Increased combined anteversion is associated with larger posterior acetabular rim ossification in patients with femoroacetabular impingement syndrome.

PURPOSE: (1) To determine the prevalence, magnitude and distribution pattern of acetabular rim ossification in patients with femoroacetabular impingement syndrome (FAIS) and (2) to determine the association between acetabular rim ossification and rotational abnormalities of the hip. METHODS: Patients underwent hip arthroscopic surgery for FAIS at our institute between January 2021 and May 2022 were retrospectively reviewed. Patients were included if preoperative computed tomography (CT) images of the operated hip and ipsilateral distal femur were available for the measurement of femoral and acetabular anteversion. The presence and size of acetabular rim ossification were evaluated on coronal CT sections for the superior half of the acetabulum on each clockface location. The associations between acetabular rim ossification and radiographic parameters of hip rotational morphology were examined. RESULTS: A total of 214 hips were included. Acetabular rim ossification was found in 167 hips (78%) and the most common locations were 10 and 11 o'clock. Patients presenting with acetabular rim ossification had a mean size of 4.6 ± 1.6 mm. It was the largest at 9 o'clock position (4.9 ± 2.2 mm), with a decreasing trend in size from posterior to anterior. Logistics regression analysis found age was associated with the occurrence of posterior ossification (p = 0.002). Linear regression analysis found age (p = 0.049) and male sex (p < 0.001) were significantly correlated with the size of ossification. Patients with increased cranial combined anteversion had larger posterior ossification than patients with normal and decreased cranial combined anteversion (4.2 ± 2.9 vs. 3.1 ± 2.5 mm, p = 0.016; 4.2 ± 2.9 vs. 2.5 ± 2.4 mm, p = 0.005). CONCLUSION: Increased combined anteversion is associated with greater posterior acetabular rim ossification. The presence and size of acetabular rim ossification are positively associated with older age and male sex. LEVEL OF EVIDENCE: Level III.

The severity of preoperative bone marrow oedema negatively influences short-term clinical outcomes following arthroscopic bone marrow stimulation for osteochondral lesions of the talus.

PURPOSE: The purpose of this study was to study the effects of the severity of preoperative bone marrow oedema (BME) on the postoperative short-term outcomes following bone marrow stimulation (BMS) for osteochondral lesions of the talus (OLTs) and to propose a new metric that combines volume and signal density to evaluate BME. METHODS: Sixty-five patients with symptomatic OLTs (<100 mm2) and preoperative BME, who received BMS in our institution from April 2017 to July 2021 with follow-ups of 3, 6 and 12 months, were analysed retrospectively. The area, volume and signal value of the BME were collected on preoperative magnetic resonance imaging. The enroled patients were divided into two groups according to the BME index (BMEI), which was defined as the product of oedema relative signal intensity and the relation of oedema volume to total talar volume. Visual analogue scale, American Orthopedic Foot and Ankle Society (AOFAS), Tegner, Foot and Ankle Ability Measure (FAAM)-activities of daily living (ADL) and Sports scores were assessed before surgery and at each follow-up. The relationship between the scores and the volume, relative signal intensity and BMEI was explored. RESULTS: Sixty-five patients with preoperative BME were divided into the mild (n = 33) and severe (n = 32) groups based on the BMEI. A significant difference was found for each score with the general linear model for repeated measures through all follow-up time points (p < 0.001). For the preoperative and 12-month postoperative changes of the enroled patients, 53 patients (81.5%) exceeded the minimal clinically important difference of AOFAS and 26 (40.0%) exceeded that of FAAM-sports in this study. The mild group showed significantly more improvement in AOFAS scores at 12 months (89.6 ± 7.0 vs. 86.2 ± 6.2) and FAAM-ADL scores at 6 months (83.6 ± 7.6 vs. 79.7 ± 7.7) and 12 months (88.5 ± 8.5 vs. 84.4 ± 7.7) than the severe group (p < 0.05). No significant difference of all the scores between the groups was found at 3 months. No significant correlation was found in each group between BMEI and clinical outcomes. CONCLUSION: The severity of the preoperative BME negatively affected short-term clinical outcomes following arthroscopic BMS for OLTs. Worse clinical outcomes were shown at postoperative 6 and 12 months in patients with a high preoperative BMEI, which could be a favourable parameter for assessing the severity of BME and assist in developing personalised rehabilitation plans and determining the approach and timing of surgery. LEVEL OF EVIDENCE: Level III.

