Developmental Patterning and Neurogenetic Gradients of Nurr1 Positive Neurons in the Rat Claustrum and Lateral Cortex

The claustrum is an enigmatic brain structure thought to be important for conscious sensations. Recent studies have focused on gene expression patterns, connectivity, and function of the claustrum, but relatively little is known about its development. Interestingly, claustrum-enriched genes, including the previously identified marker Nurr1, are not only expressed in the classical claustrum complex, but also embedded within lateral neocortical regions in rodents. Recent studies suggest that Nurr1 positive neurons in the lateral cortex share a highly conserved genetic expression pattern with claustrum neurons. Thus, we focus on the developmental progression and birth dating pattern of the claustrum and Nurr1 positive neurons in the lateral cortex. We comprehensively investigate the expression of Nurr1 at various stages of development in the rat and find that Nurr1 expression first appears as an elongated line along the anterior-posterior axis on embryonic day 13.5 (E13.5) and then gradually differentiates into multiple sub-regions during prenatal development. Previous birth dating studies of the claustrum have led to conflicting results, therefore, we combine 5-ethynyl-2′-deoxyuridine (EdU) labeling with in situ hybridization for Nurr1 to study birth dating patterns. We find that most dorsal endopiriform (DEn) neurons are born on E13.5 to E14.5. Ventral claustrum (vCL) and dorsal claustrum (dCL) are mainly born on E14.5 to E15.5. Nurr1 positive cortical deep layer neurons (dLn) and superficial layer neurons (sLn) are mainly born on E14.5 to E15.5 and E15.5 to E17.5, respectively. Finally, we identify ventral to dorsal and posterior to anterior neurogenetic gradients within vCL and DEn. Thus, our findings suggest that claustrum and Nurr1 positive neurons in the lateral cortex are born sequentially over several days of embryonic development and contribute toward charting the complex developmental pattern of the claustrum in rodents.

Anterior Glenoid Reconstruction With Distal Tibial Allograft: Biomechanical Impact of Fixation and Presence of a Retained Lateral Cortex

Background: Glenoid reconstruction with distal tibial allograft (DTA) is a known surgical option for treating recurrent glenohumeral instability with anterior glenoid bone loss; however, biomechanical analysis has yet to determine how graft variability and fixation options alter the torque of screw insertion and load to failure. Hypothesis: It was hypothesized that retention of the lateral cortex of the DTA graft and the presence of a washer with the screw will significantly increase the maximum screw placement torque as well as the load to failure. Study Design: Controlled laboratory study. Methods: Whole, fresh distal tibias were used to harvest 28 DTA grafts, half of which had the lateral cortex removed and half of which had the lateral cortex intact. The grafts were secured to polyurethane solid foam blocks with a 2-mm epoxy laminate to simulate a glenoid with an intact posterior glenoid cortex. Grafts underwent fixation with 4.0-mm cannulated drills, and screws and washers were used for half of each group of grafts while screws alone were used for the other half, creating 4 equal groups of 7 samples each. A digital torque-measuring screwdriver recorded peak torque for screw insertion. Constructs were then tested in compression with a uniaxial materials testing system and loaded in displacement control at 100 mm/min until at least 3 mm of displacement occurred. Ultimate load was defined as the load sustained at clinical failure. Results: The use of a washer significantly improved the ultimate torque that could be applied to the screws (+cortex and +washer = 12.42 N·m [SE, 0.82]; –cortex and +washer = 10.54 N·m [SE, 0.59]) ( P < .0001), whereas the presence of the native bone cortex did not have a significant effect (+cortex and –washer = 7.83 N·m [SE, 0.40]; –cortex and –washer = 8.03 N·m [SE, 0.56]) ( P = .181). Conclusion: In a hybrid construct of fresh cadaveric DTA grafts secured to a foam block glenoid model, the addition of washers was more effective than the retention of the lateral distal tibial cortex for both load to failure and peak torque during screw insertion. Clinical Relevance: This biomechanical study is relevant to the surgeon when choosing a graft and selecting fixation options during glenoid reconstruction with a DTA graft.

