The Role of Osteotomy in Anterior Cruciate Ligament Reconstruction.

Coronal and sagittal plane knee malalignments have been shown to increase the forces on anterior cruciate ligament (ACL) grafts after ACL reconstruction (ACLR). Studies have shown the benefit of high tibial osteotomy to address coronal and sagittal imbalance in revision ACLR. The purpose of this article is to further describe the use of osteotomy by reviewing preoperative planning, indications, techniques, and outcomes of high tibial opening and closing wedge as well as anterior tibial closing wedge osteotomies in the setting of ACLR.

Distribution, development, and identity of retinal ganglion cells labeled in the Sert-Cre reporter mouse.

The mouse retina contains over 40 types of retinal ganglion cells (RGCs) that differ in morphology, function, or gene expression. RGCs also differ by whether their axons target the brain.s ipsilateral or contralateral hemisphere. Contralaterally projecting RGCs (contraRGCs) are widespread in mouse retina, whereas ipsilateral projecting RGCs (ipsiRGCs) are confined to the ventro-temporal (VT) crescent of retina. In this study, we employed the Sert-Cre transgenic line, which had been reported to selectively label ipsiRGCs, to study ipsiRGCs during development. Although the number of Cre-expressing ipsiRGCs did not significantly increase with postnatal age, the region of retina that they occupied did, and by adulthood represented ~30% of the retinal surface. Unexpectedly, genetic ablation of Sert-Cre cells failed to fully disrupt ipsilateral projecting retinal axons, suggesting that not all ipsiRGCs generated Cre in Sert-Cre mice. To test this hypothesis, we retrogradely labeled ipsiRGCs in Sert-Cre mice which revealed that not all ipsiRGCs are labeled in Sert-Cre mice and a small population of contraRGCs flanking the VT crescent generates Cre in this line. These results do not negate the usefulness of the Sert-Cre mouse but do raise important caveats to the interpretation of such studies.

Defining Critical Humeral Bone Loss: Inferior Craniocaudal Hill-Sachs Extension as Predictor of Recurrent Instability After Primary Arthroscopic Bankart Repair.

BACKGROUND: The glenoid track concept for shoulder instability primarily describes the medial-lateral relationship between a Hill-Sachs lesion and the glenoid. However, the Hill-Sachs position in the craniocaudal dimension has not been thoroughly studied. HYPOTHESIS: Hill-Sachs lesions with greater inferior extension are associated with increased risk of recurrent instability after primary arthroscopic Bankart repair. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The authors performed a retrospective analysis of patients with on-track Hill-Sachs lesions who underwent primary arthroscopic Bankart repair (without remplissage) between 2007 and 2019 and had a minimum 2-year follow-up. Recurrent instability was defined as recurrent dislocation or subluxation after the index procedure. The craniocaudal position of the Hill-Sachs lesion was measured against the midhumeral axis on sagittal magnetic resonance imaging (MRI) using either a Hill-Sachs bisecting line through the humeral head center (sagittal midpoint angle [SMA], a measure of Hill-Sachs craniocaudal position) or a line tangent to the inferior Hill-Sachs edge (lower-edge angle [LEA], a measure of Hill-Sachs caudal extension). Univariate and multivariate regression were used to determine the predictive value of both SMA and LEA for recurrent instability. RESULTS: In total, 176 patients were included with a mean age of 20.6 years, mean follow-up of 5.9 years, and contact sport participation of 69.3%. Of these patients, 42 (23.9%) experienced recurrent instability (30 dislocations, 12 subluxations) at a mean time of 1.7 years after surgery. Recurrent instability was found to be significantly associated with LEA >90° (ie, Hill-Sachs lesions extending below the humeral head equator), with an OR of 3.29 (P = .022). SMA predicted recurrent instability to a lesser degree (OR, 2.22; P = .052). Post hoc evaluation demonstrated that LEA >90° predicted recurrent dislocations (subset of recurrent instability) with an OR of 4.80 (P = .003). LEA and SMA were found to be collinear with Hill-Sachs interval and distance to dislocation, suggesting that greater LEA and SMA proportionally reflect lesion severity in both the craniocaudal and medial-lateral dimensions. CONCLUSION: Inferior extension of an otherwise on-track Hill-Sachs lesion is a highly predictive risk factor for recurrent instability after primary arthroscopic Bankart repair. Evaluation of Hill-Sachs extension below the humeral equator (inferior equatorial extension) on sagittal MRI is a clinically facile screening tool for higher-risk lesions with subcritical glenoid bone loss. This threshold for critical humeral bone loss may inform surgical stratification for procedures such as remplissage or other approaches for at-risk on-track lesions.