Predictive model based on DCE-MRI and clinical features for the evaluation of pain response after stereotactic body radiotherapy in patients with spinal metastases.

OBJECTIVE: To investigate the correlation of conventional MRI, DCE-MRI and clinical features with pain response after stereotactic body radiotherapy (SBRT) in patients with spinal metastases and establish a pain response prediction model. METHODS: Patients with spinal metastases who received SBRT in our hospital from July 2018 to April 2022 consecutively were enrolled. All patients underwent conventional MRI and DCE-MRI before treatment. Pain was assessed before treatment and in the third month after treatment, and the patients were divided into pain-response and no-pain-response groups. A multivariate logistic regression model was constructed to obtain the odds ratio and 95% confidence interval (CI) for each variable. C-index was used to evaluate the model's discrimination performance. RESULTS: Overall, 112 independent spinal lesions in 89 patients were included. There were 73 (65.2%) and 39 (34.8%) lesions in the pain-response and no-pain-response groups, respectively. Multivariate analysis showed that the number of treated lesions, pretreatment pain score, Karnofsky performance status score, Bilsky grade, and the DCE-MRI quantitative parameter Ktrans were independent predictors of post-SBRT pain response in patients with spinal metastases. The discrimination performance of the prediction model was good; the C index was 0.806 (95% CI: 0.721-0.891), and the corrected C-index was 0.754. CONCLUSION: Some imaging and clinical features correlated with post-SBRT pain response in patients with spinal metastases. The model based on these characteristics has a good predictive value and can provide valuable information for clinical decision-making. KEY POINTS: • SBRT can accurately irradiate spinal metastases with ablative doses. • Predicting the post-SBRT pain response has important clinical implications. • The prediction models established based on clinical and MRI features have good performance.

Morphological Measurement of Asian Osteal Nasal Base for Paranasal Augmentation.

BACKGROUND: Paranasal augmentation has been a popular approach in restoring Asian patients' lateral profile. Irregular surface in the surgical area emphasizes the importance of morphological evidence for the preoperative evaluation and the design of paranasal implants. METHODS: We retrospectively collected craniofacial computer tomography scans of patients in the department of plastic surgery from 2020 to 2022. The imaging data were imported to Mimics (version 20.0; Materialize, Leuven, Belgium) for three-dimensional reconstruction. Measurements of osteal nasal base were performed in 3-matics (version 12.0; Materialize). The severity of paranasal concavity was graded by a senior doctor to study the correlation with measured variables. RESULTS: Fifty-seven patients with a median age of 27 years (IQR: 22-33) were included in the study. For design of paranasal implants, the lengths of both lower and lateral edge were measured for reference. In the regression analysis, the alar base-alveolar process angle was significantly associated with the degrees of paranasal concavity (OR = 1.222, p = 0.00001). CONCLUSIONS: Morphological data of osteal nasal base were measured and presented in the current study. The analysis supported that alar base-alveolar process angle be used for preoperative grading and evaluation to help guiding treatment decisions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comparison of the diagnostic value of measurements of transverse syndesmotic interval and 'lambda sign' in distinguishing latent syndesmotic diastasis in chronic lateral ankle instability: a cross-sectional study of 188 cases.

INTRODUCTION: Chronic lateral ankle instability (CLAI) could accompany with latent syndesmotic diastasis (LSD), which is difficult to distinguish before surgery. Tibiofibular interval width and extravasation of joint fluid ('lambda sign') on MRI are widely used in the diagnosis of syndesmotic injury, but the reliability of these methods in distinguishing the associated LSD in CLAI was rarely studied. Our objective was to compare the diagnostic value of the measurement of the transverse tibiofibular interval and 'lambda sign' on MRI in distinguishing LSD in CLAI and to investigate the radiological predictor that best matched the intraoperatively measured syndesmotic width. METHODS: 138 CLAI patients undergoing arthroscopy in our institute from March 2017 to June 2020 were enrolled (CLAI group). Anterior space width (ASW) and posterior space width (PSW) at 10 mm layer above tibial articular and fluid height above tibial articular surface (FH) were measured on preoperative MRI. The same parameters were measured on MRI of 50 healthy volunteers as control group. At arthroscopy, syndesmotic width was measured and the patients were divided into arthroscopic widening (AW) and arthroscopic normal (AN) subgroup taking 2 mm as critical value. The CLAI group was compared with the control group to explore the interval changes related to CLAI. The AW and AN subgroups were compared to explore the potential diagnostic indicators and reference values for the LSD. RESULTS: All parameters showed significant difference between CLAI group and control group (p < 0.05), but only PSW (p = 0.004) showed significant difference between AW and AN subgroups other than FH (p = 0.461). Only PSW was involved in formula of multiple-factor analysis (p = 0.005; OR, 1.819; 95%CI, 1.196-2.767). ROC analysis showed critical value of PSW was 3.8 mm (sensitivity, 66%; specificity, 66%; accuracy, 66.7%), while accuracy of lambda sign was 41.3%. CONCLUSIONS: Transverse tibiofibular interval measurements were more reliable than the 'lambda sign' in distinguishing associated LSD in CLAI patients. The PSW ≥ 3.8 mm could be a predictor of syndesmotic diastasis.

