Modified Dunn Procedure for Open Reduction of Chronic Slipped Capital Femoral Epiphysis.

Background: Abnormal femoral head anatomy following moderate-to-severe slipped capital femoral epiphysis (SCFE) can lead to femoroacetabular impingement and premature osteoarthritis4-10. Surgical correction at the deformity site through capital reorientation has the potential to fully ameliorate this but has traditionally been associated with high rates of osteonecrosis11-15. The modified Dunn procedure has the potential to restore anatomy in hips with SCFE while protecting the blood supply to the femoral head. Description: A surgical dislocation of the hip is performed according to the technique described by Ganz et al.16. The remaining posterosuperior portion of the greater trochanter is trimmed to the level of the femoral neck by subperiosteal bone removal performed in an inside-out manner. The periosteum of the femoral neck is gradually elevated. The resulting soft-tissue flap, consisting of the retinaculum and external rotators, holds the blood vessels supplying the epiphysis. The femoral epiphysis is pinned in situ (in unstable cases) with threaded Kirschner wires, the ligamentum teres is transected, and the femoral head is dislocated. With the femoral neck exposed, the epiphysis is gradually mobilized from the metaphysis, allowing exposure of the residual femoral neck and inspection of any posteroinferior callus. To avoid tension on the retinacular vessels during reduction of the epiphysis, the posterior neck callus is completely excised. The remaining physis is removed with use of a burr while holding the epiphysis stable. The epiphysis is gently reduced onto the femoral neck, avoiding tension on the retinacular vessels. If tension is noted, the femoral neck is rechecked for residual callus, which is excised. If no callus is found, the neck may be carefully shortened in order to minimize tension. Epiphyseal fixation is achieved with use of a 3-mm fully threaded wire inserted antegrade through the fovea to the lateral cortex below the greater trochanter. A second wire is inserted retrograde under fluoroscopy. After reducing the hip, the capsule is closed and the greater trochanter is reattached with use of 3.5-mm cortical screws. Alternatives: Alternatives include nonoperative treatment, in situ fixation (e.g., pinning or screw fixation), gentle closed reduction with pinning, and triplanar trochanteric osteotomy (e.g., Imhauser or Southwick osteotomies). Rationale: In situ pinning of mild-to-moderate, stable SCFE yields good long-term results with low rates of osteonecrosis9. Treatment of higher-grade SCFE without reduction aims to avoid osteonecrosis and assumes that the proximal femoral deformity will remodel; however, the head-neck offset will remain abnormal, risking impingement and early-onset osteoarthritis5,8. The procedure described in the present article allows anatomic reduction of the epiphysis with a low risk of osteonecrosis. Surgical dislocation of the hip16 with development of an extended retinacular soft-tissue flap17 provides extensive subperiosteal exposure of the circumferential femoral neck and preserves the vulnerable blood supply to the epiphysis18. The Dunn subcapital realignment procedure15 with callus removal and slip angle correction allows anatomic restoration of the proximal femur. Expected Outcomes: Reported results of various centers performing the procedure vary greatly with regard to the number of hips treated and the follow-up time. Most studies have been retrospective and have lacked a control group. The reported risk of osteonecrosis ranges from 0% to 25.9%19, with the wide range most likely because of the challenging nature of the technique, the low number of cases per surgeon, and the long learning curve associated with the procedure. In centers with extensive experience in pediatric hip-preserving surgery, the reported rate of osteonecrosis is low3. Studies with mid to long-term follow-up have shown no conversion to total hip arthroplasty3,20,21, but residual deformities can persist, and subsequent surgery is possible. Important Tips: Extensive experience in surgical hip dislocation and retinacular flap development is a prerequisite for successful outcomes and low rates of osteonecrosis.Sufficient callus and physeal remnant resections are needed to avoid tension on the retinacular vessels during epiphyseal reduction.The skin incision should be centered over the greater trochanterThe Gibson interval must be carefully prepared for adequate release and to avoid injury.Tension on the periosteal flap should be avoided to prevent stress on the retinacular vessels. Acronyms and Abbreviations: AP = anteroposteriorAVN = avascular necrosis (i.e., osteonecrosis)CI = confidence intervalCT = computed tomographyK-wire = Kirschner wireMRI = magnetic resonance imagingOA = osteoarthritisSHD = surgical hip dislocationTHA = total hip arthroplastyVTE = venous thromboembolism.

Open Microsurgical Cerebral Aneurysm Treatment After Failed Endovascular Therapy: An Evaluation of Aneurysm Treatment Frequencies in All Neurovascular Centers Across Austria and the Czech Republic Over 20 Years.