Retinal input is required for the maintenance of neuronal laminae in the ventral lateral geniculate nucleus.

Retinal ganglion cell (RGC) axons provide direct input into several nuclei of the mouse visual thalamus, including the dorsal lateral geniculate nucleus (dLGN), which is important for classical image-forming vision, and the ventral lateral geniculate nucleus (vLGN), which is associated with non-image-forming vision. Through both activity- and morphogen-dependent mechanisms, retinal inputs play important roles in the development of dLGN, including the refinement of retinal projections, morphological development of thalamocortical relay cells (TRCs), the timing of corticogeniculate innervation, and the recruitment of inhibitory interneurons from progenitor zones. In contrast, little is known about the role of retinal inputs in the development of vLGN. Grossly, vLGN is divided into two domains, the retinorecipient external vLGN (vLGNe) and the non-retinorecipient internal vLGN (vLGNi). We previously found that vLGNe consists of transcriptionally distinct GABAergic subtypes that are distributed into at least four adjacent laminae. At present, it remains unclear whether retinal inputs influence the development of these cell-specific neuronal laminae in vLGNe. Here, we elucidated the developmental timeline for the formation and maintenance of these laminae in the mouse vLGNe and results indicate that these laminae are specified at or before birth, well before eye-opening and the emergence of experience-dependent visual activity. We observed that mutant mice without retinal inputs have a normal laminar distribution of GABAergic cells at birth; however, after the first week of postnatal development, these mutants exhibited a dramatic disruption in the laminar organization of inhibitory neurons and clear boundaries between vLGNe and vLGNi. Overall, our results show that while the formation of cell type-specific layers in vLGNe does not depend on RGC inputs, retinal signals are critical for their maintenance.

Anatomic Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament reconstruction (ACLR) techniques have substantially evolved over the past several decades, driven by evidence that nonanatomic techniques increase the risk for instability, loss of motion, surgical failure, and posttraumatic osteoarthritis. Early techniques used transtibial femoral tunnel drilling, although improved understanding of the anatomy and biomechanics has led to independent femoral tunnel. Anatomic ACLR requires careful consideration of the native ACL dimensions and orientation. Although there is significant variation between patients, understanding of anatomic patterns allows for reliable identification of the ACL footprints and appropriate tunnel positioning, particularly in chronic injuries where the remanent ACL stump is degraded or absent. The femoral tunnel should be placed low and posterior on the lateral femoral condyle using the lateral intercondylar and bifurcate ridges as landmarks. The center of the tibial footprint can be determined by referencing the medial tibial spine and posterior border of anterior horn of lateral meniscus. Measurement of the dimensions of the native ACL and intercondylar notch is also critical for determining graft size and minimizing the risk of impingement, with a goal of reconstructing 50% to 80% of the tibial footprint area. Clinical outcome studies have demonstrated superior anteroposterior and rotatory knee stability with low surgical revision rates (reported between 3% and 5%). By adhering to the principles of anatomic ACLR, surgeons can produce an appropriately sized and located graft for the individual patient, thereby best restoring native knee kinematics and maximizing function. The aim of this infographic is to highlight essential features of anatomic ACLR techniques, which a focus on the native anatomy and surgical planning to achieve an anatomic ACLR.

Collagen XIX is required for pheromone recognition and glutamatergic synapse formation in mouse accessory olfactory bulb.

In mammals, the accessory olfactory bulb (AOB) receives input from vomeronasal sensory neurons (VSN) which detect pheromones, chemical cues released by animals to regulate the physiology or behaviors of other animals of the same species. Cytoarchitecturally, cells within the AOB are segregated into a glomerular layer (GL), mitral cell layer (MCL), and granule cell layer (GCL). While the cells and circuitry of these layers has been well studied, the molecular mechanism underlying the assembly of such circuitry in the mouse AOB remains unclear. With the goal of identifying synaptogenic mechanisms in AOB, our attention was drawn to Collagen XIX, a non-fibrillar collagen generated by neurons in the mammalian telencephalon that has previously been shown to regulate the assembly of synapses. Here, we used both a targeted mouse mutant that lacks Collagen XIX globally and a conditional allele allowing for cell-specific deletion of this collagen to test if the loss of Collagen XIX causes impaired synaptogenesis in the mouse AOB. These analyses not only revealed defects in excitatory synapse distribution in these Collagen XIX-deficient mutants, but also showed that these mutant mice exhibit altered behavioral responses to pheromones. Although this collagen has been demonstrated to play synaptogenic roles in the telencephalon, those roles are at perisomatic inhibitory synapses, results here are the first to demonstrate the function of this unconventional collagen in glutamatergic synapse formation.

