Helios is a key transcriptional regulator of outer hair cell maturation.

The sensory cells that are responsible for hearing include the cochlear inner hair cells (IHCs) and outer hair cells (OHCs), with the OHCs being necessary for sound sensitivity and tuning1. Both cell types are thought to arise from common progenitors; however, our understanding of the factors that control the fate of IHCs and OHCs remains limited. Here we identify Ikzf2 (which encodes Helios) as an essential transcription factor in mice that is required for OHC functional maturation and hearing. Helios is expressed in postnatal mouse OHCs, and in the cello mouse model a point mutation in Ikzf2 causes early-onset sensorineural hearing loss. Ikzf2cello/cello OHCs have greatly reduced prestin-dependent electromotile activity, a hallmark of OHC functional maturation, and show reduced levels of crucial OHC-expressed genes such as Slc26a5 (which encodes prestin) and Ocm. Moreover, we show that ectopic expression of Ikzf2 in IHCs: induces the expression of OHC-specific genes; reduces the expression of canonical IHC genes; and confers electromotility to IHCs, demonstrating that Ikzf2 can partially shift the IHC transcriptome towards an OHC-like identity.

The Association Between Magnetic Resonance Imaging Disc Pathology and Provocative Discography at the Lumbar Level.

OBJECTIVE: The objective of this study was to show that degenerative lumbar magnetic resonance imaging findings variably increase discography pain by level. METHODS: Lumbar discography and magnetic resonance imaging of 736 patients were retrospectively reviewed. Univariate/multivariate logistic regressions calculated the odds ratio (OR) (95% confidence interval, P < 0.05). RESULTS: L3-4 multivariate regression OR for a degenerative disc is 9.9; for bulge, 10.9; for annular tear, 38.9; for herniation, 51.5; and for degenerative facet, 2.158. Endplate changes were not significant. L4-5 OR for a degenerative disc is 4.52; for bulge, 13.74, for tear, 19.13; for herniation, 28.65; for endplate edema, 3.47; and fatty change, 3.84. Degenerative facet ORs were not significant. L5-S1 OR for a degenerative disc is 6.86; for bulge, 5.65; for tear, 40.56; and for herniation, 77.98. Endplate changes and degenerative facet OR's were not significant. CONCLUSIONS: Advancing degeneration increases pain at L5-S1 followed by L3-4. Endplate signal is significant only at L4-5.

Positive Predictive Values of Lumbar Spine Magnetic Resonance Imaging Findings for Provocative Discography.

PURPOSE: The purpose of this study was to calculate the positive predictive value (PPV) of lumbar spine magnetic resonance imaging (MRI) findings for a painful disc using provocative discography. MATERIALS AND METHODS: Lumbar spine discography records and prediscography MRIs of 736 patients (2457 discs) who underwent discography for diagnostic purposes from 2003 to 2007 were retrospectively reviewed in an Institutional Review Board-exempt and Health Insurance Portability and Accountability Act-compliant protocol. Each level was identified as having high-intensity zone (HIZ) disc, disc protrusion, disc extrusion, or combination (any herniation type), disc bulge, disc degeneration, and spondylolisthesis. Statistical analysis used a 2 × 2 contingency table of significant discography results for each of the MRI variables to calculate P value and PPV with a confidence interval from a binomial distribution. RESULTS: An HIZ disc has a PPV of 0.71 (0.65-0.76, P = 4.31E - 44) for a provocative discography. A disc protrusion has a PPV of 0.79 (0.73-0.83, P = 2.68E - 53). A disc extrusion has a PPV of 0.93 (0.79-0.98, P = 1.34E - 14), a bulge of 0.43 (0.37-0.48, P = 0.002), and a degenerative disc of 0.32 (0.28-0.35, P = 0.08), and spondylolisthesis has a PPV of 0.67 (0.59-0.73, P = 1.70E - 20). A herniation of either type (extrusion or protrusion) has a PPV of 0.80 (0.75-0.84, P = 5.86E - 69). CONCLUSIONS: Disc herniations and HIZ discs have high predictive value in identifying a pain generator. An extruded disc herniation has the highest PPV for discogenic pain.