The spatial analysis, risk assessment and source identification for mercury in a typical area with multiple pollution sources in southern China.

Mercury (Hg) has always been a research hot spot because of its high toxicity. This study conducted in farmland near rare earth mining area and traffic facilities, which considered multiple pollution sources innovatively. It not only analyzed Hg spatial characteristics using inverse distance weighting and self-organizing map (SOM), but also assessed its pollution risk by potential ecological risk index (Er) as well as geoaccumulation index (Igeo), and identified the pollution sources with positive matrix factorization. The results showed that there was no heavy Hg pollution in most farmland, while a few sampling sites with Hg pollution were close to highway, railway station and petrol station in Xinfeng or in the farmland of Anyuan, which were divided into the cluster with highest Hg concentration in SOM. The vehicle exhaust emission and pesticide as well as fertilizer additions significantly contributed to the local Hg pollution. Besides, there was moderate pollution and high ecological risk in Anyuan assessed by Igeo and Er, respectively. In contrast, Xinfeng had the moderate and considerable ecological risks in a larger scale. The enriched Hg might harmed not only the nearby ecological environment, but also the human health when it entered human body through food chain. The three factors that contributed to mercury concentration in this area according to positive matrix factorization were natural source, traffic source and agricultural source, respectively. This study about Hg pollution in the typical area would provide scientific evidence for the particular treatment of Hg pollution from various pollution sources like traffic source, agricultural source, etc.

Simultaneous bilateral total knee arthroplasty has higher in-hospital complications than both staged surgeries: a nationwide propensity score matched analysis of 38,764 cases.

PURPOSE: To investigate (1) healthcare utilization, (2) in-hospital metrics and (3) total in-hospital costs associated with simultaneous versus staged BTKA while evaluating staged BTKA as a single process consisting of two combined episodes. METHODS: The national readmissions database was reviewed for simultaneous and staged (two primary unilateral TKAs12 months apart) BTKA patients (2016-2017). A total of 19,382 simultaneous BTKAs were identified, and propensity score matched (1:1) to staged BTKA patients (19,382 patients; 38,764 surgeries) based on demographics, comorbidities, and socioeconomic determinants. Outcomes included healthcare utilization [length of stay (LOS) and discharge disposition], in-hospital periprosthetic fractures, non-mechanical complications, and costs. Staged BTKA was evaluated as one process consisting of two episodes. For each staged patient, continuous outcomes were evaluated via the sum of both episodes. Categorical outcomes were added, and percents were expressed relative to total number of surgeries (n = 38,764). RESULTS: Simultaneous BTKA had longer LOS (5.0 days ± 4.7 vs. 4.5 days ± 3.5; p < 0.001), higher non-home discharge [36.9% (n = 7150/19,382) vs. 13.6% (n = 5451/38,764)], in-hospital periprosthetic fractures [0.13% (26/19,382) vs. 0.08% (31/38,764); p = 0.049], any non-mechanical complication [33.76% (6543/19,382) vs.15.93% (6177/38,764); p < 0.0001], hematoma/seroma formation [0.11% (22/19,382) vs. 0.05% (20/38,764); p = 0.0088], wound disruption [0.08% (16/19,382) vs. 0.04% (16/38,764); p = 0.0454], and any infection [1.13% (219/19,382) vs. 0.50% (194/38,764); p < 0.0001]. Average in-hospital costs for the two staged BTKA episodes combined were $5006 higher than those of simultaneous BTKA ($28,196 ± $18,488 vs. $33,202 ± $15,240; p < 0.001). CONCLUSION: Simultaneous BTKA had higher healthcare utilization and in-hospital complications than both episodes of staged BTKA combined, with a minimal in-hospital cost savings. Future studies are warranted to further explore patient selection who would benefit from BTKA.