Patterns of Unilateral and Bilateral Projections From Layers 5 and 6 of the Auditory Cortex to the Inferior Colliculus in Mouse

The auditory cortex sends massive projections to the inferior colliculus, but the organization of this pathway is not yet well understood. Previous work has shown that the corticocollicular projection emanates from both layers 5 and 6 of the auditory cortex and that neurons in these layers have different morphological and physiological properties. It is not yet known in the mouse if both layer 5 and layer 6 project bilaterally, nor is it known if the projection patterns differ based on projection location. Using targeted injections of Fluorogold into either the lateral cortex or dorsal cortex of the inferior colliculus, we quantified retrogradely labeled neurons in both the left and right lemniscal regions of the auditory cortex, as delineated using parvalbumin immunostaining. After dorsal cortex injections, we observed that approximately 18–20% of labeled cells were in layer 6 and that this proportion was similar bilaterally. After lateral cortex injections, only ipsilateral cells were observed in the auditory cortex, and they were found in both layer 5 and layer 6. The ratio of layer 5:layer 6 cells after lateral cortex injection was similar to that seen after dorsal cortex injection. Finally, injections of different tracers were made into the two inferior colliculi, and an average of 15–17% of cells in the auditory cortex were double-labeled, and these proportions were similar in layers 5 and 6. These data suggest that (1) only the dorsal cortex of the inferior colliculus receives bilateral projections from the auditory cortex, (2) both the dorsal and lateral cortex of the inferior colliculus receive similar layer 5 and layer 6 auditory cortical input, and (3) a subpopulation of individual neurons in both layers 5 and 6 branch to innervate both dorsal cortices of the inferior colliculus.

A comparative biomechanical study of the Distal Tibia Nail against compression plating for the osteosynthesis of supramalleolar corrective osteotomies

The Distal Tibia Nail (DTN; Mizuho, Japan) has demonstrated higher biomechanical stiffness to locking plates in previous research for A3 distal tibia fractures. It is here investigated as a fixation option for supramalleolar corrective osteotomies (SMOT). Sixteen Sawbones tibiae were implanted with either a DTN (n = 8) or Medial Distal Tibia Plate (MDTP; n = 8) and a SMOT simulated. Two surgical outcome scenarios were envisaged: “best-case” representing an intact lateral cortex, and “worst-case” representing a fractured lateral cortex. All samples were subjected to compressive (350 N, 700 N) and torsional (± 4 Nm, ± 8 Nm) testing. Samples were evaluated using calculated construct stiffness from force–displacement data, interfragmentary movement and Von Mises’ strain distribution. The DTN demonstrated a greater compressive stiffness for the best-case surgical scenario, whereas the MDTP showed higher stiffness (p < 0.05) for the worst-case surgical scenario. In torsional testing, the DTN proved more resistant to torsion in the worst-case surgical setup (p < 0.05) for both ± 4 Nm and ± 8 Nm. The equivalent stiffness of the DTN against the MDTP supports the use of this implant for SMOT fixation and should be considered as a treatment option particularly in patients presenting vascularisation problems where the MDTP is an inappropriate choice.

Opening Wedge Tibial Osteotomy in Medial Osteoarthritis of Varus Knee: Is it Necessary to Graft?

Background: Opening wedge high tibial osteotomy (OWHTO) is accepted and commonly used procedure in selected patients with medial osteoathrosis in the varus knee. The aim of this study is to demonstrate that OWHTO can be performed without graft interposition to filling the osteotomy defect and we evaluate bone union, its complications (delayed or nonunion), and functional results. Materials and Methods: This is a continuous retrospective study of patients treated by OWHTO from July 2008 to August 2018. OWHTO was performed using a 4 holes wedges-plate of Puddu without interposition of graft. HKA angle was assessed preoperatively and postoperatively and at 3 months. Clinical and radiological follow-up at 6 weeks, 3 months and 6 months assessed consolidation in terms of filing the defect of the osteotomy according to the method recommended by Brosset. Results: Mean age was 53.2 years. Mean body mass index was 24, 8 and 30% of patients had BMI >30. The average varus was 171° (165°-177°); postoperatively, the HKA angle was 182° (176°-186°). Radiological union occurred on average after 3.5 months, with a minimum of 2 months and a maximum of 5. The time to union was 3.7 months for opening wedges of more than 10° and 3.4 months for opening wedges of 10° or less. 9 patients showed delayed union; in all these cases the lateral cortex was broken initially (stage II Takeuchi) with large correction>10°, 4 of them had BMI>30. The IKS knee score increased from 69 to 90 and the functional score increased 84 to 95 with 95% of patients scoring between 92 and 97. Conclusion: OWHTO without graft interposition using a wedges plate can be considered an alternative in the treatment of medial osteoarthritis of the varus knee, enabling the correction of the deformity and improvement of the clinical picture. Precautions must be taken event of large correction>10° and unstable lateral cortex fracture (stage II Takeuchi).