3D electron microscopy and volume-based bouton sorting reveal the selectivity of inputs onto geniculate relay cell and interneuron dendrite segments.

Introduction: The visual signals evoked at the retinal ganglion cells are modified and modulated by various synaptic inputs that impinge on lateral geniculate nucleus cells before they are sent to the cortex. The selectivity of geniculate inputs for clustering or forming microcircuits on discrete dendritic segments of geniculate cell types may provide the structural basis for network properties of the geniculate circuitry and differential signal processing through the parallel pathways of vision. In our study, we aimed to reveal the patterns of input selectivity on morphologically discernable relay cell types and interneurons in the mouse lateral geniculate nucleus. Methods: We used two sets of Scanning Blockface Electron Microscopy (SBEM) image stacks and Reconstruct software to manually reconstruct of terminal boutons and dendrite segments. First, using an unbiased terminal sampling (UTS) approach and statistical modeling, we identified the criteria for volume-based sorting of geniculate boutons into their putative origins. Geniculate terminal boutons that were sorted in retinal and non-retinal categories based on previously described mitochondrial morphology, could further be sorted into multiple subpopulations based on their bouton volume distributions. Terminals deemed non-retinal based on the morphological criteria consisted of five distinct subpopulations, including small-sized putative corticothalamic and cholinergic boutons, two medium-sized putative GABAergic inputs, and a large-sized bouton type that contains dark mitochondria. Retinal terminals also consisted of four distinct subpopulations. The cutoff criteria for these subpopulations were then applied to datasets of terminals that synapse on reconstructed dendrite segments of relay cells or interneurons. Results: Using a network analysis approach, we found an almost complete segregation of retinal and cortical terminals on putative X-type cell dendrite segments characterized by grape-like appendages and triads. On these cells, interneuron appendages intermingle with retinal and other medium size terminals to form triads within glomeruli. In contrast, a second, presumed Y-type cell displayed dendrodendritic puncta adherentia and received all terminal types without a selectivity for synapse location; these were not engaged in triads. Furthermore, the contribution of retinal and cortical synapses received by X-, Y- and interneuron dendrites differed such that over 60% of inputs to interneuron dendrites were from the retina, as opposed to 20% and 7% to X- and Y-type cells, respectively. Conclusion: The results underlie differences in network properties of synaptic inputs from distinct origins on geniculate cell types.

Arthroscopic all-inside repair of challenging meniscus tears.

Meniscus tears are prevalent in isolation and in combination with anterior cruciate ligament (ACL) injury. Meniscus lesions can be difficult to access and often display complex tear patterns, which result in technical challenges for the operating surgeon during surgical treatment. The aim of this video article is to demonstrate technical tips and tricks for performing all-inside repair of challenging meniscus tears. The presented techniques are indicated in young, physically active patients with symptomatic tears of the lateral and medial menisci, with or without concomitant ACL injury. The procedure is performed using standard anterolateral and anteromedial arthroscopic portals for direct visualization of complex meniscus tear patterns and all-inside instrument access. A suture passing device is used for the placement of suture loops for meniscus root repair. All-inside repair devices are used to repair the radial meniscal tears along the native circumferential fibers using a horizontal mattress suture configuration, with curved devices to achieve optimal access to challenging tears affecting the anterior and posterior aspects at the mid-body of the meniscus. Repair of radial tears at the avascular zone of the meniscus may be augmented with an autologous fibrin clot delivered using an arthroscopic cannula.

Increased Failure Rates After Arthroscopic Bankart Repair After Second Dislocation Compared to Primary Dislocation With Comparable Clinical Outcomes.