BACKGROUND AND OBJECTIVES: Endovascular treatment of cerebral aneurysms has tremendously advanced over the past decades. Nevertheless, aneurysm residual and recurrence remain challenges after embolization. The objective of this study was to elucidate the portion of embolized aneurysms requiring open surgery and evaluate whether newer endovascular treatments have changed the need for open surgery after failed embolization. METHODS: All 15 cerebrovascular centers in Austria and the Czech Republic provided overall aneurysm treatment frequency data and retrospectively reviewed consecutive cerebral aneurysms treated with open surgical treatment after failure of embolization from 2000 to 2022. All endovascular modalities were included. RESULTS: On average, 1362 aneurysms were treated annually in the 2 countries. The incidence increased from 0.006% in 2005 to 0.008% in 2020 in the overall population. Open surgery after failed endovascular intervention was necessary in 128 aneurysms (0.8%), a proportion that remained constant over time. Subarachnoid hemorrhage was the initial presentation in 70.3% of aneurysms. The most common location was the anterior communicating artery region (40.6%), followed by the middle cerebral artery (25.0%). The median diameter was 6 mm (2-32). Initial endovascular treatment included coiling (107 aneurysms), balloon-assist (10), stent-assist (4), intrasaccular device (3), flow diversion (2), and others (2). Complete occlusion after initial embolization was recorded in 40.6%. Seventy-one percent of aneurysms were operated within 3 years after embolization. In 7%, the indication for surgery was (re-)rupture and, in 88.3%, reperfusion. Device removal was performed in 16.4%. Symptomatic intraoperative and postoperative complications occurred in 10.2%. Complete aneurysm occlusion after open surgery was achieved in 94%. CONCLUSION: Open surgery remains a rare indication for cerebral aneurysms after failed endovascular embolization even in the age of novel endovascular technology, such as flow diverters and intrasaccular devices. Regardless, it is mostly performed for ruptured aneurysms initially treated with primary coiling that are in the anterior circulation.

The neutral CB1 antagonist AM6527 reduces ethanol seeking, binge-like consumption, reinforcing, and withdrawal effects in male and female mice.

RATIONALE: Alcohol use disorder (AUD) is a debilitating physiological and psychiatric disorder which affects individuals globally. The current pharmacological interventions to treat AUD are limited, and hence there is an urgent need for a novel pharmacological therapy which can be effective and safe across the population. OBJECTIVE: We aimed to investigate a novel neutral cannabinoid receptor-1 (CB1R) antagonist, AM6527, in several preclinical models of ethanol consumption using male and female C57BL6/J mice. METHODS: Independent groups of male and female mice were subjected to repeated cycles of drinking in the dark (DID), or intermittent access to alcohol (IAA) procedures. Twenty minutes prior to ethanol access in each procedure, animals were treated with intraperitoneal injections of either 1, 3, and 10 mg/kg of AM6527 or its respective vehicle. Acamprosate (100, 200, 300, and 400 mg/kg) or its respective vehicle was used as a positive control. Separate groups of male mice were subjected to a chain schedule of ethanol reinforcement to gain access to ethanol wherein completion of a fixed interval (FI; 5 min) schedule (link 1: "Seeking") was reinforced with continuous access to ethanol (fixed ratio; FR1) for up to 1.8 g/kg (link 2: "consumption"). All the animals were treated with 1, 3, and 10 mg/kg of AM6527 or its respective vehicle 20 mins prior to the start of the FI chain of the procedure. Separately, AM6527 was also evaluated in male and female mice undergoing acute ethanol withdrawal following 8 weeks of intermittent or continuous access to 20% ethanol drinking. RESULTS: In both DID and IAA procedures, AM6527 reduced ethanol consumption in a dose-related manner in both male and female mice. AM6527 produced no tolerance in the DID procedure; mice treated with 3 mg/kg of AM6527 for 3 weeks continuously drank significantly smaller amounts of ethanol as compared to vehicle-treated mice over a period of three DID cycles. Moreover, in the IAA procedure, AM6527 caused an increase in water intake over the 24-h period. Acamprosate transiently reduced ethanol intake in male mice in both the DID and the IAA procedures but failed to produce any significant effect in female mice. AM6527 also produced a decrease in the FI responding ("ethanol seeking") in animals trained to self-administer ethanol. Lastly, AM6527 mitigated neurological withdrawal signs, i.e., handling induced convulsions (HIC) in mice undergoing acute ethanol withdrawal. CONCLUSIONS: Current findings support previous studies with CB1R neutral antagonist in reducing voluntary ethanol intake and seeking behavior. Based on results shown in this work, AM6527 can be developed as a first in class CB1R neutral antagonist to treat AUD in both males and females.

Hip Impingement of severe SCFE patients after in situ pinning causes decreased flexion and forced external rotation in flexion on 3D-CT.