Confirming Proper Button Deployment of Suspensory Fixation During ACL Reconstruction

Background: Suspensory fixation of anterior cruciate ligament (ACL) reconstruction (ACLR) grafts has emerged as a popular device for femoral graft fixation. However, improper deployment of the suspensory fixation can compromise proper graft tensioning, leading to failure and revision. Also, soft tissue interposition between the button and bone has been associated with graft migration and pain, occasionally requiring revision surgery. Many surgeons rely on manual testing and application of distal tension to the graft to confirm proper button deployment on the lateral cortex of the femur for ACL graft fixation. Purpose: To determine the reliability of the manual resistance maneuver when applying distal tension to deploy the suspensory device along the lateral cortex of the femur. Study Design: Case series; Level of evidence, 4. Methods: All patients undergoing ACLR with a suture button suspensory device for femoral fixation were eligible for enrollment in the study. The surgeries were performed by 3 board-certified, sports medicine fellowship–trained orthopaedic surgeons at a single outpatient surgical center between May 2018 and June 2019. All grafts were passed in a retrograde manner into the femoral tunnel, and a vigorous manual tensioning maneuver in a distal direction was placed on the graft to deploy and secure along the lateral cortex of the femur. Intraoperative mini c-arm fluoroscopy was obtained to demonstrate proper suture button positioning. If interposing tissue or an improperly flipped button was identified, rectifying steps were undertaken and recorded. Results: A total of 51 patients with a mean age of 33.3 years were included in the study. Of these patients, 74.5% had normal suture button positioning identified via intraoperative fluoroscopic imaging, while 15.7% had interposed soft tissue and 9.8% had an improperly flipped button. In all cases, the surgeon was able to rectify the malpositioning intraoperatively. Conclusion: Despite the manual sensation of proper suspensory button positioning, intraoperative fluoroscopy identified suture button deployment errors in ACLR 25% of the time. Correcting the malpositioning is not technically demanding. These findings advocate for routine intraoperative surveillance to confirm appropriate suture button seating during ACLR.

Minimally Invasive vs Open Akin Osteotomy

Background: Minimally invasive techniques of Akin osteotomy have grown in popularity, as early results suggest faster recovery, earlier return to work, and minimized wound healing problems. Preserving lateral cortex integrity during first phalanx osteotomy thereby presents a challenge because of the lack of direct visual control. This retrospective comparative study investigated clinical and radiographic outcomes of minimally invasive and open Akin osteotomy with different fixation methods and analyzed whether or not intraoperative violation of the lateral cortex caused loss of correction or delayed bone healing. Methods: One hundred eighty-four patients (210 feet) with symptomatic hallux valgus and pathologic interphalangeal angle (IPA) of at least 10 degrees underwent surgery combined with Akin osteotomy. Minimally invasive Akin osteotomies were fixed in 124 feet with 2 crossing percutaneous K-wires and compared to 86 Akin osteotomies by open technique with double-threaded (head and shank) screw fixation. At 1 day and 6 and 12 weeks postoperatively, IPA and bony consolidation were radiographically and clinically assessed. Results: Mean preoperative IPA was 13.4 ± 3.6 degrees in minimally invasive (MI) and 13.3 ± 3.5 degrees in open surgery (OS) cases ( P > .05). Intraoperative breach of the lateral cortex occurred in 12 (13.9%) in OS and 64 (51.6%) in MI cases. Whereas the breach occurred in open technique mainly during manual correction by applying a medial closing force, it was caused predominantly by the use of the burr in minimally invasive technique. After 12 weeks, the mean IPA was 4.1 ± 1.4 degrees in MI and 4.8 ± 1.2 degrees in OS cases ( P > .05). Bony consolidation was complete after 6 and 12 weeks in OS and MI, respectively. Three deep infections occurred in the OS Group after Lapidus arthrodesis and 2 deep infections were registered in the MI Group after minimally invasive chevron and Akin osteotomy. The infections were not at the site of the Akin osteotomy. Conclusion: Breach of the lateral cortex did not impair bone healing or correction of IPA. Minimally invasive Akin osteotomy with K-wire fixation provided equivalent correction of IPA compared to open surgery with screw fixation. Level of Evidence: Level III, retrospective comparative series.