Targeting the safe zones for cup position without fluoroscopic guidance in total hip arthroplasty: does the surgical approach affect the outcomes?

BACKGROUND: Proper acetabular cup positioning is crucial for achieving implant longevity and stability in total hip arthroplasty (THA). One of the elements that may affect the accuracy and precision of the positioning of the cup is the type of surgical approach used. This study compares the accuracy and the precision of conventional free-hand acetabular cup positioning relative to different "safe zones" in two groups of patients operated with THA using two different surgical approach. METHODS: Retrospective radiological comparative matched-pair controlled study of two groups of patients operated with primary THA: the first group was operated in supine decubitus with a mini-invasive direct anterior approach (DA group), the second group was operated in lateral decubitus with a conventional posterolateral approach (PL group). Cup inclination and anteversion were assessed using the digital planning software TraumaCad. Cup position in the two groups were compared in terms of accuracy and precision. RESULTS: Forty four patients were enrolled for each group. The DA group showed a less inclined and less anteverted cup compared to the PL group (respectively 38.5 ± 5.2 vs. 49.6 ± 5.6 and 16.2 ± 3.6 vs. 22.9 ± 6.4; p < 0.01). The DA group showed a significantly higher percentage of cups within the "safe zone" in 4 out of 6 reference zones and a significantly lower variance in anteversion (12.96 vs. 40.96, p < .01). There was no difference in the variance for inclination. CONCLUSIONS: Our study found greater accuracy and precision in the positioning of the cup when surgery was performed through a direct anterior approach compared to the posterolateral approach due to the supine position of the patient which allows greater stability of the pelvis during surgery and makes it easier to target the desired angular references for cup positioning.

In silico Investigations of the Mode of Action of Novel Colchicine Derivatives Targeting ß-Tubulin Isotypes: A Search for a Selective and Specific ß-III Tubulin Ligand.

The cardinal role of microtubules in cell mitosis makes them interesting drug targets for many pharmacological treatments, including those against cancer. Moreover, different expression patterns between cell types for several tubulin isotypes represent a great opportunity to improve the selectivity and specificity of the employed drugs and to design novel compounds with higher activity only on cells of interest. In this context, tubulin isotype ßIII represents an excellent target for anti-tumoral therapies since it is overexpressed in most cancer cells and correlated with drug resistance. Colchicine is a well-known antimitotic agent, which is able to bind the tubulin dimer and to halt the mitotic process. However, it shows high toxicity also on normal cells and it is not specific for isotype ßIII. In this context, the search for colchicine derivatives is a matter of great importance in cancer research. In this study, homology modeling techniques, molecular docking, and molecular dynamics simulations have been employed to characterize the interaction between 55 new promising colchicine derivatives and tubulin isotype ßIII. These compounds were screened and ranked based on their binding affinity and conformational stability in the colchicine binding site of tubulin ßIII. Results from this study point the attention on an amide of 4-chlorine thiocolchicine. This colchicine-derivative is characterized by a unique mode of interaction with tubulin, compared to all other compounds considered, which is primarily characterized by the involvement of the α-T5 loop, a key player in the colchicine binding site. Information provided by the present study may be particularly important in the rational design of colchicine-derivatives targeting drug resistant cancer phenotypes.

Diabetic Vascular Calcification Mediated by the Collagen Receptor Discoidin Domain Receptor 1 via the Phosphoinositide 3-Kinase/Akt/Runt-Related Transcription Factor 2 Signaling Axis.

Objective- Vascular calcification is a common and severe complication in patients with atherosclerosis which is exacerbated by type 2 diabetes mellitus. Our laboratory recently reported that the collagen receptor discoidin domain receptor 1 (DDR1) mediates vascular calcification in atherosclerosis; however, the underlying mechanisms are unknown. During calcification, vascular smooth muscle cells transdifferentiate into osteoblast-like cells, in a process driven by the transcription factor RUNX2 (runt-related transcription factor 2). DDR1 signals via the phosphoinositide 3-kinase/Akt pathway, which is also central to insulin signaling, and upstream of RUNX2, and this led us to investigate whether DDR1 promotes vascular calcification in diabetes mellitus via this pathway. Approach and Results- Ddr1+/+ ; Ldlr-/- (single knock-out) and Ddr1-/- ; Ldlr-/- (double knock-out) mice were placed on high-fat diet for 12 weeks to induce atherosclerosis and type 2 diabetes mellitus. Von Kossa staining revealed reduced vascular calcification in the aortic arch of double knock-out compared with single knock-out mice. Immunofluorescent staining for RUNX2 was present in calcified plaques of single knock-out but not double knock-out mice. Primary vascular smooth muscle cells obtained from Ddr1+/+ and Ddr1-/- mice were cultured in calcifying media. DDR1 deletion resulted in reduced calcification, a 74% reduction in p-Akt levels, and an 88% reduction in RUNX2 activity. Subcellular fractionation revealed a 77% reduction in nuclear RUNX2 levels in Ddr1-/- vascular smooth muscle cells. DDR1 associated with phosphoinositide 3-kinase, and treatment with the inhibitor wortmannin attenuated calcification. Finally, we show that DDR1 is important to maintain the microtubule cytoskeleton which is required for the nuclear localization of RUNX2. Conclusions- These novel findings demonstrate that DDR1 promotes RUNX2 activity and atherosclerotic vascular calcification in diabetes mellitus via phosphoinositide 3-kinase/Akt signaling.

Evaluation of an automated auditory brainstem response in a multi-stage infant hearing screening.

An automated auditory brainstem response (AABR) method, the Maico MB-11 with BERAphone, has been developed for hearing screening in newborns. The aim of this study was to test the validity of this automated ABR screening method in a multistage newborn hearing screening (NHS). We applied a "five level" protocol using transient evoked otoacoustic emission (TEOAE), AABR-MB-11 with BERAphone and conventional auditory brainstem response (ABR). TEOAE, AABR, and conventional ABR testing were performed by ENT specialists experienced in neonatal screening techniques. Among the 8,671 newborns tested (males 3,889; females 4,782), only 42 newborns were lost to follow-up and the final false-positive rate was of 0.03%. Our experience highlights that for the neonatal period, conventional auditory brainstem response is the most reliable method for assessing the hearing level and minimizing the false-positive rate. Although AABR (performed by ENT specialists experienced in neonatal screening techniques) is easy to use, fast and with a good compliance, the device is unable to provide accurate and certain diagnosis on the degree of hearing loss to allow a proper treatment.