Introduction: In situ pinning is an accepted treatment for stable slipped capital femoral epiphysis. However, residual deformity of severe slipped capital femoral epiphysis can cause femoroacetabular impingement and forced external rotation. Purpose/questions: The aim of this study was to evaluate the (1) hip external rotation and internal rotation in flexion, (2) hip impingement location, and (3) impingement frequency in early flexion in severe slipped capital femoral epiphysis patients after in situ pinning using three-dimensional computed tomography. Patients and methods: A retrospective Institutional Review Board-approved study evaluating 22 patients (26 hips) with severe slipped capital femoral epiphysis (slip angle > 60°) using postoperative three-dimensional computed tomography after in situ pinning was performed. Mean age at slipped capital femoral epiphysis diagnosis was 13 ± 2 years (58% male, four patients bilateral, 23% unstable, 85% chronic). Patients were compared to contralateral asymptomatic hips (15 hips) with unilateral slipped capital femoral epiphysis (control group). Pelvic three-dimensional computed tomography after in situ pinning was used to generate three-dimensional models. Specific software was used to determine range of motion and impingement location (equidistant method). And 22 hips (85%) underwent subsequent surgery. Results: (1) Severe slipped capital femoral epiphysis patients had significantly (p < 0.001) decreased hip flexion (43 ± 40°) and internal rotation in 90° of flexion (-16 ± 21°, IRF-90°) compared to control group (122 ± 9° and 36 ± 11°). (2) Femoral impingement in maximal flexion was located anterior to anterior-superior (27% on 3 o'clock and 27% on 1 o'clock) of severe slipped capital femoral epiphysis patients and located anterior to anterior-inferior (38% on 3 o'clock and 35% on 4 o'clock) in IRF-90°. (3) However, 21 hips (81%) had flexion < 90° and 22 hips (85%) had < 10° of IRF-90° due to hip impingement and 21 hips (81%) had forced external rotation in 90° of flexion (< 0° of IRF-90°). Conclusion: After in situ pinning, patient-specific three-dimensional models showed restricted flexion and IRF-90° and forced external rotation in 90° of flexion due to early hip impingement and residual deformity in most of the severe slipped capital femoral epiphysis patients. This could help to plan subsequent hip preservation surgery, such as hip arthroscopy or femoral (derotation) osteotomy.

Composition and micromechanical properties of the femoral neck compact bone in relation to patient age, sex and hip fracture occurrence.

Current clinical methods of bone health assessment depend to a great extent on bone mineral density (BMD) measurements. However, these methods only act as a proxy for bone strength and are often only carried out after the fracture occurs. Besides BMD, composition and tissue-level mechanical properties are expected to affect the whole bone's strength and toughness. While the elastic properties of the bone extracellular matrix (ECM) have been extensively investigated over the past two decades, there is still limited knowledge of the yield properties and their relationship to composition and architecture. In the present study, morphological, compositional and micropillar compression bone data was collected from patients who underwent hip arthroplasty. Femoral neck samples from 42 patients were collected together with anonymous clinical information about age, sex and primary diagnosis (coxarthrosis or hip fracture). The femoral neck cortex from the inferomedial region was analyzed in a site-matched manner using a combination of micromechanical testing (nanoindentation, micropillar compression) together with micro-CT and quantitative polarized Raman spectroscopy for both morphological and compositional characterization. Mechanical properties, as well as the sample-level mineral density, were constant over age. Only compositional properties demonstrate weak dependence on patient age: decreasing mineral to matrix ratio (p = 0.02, R2 = 0.13, 2.6 % per decade) and increasing amide I sub-peak ratio I∼1660/I∼1683 (p = 0.04, R2 = 0.11, 1.5 % per decade). The patient's sex and diagnosis did not seem to influence investigated bone properties. A clear zonal dependence between interstitial and osteonal cortical zones was observed for compositional and elastic bone properties (p < 0.0001). Site-matched microscale analysis confirmed that all investigated mechanical properties except yield strain demonstrate a positive correlation with the mineral fraction of bone. The output database is the first to integrate the experimentally assessed microscale yield properties, local tissue composition and morphology with the available patient clinical information. The final dataset was used for bone fracture risk prediction in-silico through the principal component analysis and the Naïve Bayes classification algorithm. The analysis showed that the mineral to matrix ratio, indentation hardness and micropillar yield stress are the most relevant parameters for bone fracture risk prediction at 70 % model accuracy (0.71 AUC). Due to the low number of samples, further studies to build a universal fracture prediction algorithm are anticipated with the higher number of patients (N > 200). The proposed classification algorithm together with the output dataset of bone tissue properties can be used for the future comparison of existing methods to evaluate bone quality as well as to form a better understanding of the mechanisms through which bone tissue is affected by aging or disease.

Radial access for peripheral vascular intervention: the S.M.A.R.T. RADIANZ Vascular Stent System.

INTRODUCTION: Radial access is the standard of care for nearly all cardiac catheterization procedures. It improves patient satisfaction, reduces the length of stay, and is associated with fewer complications. However, few devices and tools are available for the treatment of peripheral arterial disease via a transradial approach (TRA). The S.M.A.R.T. RADIANZ Vascular Stent System is among the RADIANZ suite of products, which is aimed at expanding the portfolio of devices to treat peripheral arterial disease. AREAS COVERED: In this Expert review, the following areas will be covered: (1) Current Landscape of peripheral vascular intervention (PVI) using TRA (2) Detailed description of the S.M.A.R.T. RADIANZ Vascular Stent System. (3) Ongoing clinical trials to evaluate safety of this approach. (4) Future directions and current regulatory status. EXPERT OPINION: TRA for PVI is a promising approach. It holds the possibility of substantially improving the care of patients with peripheral arterial disease (PAD). Numerous challenges must be overcome to realize the full potential of a radial-to-peripheral (RTP) approach. The length of devices and the small sheath size are the main constraints of this approach. The results of the ongoing RADIANCY trial will demonstrate the safety, in selected patients, of the RADIANZ suite of products.

