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The transcription factor ΔNp63 plays a pivotal role in maintaining the integrity of stratified epithelial tissues by regulating the expression of distinct target genes involved in lineage specification, cell stemness, cell proliferation and differentiation. Here, we identified the ABC transporter subfamily member ABCC1 as a novel ΔNp63 target gene. We found that in immortalized human keratinocytes and in squamous cell carcinoma (SCC) cells, ∆Np63 induces the expression of ABCC1 by physically occupying a p63-binding site (p63 BS) located in the first intron of the ABCC1 gene locus. In cutaneous SCC and during the activation of the keratinocyte differentiation program, ∆Np63 and ABCC1 levels are positively correlated raising the possibility that ABCC1 might be involved in the regulation of the proliferative/differentiative capabilities of squamous tissue. However, we did not find any gross alteration in the structure and morphology of the epidermis in humanized hABCC1 knock-out mice. Conversely, we found that the genetic ablation of ABCC1 led to a marked reduction in inflammation-mediated proliferation of keratinocytes, suggesting that ABCC1 might be involved in the regulation of keratinocyte proliferation upon inflammatory/proliferative signals. In line with these observations, we found a significant increase in ABCC1 expression in squamous cell carcinomas (SCCs), a tumor type characterized by keratinocyte hyper-proliferation and a pro-inflammatory tumor microenvironment. Collectively, these data uncover ABCC1 as an additional ∆Np63 target gene potentially involved in those skin diseases characterized by dysregulation of proliferation/differentiation balance.

Introduction and Importance: Repairing massive rotator cuff tears (MRCTs) can often be technically challenging due to tendon retraction, bursal fibrosis, and muscular fatty infiltration that usually occurs, often resulting in poor outcomes and an unpredictable prognosis. Although some other surgical management options have been reported, there is a lack of literature supporting tendon transfers in the presence of combined anterior and posterior-superior irreparable rotator cuff tears. We describe a case where a combined transfer of the latissimus dorsi and lower trapezius tendons was employed to treat an MRCT affecting the anterior and posterior superior portions of the rotator cuff., Case Presentation: A 64-year-old male presented significant pain and limited range of motion in the right shoulder following a traumatic anterior shoulder dislocation seven months prior. MRI showed retracted tears (> 5 cm) of the supraspinatus, infraspinatus, and subscapularis tendons with significant fatty infiltration (Goutallier IV). The patient underwent an open transfer of the lower trapezius tendon to the greater tuberosity and the latissimus dorsi to the lesser tuberosity. At the final follow-up, 2.5 years postoperatively, the patient exhibited a painless functional range of motion and could resume daily activities., Clinical Discussion: Although there are alternative surgical options available, the positive outcomes observed in the presented case may be attributed to the restoration of rotational strength and the re-establishment of force coupling across the shoulder., Conclusion: This report describes the successful implementation of a surgical treatment option for managing MRCT affecting the anterior and posterior superior portions of the rotator cuff., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Latissimus dorsi transfer is a surgical procedure that can be used for treating posterosuperior rotator cuff tears. The procedure leads to improved shoulder function via alterations in the force vector couple around the shoulder. However, there is still no consensus on the biomechanical changes resulting from latissimus dorsi transfer., Methods: We performed a systematic review of the literature on 3D motion analysis studies evaluating the effects of latissimus dorsi transfer on shoulder kinematics. The available data on segment and joint range of motion was extracted and subject to meta-analysis when consistent across the studies., Findings: Our meta-analysis of pre- and post-operative studies revealed a significant improvement in forward flexion and abduction following latissimus dorsi transfer. When comparing the latissimus transferred shoulder with an uninjured contralateral side the meta-analysis found no significant difference in flexion range of motion, while abduction and external rotation was significantly higher in the uninjured shoulders. The overall risk of bias was moderate to high. High heterogeneity was found in the reporting of data, which limited our ability to perform a meta-analysis across the studies for all interest outcomes., Interpretations: Our findings suggest that latissimus dorsi transfer for posterosuperior rotator cuff tears effectively improves shoulder flexion and abduction. External rotation is also expected to improve but at inferior levels as compared to the unaffected side. However, the heterogeneity of the reported data on 3D motion analysis studies highlights the need for better standardization in research and reporting as to conclude the impact of different joints., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Clavicle fractures are among the most common upper limb fractures in adults, with the midshaft region being the most frequently affected site. Minimally invasive plate osteosynthesis (MIPO) has emerged as an alternative to the traditional open reduction and internal fixation (ORIF) technique, offering potential advantages. The purpose of this study was to conduct a systematic review to explore the results of this technique in the existing literature, with emphasis on the occurrence of surgical complications and functional outcomes and also to provide a comprehensive comparison of MIPO and ORIF in the management of midshaft clavicle fractures., Methods: We conducted a systematic review to evaluate the complication incidence and clinical outcomes of MIPO for midshaft clavicle fractures. We searched PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Scopus, the Cochrane Database of Controlled Trials, and the Cochrane Database of Systematic Reviews databases without language or date restrictions. Studies focusing on midshaft clavicle fractures treated with MIPO were included, while other clavicle fractures and nonclinical studies were excluded. The risk of bias was assessed using the Methodological Index for Nonrandomized Studies criteria and the Risk of Bias Tool 2 Cochrane tool. Data synthesis included qualitative analysis, and if applicable, quantitative analysis and meta-analysis. Adherence to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines ensured reporting quality., Results: A total of 107 studies were initially identified, after applying inclusion and exclusion criteria, 22 studies were included for data extraction. These studies involved the evaluation of 714 clavicles treated with the MIPO technique. Of the 714 MIPO cases, 11 cases of implant failure, 5 nonunions, 2 infections, and 28 cases with neurological impairment were observed. Quantitative analysis comparing MIPO with ORIF revealed that MIPO had significantly shorter surgery time (mean difference -12.95, 95% confidence interval [-25.27 to -0.63], P  = .04) and lower occurrence of numbness (odds ratio 0.29, 95% CI [0.15-0.56], P  = .0002) compared to ORIF. Time to bone union, functional outcomes, and other complications were similar between MIPO and ORIF at the final follow-up. An overall moderate risk of bias was found across the studies., Conclusion: The MIPO technique yields good and comparable results to ORIF for midshaft clavicle fractures. Additionally, the MIPO technique may offer advantages such as reduced surgical time and lower chances of neurological impairment., (© 2023 The Author(s).)