PURPOSE: The purpose of this study was to compare rates of recurrent dislocation and postsurgical outcomes in patients undergoing arthroscopic Bankart repair for anterior shoulder instability immediately after a first-time traumatic anterior dislocation versus patients who sustained a second dislocation event after initial nonoperative management. METHODS: A retrospective chart review was performed of patients undergoing primary arthroscopic stabilization for anterior shoulder instability without concomitant procedures and minimum 2-year clinical follow-up. Primary outcome was documentation of a recurrent shoulder dislocation. Secondary clinical outcomes included range of motion, Visual Analog Scale (VAS), American Shoulder and Elbow Surgeons Shoulder Score (ASES), and Shoulder Activity Scale (SAS). RESULTS: Seventy-seven patients (mean age 21.3 years ± 7.3 years) met inclusion criteria. Sixty-three shoulders underwent surgical stabilization after a single shoulder dislocation, and 14 underwent surgery after 2 dislocations. Average follow-up was 35.9 months. The rate of recurrent dislocation was significantly higher in the 2-dislocation group compared to single dislocations (42.8% vs 14.2%, P = .03). No significant difference was present in range of motion, VAS, ASES, and SAS scores. The minimal clinically important difference (MCID) was 1.4 for VAS and 1.8 for SAS scores. The MCID was met or exceeded in the primary dislocation group in 31/38 (81.6%) patients for VAS, 23/31 (74.1%) for ASES, and 24/31 for SES (77.4%) scores. For the second dislocation cohort, MCID was met or exceeded in 7/9 (77.8%) for VAS, 4/7 (57.1%) for ASES, and 5/7 for SES (71.4%) scores. CONCLUSION: Immediate arthroscopic surgical stabilization after a first-time anterior shoulder dislocation significantly decreases the risk of recurrent dislocation in comparison to those who undergo surgery after 2 dislocation events, with comparable clinical outcome scores. These findings suggest that patients who return to activities after a primary anterior shoulder dislocation and sustain just 1 additional dislocation event are at increased risk of a failing arthroscopic repair. STUDY DESIGN: Retrospective comparative study; Level of evidence, 3.

Reverse shoulder arthroplasty with preservation of the rotator cuff for primary glenohumeral osteoarthritis has similar outcomes to anatomic total shoulder arthroplasty and reverse shoulder arthroplasty for cuff arthropathy.

INTRODUCTION: Indications for reverse total shoulder arthroplasty (RSA) have expanded to include individuals with intact rotator cuffs such as patients with severe glenoid deformity or with concern of future rotator cuff insufficiency. The purpose of this study was to compare outcomes of RSA with an intact rotator cuff to RSA for cuff arthropathy and anatomic total shoulder arthroplasty (TSA). We hypothesized that outcomes of RSA with an intact rotator cuff would be comparable to RSA for cuff arthropathy and TSA but with diminished range of motion (ROM) compared with TSA. MATERIALS AND METHODS: Patients at one institution who underwent RSA and TSA between 2015 and 2020 with minimum 12-month follow-up were identified. RSA with preservation of the rotator cuff (+rcRSA) was compared to RSA for cuff arthropathy (-rcRSA) and anatomic TSA (TSA). Demographics and glenoid version/inclination were obtained. Pre- and postoperative ROM; patient-reported outcomes including visual analog scale (VAS), Subjective Shoulder Value (SSV), and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores; and complications were obtained. RESULTS: Twenty-four patients underwent +rcRSA, 69 underwent -rcRSA, and 93 underwent TSA. There were more women in the +rcRSA cohort (75.8%) than in the -rcRSA (37.7%, P = .001) and TSA (37.6%, P = .001) cohorts. Mean age of the +rcRSA cohort (71.1) was greater than that of TSA (66.0, P = .021) but similar to that of -rcRSA (72.4, P = .237). Glenoid retroversion was greater in +rcRSA (18.2°) compared with -rcRSA (10.5°, P = .011) but was similar to TSA (14.7°; P = .244). Postoperatively, there were no differences in VAS or ASES between +rcRSA vs. -rcRSA and +rcRSA vs. TSA. SSV was lower in +rcRSA (83.9) compared with -rcRSA (91.8, P = .021), but was similar to TSA (90.5, P = .073). Similar ROM was achieved in forward flexion, external rotation, and internal rotation at final follow-up between +rcRSA and -rcRSA, but TSA had greater external rotation (44° vs. 38°, P = .041) and internal rotation (6.5° vs. 5.0°, P = .001) compared with +rcRSA. There were no differences in complication rates. DISCUSSION: At short-term follow-up, preservation of the rotator cuff in RSA demonstrated similarly excellent outcomes and low complication rates compared with RSA with a deficient rotator cuff and TSA, except for slightly lower internal and external rotation compared with TSA. Although multiple factors deserve consideration when choosing between RSA and TSA, RSA with preservation of the posterosuperior cuff is a viable treatment option for glenohumeral osteoarthritis, particularly in patients with severe glenoid deformity or those at risk for future rotator cuff insufficiency.

