Metformin alters dendrite development and synaptic plasticity in rat cortical neurons.

Synaptic plasticity is crucial as it dynamically molds the strength and connectivity of neural circuits, influencing learning, memory, and the development of neurological disorders. Metformin, a widely prescribed anti-diabetic medication, has been shown to readily cross the blood-brain barrier (BBB) and the placenta. However, its prolonged impact on neuronal morphology and functions remains underexplored. In this study, we investigated the influence of metformin on dendrite development and synaptic plasticity in embryonic brains and primary rat cortical neurons. Our findings reveal a negative modulation of dendrite development by metformin, as evidenced by altered dendritic arborization, impaired dendritic spine morphology and disruptions in synaptic plasticity, suggesting a potential link between metformin exposure and aberrations in neuronal connectivity. In addition, we extend our insights to the impact of maternal metformin exposure on embryonic brains, revealing a significant inhibition of dendrite development in E18.5 rat brains. In conclusion, this study adds to the expanding knowledge base on the non-metabolic effects of metformin, emphasizing the significance of assessing its potential influence on both neuronal structure and function. There is an urgent need for further investigations into the enduring impact of prolonged metformin administration on the structural and functional aspects of neurons.

Metformin inhibits nerve growth factor (NGF)-induced sympathetic neuron differentiation through p35/CDK5 inhibition.

The authors' previous research has shown the pivotal roles of Cyclin-dependent kinase 5 (CDK5) and its regulatory protein p35 in nerve growth factor (NGF)-induced differentiation of sympathetic neurons in PC12 cells. During the process of differentiation, neurons are susceptible to environmental influences, including the effects of drugs. Metformin is commonly used in the treatment of diabetes and its associated symptoms, particularly in diabetic neuropathy, which is characterized by dysregulation of the sympathetic neurons. However, the impacts of metformin on sympathetic neuronal differentiation remain unknown. In this study, we investigated the impact of metformin on NGF-induced sympathetic neuronal differentiation using rat pheochromocytoma PC12 cells as a model. We examined the regulation of TrkA-p35/CDK5 signaling in NGF-induced PC12 differentiation. Our results demonstrate that metformin reduces NGF-induced PC12 differentiation by inactivating the TrkA receptor, subsequently inhibiting ERK and EGR1. Inhibition of this cascade ultimately leads to the down-regulation of p35/CDK5 in PC12 cells. Furthermore, metformin inhibits the activation of the pre-synaptic protein Synapsin-I, a substrate of CDK5, in PC12 differentiation. Additionally, metformin alters axonal and synaptic bouton formation by inhibiting p35 at both the axons and axon terminals in fully differentiated PC12 cells. In summary, our study elucidates that metformin inhibits sympathetic neuronal differentiation in PC12 cells by disrupting TrkA/ERK/EGR1 and p35/CDK5 signaling. This research contributes to uncovering a novel signaling mechanism in drug response during sympathetic neuronal differentiation, enhancing our understanding of the intricate molecular processes governing this critical aspect of neurodevelopment.

Anatomic versus Low Tibial Tunnel in Double-Bundle Posterior Cruciate Ligament Reconstruction: Clinical and Radiologic Outcomes with a Minimum 2-Year Follow-Up.

There is currently no consensus on the optimal placement of the tibial tunnel for double-bundle posterior cruciate ligament (PCL) reconstruction. The purpose of this study was to compare the clinical and radiologic outcomes of double-bundle PCL reconstruction utilizing anatomic versus low tibial tunnels. We conducted a retrospective cohort study involving patients who underwent double-bundle PCL reconstruction between Jan 2019 and Jan 2022, with a minimum follow-up of 2 years (n = 36). Based on the tibial tunnel position on postoperative computed tomography, patients were categorized into two groups: anatomic placement (group A; n = 18) and low tunnel placement (group L; n = 18). We compared the range of motion, stability test, complications, and side-to-side differences in tibial posterior translation using kneeling stress radiography between the two groups. There were no significant differences between the groups regarding clinical outcomes or complication rates. No significant differences in the posterior drawer test and side-to-side difference on kneeling stress radiography (2.5 ± 1.2 mm in group A vs. 3.7 ± 2.0 mm in group L; p = 0.346). In conclusion, the main findings of this study indicate that both anatomic tunnel and low tibial tunnel placements in double-bundle PCL reconstruction demonstrated comparable and satisfactory clinical and radiologic outcomes, with similar overall complication rates at the 2-year follow-up.