Excess cancer prevalence in men with HIV: A nationwide analysis of Medicaid data.

BACKGROUND: Cancer is one of the most common comorbidities in men living with HIV (MLWH). However, little is known about the MLWH subgroups with the highest cancer burden to which cancer prevention efforts should be targeted. Because Medicaid is the most important source of insurance for MLWH, we evaluated the excess cancer prevalence in MLWH on Medicaid relative to their non-HIV counterparts. METHODS: In this cross-sectional study using 2012 Medicaid Analytic eXtract data nationwide, we flagged the presence of HIV, 13 types of cancer, symptomatic HIV, and viral coinfections using codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. The study population included individuals administratively noted to be of male sex (men), aged 18 to 64 years, with (n = 82,495) or without (n = 7,302,523) HIV. We developed log-binomial models with cancer as the outcome stratified by symptomatic status, age, and race/ethnicity. RESULTS: Cancer prevalence was higher in MLWH than in men without HIV (adjusted prevalence ratio [APR], 1.84; 95% confidence interval [CI], 1.78-1.90) and was higher among those with symptomatic HIV (APR, 2.74; 95% CI, 2.52-2.97) than among those with asymptomatic HIV (APR, 1.73; 95% CI, 1.67-1.79). The highest APRs were observed for anal cancer in younger men, both in the symptomatic and asymptomatic groups: APR, 312.97; 95% CI, 210.27-465.84, and APR, 482.26; 95% CI, 390.67-595.32, respectively. In race/ethnicity strata, the highest APRs were among Hispanic men for anal cancer (APR, 198.53; 95% CI, 144.54-272.68) and for lymphoma (APR, 9.10; 95% CI, 7.80-10.63). CONCLUSIONS: Given the Medicaid program's role in insuring MLWH, the current findings highlight the importance of the program's efforts to promote healthy behaviors and vaccination against human papillomavirus in all children and adolescents and to provide individualized cancer screening for MLWH.

What Are Drivers of Readmission for Readmission-Requiring Venous Thromboembolic Events After Primary Total Hip Arthroplasty? An Analysis of 544,443 Cases.

BACKGROUND: Venous thromboembolism (VTE) is a potential postoperative complication after total hip arthroplasty (THA). These events present with a range of severity, and some require readmission. The present study aimed to identify unexplored risk factors for severe VTE that lead to hospital readmission. METHODS: The Agency of Healthcare Research and Quality's National Readmissions Database was retrospectively queried for all patients who underwent primary THA (January 2016 to December 2018). Study population included patients who were readmitted for VTE within 90 days after an elective THA. Bivariate and multivariate regression analyses were performed using patient demographics, insurance status, elective nature of the surgery, healthcare institution characteristics, and baseline comorbidities. RESULTS: Higher risk of readmission for VTE was evident among elderly (71-80 years vs <40 years: odds ratio [OR] 1.7, 95% confidence interval [CI] 1.3-2.2, P = .0002), male patients (OR 1.2, 95% CI 1.2-1.3). Nonelective THAs were associated with markedly higher odds of readmission for VTE (OR 20.5, 95% CI 18.9-22.2), peripheral vascular disease (OR 1.2, 95% CI 1.1-1.4), lymphoma (OR 1.5, 95% CI 1.1-2.1), metastatic cancer (OR 1.8, 95% CI 1.4-2.2), obesity (OR 1.5, 95% CI 1.4-1.6), and fluid-electrolyte imbalance (OR 1.1, 95% CI 1.0-1.2). Home health care (OR 0.8, 95% CI 0.7-0.8) and discharge to skilled nursing facility (OR 0.7, 95% CI 0.7-0.8) had lower odds of readmission for VTE vs unsupervised home discharge, while insurance type was not a significant driver(P > .05). CONCLUSION: One in 135 THA patients is likely to experience a VTE requiring readmission after THA. Male patients, age >70 years, and specific baseline comorbidities increase such risk. Furthermore, discharge to a supervised setting mitigated the risk of VTE requiring readmission compared to unsupervised discharge. As VTE prophylaxis protocols continue to evolve, these patients may require optimized perioperative care pathways to mitigate VTE complications.