Remplissage reduces recurrent instability in high-risk patients with on-track Hill-Sachs lesions.

BACKGROUND: The purpose of this study was to compare recurrent instability rates between patients with on-track Hill-Sachs lesions who underwent arthroscopic labral repair (ALR) alone and those who underwent ALR with remplissage (ALR-R). Our hypothesis was that ALR-R would decrease the rate of recurrent instability, especially among patients at high risk of recurrent instability after ALR, such as contact athletes with near-track Hill-Sachs lesions. METHODS: We performed a multicenter, retrospective analysis of patients aged 14-50 years with on-track Hill-Sachs lesions who underwent ALR-R or ALR without remplissage between January 2014 and December 2019 with minimum 2-year follow-up. The exclusion criteria included prior ipsilateral shoulder surgery, >15% glenoid bone loss (GBL), off-track Hill-Sachs lesion, concomitant shoulder procedure, and connective tissue disorder. Age, sex, follow-up, and contact sports participation were recorded. GBL, Hills-Sachs interval (HSI), glenoid track, and distance to dislocation (DTD) were determined from preoperative magnetic resonance imaging scans. Affected-shoulder range of motion, Western Ontario Shoulder Instability Index scores, Subjective Shoulder Value scores, and recurrent dislocation and/or revision surgery status were also collected. A subgroup analysis was performed on "high-risk" patients (defined as participants in contact sports with DTD <10 mm) from each cohort. RESULTS: The ALR-R cohort included 56 patients, and the ALR cohort included 127. ALR-R patients had greater GBL (P = .004) and a greater HSI (P < .001). In the ALR-R cohort, only 1 patient (1.8%) had a recurrent dislocation and there were no revision operations. In comparison, in the ALR cohort, 14 patients (11.0%) had recurrent dislocations (P = .040) and 8 (6.3%) underwent revision operations (P = .11). Univariate analysis showed that remplissage protected against recurrent dislocation (P = .040) whereas younger age (P = .004), contact sports participation (P = .001), and increased GBL (P = .048) were associated with recurrent dislocation. Multivariate analysis showed that HSI (P = .001) and contact sports participation (P = .002) predicted recurrent dislocation. Among high-risk patients, only 1 patient (4.2%) in the ALR-R group had a recurrent instability event vs. 6 (66.7%) in the ALR group (P < .001). The high-risk ALR-R subgroup also had significantly better final Western Ontario Shoulder Instability Index (P = .008) and Subjective Shoulder Value (P = .001) scores than the high-risk ALR subgroup. CONCLUSIONS: Anterior shoulder instability patients with on-track Hill-Sachs lesions have lower recurrent dislocation rates after ALR plus remplissage when compared with ALR alone. This is especially true for high-risk patients, such as contact athletes with a DTD <10 mm.

Complement-dependent loss of inhibitory synapses on pyramidal neurons following Toxoplasma gondii infection.

The apicomplexan parasite Toxoplasma gondii has developed mechanisms to establish a central nervous system infection in virtually all warm-blooded animals. Acute T. gondii infection can cause neuroinflammation, encephalitis, and seizures. Meanwhile, studies in humans, nonhuman primates, and rodents have linked chronic T. gondii infection with altered behavior and increased risk for neuropsychiatric disorders, including schizophrenia. These observations and associations raise questions about how this parasitic infection may alter neural circuits. We previously demonstrated that T. gondii infection triggers the loss of inhibitory perisomatic synapses, a type of synapse whose dysfunction or loss has been linked to neurological and neuropsychiatric disorders. We showed that phagocytic cells (including microglia and infiltrating monocytes) contribute to the loss of these inhibitory synapses. Here, we show that these phagocytic cells specifically ensheath excitatory pyramidal neurons, leading to the preferential loss of perisomatic synapses on these neurons and not those on cortical interneurons. Moreover, we show that infection induces an increased expression of the complement C3 gene, including by populations of these excitatory neurons. Infecting C3-deficient mice with T. gondii revealed that C3 is required for the loss of perisomatic inhibitory synapses. Interestingly, loss of C1q did not prevent the loss of perisomatic synapses following infection. Together, these findings provide evidence that T. gondii induces changes in excitatory pyramidal neurons that trigger the selective removal of inhibitory perisomatic synapses and provide a role for a nonclassical complement pathway in the remodeling of inhibitory circuits in the infected brain.