Endovascular stroke therapy outside core working hours in a nationwide stroke system.

BACKGROUND: Endovascular therapy (EVT) has been established as a major component in the acute treatment of large vessel occlusion stroke. However, it is unclear whether outcome and other treatment-related factors differ if patients are treated within or outside core working hours. METHODS: We analyzed data from the prospective nationwide Austrian Stroke Unit Registry capturing all consecutive stroke patients treated with EVT between 2016 and 2020. Patients were trichotomized according to the time of groin puncture into treatment within regular working hours (08:00-13:59), afternoon/evening (14:00-21:59) and night-time (22:00-07:59). Additionally, we analyzed 12 EVT treatment windows with equal patient numbers. Main outcome variables included favorable outcome (modified Rankin Scale scores of 0-2) 3 months post-stroke as well as procedural time metrics, recanalization status and complications. RESULTS: We analyzed 2916 patients (median age 74 years, 50.7% female) who underwent EVT. Patients treated within core working hours more frequently had a favorable outcome (42.6% vs 36.1% treated in the afternoon/evening vs 35.8% treated at night-time; p=0.007). Similar results were found when analyzing 12 treatment windows. All these differences remained significant in multivariable analysis adjusting for outcome-relevant co-factors. Onset-to-recanalization time was considerably longer outside core working hours, which was mainly explained by longer door-to-groin time (p<0.001). There was no difference in the number of passes, recanalization status, groin-to-recanalization time and EVT-related complications. CONCLUSIONS: The findings of delayed intrahospital EVT workflows and worse functional outcomes outside core working hours in this nationwide registry are relevant for optimization of stroke care, and might be applicable to other countries with similar settings.

Do Osteochondroplasty Alone, Intertrochanteric Derotation Osteotomy, and Flexion-Derotation Osteotomy Improve Hip Flexion and Internal Rotation to Normal Range in Hips With Severe SCFE? - A 3D-CT Simulation Study.

BACKGROUND: Severe slipped capital femoral epiphysis (SCFE) leads to femoroacetabular impingement and restricted hip motion. We investigated the improvement of impingement-free flexion and internal rotation (IR) in 90 degrees of flexion following a simulated osteochondroplasty, a derotation osteotomy, and a combined flexion-derotation osteotomy in severe SCFE patients using 3D-CT-based collision detection software. METHODS: Preoperative pelvic CT of 18 untreated patients (21 hips) with severe SCFE (slip-angle>60 degrees) was used to generate patient-specific 3D models. The contralateral hips of the 15 patients with unilateral SCFE served as the control group. There were 14 male hips (mean age 13±2 y). No treatment was performed before CT. Specific collision detection software was used for the calculation of impingement-free flexion and IR in 90 degrees of flexion and simulation of osteochondroplasty, derotation osteotomy, and combined flexion-derotation osteotomy. RESULTS: Osteochondroplasty alone improved impingement-free motion but compared with the uninvolved contralateral control group, severe SCFE hips had persistently significantly decreased motion (mean flexion 59±32 degrees vs. 122±9 degrees, P <0.001; mean IR in 90 degrees of flexion -5±14 degrees vs. 36±11 degrees, P <0.001). Similarly, the impingement-free motion was improved after derotation osteotomy, and impingement-free flexion after a 30 degrees derotation was equivalent to the control group (113± 42 degrees vs. 122±9 degrees, P =0.052). However, even after the 30 degrees derotation, the impingement-free IR in 90 degrees of flexion persisted lower (13±15 degrees vs. 36±11 degrees, P <0.001). Following the simulation of flexion-derotation osteotomy, mean impingement-free flexion and IR in 90 degrees of flexion increased for combined correction of 20 degrees (20 degrees flexion and 20 degrees derotation) and 30 degrees (30 degrees flexion and 30 degrees derotation). Although mean flexion was equivalent to the control group for both (20 degrees and 30 degrees) combined correction, the mean IR in 90 degrees of flexion persisted decreased, even after the 30 degrees combined flexion-derotation (22±22 degrees vs. 36 degrees±11, P =0.009). CONCLUSIONS: Simulation of derotation-osteotomy (30 degrees correction) and flexion-derotation-osteotomy (20 degrees correction) normalized hip flexion for severe SCFE patients, but IR in 90 degrees of flexion persisted slightly lower despite significant improvement. Not all SCFE patients had improved hip motion with the performed simulations; therefore, some patients may need a higher degree of correction or combined treatment with osteotomy and cam-resection, although not directly investigated in this study. Patient-specific 3D-models could help individual preoperative planning for severe SCFE patients to normalize the hip motion. LEVEL OF EVIDENCE: III, case-control study.