The myeloid transcription factor KLF2 regulates the host response to polymicrobial infection and endotoxic shock.

Precise control of myeloid cell activation is required for optimal host defense. However, this activation process must be under exquisite control to prevent uncontrolled inflammation. Herein, we identify the Kruppel-like transcription factor 2 (KLF2) as a potent regulator of myeloid cell activation in vivo. Exposure of myeloid cells to hypoxia and/or bacterial products reduced KLF2 expression while inducing hypoxia inducible factor-1α (HIF-1α), findings that were recapitulated in human septic patients. Myeloid KLF2 was found to be a potent inhibitor of nuclear factor-kappaB (NF-κB)-dependent HIF-1α transcription and, consequently, a critical determinant of outcome in models of polymicrobial infection and endotoxemia. Collectively, these observations identify KLF2 as a tonic repressor of myeloid cell activation in vivo and an essential regulator of the innate immune system.

The value of dynamic MRI in the treatment of cervical spondylotic myelopathy: a protocol for a prospective randomized clinical trial.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is the most severe type of cervical spondylosis and the most common cause of spinal cord dysfunction among adults over 55 years old. MRI plays an important role in the diagnosis and evaluation of CSM, which can directly demonstrate the correlation between disc, spinal cord, posterior structures and abnormal signal in spinal cord. Static MRI can only show the static and neutral position of spinal cord, which is not enough to understand the pathogenesis of CSM. Dynamic MRI demonstrating the extension and flexion position of spinal cord can be a better tool for the treatment of CSM, especially the surgical decision making. METHOD: A total of 180 CSM patients who have indications for surgery will be recruited in outpatient of Peking University Third Hospital and assigned to three groups (Group A, B and C) based on their static MRI after consent. Group A (incomplete dura compression) means the signal of cerebral spinal fluid (CSF) is still visible. Group B (complete dura compression) means no CSF signal and no shape change of spinal cord. Group C (spinal cord compression) means shape change of spinal cord. Two surgical plans will be made for each participant by one professional surgeon according to the static MRI and dynamic MRI respectively and we will randomly choose one to perform via a random number system. Follow-up will be maintained at 3, 6, and 12 months after surgery through outpatient or telephone interview, including mJOA score, 10-s G&R (grip and release) and 10-s step test, SF-36 score, radiographic examination and complications. Finally, data collection and statistical analysis will be finished by researchers who are blinded to recruitment and treatment. DISCUSSION: This study will help us to explore the indication of dynamic MRI and the value of dynamic MRI in the treatment of CSM, especially the surgical decision making. Dynamic MRI can be a useful tool in the treatment of CSM patients. TRIAL REGISTRATION: ChiCTR1900023014. Registered on May 7th, 2019.

Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility.

BACKGROUND: Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall (eg, endothelial cells [ECs]), as well as circulating and resident immunogenic cells (eg, monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of SREBP2 (sterol regulatory element-binding protein 2), 25-hydroxycholesterol, and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages. METHODS: Bioinformatic analyses were used to investigate RNA-sequencing data to identify cholesterol oxidation and efflux genes regulated by Krüppel-like factor 4 (KLF4). In vitro experiments involving cultured ECs and macrophages and in vivo methods involving mice with Ch25h ablation were then used to explore the atheroprotective role of KLF4-Ch25h/LXR. RESULTS: Vasoprotective stimuli increased the expression of Ch25h and LXR via KLF4. The KLF4-Ch25h/LXR homeostatic axis functions through suppressing inflammation, evidenced by the reduction of inflammasome activity in ECs and the promotion of M1 to M2 phenotypic transition in macrophages. The increased atherosclerosis in apolipoprotein E-/-/Ch25h-/- mice further demonstrates the beneficial role of the KLF4-Ch25h/LXR axis in vascular function and disease. CONCLUSIONS: KLF4 transactivates Ch25h and LXR, thereby promoting the synergistic effects between ECs and macrophages to protect against atherosclerosis susceptibility.

Regulation of endothelial hemoglobin alpha expression by Kruppel-like factors.