Impact of metformin on neocortical development during pregnancy: Involvement of ERK and p35/CDK5 pathways.

Metformin, the most commonly prescribed drug for the treatment of diabetes, is increasingly used during pregnancy to address various disorders such as diabetes, obesity, preeclampsia, and metabolic diseases. However, its impact on neocortex development remains unclear. Here, we investigated the direct effects of metformin on neocortex development, focusing on ERK and p35/CDK5 regulation. Using a pregnant rat model, we found that metformin treatment during pregnancy induces small for gestational age (SGA) and reduces relative cortical thickness in embryos and neonates. Additionally, we discovered that metformin inhibits neural progenitor cell proliferation in the sub-ventricular zone (SVZ)/ventricular zone (VZ) of the developing neocortex, a process possibly mediated by ERK inactivation. Furthermore, metformin induces neuronal apoptosis in the SVZ/VZ area of the developing neocortex. Moreover, metformin retards neuronal migration, cortical lamination, and differentiation, potentially through p35/CDK5 inhibition in the developing neocortex. Remarkably, compensating for p35 through in utero electroporation partially rescues metformin-impaired neuronal migration and development. In summary, our study reveals that metformin disrupts neocortex development by inhibiting neuronal progenitor proliferation, neuronal migration, cortical layering, and cortical neuron maturation, likely via ERK and p35/CDK5 inhibition. Consequently, our findings advocate for caution in metformin usage during pregnancy, given its potential adverse effects on fetal brain development.

Metastasis-associated protein 1 participates in regulating luminal acidification of the epididymis via repressing estrogen receptor alpha transcription.

BACKGROUND: As a component of the nucleosome remodeling and deacetylating (NuRD) complex, metastasis-associated protein 1 (MTA1) has been reported to be abundant in male reproductive system and might participate in spermatogenesis and sperm maturation, whereas the precise functional role of MTA1 in these processes is still undetermined. OBJECTIVE: To investigate the effect and potential function of MTA1 in male fertility. MATERIALS AND METHODS: Mta1 knockout mice (Mta1-/- ) were employed to detect their reproductive phenotype. The pH value of Mta1-/- epididymal luminal fluid was measured, and the potential mechanism of MTA1 involved in regulating luminal acidification was detected in vivo and in vitro. A vasectomy model with abnormal pH of epididymal lumen was established to further detect the effect of MTA1 on epididymal luminal microenvironment. RESULTS: Mta1-/- mice were fertile without any detectable defects in spermatogenesis or sperm motility while the deficiency of MTA1 could acidify the initial segment of epididymis to a certain extent. MTA1 could interact with estrogen receptor alpha (ERα) and inhibit the transcription of ERα target gene, hydrogen exchanger 3 (NHE3), and ultimately affect the epididymal luminal milieu. After vasectomy, the Mta1-/- mice presented a more acidic epididymal lumen which was closer to the normal state compared to the wild-type model. DISCUSSION AND CONCLUSION: MTA1 is dispensable for male fertility in mice, but plays a potentially important function in regulating luminal acidification of the epididymis.

Addition of Preoperative Ultrasound-Guided Suprascapular Nerve Block and Axillary Nerve Block to Parecoxib Is More Effective in Early Postoperative Pain Control After Arthroscopic Rotator Cuff Repair: A Prospective Randomized Controlled Study.