A Deep Learning Method for Quantification of Femoral Head Necrosis Based on Routine Hip MRI for Improved Surgical Decision Making.

(1) Background: To evaluate the performance of a deep learning model to automatically segment femoral head necrosis (FHN) based on a standard 2D MRI sequence compared to manual segmentations for 3D quantification of FHN. (2) Methods: Twenty-six patients (thirty hips) with avascular necrosis underwent preoperative MR arthrography including a coronal 2D PD-w sequence and a 3D T1 VIBE sequence. Manual ground truth segmentations of the necrotic and unaffected bone were then performed by an expert reader to train a self-configuring nnU-Net model. Testing of the network performance was performed using a 5-fold cross-validation and Dice coefficients were calculated. In addition, performance across the three segmentations were compared using six parameters: volume of necrosis, volume of unaffected bone, percent of necrotic bone volume, surface of necrotic bone, unaffected femoral head surface, and percent of necrotic femoral head surface area. (3) Results: Comparison between the manual 3D and manual 2D segmentations as well as 2D with the automatic model yielded significant, strong correlations (Rp > 0.9) across all six parameters of necrosis. Dice coefficients between manual- and automated 2D segmentations of necrotic- and unaffected bone were 75 ± 15% and 91 ± 5%, respectively. None of the six parameters of FHN differed between the manual and automated 2D segmentations and showed strong correlations (Rp > 0.9). Necrotic volume and surface area showed significant differences (all p < 0.05) between early and advanced ARCO grading as opposed to the modified Kerboul angle, which was comparable between both groups (p > 0.05). (4) Conclusions: Our deep learning model to automatically segment femoral necrosis based on a routine hip MRI was highly accurate. Coupled with improved quantification for volume and surface area, as opposed to 2D angles, staging and course of treatment can become better tailored to patients with varying degrees of AVN.

Combined femoral and acetabular version is sex-related and differs between patients with hip dysplasia and acetabular retroversion.

AIMS: Frequency of abnormal femoral and acetabular version (AV) and combinations are unclear in patients with developmental dysplasia of the hip (DDH). This study aimed to investigate femoral version (FV), the proportion of increased FV and femoral retroversion, and combined-version (CV, FV+AV) in DDH patients and acetabular-retroversion (AR). PATIENTS AND METHODS: A retrospective IRB-approved observational study was performed with 78 symptomatic DDH patients (90 hips) and 65 patients with femoroacetabular-impingement (FAI) due to AR (77 hips, diagnosis on AP radiographs). CT/MRI-based measurement of FV (Murphy method) and central AV were compared. Frequency of increased FV(FV > 25°), severely increased FV (FV > 35°) and excessive FV (FV > 45°) and of decreased FV (FV < 10°) and CV (McKibbin-index/COTAV-index) was analysed. RESULTS: Mean FV and CV was significantly (p < 0.001) increased of DDH patients (mean ± SD of 25 ± 11° and 47 ± 18°) compared to AR (16 ± 11° and 28 ± 13°). Mean FV of female DDH patients (27 ± 16°) and AR (19 ± 12°) was significantly (p < 0.001) increased compared to male DDH patients (18 ± 13°) and AR (13 ± 8°). Frequency of increased FV (>25°) was 47% and of severely increased FV (>35°) was 23% for DDH patients. Proportion of femoral retroversion (FV < 10°) was significantly (p < 0.001) higher in patients AR (31%) compared to DDH patients (17%). 18% of DDH patients had AV > 25° combined with FV > 25°. Of patients with AR, 12% had FV < 10° combined with AV < 10°. CONCLUSION: Patients with DDH and AR have remarkable sex-related differences of FV and CV. Frequency of severely increased FV > 35° (23%) is considerable for patients with DDH, but 17% exhibited decreased FV, that could influence management. The different combinations underline the importance of patient-specific evaluation before open hip preservation surgery (periacetabular osteotomy and femoral derotation osteotomy) and hip-arthroscopy.

Genome-wide transcriptomics of the amygdala reveals similar oligodendrocyte-related responses to acute and chronic alcohol drinking in female mice.