Hemoglobin subunit alpha (HBA) expression in endothelial cells (ECs) has recently been shown to control vascular tone and function. We sought to elucidate the transcriptional regulation of HBA expression in the EC. Gain of KLF2 or KLF4 function studies led to significant induction of HBA in ECs. An opposite effect was observed in ECs isolated from animals with endothelial-specific ablation of Klf2, Klf4 or both. Promoter reporter assays demonstrated that KLF2/KLF4 transactivated the hemoglobin alpha promoter, an effect that was abrogated following mutation of all four putative KLF-binding sites. Fine promoter mutational studies localized three out of four KLF-binding sites (sites 2, 3, and 4) as critical for the transactivation of the HBA promoter by KLF2/KLF4. Chromatin immunoprecipitation studies showed that KLF4 bound to the HBA promoter in ECs. Thus, KLF2 and KLF4 serve as important regulators that promote HBA expression in the endothelium.

Endothelial Krüppel-like factor 4 modulates pulmonary arterial hypertension.

Krüppel-like factor 4 (KLF4) is a transcription factor expressed in the vascular endothelium, where it promotes anti-inflammatory and anticoagulant states, and increases endothelial nitric oxide synthase expression. We examined the role of endothelial KLF4 in pulmonary arterial (PA) hypertension (PAH). Mice with endothelial KLF4 knockdown were exposed to hypoxia for 3 weeks, followed by measurement of right ventricular and PA pressures, pulmonary vascular muscularization, and right ventricular hypertrophy. The effect of KLF4 on target gene expression was assessed in lungs from these mice, verified in vitro by small interfering RNA (siRNA) knockdown of KLF4, and further studied at the promoter level with cotransfection experiments. KLF4 expression was measured in lung tissue from patients with PAH and normal control subjects. We found that, after hypoxia, right ventricular and PA pressures were significantly higher in KLF4 knockdown animals than controls. Knockdown animals also had more severe pulmonary vascular muscularization and right ventricular hypertrophy. KLF4 knockdown resulted in increased pulmonary expression of endothelin-1 and decreased expression of endothelial nitric oxide synthase, endothelin receptor subtype B, and prostacyclin synthase. Concordant findings were observed in vitro, both with siRNA knockdown of KLF4 and promoter activity assays. Finally, KLF4 expression was reduced in lungs from patients with PAH. In conclusion, endothelial KLF4 regulates the transcription of genes involved in key pathways implicated in PAH, and its loss exacerbates pulmonary hypertension in response to chronic hypoxia in mice. These results introduce a novel transcriptional modulator of PAH, with the potential of becoming a new therapeutic target.

Hu proteins regulate alternative splicing by inducing localized histone hyperacetylation in an RNA-dependent manner.

Recent studies have provided strong evidence for a regulatory link among chromatin structure, histone modification, and splicing regulation. However, it is largely unknown how local histone modification patterns surrounding alternative exons are connected to differential alternative splicing outcomes. Here we show that splicing regulator Hu proteins can induce local histone hyperacetylation by association with their target sequences on the pre-mRNA surrounding alternative exons of two different genes. In both primary and mouse embryonic stem cell-derived neurons, histone hyperacetylation leads to an increased local transcriptional elongation rate and decreased inclusion of these exons. Furthermore, we demonstrate that Hu proteins interact with histone deacetylase 2 and inhibit its deacetylation activity. We propose that splicing regulators may actively modulate chromatin structure when recruited to their target RNA sequences cotranscriptionally. This "reaching back" interaction with chromatin provides a means to ensure accurate and efficient regulation of alternative splicing.

Robot-assisted anterior cruciate ligament reconstruction based on three-dimensional images.

Background Tunnel placement is a key step in anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to evaluate the accuracy of bone tunnel drilling in arthroscopic ACL reconstruction assisted by a three-dimensional (3D) image-based robot system. Methods Robot-assisted ACL reconstruction was performed on twelve freshly frozen knee specimens. During the operation, three-dimensional images were used for ACL bone tunnel planning, and the robotic arm was used for navigation and drilling. Twelve patients who underwent traditional arthroscopic ACL reconstruction were included. 3D computed tomography was used to measure the actual position of the ACL bone tunnel and to evaluate the accuracy of the robotic and traditional ACL bone tunnel. Results On the femoral side, the positions of robotic and traditional surgery tunnels were 29.3 ± 1.4% and 32.1 ± 3.9% in the deep-to-shallow direction of the lateral femoral condyle (p = 0.032), and 34.6 ± 1.2% and 21.2 ± 9.4% in the high-to-low direction (p < 0.001), respectively. On the tibial side, the positions of the robotic and traditional surgical tunnels were located at 48.4 ± 0.9% and 45.8 ± 2.8% of the medial-to-lateral diameter of the tibial plateau (p = 0.008), 38.1 ± 0.8% and 34.6 ± 6.0% of the anterior-to-posterior diameter (p = 0.071), respectively. Conclusions In this study, ACL reconstruction was completed with the assistance of a robot arm and 3D images, and the robot was able to drill the bone tunnel more accurately than the traditional arthroscopic ACL reconstruction.

