A new perspective on intervertebral disc calcification—from bench to bedside

Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

Trends in leadership at orthopaedic surgery sports medicine fellowships

BACKGROUND Fellowship directors(FDs)in sports medicine influence the future of trainees in the field of orthopaedics.Understanding the characteristics these leaders share must be brought into focus.For all current sports medicine FDs,our group analyzed their demographic background,institutional training,and academic experience.AIM To serve as a framework for those aspiring to achieve this position in orthopaedics and also identify opportunities to improve the position.METHODS Fellowship programs were identified using both the American Orthopaedic Society for Sports Medicine and the Arthroscopy Association of North America Sports Medicine Fellowship Directories.The demographic and educational background data for each FD was gathered via author review of current curriculum vitae(CVs).Any information that was unavailable on CV review was gathered from institutional biographies,Scopus Web of Science,and emailed questionnaires.To ensure the collection of as many data points as possible,fellowship program coordinators,orthopaedic department offices and FDs were directly contacted via phone if there was no response via email.Demographic information of interest included:Age,gender,ethnicity,residency/fellowship training,residency/fellowship graduation year,year hired by current institution,time since training completion until FD appointment,length in FD role,status as a team physician and H-index.RESULTS Information was gathered for 82 FDs.Of these,97.5%(n=80)of the leadership were male;84.15%(n=69)were Caucasian,7.32%(n=6)were Asian-American,2.44%(n=2)were Hispanic and 2.44%(n=2)were African American,and 3.66%(n=3)were of another race or ethnicity.The mean age of current FDs was 56 years old(±9.00 years),and the mean Scopus H-index was 23.49(±16.57).The mean calendar years for completion of residency and fellowship training were 1996(±15 years)and 1997(±9.51 years),respectively.The time since fellowship training completion until FD appointment was 9.77 years.17.07%(n=14)of FDs currently work at the same institution where they completed residency training;21.95%(n=18)of FDs work at the same institution where they completed fellowship training;and 6.10%(n=5)work at the same institution where they completed both residency and fellowship training.Additionally,69.5%(n=57)are also team physicians at the professional and/or collegiate level.Of those that were found to currently serve as team physicians,56.14%(n=32)of them worked with professional sports teams,29.82%(n=17)with collegiate sports teams,and 14.04%(n=8)with both professional and collegiate sports teams.Seven residency programs produced the greatest number of future FDs,included programs produced at least three future FDs.Seven fellowship programs produced the greatest number of future FDs,included programs produced at least four future FDs.Eight FDs(9.75%)completed two fellowships and three FDs(3.66%)finished three fellowships.Three FDs(3.66%)did not graduate from any fellowship training program.The Scopus H-indices for FDs are displayed as ranges that include 1 to 15(31.71%,n=26),15 to 30(34.15%,n=28),30 to 45(20.73%,n=17),45 to 60(6.10%,n=5)and 60 to 80(3.66%,n=3).Specifically,the most impactful FD in research currently has a Scopus H-index value of 79.By comparison,the tenth most impactful FD in research had a Scopus H-index value of 43(accessed December 1,2019).CONCLUSION This study provides an overview of current sports medicine FDs within the United States and functions as a guide to direct initiatives to achieve diversity equality.