Repeated excessive alcohol consumption is a risk factor for alcohol use disorder (AUD). Although AUD has been more common in men than women, women develop more severe behavioral and physical impairments. However, relatively few new therapeutics targeting development of AUD, particularly in women, have been validated. To gain a better understanding of molecular mechanisms underlying alcohol intake, we conducted a genome-wide RNA-sequencing analysis in female mice exposed to different modes (acute vs chronic) of ethanol drinking. We focused on transcriptional profiles in the amygdala including the central and basolateral subnuclei, brain areas previously implicated in alcohol drinking and seeking. Surprisingly, we found that both drinking modes triggered similar changes in gene expression and canonical pathways, including upregulation of ribosome-related/translational pathways and myelination pathways, and downregulation of chromatin binding and histone modification. In addition, analyses of hub genes and upstream regulatory pathways revealed that voluntary ethanol consumption affects epigenetic changes via histone deacetylation pathways, oligodendrocyte and myelin function, and the oligodendrocyte-related transcription factor, Sox17. Furthermore, a viral vector-assisted knockdown of Sox17 gene expression in the amygdala prevented a gradual increase in alcohol consumption during repeated accesses. Overall, these results suggest that the expression of oligodendrocyte-related genes in the amygdala is sensitive to voluntary alcohol drinking in female mice. These findings suggest potential molecular targets for future therapeutic approaches to prevent the development of AUD, due to repeated excessive alcohol consumption, particularly in women.

Limited Hip Flexion and Internal Rotation Resulting From Early Hip Impingement Conflict on Anterior Metaphysis of Patients With Untreated Severe SCFE Using 3D Modelling.

INTRODUCTION: Slipped capital femoral epiphysis (SCFE) is the most common hip disorder in adolescent patients that can result in complex 3 dimensional (3D)-deformity and hip preservation surgery (eg, in situ pinning or proximal femoral osteotomy) is often performed. But there is little information about location of impingement.Purpose/Questions: The purpose of this study was to evaluate (1) impingement-free hip flexion and internal rotation (IR), (2) frequency of impingement in early flexion (30 to 60 degrees), and (3) location of acetabular and femoral impingement in IR in 90 degrees of flexion (IRF-90 degrees) and in maximal flexion for patients with untreated severe SCFE using preoperative 3D-computed tomography (CT) for impingement simulation. METHODS: A retrospective study involving 3D-CT scans of 18 patients (21 hips) with untreated severe SCFE (slip angle>60 degrees) was performed. Preoperative CT scans were used for bone segmentation of preoperative patient-specific 3D models. Three patients (15%) had bilateral SCFE. Mean age was 13±2 (10 to 16) years and 67% were male patients (86% unstable slip, 81% chronic slip). The contralateral hips of 15 patients with unilateral SCFE were evaluated (control group). Validated software was used for 3D impingement simulation (equidistant method). RESULTS: (1) Impingement-free flexion (46±32 degrees) and IRF-90 degrees (-17±18 degrees) were significantly ( P <0.001) decreased in untreated severe SCFE patients compared with contralateral side (122±9 and 36±11 degrees).(2) Frequency of impingement was significantly ( P <0.001) higher in 30 and 60 degrees flexion (48% and 71%) of patients with severe SCFE compared with control group (0%).(3) Acetabular impingement conflict was located anterior-superior (SCFE patients), mostly 12 o'clock (50%) in IRF-90 degrees (70% on 2 o'clock for maximal flexion). Femoral impingement was located on anterior-superior to anterior-inferior femoral metaphysis (between 2 and 6 o'clock, 40% on 3 o'clock and 40% on 5 o'clock) in IRF-90 degrees and on anterior metaphysis (40% on 3 o'clock) in maximal flexion and frequency was significantly ( P <0.001) different compared with control group. CONCLUSION: Severe SCFE patients have limited hip flexion and IR due to early hip impingement using patient-specific preoperative 3D models. Because of the large variety of hip motion, individual evaluation is recommended to plan the osseous correction for severe SCFE patients. LEVEL OF EVIDENCE: Level III.

Revision of a Failed Primary Total Hip Arthroplasty following Excessive Reaming with a Medial Cup Protrusion.

Background and Objectives: Atraumatic intrapelvic protrusion of the acetabular component following excessive reaming of the acetabulum with a far medial positioning of the cup is a rare, but serious complication of a total hip arthroplasty (THA). This study analyzes the factors contributing to this uncommon complication and presents the outcome after the revision surgery using the Ganz reinforcement ring combined with a bone graft and plating of the posterior column and/or screws for the anterior column. Materials and Methods: A retrospective case series study with seven patients (four males, mean age 76 ± 10 years (60−86)) that underwent a revision THA within 24 ± 17 days (5−60) after an atraumatic periprosthetic acetabular fracture with a medial cup protrusion was performed. All fractures were reconstructed with a Ganz reinforcement ring and bone graft with a mean follow-up of 1.7 ± 1.7 years (0.5−5). Radiographs were evaluated for the following: (i) cup positioning immediately after the primary THA and the revision surgery, (ii) cup migration in the follow-up, and (iii) fracture healing. Results: The position of the acetabular component as assessed on the postoperative radiographs after the index surgery and before the complete medial cup protrusion showed a cup placement beyond the ilioischial line indicative of a fracture of the medial wall. The revision surgery with the reconstruction of the medial wall with a Ganz reinforcement ring combined with a bone graft restored in the presented cases the center of rotation in the horizontal direction with a statistical significance (p < 0.05). During the follow-up, there was no aseptic loosening with the relevant cup migration or significant change in the position of the acetabular cup at the final follow-up (p > 0.05) after the revision. All seven fractures and bone grafts realized a bone union until the latest follow-up. Conclusions: Following excessive reaming, the acetabular component was placed too far medially and resulted in an intrapelvic cup protrusion. An unstable cup following a fracture of the medial wall was evident on the immediate postoperative radiographs. In the case of the medial wall perforation with an intrapelvic cup protrusion after the primary THA, the reconstruction with a Ganz reinforcement ring was a successful treatment option resulting in the fracture healing and a stable cup positioning. Surgeons should be aware of that rare and probably underreported complication and restore the anatomic center of rotation by treating the defect intraoperatively.