During anatomic total shoulder arthroplasty, careful dissection and meticulous soft tissue management ensure adequate visualization of the articular and bony surfaces, allowing the proper use of surgical instrumentation and ensuring accurate placement of prosthetic components. Exposure must be balanced with protection of the surrounding soft tissues, as well as neurovascular structures, which can have long-term postoperative implications. In Part 2 of this technique series for the management of glenohumeral osteoarthritis, we describe our technical approach for dissection, exposure, and management of soft tissues in anatomic total shoulder arthroplasty, including pearls and pitfalls, as well as a discussion of the benefits and risks of the most common approaches., (© 2023 The Authors.)

The proposed benefits of stemless humeral implants include greater bone preservation, decreased cortical stress shielding, less risk of diaphyseal stress risers, decreased surgical time, and greater ease of implant removal during revision surgery. In part 3 of this comprehensive technique series on the management of glenohumeral arthritis, we present our step-by-step surgical technique for use of a patient-specific 3-dimensionally printed glenoid drill guide, placement of a stemless anatomic total shoulder prosthesis, and subscapularis repair, and we highlight our protocol for postoperative rehabilitation., (© 2023 The Authors.)

Successful total shoulder arthroplasty relies on a multitude of factors specific to patients, implant selection, and surgical technique. Among technical factors, correct intraoperative placement of prosthetic components is paramount. Three-dimensional computed tomography has emerged as a vital tool, allowing surgeons to measure glenoid inclination, glenoid version, and humeral head subluxation more accurately and reproducibly. Several commercial preoperative planning software resources are available to determine the optimal size and positioning of prosthetic components yet do so at significant cost and with meaningful time constraints. At our institution, we have applied the principles of these technologies to develop a custom, 3-dimensionally printed glenoid guide for accurate placement of the central pin. In this technical note, we describe our evaluation of patients with glenohumeral arthritis, as well as our step-by-step procedure for designing and printing a custom patient-specific instrumentation glenoid guide for anatomic total shoulder arthroplasty., (© 2023 The Authors.)