Pattern of Driver-Like Input onto Neurons of the Mouse Ventral Lateral Geniculate Nucleus.

The ventral lateral geniculate nucleus (vLGN) is a retinorecipient region of thalamus that contributes to a number of complex visual behaviors. Retinal axons that target vLGN terminate exclusively in the external subdivision (vLGNe), which is also transcriptionally and cytoarchitectonically distinct from the internal subdivision (vLGNi). While recent studies shed light on the cell types and efferent projections of vLGNe and vLGNi, we have a crude understanding of the source and nature of the excitatory inputs driving postsynaptic activity in these regions. Here, we address this by conducting in vitro whole-cell recordings in acutely prepared thalamic slices and using electrical and optical stimulation techniques to examine the postsynaptic excitatory activity evoked by the activation of retinal or cortical layer V input onto neurons in vLGNe and vLGNi. Activation of retinal afferents by electrical stimulation of optic tract or optical stimulation of retinal terminals resulted in robust driver-like excitatory activity in vLGNe. Optical activation of corticothalamic terminals from layer V resulted in similar driver-like activity in both vLGNe and vLGNi. Using a dual-color optogenetic approach, we found that many vLGNe neurons received convergent input from these two sources. Both individual pathways displayed similar driver-like properties, with corticothalamic stimulation leading to a stronger form of synaptic depression than retinogeniculate stimulation. We found no evidence of convergence in vLGNi, with neurons only responding to corticothalamic stimulation. These data provide insight into the influence of excitatory inputs to vLGN and reveal that only neurons in vLGNe receive convergent input from both sources.

Anatomic anterior cruciate ligament reconstruction: Freddie Fu's paradigm.

Anterior cruciate ligament (ACL) reconstruction techniques have evolved over the past four decades. There is evidence that non-anatomic reconstruction techniques, such as traditional transtibial drilling, fail to recreate the native anatomy of the ACL, which can lead to increased rotatory knee instability, revision risk, and post-traumatic osteoarthritis. Anatomic ACL reconstruction has emerged as the gold standard, with the goal of restoring the patient's native anatomy and knee kinematics. This review will summarise the relevant anatomy, modern anatomic ACL reconstruction techniques, and literature supporting anatomic ACL reconstruction as the new paradigm. LEVEL OF EVIDENCE: Level V, review article.

Knotted and knotless double row transosseous equivalent repair techniques for arthroscopic rotator cuff repair demonstrate comparable post-operative outcomes.

PURPOSE: To compare failure rates and outcomes after transosseous equivalent (TOE) double row (DR) knotted suture bridge versus knotless suture tape bridge repair techniques for rotator cuff tears. METHODS: A consecutive series of 272 shoulders in 256 patients who underwent arthroscopic, double row, TOE repair for full-thickness tears of the supraspinatus tendon were reviewed. Eighty-four shoulders were repaired using knotted suture bridge (KSB) technique, and 188 shoulders were repaired using all knotless suture tape bridge (KTB) technique. Revision procedures and concomitant subscapularis tendon repairs were excluded from analysis. The minimum follow-up was 12 months. Primary outcome was failure of surgical repair, defined as either confirmed retear on MRI and/or need for revision surgery. Secondary clinical outcome measures were assessed including range of motion, strength, visual analog scale (VAS), operative time, subjective shoulder value (SSV), Patient-Reported Outcomes Measurement Information System (PROMIS) mental and physical health, American Shoulder and Elbow Surgeons Shoulder Score (ASES), Brophy shoulder activity scores, and need for manipulation under anesthesia (MUA). RESULTS: A total of 127 shoulders (38 KSB and 89 KTB) met inclusion criteria for the study. No significant difference in demographic variables were present between the groups at baseline. Supraspinatus tear size and average follow-up time did not differ significantly between groups. Failure rates were similar between the KSB and KTB repairs (13.1 vs 7.9%, n.s.). There was no significant difference in functional outcomes including strength, range of motion in forward flexion and external rotation, as well as patient reported outcomes including VAS, SSV, PROMIS, ASES, and Brophy scores between the groups. There was also no difference in post-operative stiffness requiring MUA. CONCLUSION: Both KSB and KTB repair techniques demonstrate low retear rates with excellent functional outcomes when compared to pre-operative examination. Both KSB and KTB techniques are viable options for achieving a successful rotator cuff repair. LEVEL OF EVIDENCE: Level III.