National Inpatient Datasets May No Longer Be Appropriate for Overall Total Hip and Knee Arthroplasties Projections after Removal from Inpatient-Only Lists.

It is unknown if the National Inpatient Sample (NIS) remains suitable to conduct projections for total knee arthroplasty (TKA) and total hip arthroplasty (THA), after their removal from "inpatient-only lists" in 2018 and 2020, respectively. We aimed to: (1) quantify primary THA and TKA volume from 2008 to 2018; (2) project estimates of future volume of THA and TKA until 2050; and (3) compare projections based on NIS data from 2008 to 2018 and 2008 to 2017, respectively. We identified all primary THA and TKA performed from 2008 to 2018 from the NIS. The projected volumes of THA and TKA were modeled using negative binomial regression models while incorporating log-transformed population data from the Centers for Disease Control and Prevention. Annual volume increased by 26% for THA and 11% for TKA (2008/2018: THA: 360,891/465,559; TKA:592,352/657,294). Based on 2008 to 2018 data, THA volume is projected to grow 120%, to 1,119,942 THAs by 2050. While, based on 2008 to 2017 data, THA volume is projected to grow 136%, to 1,219,852 THAs by 2050. Based on 2008 to 2018 data, TKA volume is projected to grow 4%, to 794,852 TKAs by 2050. While, based on 2008 to 2017 data, TKA volume is projected to grow 28%, to 1,037,474 TKAs by 2050. Projections based on 2008 to 2017 data estimated up to 240,000 (23%) more annual TKAs by 2050, compared with projections based on 2008 to 2018 data. The largest discrepancy among THA projections was an 8.2% difference (99,000 THAs) for 2050. After 2018 for TKA, and potentially 2020 for THA, projections based on the NIS will have to be interpreted with caution and may only be appropriate to estimate future inpatient volume. Level of evidence is prognostic level II.

Patient-specific 3D-printed Brace for Adolescent Idiopathic Scoliosis: A Prospective Cohort Study.

OBJECTIVE: To evaluate the efficacy, safety of patient-tailored 3D printed brace in the treatment of adolescent idiopathic scoliosis (AIS), and to compare the health-related quality of life (HRQoL) of patients treated with two different types of brace. MATERIALS AND METHODS: From September 2017 to August 2020, 103 AIS patients requiring non-operative management were prospectively recruited in this study. All patients were followed up every 6 months, clinical and radiological examination were assessed at each follow-up time. Full-length anteroposterior X-ray of the spine in the standing position was performed obtained. At the last follow-up, each patient completed a standardized HRQoL questionnaire. Compliance is defined as that the patient insists on wearing the brace for ≥ 23h every day (full-time wearing) and follow-up every 6 months until bone maturity.The rate of major curve Cobb progression was defined that maximum Cobb Angle of major curve greater than 6° compared with that at the initial diagnosis, or aggravated to more than 45° so that orthopedic surgery was recommended during treatment, which was defined as the rate of conversion to surgery. The effects of these two types of braces on the rate of major curve Cobb progression and HRQoL were analyzed by independent sample t-test ad Chi-square test. RESULTS: The thickness was 4 mm for thoracolumbosacral orthosis (TLSO) and 3 mm for 3D-printed brace (3DPB). In addition, compared with the material used in TLSO, the weight (600-800 grams) of the 3DPB materials with the same area is reduced by about 25-30%. 55 patients (49.1%) and 48 patients (33.1%) were respectively included in the 3DPB cohort and the TLSO cohort.The maximum Cobb angle of major curve in the 3DPB cohort was significantly lower than those in the TLSO cohort at 6 months, 12 months and the last follow-up (p < 0.01). The thoracic kyphosis (TK) and lumbar lordosis (LL) of the two cohorts at the last follow-up were lower than those before brace treatment, in addition, there was a significant difference in TK (p = 0.001) and LL (p = 0.004) between the two cohorts at the follow-up. The scores of physical function, pain, self-image, mental health and treatment satisfaction in the Chinese version of SRS-22 in the 3DPB cohort were higher than those in the TLSO cohort (p < 0.01 and p < 0.05, respectively). The scores of the 3DPB cohort were significantly higher than those of the TLSO group in the four dimensions (p = 0.008, 0.013, 0.015, and 0.002, respectively) of the EuroQol-5D health description system except for mobility, and the overall health status of EuroQol-5D was higher for the 3DPB cohort (p < 0.001). At the last follow-up, One patient in the 3DPB cohort and ten patients in the TLSO cohort had major curve Cobb progression of greater than 6°, and the rate of major curve Cobb progression in 3DPB cohort was significantly lower than that in the TLSO cohort (OR 14.2, 95% CI 1.7∼115.8, p < 0.01). One patient in the 3DPB and seven patients in the TLSO cohorts received subsequent surgery or was recommended for surgery, and the rate of conversion to surgery was significantly lower than in the 3DPB cohort (OR 9.2, 95% CI 1.1∼77.9, p < 0.05). CONCLUSIONS: Patient-tailored 3D-printed brace is lighter, thinner, and more comfortable than conventional braces in the treatment of AIS. It can substantially improve the HRQoL of patients and can significantly reduce the progression of major curve Cobb progression and rate of conversion of surgery.