Biological response to prosthetic debris

Joint arthroplasty had revolutionized the outcome of orthopaedic surgery. Extensive and collaborative work of many innovator surgeons had led to the development of durable bearing surfaces, yet no single material is considered absolutely perfect. Generation of wear debris from any part of the prosthesis is unavoidable. Implant loosening secondary to osteolysis is the most common mode of failure of arthroplasty. Osteolysis is the resultant of complex contribution of the generated wear debris and the mechanical instability of the prosthetic components. Roughly speaking, all orthopedic biomaterials may induce a universal biologic hostresponse to generated wear débris with little specific characteristics for each material; but some debris has been shown to be more cytotoxic than others. Prosthetic wear debris induces an extensive biological cascade of adverse cellular responses, where macrophages are the main cellular type involved in this hostile inflammatory process. Macrophages cause osteolysis indirectly by releasing numerous chemotactic inflammatory mediators, and directly by resorbing bone with their membrane microstructures. The bio-reactivity of wear particles depends on two major elements: particle characteristics(size, concentration and composition) and host characteristics. While any particle type may enhance hostile cellular reaction, cytological examination demonstrated that more than 70% of the debris burden is constituted of polyethylene particles. Comprehensive understanding of the intricate process of osteolysis is of utmost importance for future development of therapeutic modalities that may delay or prevent the disease progression.

腰椎间盘突出症的手术与非手术治疗比较——脊柱患者治疗结果研究试验（SPORT）：随机试验

背景：在美国，腰椎间盘切除术是治疗腰背部及下肢症状患者最常用的手术。但是，这种手术方式的疗效较之非手术治疗仍存在争议。 目的：评价手术治疗腰椎间盘突出症的疗效。 设计、地点及参试者：“脊柱患者治疗结果研究试验（Spine Patient Outcomes Research Trial，SPORT）”是一项随机临床试验。研究人员于2000年3月至2004年11月在美国11个州的13所多学科脊柱医院进行患者注册。参试者为501例将要实施手术治疗的患者（平均年龄为42岁，女性占42％），患者经影像学检查确定患有腰椎间盘突出症，有持续性神经根性症状和体征至少6周。 干预：为不同患者实施标准的开放性椎间盘切除术或非手术治疗。 主要观测指标：主要观测指标为36项健康调查表中的疼痛躯体功能评分以及改良的Oswestry残疾指数（美国骨科医师协会MODEMS版）在6周、3个月、1年及2年时较基线值发生的变化。次要观测指标包括坐骨神经痛的严重程度（采用坐骨神经疼痛的焦虑指数进行评估）、症状缓解的满意程度、疾病改善的自我报告及就业状况。 结果：坚持按计划接受治疗的患者比较有限。在计划接受手术治疗的患者中，50％的患者在注册后3个月内进行了手术治疗；而在计划接受非手术治疗的患者中，有30％的患者在注册后3个月内接受了手术治疗。意向治疗分析表明，两个治疗组主要指标和次要指标都有实质性改善。在整个试验期间，改善情况的组间差异表明手术治疗效果较好，但是主要指标的差异较小，而且无统计学显著性。 结论：手术治疗组和非手术治疗组患者的病情在2年随访期内都有实质性地改善。由于两组均有许多患者改变了治疗计划，所以我们难以根据治疗意向分析比较、确定两种治疗方式的优越性或等效性。

Fungal periprosthetic joint infection:Rare but challenging problem

Periprosthetic joint infection (PJI) is the most difficult complication following total joint arthroplasty. Most of the etiological strains, accounting for over 98% of PJI, are bacterial species, with Staphylococcus aureus and Coagulase-negative staphylococci present in between 50% and 60% of all PJIs. Fungi, though rare, can also cause PJI in 1%—2% of cases and can be challenging to manage. The management of this uncommon but complex condition is challenging due to the absence of a consistent algorithm. Diagnosis of fungal PJI is difficult as isolation of the organisms by traditional culture may take a long time, and some of the culture-negative PJI can be caused by fungal organisms. In recent years, the introduction of next-generation sequencing has provided opportunity for isolation of the infective organisms in culture-negative PJI cases. The suggested treatment is based on consensus and includes operative and non-operative measures. Two-stage revision surgery is the most reliable surgical option for chronic PJI caused by fungi. Pharmacological therapy with antifungal agents is required for a long period of time with antibiotics and included to cover superinfections with bacterial species. The aim of this review article is to report the most up-to-date information on the diagnosis and treatment of fungal PJI with the intention of providing clear guidance to clinicians, researchers and surgeons.