PURPOSE: To prospectively compare pain intensity and patient-reported outcomes (PROs) after arthroscopic rotator cuff repair (ARCR) between patients who received ultrasound-guided suprascapular nerve block (SSNB) and axillary nerve block (ANB) as well as preincisional parecoxib and patients who received preincisional parecoxib only. METHODS: Sixty-one patients receiving ARCR between March 2020 and March 2021 were prospectively enrolled. They were randomly assigned to the peripheral nerve block group (group N, n = 30) or control group (group C, n = 31). Two patients in group C were excluded because of miscommunication. All patients were administered 40 mg of parecoxib intravenously prior to induction of anesthesia. SSNB and ANB were performed after general anesthesia in group N, whereas no nerve block was performed in group C. Pain intensity was compared before surgery, as well as immediately, 24 hours, and 2 weeks after surgery. PROs, including the Oxford Shoulder Score, University of California-Los Angeles shoulder score, and Single Assessment Numeric Evaluation score, were compared before and 6 months after surgery. RESULTS: The numerical rating scale (NRS) score for resting pain was significantly lower in group N (4.9 ± 3.1 vs 7.6 ± 2.5, P < .001) immediately after surgery, but no difference was noted 24 hours after surgery. The resting pain NRS score 2 weeks after surgery was significantly lower in group N (1.4 ± 1.6 vs 2.7 ± 2.7, P = .03), but the scores for movement-evoked pain and night pain were similar. All PROs significantly improved 6 months after surgery in both groups, but there was no difference between the 2 groups. CONCLUSIONS: The addition of preoperative ultrasound-guided SSNB and ANB to parecoxib offered better resting pain control immediately and 2 weeks after ARCR, but there was no benefit for PROs 6 months after surgery. LEVEL OF EVIDENCE: Level II, prospective randomized controlled trial.

Relationship between shoulder and elbow range of motion and ultrasonographic structural abnormalities in the elbow of Taiwanese high school baseball players.

BACKGROUND: Ultrasonographic structural abnormalities are regarded as one of the risk factors of elbow injuries. Elbow injuries are commonly associated with decreased shoulder/elbow range of motion (ROM). The purpose of this study is to determine the relationship between shoulder/elbow ROM and elbow ultrasonographic structural abnormalities in Taiwan high school baseball players. METHODS: A total of 533 Taiwan high school baseball players were enrolled. Physical examinations including measurements on shoulder/elbow ROM and elbow sonographic examinations were performed and recorded by professional physicians. The analyses were conducted in three subgroups according to their defensive position because the training programs were different. All players pooled, pitchers-only, and fielders-only, due to several demographic differences among these subgroups. In all the subgroups, univariate analyses were conducted separately for participants with and those without elbow ultrasonographic structural abnormalities, and then multivariate analyses were conducted to identify factors significantly related. The odds ratios (ORs) were used to estimate the risk of elbow ultrasonographic structural abnormalities. RESULTS: Demographic data showed that pitchers had taller body height (P < 0.001) and greater elbow flexion/extension ROM (P < 0.001). When all players were pooled, significant risk factors included started playing baseball at an younger age (OR = 1.202; 95% CI = 1.064-1.357; P = 0.003), longer experience of official baseball (OR = 1.154; 95% CI = 1.038-1.283; P = 0.008), lower total shoulder rotation angle (OR = 1.007; 95% CI = 1.000-1.014; P = 0.050), and less total elbow arm angle (OR = 1.052; 95% CI = 1.017-1.088; P = 0.003) For pitchers, significant risk factors included longer experience of official baseball (OR = 1.342; 95% CI = 1.098-1.640; P = 0.004), lower total shoulder rotation angle (OR = 1.016; 95% CI = 1.004-1.027; P = 0.006), and lower total elbow arm angle (OR = 1.075; 95% CI = 1.024-1.129; P = 0.004) (Table 5). There were no significant risk factors for elbow structural abnormalities in fielders. CONCLUSION: For Taiwan high school pitchers, longer official baseball experience, decreased shoulder total rotational angle, and decreased elbow total flexion/extension angle, were related to ultrasonographic structural abnormalities in elbows.

The increased lateral tibial slope may result in inferior long-term clinical outcome after DB-ACL reconstruction.