Outcomes After Left Atrial Appendage Clip Placement During Cardiac Surgery: A Nationwide Analysis.

This study evaluated the nationwide associations between concomitant left atrial appendage clip (LAAC) placement during cardiac surgery and postoperative outcomes. We identified 1,260,999 patients who underwent coronary artery bypass grafting, valve, and aortic surgeries in the 2016 to 2020 Nationwide Readmissions Database and stratified by concomitant LAAC versus no LAAC placement. Patients who underwent surgical ablation were excluded. Mortality and complications were compared during index admissions and for patients readmitted within 30 and 90 days of the index discharge date for unmatched and propensity score-matched groups. Overall, 6.7% (84,293) of patients underwent cardiac surgery and concomitant LAAC placement without surgical ablation. After propensity score matching, the index admission mortality and overall complications were not different in patients with LAAC versus patients without LAAC. LAAC placement was associated with increased any-cause 30-day readmissions (15% vs 13%, p <0.01). In patients with LAAC, within 30 days, there were no differences in mortality (3.9% vs 3.8%, p = 0.60) or overall complications (64% vs 63%, p = 0.20), whereas stroke was lower (5.3% vs 6.5%, p <0.01) and heart failure was higher (35% vs 30%, p <0.01). For patients readmitted within 90 days, similar findings were observed for any-cause readmissions, mortality, overall complications, stroke, and heart failure. In conclusion, concomitant LAAC placement during cardiac surgery was associated with lower early postdischarge incidence of stroke and a favorable overall risk-benefit profile. Given these short-term findings in a real-world population of all patients who underwent cardiac surgery, longer-term studies with more granular data are needed to evaluate the potential benefit of this practice.

FAK regulates tension transmission to the nucleus and endothelial transcriptome independent of kinase activity.

The mechanical environment generated through the adhesive interaction of endothelial cells (ECs) with the matrix controls nuclear tension, preventing aberrant gene synthesis and the transition from restrictive to leaky endothelium, a hallmark of acute lung injury (ALI). However, the mechanisms controlling tension transmission to the nucleus and EC-restrictive fate remain elusive. Here, we demonstrate that, in a kinase-independent manner, focal adhesion kinase (FAK) safeguards tension transmission to the nucleus to maintain EC-restrictive fate. In FAK-depleted ECs, robust activation of the RhoA-Rho-kinase pathway increased EC tension and phosphorylation of the nuclear envelope protein, emerin, activating DNMT3a. Activated DNMT3a methylates the KLF2 promoter, impairing the synthesis of KLF2 and its target S1PR1 to induce the leaky EC transcriptome. Repleting FAK (wild type or kinase dead) or inhibiting RhoA-emerin-DNMT3a activities in damaged lung ECs restored KLF2 transcription of the restrictive EC transcriptome. Thus, FAK sensing and control of tension transmission to the nucleus govern restrictive endothelium to maintain lung homeostasis.