Sonic hedgehog-dependent recruitment of GABAergic interneurons into the developing visual thalamus.

Axons of retinal ganglion cells (RGCs) play critical roles in the development of inhibitory circuits in visual thalamus. We previously reported that RGC axons signal astrocytes to induce the expression of fibroblast growth factor 15 (FGF15), a motogen required for GABAergic interneuron migration into visual thalamus. However, how retinal axons induce thalamic astrocytes to generate Fgf15 and influence interneuron migration remains unknown. Here, we demonstrate that impairing RGC activity had little impact on interneuron recruitment into mouse visual thalamus. Instead, our data show that retinal-derived sonic hedgehog (SHH) is essential for interneuron recruitment. Specifically, we show that thalamus-projecting RGCs express SHH and thalamic astrocytes generate downstream components of SHH signaling. Deletion of RGC-derived SHH leads to a significant decrease in Fgf15 expression, as well as in the percentage of interneurons recruited into visual thalamus. Overall, our findings identify a morphogen-dependent neuron-astrocyte signaling mechanism essential for the migration of thalamic interneurons.

Complete loss of the X-linked gene CASK causes severe cerebellar degeneration.

BACKGROUND: Heterozygous loss of X-linked genes like CASK and MeCP2 (Rett syndrome) causes developmental delay in girls, while in boys, loss of the only allele of these genes leads to epileptic encephalopathy. The mechanism for these disorders remains unknown. CASK-linked cerebellar hypoplasia is presumed to result from defects in Tbr1-reelin-mediated neuronal migration. METHOD: Here we report clinical and histopathological analyses of a deceased 2-month-old boy with a CASK-null mutation. We next generated a mouse line where CASK is completely deleted (hemizygous and homozygous) from postmigratory neurons in the cerebellum. RESULT: The CASK-null human brain was smaller in size but exhibited normal lamination without defective neuronal differentiation, migration or axonal guidance. The hypoplastic cerebellum instead displayed astrogliosis and microgliosis, which are markers for neuronal loss. We therefore hypothesise that CASK loss-induced cerebellar hypoplasia is the result of early neurodegeneration. Data from the murine model confirmed that in CASK loss, a small cerebellum results from postdevelopmental degeneration of cerebellar granule neurons. Furthermore, at least in the cerebellum, functional loss from CASK deletion is secondary to degeneration of granule cells and not due to an acute molecular functional loss of CASK. Intriguingly, female mice with heterozygous deletion of CASK in the cerebellum do not display neurodegeneration. CONCLUSION: We suggest that X-linked neurodevelopmental disorders like CASK mutation and Rett syndrome are pathologically neurodegenerative; random X-chromosome inactivation in heterozygous mutant girls, however, results in 50% of cells expressing the functional gene, resulting in a non-progressive pathology, whereas complete loss of the only allele in boys leads to unconstrained degeneration and encephalopathy.

Low posterior tibial slope is associated with increased risk of PCL graft failure.