PURPOSE: To determine if there is a correlation between lateral tibial slope and long-term clinical results in patients who underwent double-bundle ACL reconstruction. METHODS: We retrospectively reviewed patients that received double-bundle ACL reconstruction at a single institution by a single surgeon from January 2011 to December 2014. All the magnetic resonance imaging were reviewed and lateral tibial slopes (LTS) were recorded by an experienced surgeon and rechecked by the other two authors of this study that specialized in orthopedic knee surgery. The relationship between PROMs measurement and lateral tibial slope were analyzed. The patients were then separated into two groups (LTS > 7.4° and < 7.4°) according to the previous study. RESULTS: A total of 119 patients were enrolled in this study. All enrolled patients were followed for at least 8 years. The PROMS result were negatively correlated with the lateral tibial slope (p values all < 0.001). The patients with high lateral tibial slope had significantly lower PROMS values (Lysholm 94.26 ± 5.61 vs 80.15 ± 8.28, p = 0.013; IKDC 82.99 ± 4.55 vs 70.09 ± 7.15, p = 0.003; Tegner 9.32 ± 0.95 vs 6.85 ± 1.99, p < 0.001). Finally, the LTS cutoff value between patients with "Good" and "Fair" Lysholm score in our study was 7.55 degrees. CONCLUSIONS: Patients with high lateral tibial slope may result in inferior long-term subjective outcomes. The using of double-bundle ACL reconstruction along cannot overcome the negative impact caused by steep lateral tibial slope. A lateral tibial slope of 7.55° may be used as a cut-off for a good clinical outcome. LEVEL OF EVIDENCE: III retrospective comparative prognostic trial.

Dinaciclib inhibits the growth of acute myeloid leukemia cells through either cell cycle-related or ERK1/STAT3/MYC pathways.

Although immature differentiation and uncontrolled proliferation of hematopoietic stem cells are thought to be the primary mechanisms of acute myeloid leukemia (AML), the pathophysiology in most cases remains unclear. Dinaciclib, a selective small molecule targeting multiple cyclin-dependent kinases (CDKs), is currently being evaluated in oncological clinical trials. Despite the proven anticancer potential of dinaciclib, the differential molecular mechanisms by which it inhibits the growth of different AML cell lines remain unclear. In the current study, we treated HL-60 and KG-1 AML cell lines with dinaciclib and investigated the potential mechanisms of dinaciclib-induced AML cell growth inhibition using flow cytometry and western blotting assays. Data from HL-60 and KG-1 AML cells were validated using human primary AML cells. The results showed that the growth inhibitory effect of dinaciclib was more sensitive in HL-60 cells (IC50: 8.46 nM) than in KG-1 cells (IC50: 14.37 nM). The protein decline in Cyclin A/B and CDK1 and cell cycle arrest in the G2/M phase were more profound in HL-60 cells, corresponding to its growth inhibition. Although the growth inhibition of KG-1 cells by dinaciclib was still pronounced, the cell cycle-associated proteins were relatively insensitive. In addition to cell cycle regulation, the activation/expression of ERK1/STAT3/MYC signaling was significantly reduced by dinaciclib in KG-1 cells compared with that in HL-60 cells. Regarding the results of primary AML cells, we observed ERK1/STAT3/MYC inhibition and cell cycle regulation in different patients. These findings suggest that the cell cycle-associated and ERK1/STAT3/MYC signaling pathways might be two distinct mechanisms by which dinaciclib inhibits AML cells, which could facilitate the development of combination therapy for AML in the future.

Arthroscopic Lower Trapezius Tendon Transfer for a Patient with Axillary Nerve Injury and Concomitant Rotator Cuff Tear: A Case Report and Technical Notes.

Introduction: Concomitant nerve injuries with musculoskeletal injuries present a challenging problem. The goals of nerve reconstruction for the shoulder include shoulder abduction and external rotation. When patients fail to achieve acceptable shoulder external rotation and shoulder abduction, tendon transfers such as trapezius transfer offer a reliable option in the subsequent stage. Case Presentation: A 32-year-old male presented with weak external rotation in his left shoulder, after previous axillary nerve reconstruction. He received the ipsilateral lower trapezius transfer with the aim of improving the external rotation. Discussion: The lower trapezius restores a better joint reaction force in both the compressive-distractive and anterior-posterior balancing and provides a centering force through the restoration of the anterior-posterior force couple. Conclusion: We believe that the ipsilateral lower trapezius transfer to the infraspinatus is a good outcome and is effective in improving overall shoulder stability and the shoulder external rotation moment arm or at least maintaining in neutral position with the arm fully adducted in patients with post axillary nerve injuries post unsatisfactory nerve reconstruction to increase the quality of life and activities of daily living.

Feasibility of predicting maximal oxygen uptake by using the efficiency factor in healthy men.