Reactive Oxygen Species-Responsive Polymer Nanoparticles to Improve the Treatment of Inflammatory Skin Diseases.

To improve the quality of life for people living with chronic inflammatory skin diseases, we propose a new treatment strategy by exploring a stimuli-responsive drug delivery system. Formulations designed by exploiting smart materials can be programmed to perform a specific action upon exposure to disease-related stimuli. For instance, increased levels of reactive oxygen species (ROS), especially the accumulation of hydrogen peroxide, can be utilized to differentiate between healthy and inflamed tissues. In this concept-proofing study, the polymer poly(1,4 phenyleneacetone dimethylene thioketal) (PPADT) was investigated for its ROS-responsive properties and potential to treat inflammatory skin diseases. PPADT nanoparticles were formulated by oil-in-water emulsification followed by solvent evaporation and characterized by size, zeta-potential, and release kinetic profiles. Release profiles revealed that the PPADT nanoparticles were sensitive toward elevated levels of ROS in an ROS-stimulus concentration (0.1-10 mM) and time-dependent manner (flare-up mimicked). The safety assessment proved that the PPADT polymer and the monomers generated by oxidation do not show any sign of being cytotoxic to fibroblasts and no mutagenic liabilities were observed. In conclusion, the PPADT polymer demonstrated to be a promising material for stimuli-responsive delivery of hydrophobic small molecules in the treatment of inflammatory skin diseases.

Excessive alcohol consumption after exposure to two types of chronic social stress: intermittent episodes vs. continuous exposure in C57BL/6J mice with a history of drinking.

RATIONALE: The attraction to alcohol can be greatly increased when it is consumed in a social context. While pro-social interactions can potentiate voluntary alcohol drinking under some conditions, aversive social experience (i.e., social stress) can similarly intensify alcohol consumption. OBJECTIVE: We sought to determine how exposure to different types of chronic social stress (i.e., intermittent episodes of social defeat or continuous social stress) influences alcohol consumption and the reinforcing effects of alcohol in mice with a history of drinking. METHODS: Separate cohorts of male C57BL/6J mice were exposed to either 10 days of continuous or intermittent social defeat stress. In experiment 1, mice were assigned to 20% w/v alcohol consumption in a two-bottle choice protocol both prior to and after exposure to social defeat stress. In a second experiment, mice engaged in an operant response sequence to gain access to alcohol wherein completion of a fixed interval (FI; 5 min) schedule was reinforced with continuous access to alcohol (fixed ratio; FR1) for up to 1.8 g/kg. Alcohol-reinforced responding and subsequent alcohol consumption were assessed daily for 4 weeks prior to the 10-day social stress exposure and for 6-week post-stress. Machine learning was implemented to standardize the analysis of defeat behaviors exhibited by the intruder mouse during confrontation with an attacking resident. RESULTS: In mice with a prior history of alcohol drinking, intermittent episodes of social defeat stress produced a significant increase in 20% EtOH consumption in preference over concurrently available water. This increased intake persisted for at least 6 weeks after the final social stress experience. Intermittently stressed mice also accelerated their anticipatory responding during the fixed interval component of the operant response chain that was reinforced by alcohol. Neither unstressed controls nor mice exposed to continuous social stress exhibited significant increases in alcohol consumption and alcohol reinforcement. DISCUSSION: Episodic social defeat stress promotes the seeking and consumption of alcohol, extending earlier work to alcohol-experienced mice. We hypothesize that intermittent access to alcohol and intermittent episodes of social stress are additive and share common sensitizing neural mechanisms that engender excessive alcohol consumption.

Automated quantification of cartilage quality for hip treatment decision support.