The transcription factor ΔNp63 regulates epithelial stem cell function and maintains the integrity of stratified epithelial tissues by acting as transcriptional repressor or activator towards a distinct subset of protein-coding genes and microRNAs. However, our knowledge of the functional link between ∆Np63 transcriptional activity and long non-coding RNAs (lncRNAs) expression is quite limited. Here, we show that in proliferating human keratinocytes ∆Np63 represses the expression of the lncRNA NEAT1 by recruiting the histone deacetylase HDAC1 to the proximal promoter of NEAT1 genomic locus. Upon induction of differentiation, ∆Np63 down-regulation is associated by a marked increase of NEAT1 RNA levels, resulting in an increased assembly of paraspeckles foci both in vitro and in human skin tissues. RNA-seq analysis associated with global DNA binding profile (ChIRP-seq) revealed that NEAT1 associates with the promoter of key epithelial transcription factors sustaining their expression during epidermal differentiation. These molecular events might explain the inability of NEAT1-depleted keratinocytes to undergo the proper formation of epidermal layers. Collectively, these data uncover the lncRNA NEAT1 as an additional player of the intricate network orchestrating epidermal morphogenesis., (© 2023. The Author(s).)

Anterior shoulder instability can lead to anterior glenoid bone loss associated with humeral posterior deformity (bipolar bone loss). Latarjet procedure is a commonly used surgical option in such cases. However, the procedure is associated with complications in up 15% of the cases often associated with inadequate positioning of coracoid bone graft and screws. Considering that acknowledgment of patient anatomy and use of surgical planning intraoperatively can reduce such complications, we describe the use of 3D printing tools to obtain a 3D Patient-Specific Surgical Guide to aid in the Latarjet procedure. Such tools present advantages and limitations compared to other tools available, which are also discussed in this article., (© 2023 The Authors.)

Background: Clavicle fractures account for approximately 5% of all fractures in adults and 75% of clavicle fractures occur in the midshaft. Shortening greater than two centimeters is an indicative of surgical treatment. Radiographic exams are often used to diagnose and evaluate clavicle fractures but computed tomography (CT) scan is currently considered the best method to assess these deformities and shortening., Goal: 1- To investigate whether different methods of performing the radiographic exam interfere on the measurement of the fractured clavicle length. 2- Compare the clavicle length measurements obtained by the different radiographic exam methods with the CT scan measurements, used as a reference., Materials and Methods: Twenty-five patients with acute (< 3 weeks) midshaft clavicle fracture were evaluated. Patients underwent six radiographic images: PA Thorax (standing and lying), AP Thorax (standing and lying) and at 10° cephalic tilt (standing and lying), and the computed tomography was used as reference., Results: The mean length (cm) obtained were: 14,930 on CT scan, 14,860 on PA Thorax Standing, 14,955 on PA Thorax Lying, 14,896 on AP Thorax Standing, 14,960 AP Thorax Lying, 15,098 on 10° cephalic tilt Standing and 15,001 on 10° cephalic tilt Lying, (p > 0,05)., Conclusion: 1- There is no significant statistical difference in the clavicle fracture length measurement among the variety of radiographic exam performances. 2- The method that comes closest to computed tomography results is the PA thorax incidence, with the patient in the lying position., (© 2022. The Author(s).)

SignificanceΔNp63 is a master regulator of skin homeostasis since it finely controls keratinocyte differentiation and proliferation. Here, we provide cellular and molecular evidence demonstrating the functional role of a ΔNp63 interactor, the R-loop-resolving enzyme Senataxin (SETX), in fine-tuning keratinocyte differentiation. We found that SETX physically binds the p63 DNA-binding motif present in two early epidermal differentiation genes, Keratin 1 (KRT1) and ZNF750, facilitating R-loop removal over their 3' ends and thus allowing efficient transcriptional termination and gene expression. These molecular events translate into the inability of SETX-depleted keratinocytes to undergo the correct epidermal differentiation program. Remarkably, SETX is dysregulated in cutaneous squamous cell carcinoma, suggesting its potential involvement in the pathogenesis of skin disorders.

Introduction and Importance: Surgical treatment for clavicle injuries is indicated for displaced and shortened fractures. Osteosyntheses with plate fixation may present with complications in 6.3% to 8.5% of patients. Peri-implant clavicle fractures (PIF) are rare, and we have not found any previous cases in our literature search., Case Presentation: A 25-year-old male with previously (six years earlier) surgically treated clavicle fracture presented with a peri-implant clavicle fracture requiring surgical treatment. The management involved overlaying an implant to fix the lateral clavicle fracture without removing the previous plate. Complete bone healing was observed without any further complication., Clinical Discussion: Despite the low rate of implant failure in clavicle fractures, this complication occurs mainly in elderly patients with poor bone quality. No PIF have been described in the literature prior to this. This case report demonstrates a young patient with good bone quality and previous fracture fixation presenting with PIF which has now shown complete bone healing., Conclusion: In this case, overlying an additional plate on the lateral clavicle portion without removing the previous plate increased the stability of the fracture. It demonstrates the value of overlaying plate osteosyntheses for patients with clavicle PIF., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)