Conventionally, efficiency is indirectly estimated through a respiratory gas analyser (oxygen, carbon dioxide), which is a complex and rather costly calculation method that is difficult to perform in many situations. Therefore, the present study proposed a modified definition of efficiency, called the efficiency factor (EF) (i.e., the ratio of work to the corresponding exercise intensity), and evaluated the relation between the EF and maximal oxygen uptake ([Formula: see text]), as well as compared the prediction models established based on the EF. The heart rate (maximal heart rate: 186 ± 6 beats min-1), rating of perceived exertion (19 ± 1), and [Formula: see text] (39.0 ± 7.1 mL kg-1 min-1) of 150 healthy men (age: 20 ± 2 years; height: 175.0 ± 6.0 cm; weight: 73.6 ± 10.7 kg; body mass index [BMI]: 24.0 ± 3.0 kg m-2; percent body fat [PBF]: 17.0 ± 5.7%) were measured during the cardiopulmonary exercise test (CPET). Through multiple linear regression analysis, we established the BMI model using age and BMI as parameters. Additionally, we created the PBF modelHRR utilizing weight, PBF, and heart rate reserve (HRR) and developed PBF modelEF6 and PBF modelEF7 by incorporating EF6 from the exercise stage 6 and EF7 from the exercise stage 7 during the CPET, respectively. EF6 (r = 0.32, p = 0.001) and EF7 (r = 0.31, p = 0.002) were significantly related to [Formula: see text]. Among the models, the PBF modelEF6 showed the highest accuracy, which could explain 62.6% of the variance in the [Formula: see text] at with a standard error of estimate (SEE) of 4.39 mL kg-1 min-1 (%SEE = 11.25%, p < 0.001). These results indicated that the EF is a significant predictor of [Formula: see text], and compared to the other models, the PBF modelEF6 is the best model for estimating [Formula: see text].

Evaluation of the effect of erenumab on migraine-specific questionnaire in patients with chronic and episodic migraine.

Erenumab is a fully human anti-canonical calcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. The Migraine-Specific Quality-of-Life Questionnaire (MSQ) is a 14-item patient-reported outcome instrument that measures the impact of migraine on health-related quality of life. Erenumab data from four phase II/III clinical trials were used to develop an item response theory (IRT) model within a nonlinear mixed effects framework, (i) evaluate the MSQ item information with respect to patient disability, (ii) characterize the longitudinal progression of the MSQ, and (iii) quantify the effect of erenumab on the MSQ in patients with migraine. The majority (80%) of information was found to be contained in 9 out of 14 items, extending the current knowledge on the reliability of the MSQ as a psychometric tool. Simulations across three MSQ domains show significant improvement from baseline, exceeding minimally important differences. Overall, the IRT model platform developed herein allows for systematic quantification of the effect of erenumab on the MSQ in patients with migraine.

Using Single Peroneal Longus Tendon Graft for Segmental Meniscus Transplantation and Revision Anterior Cruciate Ligament Combined Anterolateral Reconstruction.

This case report describes a new approach to segmental meniscal reconstruction using a peroneal longus autograft in a patient with recurrent traumatic medial meniscus tear and anterior cruciate ligament reconstruction (ACLR) failure. While allograft meniscal transplantation is the preferred method for treating meniscal deficiency, its high cost and various legal regulations have limited its widespread use. Autologous tendon grafts have been proposed as a substitute for allograft meniscus transplantation, but their initial results were poor, leading to little progress in this area. However, recent animal experiments and clinical studies have demonstrated promising results in using autologous tendon grafts for meniscal transplantation, including improvements in pain and quality of life for patients. Further research is needed to evaluate the effectiveness of segmental meniscal reconstruction using autologous tendon grafts, but it could potentially lead to more accessible and cost-effective treatment options for patients with meniscal deficiency.

Arthroscopic-assisted reduction and internal fixation for complex tibial plateau fracture: radiographic and clinical outcomes with 2- to 15-year follow-up.

