Novel prognostic nomogram for predicting recurrence-free survival in medullary thyroid carcinoma.

AIMS: Recently, there have been attempts to improve prognostication and therefore better guide treatment for patients with medullary thyroid carcinoma (MTC). In 2022, the International MTC Grading System (IMTCGS) was developed and validated using a multi-institutional cohort of 327 patients. The aim of the current study was to build upon the findings of the IMTCGS to develop and validate a prognostic nomogram to predict recurrence-free survival (RFS) in MTC. METHODS AND RESULTS: Data from 300 patients with MTC from five centres across the USA, Europe, and Australia were used to develop a prognostic nomogram that included the following variables: age, sex, AJCC stage, tumour size, mitotic count, necrosis, Ki67 index, lymphovascular invasion, microscopic extrathyroidal extension, and margin status. A process of 10-fold cross-validation was used to optimize the model's performance. To assess discrimination and calibration, the area-under-the-curve (AUC) of a receiver operating characteristic (ROC) curve, concordance-index (C-index), and dissimilarity index (D-index) were calculated. Finally, the model was externally validated using a separate cohort of 87 MTC patients. The model demonstrated very strong performance, with an AUC of 0.94, a C-index of 0.876, and a D-index of 19.06. When applied to the external validation cohort, the model had an AUC of 0.9. CONCLUSIONS: Using well-established clinicopathological prognostic variables, we developed and externally validated a robust multivariate prediction model for RFS in patients with resected MTC. The model demonstrates excellent predictive capability and may help guide decisions on patient management. The nomogram is freely available online at https://nomograms.shinyapps.io/MTC_ML_DFS/.

Ghost image of an ectopic tooth in maxillary sinus: A diagnostic challenge.

Ghost images are artefacts of anatomical structures or foreign objects that oral and maxillofacial surgeons should take into consideration to prevent misdiagnosis and mistreatment. A 38-year-old male patient referred to our clinic for dental implant treatment. Orthopantomograph (OPG) revealed an impacted distomolar at the apex of maxillary right third molar and an ectopic supernumerary tooth in the left maxillary sinus. Despite the ectopic supernumerary tooth appearance on OPG, cone beam computed tomography images revealed that there was not a supernumerary tooth in the left maxillary sinus. Nasal cavity and paranasal sinuses in field of view were evaluated and maxillary ostium diameters were measured to detect if the tooth had migrated. The tooth appearance on the OPG was determined as a ghost image of the impacted distomolar at the contralateral side. Following the extraction of the distomolar, another OPG was performed and the ghost image was disappeared.

Chemical reprogramming enhances homology-directed genome editing in zebrafish embryos.

Precise genome editing is limited by the inefficiency of homology-directed repair (HDR) compared to the non-homologous end-joining (NHEJ) of double strand breaks (DSBs). The CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9 system generates precise, locus-specific DSBs that can serve as substrates for HDR. We developed an in vivo visual reporter assay to quantify HDR-mediated events at single-cell resolution in zebrafish and used this system to identify small-molecule modulators that shift the DNA repair equilibrium in favor of HDR. By further optimizing the reaction environment and repair template, we achieved dramatic enhancement of HDR-mediated repair efficiency in zebrafish. Accordingly, under optimized conditions, inhibition of NHEJ with NU7441 enhanced HDR-mediated repair up to 13.4-fold. Importantly, we demonstrate that the increase in somatic HDR events correlates directly with germline transmission, permitting the efficient recovery of large seamlessly integrated DNA fragments in zebrafish.

Sclerostin and Dkk-1 in patients with ankylosing spondylitis.

OBJECTIVE: To determine the serum Dickkopf-related protein 1 (Dkk-1) and sclerostin levels, and their relationship to structural damage and disease activity in patients with ankylosing spondylitis (AS), as well as to compare the serum Dkk-1 and sclerostin levels in patients receiving and not receiving anti-TNF-a treatment. MATERIALS AND METHOds: This cross-sectional study included 44 AS patients and 41 healthy age- and gender- -matched controls. Demographic data, disease activity parameters, and Bath Ankylosing Spondylitis Radiologic Index (BASRI) scores were recorded. Serum Dkk-1 and sclerostin levels were measured using commercially available ELISA. RESULTS: Serum Dkk-1 levels were lower (P > 0.05) and sclerostin levels were significantly lower (P < 0.05) in the AS patients than in the controls. Dkk-1 and sclerostin levels were similar in the patients that did and didn't receive anti-TNF-a treatment, and in the patients with active and inactive disease (P > 0.05). There wasn't a correlation between serum Dkk-1 or sclerostin levels, and disease activity indices (P > 0.05). BASRI scores did not correlate with serum Dkk-1 or sclerostin levels (P > 0.05). DISCUSSIOn: Sclerostin expression is impaired in AS, but this is not the case for Dkk-1. The lack of an association between Dkk-1 or sclerostin levels, and anti-TNF-a treatment, disease activity indices, and radiological damage might indicate that neither the Dkk-1 nor sclerostin level induce inflammation and radiological damage in AS patients. Pathologic bone formation in AS might be due to molecular dysfunction of sclerostin and Dkk-1 at the cellular level.

Effect of the vastus medialis obliquus on the patellofemoral joint.

In this study, the effect of dynamic stabilizers on the patellofemoral (PF) joint was investigated in normal volunteers (group I) and in patients with patellar pain (group II) or instability (group III) by using computed tomography (CT) analysis and integrated electromyography (iEMG) of the quadriceps muscle. Nine subjects (16 knees) from group I, 10 patients (12 knees) from group II and 8 patients (12 knees) from group III were included in the study. CT scans of the PF joint with quadriceps contracted (QC) and uncontracted (QU) and iEMG of vastus medialis obliquus (VMO), vastus lateralis (VL) and rectus femoris (RF) were obtained with the aid of a specially designed jig at 0 degree, 15 degrees, 30 degrees and 45 degrees of knee flexion. The same muscle contraction pattern simulating closed kinetic chain exercise was used for both CT and iEMG. The difference between the congruence angles (CA) and tilt angles (PTA) in QC and QU positions and VMO:VL ratio from the iEMG were calculated separately for each flexion angle. CA was increased in all groups with quadriceps contraction at 0 degree and 15 degrees of flexion. PTA was decreased in group I and increased in groups II and III with quadriceps contraction at the same flexion angles. This difference was statistically significant in group III at 0 degree and 15 degrees of flexion. Quadriceps contraction did not affect the patellar position significantly even in the instability group at 45 degrees of flexion. In all flexion angles the balanced VMO:VL activity ratio was observed only in group I. In the other groups, VL activity was higher than VMO activity except at 45 degrees of flexion. These findings do not support the hypothesis of dominant centralizing effect of VMO on the patella in extension, but the effect of the VMO may be more clearly demonstrated by measuring PTA in both QC and QU positions.