PURPOSE: Preservation surgery can halt the progress of joint degradation, preserving the life of the hip; however, outcome depends on the existing cartilage quality. Biochemical analysis of the hip cartilage utilizing MRI sequences such as delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), in addition to morphological analysis, can be used to detect early signs of cartilage degradation. However, a complete, accurate 3D analysis of the cartilage regions and layers is currently not possible due to a lack of diagnostic tools. METHODS: A system for the efficient automatic parametrization of the 3D hip cartilage was developed. 2D U-nets were trained on manually annotated dual-flip angle (DFA) dGEMRIC for femoral head localization and cartilage segmentation. A fully automated cartilage sectioning pipeline for analysis of central and peripheral regions, femoral-acetabular layers, and a variable number of section slices, was developed along with functionality for the automatic calculation of dGEMRIC index, thickness, surface area, and volume. RESULTS: The trained networks locate the femoral head and segment the cartilage with a Dice similarity coefficient of 88 ± 3 and 83 ± 4% on DFA and magnetization-prepared 2 rapid gradient-echo (MP2RAGE) dGEMRIC, respectively. A completely automatic cartilage analysis was performed in 18s, and no significant difference for average dGEMRIC index, volume, surface area, and thickness calculated on manual and automatic segmentation was observed. CONCLUSION: An application for the 3D analysis of hip cartilage was developed for the automated detection of subtle morphological and biochemical signs of cartilage degradation in prognostic studies and clinical diagnosis. The segmentation network achieved a 4-time increase in processing speed without loss of segmentation accuracy on both normal and deformed anatomy, enabling accurate parametrization. Retraining of the networks with the promising MP2RAGE protocol would enable analysis without the need for B1 inhomogeneity correction in the future.

To fight or not to fight: activation of the mPFC during decision to engage in aggressive behavior after ethanol consumption in a novel murine model.

RATIONALE: Alcohol consumption is a common antecedent of aggressive behavior. The effects of alcohol on the decision to engage in aggression in preference over pro-social interaction are hypothesized to arise from augmented function within the medial prefrontal cortex (mPFC). OBJECTIVE: In a newly developed procedure, we studied social decision-making in male C57BL/6 J mice based on preferentially seeking access to either sociosexual interactions with a female partner or the opportunity to attack an intruder male. While deciding to engage in aggressive vs. sociosexual behavior, corresponding neural activation was assessed via c-Fos immunoreactivity in cortical, amygdaloid and tegmental regions of interest. A further objective was to investigate how self-administered alcohol impacted social choice. METHODS: During repeated confrontations with an intruder male in their home cage, experimental mice engaged in species-specific sequence of pursuit, threat, and attack behavior within < 2 min. Mice were then conditioned to respond at one of two separate illuminated operanda in an experimental chamber (octagon) attached to their home cage; completion of 10 responses (fixed ratio 10; FR10) was reinforced by access to either a female or a male intruder which were presented in the resident's home cage. Brains were harvested following choice between the concurrently available aggressive and sociosexual options and processed for c-Fos immunoreactivity across 10 brain regions. In two separate groups, mice were trained to rapidly self-administer ethanol prior to a social choice trial in order to examine the effects of alcohol on social choice, sociosexual, aggressive acts and postures, and concurrent c-Fos activity in the mPFC and limbic regions. RESULTS AND DISCUSSION: Eight out of 65 mice consistently chose to engage in aggressive behavior in preference to sociosexual contact with a female when each outcome was concurrently available. Self-administered alcohol (experiment 1: 1.2 ± 0.02 g/kg; experiment 2: 0, 1.0, 1.5, and 1.8 g/kg) increased responding for the aggressive option in mice that previously opted predominantly for access to sociosexual interactions with the female. When choosing the aggressive, but not the sociosexual option, the prelimbic area of the mPFC revealed increased c-Fos activity, guiding future detailed inquiry into the neural mechanisms for aggressive choice.

Perioperative Fully Closed-Loop Insulin Delivery in Patients Undergoing Elective Surgery: An Open-Label, Randomized Controlled Trial.

OBJECTIVE: Perioperative management of glucose levels remains challenging. We aimed to assess whether fully closed-loop subcutaneous insulin delivery would improve glycemic control compared with standard insulin therapy in insulin-requiring patients undergoing elective surgery. RESEARCH DESIGN AND METHODS: We performed a single-center, open-label, randomized controlled trial. Patients with diabetes (other than type 1) undergoing elective surgery were recruited from various surgical units and randomly assigned using a minimization schedule (stratified by HbA1c and daily insulin dose) to fully closed-loop insulin delivery with fast-acting insulin aspart (closed-loop group) or standard insulin therapy according to local clinical practice (control group). Study treatment was administered from hospital admission to discharge (for a maximum of 20 days). The primary end point was the proportion of time with sensor glucose in the target range (5.6-10.0 mmol/L). RESULTS: Forty-five patients were enrolled and assigned to the closed-loop (n = 23) or the control (n = 22) group. One patient (closed-loop group) withdrew from the study before surgery and was not analyzed. Participants underwent abdominal (57%), vascular (23%), orthopedic (9%), neuro (9%), or thoracic (2%) surgery. The mean proportion of time that sensor glucose was in the target range was 76.7 ± 10.1% in the closed-loop and 54.7 ± 20.8% in the control group (mean difference 22.0 percentage points [95% CI 11.9; 32.0%]; P < 0.001). No episodes of severe hypoglycemia (<3.0 mmol/L) or hyperglycemia with ketonemia or any study-related adverse events occurred in either group. CONCLUSIONS: In the context of mixed elective surgery, the use of fully closed-loop subcutaneous insulin delivery improves glucose control without a higher risk of hypoglycemia.