BACKGROUND: To investigate the radiologic and prognostic outcomes after using arthroscopic-assisted reduction and internal fixation (ARIF) in complex tibial plateau fractures with mid- to long-term follow-up. METHODS: This retrospective study reviewed complex tibial plateau fractures that underwent ARIF from 1999 to 2019. Radiologic outcomes, including tibial plateau angle (TPA), posterior slope angle (PSA), Kellgren-Lawrence classification and Rasmussen radiologic assessment, were measured and evaluated. The prognosis and complications were assessed by the Rasmussen clinical assessment with a minimum follow-up of 2 years. RESULTS: Ninety-two consecutive patients (mean age: 46.9 years) with a mean follow-up of 74.8 months (24-180) were included in our series. Using AO classification, there were 20 type C1 fractures, 21 type C2 fractures, and 51 type C3 fractures. All the fractures achieved solid union. TPA was maintained well on average at the last follow-up and showed no significant difference compared to postoperatively (p = 0.208). In the sagittal plane, the mean PSA increased from 9.3 ± 2.9° to 9.6 ± 3.1° (p = 0.092). A statistically significant increase in PSA was also noted in the C3 group (p = 0.044). Superficial or deep infection was noted in 4 cases (4.3%), and total knee arthroplasty (TKA) was performed in 2 cases (2.2%) due to grade 4 osteoarthritis (OA). Ninety (97.8%) and 89 (96.7%) patients had good or excellent results in the Rasmussen radiologic assessment and Rasmussen clinical assessment, respectively. CONCLUSIONS: The complex tibial plateau fracture could be treated successfully using arthroscopy-assisted reduction and internal fixation. Most patients achieve excellent and good clinical outcomes with low complication rates. In our experience, a higher incidence of increased slope was noted, especially in type C3 fractures. Reduction of the posterior fragment should be done cautiously during the operation. LEVELS OF EVIDENCE: Level III.

Reconstruction of High-Grade Trochlea Dysplasia in a Young Female with Recurrent Patella Dislocation: A Case Report.

The patellofemoral joint involves a combination of bony structures and soft tissues to maintain stability. Patella instability is a disabling condition, and the cause is multifactorial. The main risk factors include patella alta, trochlea dysplasia, excessive tibial tuberosity to trochlea grove (TT-TG) distance, and excessive lateral patella tilt. In this case report, we highlight the thinking process of diagnosis and method for selecting the optimal treatment in accordance with the guidelines by Dejour et al. when we are presented with a patient with patella instability. A 20-year-old Asian woman without underlying medical conditions, presented with recurrent (>3 episodes) right patella dislocation for 7 years. Investigations revealed a type D trochlea dysplasia, increased TT-TG distance, and excessive lateral tilt angle. She underwent trochlea sulcus deepening, sulcus lateralization and lateral facet elevation, lateral retinacular release, and medial quadriceps tendon-femoral ligament (MQTFL) reconstruction. Due to the complexity behind the anatomy and biomechanics of patella instability, an easy-to-follow treatment algorithm is essential for the treating surgeon to provide effective and efficient treatment. MQTFL reconstruction is recommended for recurrent patella dislocation due to satisfactory clinical and patient reported outcomes and a reduced risk of iatrogenic patella fracture. Controversies for surgical indication in lateral retinacular release, and whether the sulcus angle is an accurate parameter for diagnosis of trochlea dysplasia, remain, and further research is required.

Surface effects on kinematics, kinetics and stiffness of habitual rearfoot strikers during running.

The surface effects on running biomechanics have been greatly investigated. However, the effects on rearfoot strike runners remain unknown. The purpose of this study was to investigate the effects of surfaces on the running kinematics, kinetics, and lower-limb stiffness of habitual rearfoot strikers. Thirty healthy male runners were recruited to run at 3.3 ± 0.2 m/s on a customized runway covered with three different surfaces (artificial grass, synthetic rubber, or concrete), and their running kinematics, kinetics, and lower-limb stiffness were compared. Differences among the three surfaces were examined using statistical parametric mapping and one-way repeated-measure analysis of variance. There were no statistical differences in the lower-limb joint motion, vertical ground reaction force (GRF), loading rates, and lower-limb stiffness when running on the three surfaces. The braking force (17%-36% of the stance phase) and mediolateral GRF were decreased when running on concrete surface compared with running on the other two surfaces. The moments of ankle joint in all three plane movement and frontal plane hip and knee joints were increased when running on concrete surface. Therefore, habitual rearfoot strikers may expose to a higher risk of running-related overuse injuries when running on a harder surface.