PURPOSE: To evaluate the effect of posterior tibial slope (PTS) on patient-reported outcomes (PROs) and posterior cruciate ligament (PCL) graft failure after PCL reconstruction. METHODS: Patients undergoing PCL reconstruction with a minimum 2-year follow-up were included in this retrospective cohort study. A chart review was performed to collect patient-, injury-, and surgery-related data. Medial PTS was measured on preoperative lateral radiographs. Validated PROs, including the International Knee Documentation Committee Subjective Knee Form, Knee injury and Osteoarthritis Outcome Score, Lysholm Score, Tegner Activity Scale, and Visual Analogue Scale for pain, were collected at final follow-up. A correlation analysis was conducted to assess the relationship between PTS and PROs. A logistic regression model was performed to evaluate if PTS could predict PCL graft failure. RESULTS: Overall, 79 patients with a mean age of 28.6 ± 11.7 years and a mean follow-up of 5.7 ± 3.3 years were included. After a median time from injury of 4.0 months, isolated and combined PCL reconstruction was performed in 22 (28%) and 57 (72%) patients, respectively. There were no statistically significant differences in PROs and PTS between patients undergoing isolated and combined PCL reconstruction (non-significant [n.s.]). There were no significant correlations between PTS and PROs (n.s.). In total, 14 (18%) patients experienced PCL graft failure after a median time of 17.5 months following PCL reconstruction. Patients with PCL graft failure were found to have statistically significantly lower PTS than patients without graft failure (7.0 ± 2.3° vs. 9.2 ± 3.3°, p < 0.05), while no differences were found in PROs (n.s.). PTS was shown to be a significant predictor of PCL graft failure, with a 1.3-fold increase in the odds of graft failure for each one-degree reduction in PTS (p < 0.05). CONCLUSIONS: This study showed that PTS does not affect PROs after PCL reconstruction, but that PTS represents a surgically modifiable predictor of PCL graft failure. LEVEL OF EVIDENCE: III.

Bone Block Augmentation of the Posterior Glenoid for Recurrent Posterior Shoulder Instability Is Associated With High Rates of Clinical Failure: A Systematic Review.

PURPOSE: To determine whether posterior glenoid bone block augmentation performed for the treatment of recurrent posterior shoulder instability succeeds in restoring stability and is associated with rates of complications or clinical failures comparable to other glenoid bone augmentation procedures. METHODS: A comprehensive search of PubMed, MEDLINE, and EMBASE databases was performed. Level of evidence studies I to IV pertaining to posterior bone block augmentation reporting on outcomes or complications were included. The search was carried out in accordance with the Preferred Reported Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Screening of titles, abstracts, and manuscripts with application of inclusion and exclusion criteria yielded 17 full-text articles reporting on 269 shoulders undergoing bone block augmentation. Surgical technique varied between studies with regard to graft type (iliac crest, 13 studies; scapular spine, 2; acromion, 1; distal tibia allograft, 1), graft positioning (medial to 1.5 cm lateral to glenoid surface, equatorial to subequatorial), and open versus arthroscopic technique (open, 10 studies; arthroscopic, 4; both, 3). Four of the 8 studies with pre- and postoperative patient-reported outcomes (PROs) showed significant improvements in these outcomes at final follow-up. The postoperative outcomes ranged from 60 to 90 for Rowe scores (n = 7 studies) and 79 to 90 for Walch-Duplay scores (n = 7 studies). Complications were commonly encountered, with high rates of recurrent instability (0% to 73%) and revision procedures (0% to 67%) across different studies. CONCLUSION: Posterior bone block augmentation for recurrent posterior shoulder instability does not reliably yield substantial improvements in PROs, and complications are frequently observed. The substantial heterogeneity across studies and the small number of patients precludes any substantive judgements as to the superiority of one surgical technique over another. LEVEL OF EVIDENCE: IV, systematic review of level III and IV studies.

Development of astrocyte morphology and function in mouse visual thalamus.

The rodent visual thalamus has served as a powerful model to elucidate the cellular and molecular mechanisms that underlie sensory circuit formation and function. Despite significant advances in our understanding of the role of axon-target interactions and neural activity in orchestrating circuit formation in visual thalamus, the role of non-neuronal cells, such as astrocytes, is less clear. In fact, we know little about the transcriptional identity and development of astrocytes in mouse visual thalamus. To address this gap in knowledge, we studied the expression of canonical astrocyte molecules in visual thalamus using immunostaining, in situ hybridization, and reporter lines. While our data suggests some level of heterogeneity of astrocytes in different nuclei of the visual thalamus, the majority of thalamic astrocytes appeared to be labeled in Aldh1l1-EGFP mice. This led us to use this transgenic line to characterize the neonatal and postnatal development of these cells in visual thalamus. Our data show that not only have the entire cohort of astrocytes migrated into visual thalamus by eye-opening but they also have acquired their adult-like morphology, even while retinogeniculate synapses are still maturing. Furthermore, ultrastructural, immunohistochemical, and functional approaches revealed that by eye-opening, thalamic astrocytes ensheathe retinogeniculate synapses and are capable of efficient uptake of glutamate. Taken together, our results reveal that the morphological, anatomical, and functional development of astrocytes in visual thalamus occurs prior to eye-opening and the emergence of experience-dependent visual activity.