A Consistent, Reliable Landmark to Assist in Placement of Orbital Floor Reconstruction Plates After Blowout Fractures.

OBJECTIVE: To define a reliable and consistent landmark, the superior posterior wall of the maxillary sinus, and to describe how this landmark can be used when repairing orbital floor fractures. METHODS: Retrospective chart review. Patients >18 years old diagnosed with unilateral orbital floor and/or zygomaticomaxillary complex fractures. MAIN OUTCOMES: The distance from the inferior orbital rim to the superior posterior wall of the maxillary sinus (landmark distance), and the distance from the landmark to the entrance of the optic canal were reported. RESULTS: Eighty patients were included in the study. Each had unilateral isolated orbital floor fractures (n = 46) or unilateral zygomaticomaxillary complex fractures with an orbital floor component (n = 34). The contralateral eye in all patients was uninjured, and was used as an internal control. In orbital floor fractures, the mean landmark distance was 38.8 ±â€Š1.4 mm, with a mean distance on the normal side of 38.8 ±â€Š1.6 mm (P = 0.49). Distance to the optic canal on the injured side in isolated orbital floor fracture patients was 9.0 ±â€Š0.8 mm with the same measurement on the normal side being 8.8 ±â€Š0.7 (P = 0.21). In the setting of zygomaticomaxillary complex fracture, the orbital floor length was 38.2 ±â€Š1.3 mm with a mean normal floor length of 37.8 ±â€Š1.1 mm (P = 0.18). The mean distance from the superior posterior wall to optic canal in zygomaticomaxillary complex fractured orbits was 9.2 ±â€Š1.1 mm with a normal side mean length of 9.5 ±â€Š1.0 mm (P = 0.23). No significant difference was found between the measured distances in the fractured orbit and its normal counterpart for both fracture groups. CONCLUSIONS AND RELEVANCE: The superior posterior wall of the maxillary sinus is a reliable landmark that can be used to assist in placement of an orbital floor reconstructive plate. The landmark is unchanged despite the presence of an orbital floor or zygomaticomaxillary sinus fracture.

Performance of PI-RADS v2 assessment categories assigned prior to MR-US fusion biopsy in a new fusion biopsy program.

OBJECTIVE: To validate the performance of PI-RADS v2 for detection of clinically significant prostate cancer (csPca, Gleason ≥7) within the context of a new fusion biopsy program. MATERIAL AND METHODS: Patients with a PI-RADS v2 assessment category assigned on pre-biopsy mpMRI between March 2015 and November 2017 were identified. Diagnostic performance of PI-RADS v2 was calculated using fusion biopsy results as reference standard using receiver operating characteristic curve analysis. Patient and lesion characteristics were analyzed with one-way ANOVA and Wilcoxon rank sum test. RESULTS: Of 83 patients with 175 lesions, 115/175 (65.7%) were benign, 21/175 (12%) were Gleason 6, and 39/175 (22.3%) were Gleason ≥7. csPCa rates were 0% (0/5) for PI-RADS 1, 7.4% (2/27) for PI-RADS 2, 5.8% (3/52) for PI-RADS 3, 31.2% (24/77) for PI-RADS 4, and 71.4% (10/14) for PI-RADS 5 (p < 0.0001). For prediction of csPCa, patient-level AUC was 0.68 and lesion-level AUC was 0.77. Biopsy threshold of PI-RADS ≥3 was 92.6% sensitive and 22.1% specific. A threshold of PI-RADS ≥4 was 87.2% sensitive and 58.1% specific. Rate of csPca detection on concurrent standard 12 core biopsy only was 6.7%. CONCLUSION: PI-RADS v2 assessment categories assigned prior to biopsy predict pathologic outcome reasonably well in a new prostate fusion biopsy program. Biopsy threshold of PI-RADS ≥3 is highly sensitive. A threshold of ≥4 increases specificity but misses some csPCa.