Combined 3-Dimensional CT and Multidirectional CT Arthrography for Femoroacetabular Impingement and Hip Lesions: A Cross-sectional Study Comparing Imaging and Hip Arthroscopic Surgery Findings.

Background: There is limited research investigating the diagnostic strength of 3-dimensional computed tomography (3D-CT) and multidirectional CT arthrography (CTA) for femoroacetabular impingement (FAI) and related hip lesions. Purpose: To evaluate the diagnostic strength of combined 3D-CT and CTA in patients with FAI and related hip lesions by comparing it with hip arthroscopic surgery findings. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: This study included patients who were suspected of having FAI and related hip lesions and who underwent a combination of 3D-CT and CTA and subsequent hip arthroscopic surgery between December 2013 and December 2017. The CT and intraoperative arthroscopic findings were recorded and compared. The sensitivity, specificity, and accuracy of 3D-CT for FAI and those of CTA for related hip lesions were calculated. Results: A total of 114 patients with 114 hips were included in our study. There were 101 patients with positive findings and 13 patients with negative findings for FAI (including cam, pincer, and combined morphology) according to 3D-CT. The sensitivity, specificity, and accuracy of 3D-CT for FAI were 91.58%, 57.14%, and 89.47%, respectively. The sensitivity, specificity, and accuracy of CTA for labral tears were 94.64%, 100.00%, and 94.73%, respectively. For acetabular cartilage defects, the sensitivity, specificity, and accuracy of CTA were 60.71%, 91.37%, and 76.31%, respectively. For femoral cartilage defects, the sensitivity, specificity, and accuracy of CTA were 82.22%, 76.81%, and 78.94%, respectively. Conclusion: The study results indicated that 3D-CT was able to provide excellent accuracy for FAI compared with hip arthroscopic surgery findings. In addition, multidirectional CTA demonstrated promising diagnostic strength for hip lesions such as labral tears and chondral defects.

Effect of the Brief Instructional Video Intervention on the Quality of Cardiopulmonary Resuscitation.

Background: Chest compressions are the basis of cardiopulmonary resuscitation (CPR), and high-quality chest compressions can improve survival rate in patients with out-of-hospital cardiac arrest. Although many efforts have been made to improve the quality of CPR in inexperienced adults, the results are still not high, especially during emergencies. The primary purpose of this study is to investigate whether a brief instructional chest compression-only CPR video could improve chest compression quality in inexperienced adults. Methods: One hundred adults with no CPR experience (age: 20.28 ± 2.28 years; women: 50, men: 50) participated in this study. Participants completed body composition and handgrip strength measurements, and performed two CPR quality tests on the Laerdal® Little Anne QCPR Manikin, namely without video-CPR (WV-CPR) and video-CPR (V-CPR). The WV-CPR quality test was performed first. After 2 minutes of continuous chest compression, the participants rested for 10 seconds and repeated 3 cycles (phase 1, phase 2, and phase 3). After resting for more than 72 hours, V-CPR quality test was conducted. During the V-CPR with video intervention, the participants also continued to compress the chest for 2 minutes, and then rested for 10 seconds, repeating 3 cycles. Results: In phase 1, compared with WV-CPR, the V-CPR has a significant increase (p < 0.001) in chest compression fraction (CCF) (56.31 ± 33.22% vs. 41.82 ± 32.30%) and percent of correct compression rate (PCCR) (96.17 ± 8.45% vs. 26.31 ± 37.55%). In addition, the V-CPR has significantly lower (p < 0.001) chest compression rate (CCR) (110.85 ± 2.40 cpm vs. 128.86 ± 24.52 cpm) and rating of perceived exertion (RPE) (11.89 ± 2.25 vs. 12.87 ± 2.25). For phases 2 through 3, V-CPR and WV-CPR achieved significant differences in CCF, CCD, CCR, PCCR, and RPE (p < 0.01). There were significant differences (p < 0.05) in CCF, CCD, chest compression rebound rate, and RPE among the different administration stages of both WV-CPR and V-CPR. Conclusions: The results of this study revealed that a brief instructional chest compression-only CPR video could improve chest compression quality for inexperienced adults by reducing fatigue and CCR, and increasing CCF and PCCR.

