Spacer rotation technique allows precise evaluation of gap balance in total knee arthroplasty.

The symmetry of the flexion and extension gap influences the functional and long-term outcome after total knee arthroplasty (TKA). Most surgeons check it by applying varus and valgus stress using spacers. This technique has limited accuracy and could be easily extended by rotational movement of the spacer. The objective was to determine the detection threshold and interobserver reliability of this technique. In an in vitro setting with a human cadaveric knee, gap asymmetries were simulated by different medially and laterally applied forces. Using an optical measurement system, the pivot point of the spacer was calculated as a function of the gap symmetry in the first part of the experiment. In the second part, the detection threshold and interobserver reliability of 4 surgeons were determined. For this purpose, gap asymmetries were adjusted to between 0 and 120N in a blinded trial. With a symmetrical gap, the centre of rotation of the spacer was located in the centre of the tibia. With increasing gap asymmetry, the centre of rotation of the spacer shifted to the tight side. This shift was approximately linearly dependent on the force difference. A perfectly balanced gap was detected by the examiners in 50% of the cases. From a force difference of 40N, all examiners identified the gap asymmetry in all cases (ICC = 1.0). The method of spacer rotation described is suitable for reliably detecting gap differences at ≥ 40N, independently of the examiner.

Novel AI-Based Algorithm for the Automated Measurement of Cervical Sagittal Balance Parameters. A Validation Study on Pre- and Postoperative Radiographs of 129 Patients.

STUDY DESIGN: Retrospective, mono-centric cohort research study. OBJECTIVES: The analysis of cervical sagittal balance parameters is essential for preoperative planning and dependent on the physician's experience. A fully automated artificial intelligence-based algorithm could contribute to an objective analysis and save time. Therefore, this algorithm should be validated in this study. METHODS: Two surgeons measured C2-C7 lordosis, C1-C7 Sagittal Vertical Axis (SVA), C2-C7-SVA, C7-slope and T1-slope in pre- and postoperative lateral cervical X-rays of 129 patients undergoing anterior cervical surgery. All parameters were measured twice by surgeons and compared to the measurements by the AI algorithm consisting of 4 deep convolutional neural networks. Agreement between raters was quantified, among other metrics, by mean errors and single measure intraclass correlation coefficients for absolute agreement. RESULTS: ICC-values for intra- (range: .92-1.0) and inter-rater (.91-1.0) reliability reflect excellent agreement between human raters. The AI-algorithm could determine all parameters with excellent ICC-values (preop:0.80-1.0; postop:0.86-.99). For a comparison between the AI algorithm and 1 surgeon, mean errors were smallest for C1-C7 SVA (preop: -.3 mm (95% CI:-.6 to -.1 mm), post: .3 mm (.0-.7 mm)) and largest for C2-C7 lordosis (preop:-2.2° (-2.9 to -1.6°), postop: 2.3°(-3.0 to -1.7°)). The automatic measurement was possible in 99% and 98% of pre- and postoperative images for all parameters except T1 slope, which had a detection rate of 48% and 51% in pre- and postoperative images. CONCLUSION: This study validates that an AI-algorithm can reliably measure cervical sagittal balance parameters automatically in patients suffering from degenerative spinal diseases. It may simplify manual measurements and autonomously analyze large-scale datasets. Further studies are required to validate the algorithm on a larger and more diverse patient cohort.

Does Total Hip Arthroplasty Influence the Development and Localization of Sacral Insufficiency Fractures?

BACKGROUND: Sacral insufficiency fractures (SIFs) are fractures related to reduced bone strength. In a previous study, we noticed that many patients with SIF had undergone total hip arthroplasty (THA). Therefore, the purpose of the present study was to research the localization of clinically apparent SIFs in relation to unilateral THA as well as the influence of unilateral THA on bone mineral density changes in the sacrum. METHODS: In this retrospective study, 171 patients with SIFs were screened for unilateral THA. In the group of patients with SIF and THA, the rate of SIF ipsilateral and contralateral to the side of the THA was determined. In a second cohort of 39 THA patients with healthy bone, changes in bone mineral density at the sacral alae ipsilateral and contralateral to the THA were analyzed by use of computed tomography immediately postoperatively and at the 1-year follow-up. RESULTS: Of the 171 patients with SIF, 50 (40 female; mean age, 79 years; range, 54 to 101 years) were previously treated with THA. Of the 50, 31 patients were treated with unilateral THA. The proportion of patients with an SIF contralateral to the THA was 42% (13 of 31) and ipsilateral to the THA was 19% (6 of 31). Twelve patients had bilateral SIFs. The mean age of the THA group without SIF was 62 years (range, 49 to 79 years); 17 were female. The median bone mineral density decreased significantly (p = 0.023), from 35.0 to 13.0 HU, at the sacral ala contralateral to the THA, whereas the decrease of ipsilateral bone mineral density, from 24.0 to 17.0 HU, was not significant (p = 0.361). CONCLUSIONS: The proportion of patients with an SIF contralateral to a THA was twice as high as that of patients with an SIF ipsilateral to a THA. These findings are supported by the second cohort's decrease in bone mineral density at the sacral ala contralateral to the THA at 1 year after surgery. We conclude that THA can lead to spatially different remodeling of the sacrum, possibly affecting the development of SIFs. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Significance of Lumbar MRI in Diagnosis of Sacral Insufficiency Fracture.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: The aim of the present study was to evaluate the role of lumbar magnetic resonance imaging (MRI) in the diagnostic algorithm of sacral insufficiency fractures (SIF). The primary objective was to compare the sensitivity in fracture detection and correct fracture classification according to MRI and computed tomography (CT). The secondary objective was to identify differences of additional pathologies found in MRI of the lumbar spine and the pelvis and their rates. METHODS: A total of 943 patients (from 2010 to 2017) with fracture of the pelvic ring were screened. All patients without high-energy trauma and radiologic diagnostics consisting of X-ray, CT, and MRI of the pelvis or the lumbar spine including the sacrum were included. Differences in fracture detection and description in the various radiologic procedures were evaluated. Detection rates of additional pathologies in MRI of the pelvis and lumbar spine were recorded. RESULTS: A total of 77 subjects were included. The sensitivities for SIF were 14% in X-ray and 88% in CT, and all fractures were detected in MRI. MRI showed a more complex fracture pattern compared with CT in 65% of the cases. Additional pathologies were seen in MRI of the lumbar spine (51%) and that of the pelvis (18%). CONCLUSIONS: We suggest performing MRI of the lumbar spine including the sacrum with coronal STIR (short tau inversion recovery) sequence for elderly patients with suddenly increasing low back pain at an early stage. This procedure might improve fracture detection, classification, and recognition of concomitant pathologies.

