled processing of 10 μl of plasma. The five-point calibration curve showed linearity over the range of concentrations from 100 to 1,000 nM of the oligonucleotide. The limit of detection was 50 nM. The intra- and inter-day precision and accuracies were always better than 10.2 %. Using this assay, we performed a pharmacokinetic study of the phosporothioate oligonucleotide in rat treated with a single intravenous dose of 0.39 μmol/kg. The assay sensitivity was sufficient to study the early phase elimination of the oligonucleotide. Small amounts of the oligonucleotide were detectable up to 3 h after dosing.KEY WORDS: liquid chromatography, mass spectrometry, pharmacokinetic, therapeutic oligonucleotide