Post hoc analysis of clinical trial data and pharmacokinetic data to assess wearing-off of erenumab within monthly treatment cycle.

BACKGROUND: Treatment wearing-off has been reported for calcitonin gene-related peptide-pathway monoclonal antibodies, including erenumab, specifically in the last week of the monthly dosing cycle. OBJECTIVE: We sought to determine the consistency of erenumab effect throughout the monthly treatment cycle. METHODS: In this post hoc analysis of four pivotal double-blind, randomized controlled studies of erenumab in episodic and chronic migraine, we assessed wearing-off based on change in weekly migraine days at week 4 versus average over weeks 1-3 in each monthly dosing cycle. Analyses were conducted at each monthly dosing cycle in all patients, in responders (≥50% reduction in weekly migraine days), and in consistent responders (response in ≥2monthly cycles). RESULTS: There was no evidence of wearing-off in the full study populations of two global studies (N = 946 and N = 656) and two Japan studies (N = 475 and N = 261). In the full study population, mean change in weekly migraine days at week 4 compared with the average over week 1-3 ranged from 0.15 days improvement to 0.19 days worsening in the placebo group and 0.08 days improvement to 0.20 days worsening in the erenumab groups. A subgroup of responders experienced wearing-off, but the extent of wearing-off did not differ between erenumab and placebo groups. The mean change in weekly migraine days at week 4 compared with the average over weeks 1-3 ranged from 0.34 to 0.61 days worsening in the placebo group and 0.27 to 0.78 days worsening in the erenumab groups. Few patients had persistent wearing-off in ≥2 consecutive monthly treatment cycles. For erenumab-treated responders, serum erenumab concentrations were similar among patients experiencing wearing-off and those maintaining response. CONCLUSION: No systematic wearing-off with erenumab was identified. Further research is needed to determine if wearing-off reported for some patients in clinical practice reflects a true treatment response pattern or normal fluctuations in migraine frequency.

Comparison of hook plate alone, hook plate augmented with suture anchor, and arthroscopically-assisted tightrope fixation in the treatment of patients with acute type v acromioclavicular joint dislocations.

INTRODUCTION: The best treatment for Rockwood type V acromioclavicular (AC) joint dislocation is unknown. HYPOTHESIS: Hook plate augmented with suture anchor (HA) may have different clinical and radiological results than hook plate alone (H), and arthroscopically assisted TightRope (TR) techniques in treating acute type V AC joint dislocations. MATERIAL AND METHODS: This retrospective study included 71 patients with acute type V AC joint dislocations between December 2010 and August 2018. Patients were categorized into three groups: H group (n=22), HA group (n=23) and TR group (n=26). We measured the coracoclavicular distance (CCD) differences and CCD ratio compared to uninjured side pre-operatively, immediately post-operatively, at 3-month and 2-year after operation. Clinical outcomes were assessed as well at the same time points. Loss of correction was determined by the CCD difference and ratio between surgical and uninjured sides. RESULTS: The mean age and follow-up period were 41.8±24.7 years and 30.2±4.3 months, respectively. No significant differences were found in the demographic data between the three groups. The HA group presented a trend of less overcorrection but without significance compared with the H group at immediately post-operation, 3-month, and 2-year follow-up. (CCD difference: -2.4mm vs. -3.7mm, -1.6mm vs. -1.8, and 0.2mm vs -1.9mm, CCD ratio: 67.7% vs. 40.9%, 79.3% vs. 70.1%, and 100.6% vs. 86.5%, respectively). The HA group also had significantly less loss of correction compared with the TR group at 3-month and 2-year after the operation (CCD difference: -1.6mm vs. 1.6mm, 0.2mm vs. 2.4mm; CCD ratio: 79.3% vs. 122.2%, 100.6% vs. 136.1%, all p<0.05). All three methods achieved significant improvement in function and pain without inter-group differences. No coracoid-related or tunnel complications occurred. DISCUSSION: The hook plate alone, and hook plate with suture anchor augmentation techniques provided less residual vertical instability compared to TightRope fixation at 2-year follow-up. The patient-reported functional outcomes were promising and comparable among the three groups. LEVEL OF EVIDENCE: III, Retrospective comparative therapeutic trial.