Fourier-Transform Infrared (FTIR) Spectroscopy for Typing of Clinical Enterobacter cloacae Complex Isolates.

Members of the Enterobacter (E.) cloacae complex have emerged as important pathogens frequently encountered in nosocomial infections. Several outbreaks with E. cloacae complex have been reported in recent years, especially in neonatal units. Fast and reliable strain typing methods are crucial for real-time surveillance and outbreak analysis to detect pathogen reservoirs and transmission routes. The aim of this study was to evaluate the performance of Fourier-transform infrared (FTIR) spectroscopy as a fast method for typing of clinical E. cloacae complex isolates, when whole genome sequencing (WGS) analysis was used as reference. First, the technique was used retrospectively on 24 first isolates of E. cloacae complex strains from neonatal patients and showed good concordance with SNP-based clustering [adjusted rand index (ARI) = 0.818] and with the sequence type (ST) (ARI = 0.801). 29 consecutive isolates from the same patients were shown by WGS analysis to almost always belong to the same SNP cluster as the first isolates, which was only inconsistently recognized by FTIR spectroscopy. Training of an artificial neural network (ANN) with all FTIR spectra from sequenced strains markedly improved the recognition of related and unrelated isolate spectra. In a second step, FTIR spectroscopy was applied on 14 strains during an outbreak with E. cloacae complex and provided fast typing results that were confirmed by WGS analysis. In conclusion, FTIR spectroscopy is a promising tool for strain typing of clinical E. cloacae complex strains. Discriminatory power can be improved by implementing an ANN for spectrum analysis. Due to its low costs and fast turnaround times, the method presents a valuable tool for real-time surveillance as well as outbreak analysis.

Typing and Species Identification of Clinical Klebsiella Isolates by Fourier Transform Infrared Spectroscopy and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

Klebsiella pneumoniae and related species are frequent causes of nosocomial infections and outbreaks. Therefore, quick and reliable strain typing is crucial for the detection of transmission routes in the hospital. The aim of this study was to evaluate Fourier transform infrared spectroscopy (FTIR) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) as rapid methods for typing clinical Klebsiella isolates in comparison to whole-genome sequencing (WGS), which was considered the gold standard for typing and identification. Here, 68 clinical Klebsiella strains were analyzed by WGS, FTIR, and MALDI-TOF MS. FTIR showed high discriminatory power in comparison to the WGS reference, whereas MALDI-TOF MS exhibited a low ability to type the isolates. MALDI-TOF mass spectra were further analyzed for peaks that showed high specificity for different Klebsiella species. Phylogenetic analysis revealed that the Klebsiella isolates comprised three different species: K. pneumoniae, K. variicola, and K. quasipneumoniae Genome analysis showed that MALDI-TOF MS can be used to distinguish K. pneumoniae from K. variicola due to shifts of certain mass peaks. The peaks were tentatively identified as three ribosomal proteins (S15p, L28p, L31p) and one stress response protein (YjbJ), which exhibit amino acid differences between the two species. Overall, FTIR has high discriminatory power to recognize the clonal relationship of isolates, thus representing a valuable tool for rapid outbreak analysis and for the detection of transmission events due to fast turnaround times and low costs per sample. Furthermore, specific amino acid substitutions allow the discrimination of K. pneumoniae and K. variicola by MALDI-TOF MS.

Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity.

In adaptation to oncogenic signals, pancreatic ductal adenocarcinoma (PDAC) cells undergo epithelial-mesenchymal transition (EMT), a process combining tumor cell dedifferentiation with acquisition of stemness features. However, the mechanisms linking oncogene-induced signaling pathways with EMT and stemness remain largely elusive. Here, we uncover the inflammation-induced transcription factor NFATc1 as a central regulator of pancreatic cancer cell plasticity. In particular, we show that NFATc1 drives EMT reprogramming and maintains pancreatic cancer cells in a stem cell-like state through Sox2-dependent transcription of EMT and stemness factors. Intriguingly, NFATc1-Sox2 complex-mediated PDAC dedifferentiation and progression is opposed by antithetical p53-miR200c signaling, and inactivation of the tumor suppressor pathway is essential for tumor dedifferentiation and dissemination both in genetically engineered mouse models (GEMM) and human PDAC. Based on these findings, we propose the existence of a hierarchical signaling network regulating PDAC cell plasticity and suggest that the molecular decision between epithelial cell preservation and conversion into a dedifferentiated cancer stem cell-like phenotype depends on opposing levels of p53 and NFATc1 signaling activities.