Non-invasive navigation in total knee arthroplasty : a validation study.

The purpose of this study was to evaluate intraope- rative alignment during total knee arthroplasty using a handheld navigation system, iAssist, in comparison with conventional optical surgical navigation. Sixty-two consecutive patients were enrolled in this prospective study. iAssist was used to determine implant component positioning. Orientation of the cuts were verified using a conventional optical sur- gical navigation system. We compared the iAssist system with the conventional system in terms of accuracy, percentage of outliers, bias, and precision. The occurrence of component malalignment was low. Taking standard radiography as the reference, there were no relevant differences between the handheld device and optical navigation in terms of measure- ment of accuracy or in outlier occurrence. Bias was small for both technologies, and precision was comparable. The study provides preliminary evidence that the use of iAssist leads to satisfactory implant alignment. The results from this study imply that iAssist could be a viable alternative to conventional optical navigation.

Molecular Signature of CAID Syndrome: Noncanonical Roles of SGO1 in Regulation of TGF-ß Signaling and Epigenomics.

BACKGROUND & AIMS: A generalized human pacemaking syndrome, chronic atrial and intestinal dysrhythmia (CAID) (OMIM 616201), is caused by a homozygous SGO1 mutation (K23E), leading to chronic intestinal pseudo-obstruction and arrhythmias. Because CAID patients do not show phenotypes consistent with perturbation of known roles of SGO1, we hypothesized that noncanonical roles of SGO1 drive the clinical manifestations observed. METHODS: To identify a molecular signature for CAID syndrome, we achieved unbiased screens in cell lines and gut tissues from CAID patients vs wild-type controls. We performed RNA sequencing along with stable isotope labeling with amino acids in cell culture. In addition, we determined the genome-wide DNA methylation and chromatin accessibility signatures using reduced representative bisulfite sequencing and assay for transposase-accessible chromatin with high-throughput sequencing. Functional studies included patch-clamp, quantitation of transforming growth factor-ß (TGF-ß) signaling, and immunohistochemistry in CAID patient gut biopsy specimens. RESULTS: Proteome and transcriptome studies converge on cell-cycle regulation, cardiac conduction, and smooth muscle regulation as drivers of CAID syndrome. Specifically, the inward rectifier current, an important regulator of cellular function, was disrupted. Immunohistochemistry confirmed overexpression of Budding Uninhibited By Benzimidazoles 1 (BUB1) in patients, implicating the TGF-ß pathway in CAID pathogenesis. Canonical TGF-ß signaling was up-regulated and uncoupled from noncanonical signaling in CAID patients. Reduced representative bisulfite sequencing and assay for transposase-accessible chromatin with high-throughput sequencing experiments showed significant changes of chromatin states in CAID, pointing to epigenetic regulation as a possible pathologic mechanism. CONCLUSIONS: Our findings point to impaired inward rectifier potassium current, dysregulation of canonical TGF-ß signaling, and epigenetic regulation as potential drivers of intestinal and cardiac manifestations of CAID syndrome. Transcript profiling and genomics data are as follows: repository URL: https://www.ncbi.nlm.nih.gov/geo; SuperSeries GSE110612 was composed of the following subseries: GSE110309, GSE110576, and GSE110601.

Comparison of four software packages for CT lung volumetry in healthy individuals.

OBJECTIVES: To compare CT lung volumetry (CTLV) measurements provided by different software packages, and to provide normative data for lung densitometric measurements in healthy individuals. METHODS: This retrospective study included 51 chest CTs of 17 volunteers (eight men and nine women; mean age, 30 ± 6 years), who underwent spirometrically monitored CT at total lung capacity (TLC), functional residual capacity (FRC), and mean inspiratory capacity (MIC). Volumetric differences assessed by four commercial software packages were compared with analysis of variance (ANOVA) for repeated measurements and benchmarked against the threshold for acceptable variability between spirometric measurements. Mean lung density (MLD) and parenchymal heterogeneity (MLD-SD) were also compared with ANOVA. RESULTS: Volumetric differences ranged from 12 to 213 ml (0.20 % to 6.45 %). Although 16/18 comparisons (among four software packages at TLC, MIC, and FRC) were statistically significant (P < 0.001 to P = 0.004), only 3/18 comparisons, one at MIC and two at FRC, exceeded the spirometry variability threshold. MLD and MLD-SD significantly increased with decreasing volumes, and were significantly larger in lower compared to upper lobes (P < 0.001). CONCLUSIONS: Lung volumetric differences provided by different software packages are small. These differences should not be interpreted based on statistical significance alone, but together with absolute volumetric differences. KEY POINTS: • Volumetric differences, assessed by different CTLV software, are small but statistically significant. • Volumetric differences are smaller at TLC than at MIC and FRC. • Volumetric differences rarely exceed spirometric repeatability thresholds at MIC and FRC. • Differences between CTLV measurements should be interpreted based on comparison of absolute differences. • MLD increases with decreasing volumes, and is larger in lower compared to upper lobes.

Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm.

The pacemaking activity of specialized tissues in the heart and gut results in lifelong rhythmic contractions. Here we describe a new syndrome characterized by Chronic Atrial and Intestinal Dysrhythmia, termed CAID syndrome, in 16 French Canadians and 1 Swede. We show that a single shared homozygous founder mutation in SGOL1, a component of the cohesin complex, causes CAID syndrome. Cultured dermal fibroblasts from affected individuals showed accelerated cell cycle progression, a higher rate of senescence and enhanced activation of TGF-ß signaling. Karyotypes showed the typical railroad appearance of a centromeric cohesion defect. Tissues derived from affected individuals displayed pathological changes in both the enteric nervous system and smooth muscle. Morpholino-induced knockdown of sgol1 in zebrafish recapitulated the abnormalities seen in humans with CAID syndrome. Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm.

Cystic fibrosis: unenhanced CT description of the appendix in asymptomatic adults.

OBJECTIVE: The purpose of this study was to describe the unenhanced CT appearance of the appendix in adults with cystic fibrosis. SUBJECTS AND METHODS: Among adults with cystic fibrosis undergoing follow-up at our hospital, 71 patients (35 women, 36 men; mean age, 33 years; range, 18-59 years) without a history of appendectomy or current abdominal pain were prospectively included in this study and underwent unenhanced abdominopelvic MDCT. Two readers coded visualization of the appendix, measured the diameter of the appendix, and described the attenuation of its contents in relation to the intestinal wall. They also coded the presence of colonic wall redundancy, pancreatic fatty replacement, and cirrhosis. Lung transplant status and CFTR gene mutations were recorded. Analysis of variance, linear regression analysis, Student t test, and Pearson test were used. RESULTS: The appendix was detected in all patients. The mean diameter was recorded as 10.6 ± 3.5 mm. The mean diameter was larger when the appendix contained hyperattenuating material (p = 0.001). There was no association between diameter and the other coded CT findings (p = 0.076-0.466), transplant status (p = 0.788), or CFTR mutation (p = 0.078). In 75% of the patients, the appendix contained hyperattenuating material with a higher proportion in homozygous ΔF508 mutation (p = 0.029) without any significant effect of the other CT features (p = 0.056-0.392), or transplant status (p = 1.000). CONCLUSION: The appendix is larger in adults with cystic fibrosis than in those without it and appears hyperattenuating at unenhanced CT in 75% of patients, more commonly in those with ΔF508 homozygous mutation.