Perioperative Demographic and Laboratory Characteristics of Failed Debridement, Antibiotics, and Implant Retention: Can We Determine Which Patients Will Fail?

BACKGROUND: Debridement, antibiotics, and implant retention (DAIR) are the mainstays surgical treatment for acute periprosthetic joint infection (PJI). However, reoperation following DAIR is common and the risk factors for DAIR failure remain unclear. This study aimed to assess the perioperative characteristics of patients who failed initial DAIR treatment. METHODS: A retrospective review was conducted on 83 patients who underwent DAIR for acute PJI within 3 months following index surgery from 2011 to 2022, with a minimum one-year follow-up. Surgical outcomes were categorized using the Musculoskeletal Infection Society outcome reporting tool (Tiers 1 to 4). Patient demographics, laboratory data, and perioperative outcomes were compared between patients who had failed (Tiers 3 and 4) (n = 32) and successful (Tiers 1 and 2) (n = 51) DAIR treatment. Logistic regression was also performed. RESULTS: After logistic regression, Charlson Comorbidity Index (odds ratio [OR]: 1.57; P = .003), preoperative C-reactive protein (OR: 1.06; P = .014), synovial white blood cell (OR: 1.14; P = .008), and polymorphonuclear cell (PMN%) counts (OR: 1.05; P = .015) were independently associated with failed DAIR. Compared with total hip arthroplasty, total knee arthroplasty patients (OR: 6.08; P = .001) were at increased risk of DAIR failure. The type of organism and time from primary surgery were not correlated with DAIR failure. CONCLUSIONS: Patients who had failed initial DAIR tended to have significantly higher Charlson Comorbidity Index, C-reactive protein, synovial white blood cell, and PMN%. The total knee arthroplasty DAIRs were more likely to fail than the total hip arthroplasty DAIRs. These characteristics should be considered when planning acute PJI management, as certain patients may be at higher risk for DAIR failure and may benefit from other surgical treatments. LEVEL OF EVIDENCE: III.

Vertebral Body Tethering in 49 Adolescent Patients after Peak Height Velocity for the Treatment of Idiopathic Scoliosis: 2-5 Year Follow-Up.

Vertebral Body Tethering (VBT) is a non-fusion surgical treatment for Adolescent Idiopathic Scoliosis (AIS) that elicits correction via growth modulation in skeletally immature patients. VBT after peak height velocity is controversial and is the subject of this study. A retrospective review of Risser 3−5 AIS patients treated with VBT, and min. 2-year FU was performed. Pre to post-op changes in clinical outcomes were compared using Student's t-test or the Mann-Whitney test. A total of 49 patients met criteria, age 15.0 ± 1.9 years, FU 32.5 ± 9.1 months. For thoracic (T) major curvatures, T curvature improved from 51.1 ± 6.9° to 27.2° ± 8.1° (p < 0.01) and TL from 37.2° ± 10.7° to 19.2° ± 6.8° (p < 0.01). For thoracolumbar (TL) major curvatures, T improved from 37.2° ± 10.7° to 18.8° ± 9.4° (p < 0.01) and TL from 49.0° ± 6.4° to 20.1° ± 8.5° (p < 0.01). Major curve inclinometer measurements and SRS-22 domains, except activity, improved significantly (p ≤ 0.05). At the latest FU, one (2%) patient required fusion of the T curve and revision of the TL tether due to curve progression in the previously uninstrumented T curve and tether breakage (TB) in the TL. Twenty (41%) patients experienced TB. VBT in AIS patients with limited remaining skeletal growth resulted in satisfactory clinical outcomes at the latest FU.

Tenomodulin and Chondromodulin-1 Are Both Required to Maintain Biomechanical Function and Prevent Intervertebral Disc Degeneration.

OBJECTIVE: The underlying mechanisms and molecular factors influencing intervertebral disc (IVD) homeostasis and degeneration remain clinically relevant. Tenomodulin (Tnmd) and chondromodulin (Chm1) are antiangiogenic transmembrane glycoproteins, with cleavable C-terminus, expressed by IVD cells that are implicated in the onset of degenerative processes. We evaluate the organ-level biomechanical impact of knocking out Tnmd alone, and Tnmd and Chm1, simultaneously. DESIGN: Caudal (c5-8) and lumbar vertebrae (L1-4) of skeletally mature male and female 9-month-old wildtype (WT), Tnmd knockout (Tnmd-/-), and Tnmd/Chm1 double knockout (Tnmd-/-/Chm-/-) mice were used (n = 9-13 per group). Disc height index (DHI), histomorphological changes, and axial, torsional, creep, and failure biomechanical properties were evaluated. Differences were assessed by one-way ANOVA with post hoc Bonferroni-corrected comparisons (P < 0.05). RESULTS: Tnmd-/-/Chm1-/- IVDs displayed increased DHI and histomorphological scores that indicated increased IVD degeneration compared to the WT and Tnmd-/- groups. Double knockout IVDs required significantly less torque and energy to initiate torsional failure. Creep parameters were comparable between all groups, except for the slow time constant, which indicated faster outward fluid flow. Tnmd-/- IVDs lost fluid faster than the WT group, and this effect was amplified in the double knockout IVDs. CONCLUSION: Knocking out Tnmd and Chm1 affects IVD fluid flow and organ-level biomechanical function and therefore may play a role in contributing to IVD degeneration. Larger effects of the Tnmd and Chm1 double knockout mice compared to the Tnmd single mutant suggest that Chm1 may play a compensatory role in the Tnmd single mutant IVDs.

Georg Schmorl Prize of the German Spine Society (DWG) 2020: new biomechanical in vitro test method to determine subsidence risk of vertebral body replacements.

PURPOSE: Prevention of implant subsidence in osteoporotic (thoraco)lumbar spines is still a major challenge in spinal surgery. In this study, a new biomechanical in vitro test method was developed to simulate patient activities in order to determine the subsidence risk of vertebral body replacements during physiologic loading conditions. METHODS: The study included 12 (thoraco)lumbar (T11-L1, L2-L4) human specimens. After dorsal stabilisation and corpectomy, vertebral body replacements (VBR) with (a) round centrally located and (b) lateral end pieces with apophyseal support were implanted, equally distributed regarding segment, sex, mean BMD ((a) 64.2 mgCaHA/cm3, (b) 66.7 mgCaHA/cm3) and age ((a) 78 years, (b) 73.5 years). The specimens were then subjected to everyday activities (climbing stairs, tying shoes, lifting 20 kg) simulated by a custom-made dynamic loading simulator combining corresponding axial loads with flexion-extension and lateral bending movements. They were applied in oscillating waves at 0.5 Hz and raised every 100 cycles phase-shifted to each other by 50 N or 0.25°, respectively. The range of motion (ROM) of the specimens was determined in all three motion planes under pure moments of 3.75 Nm prior to and after implantation as well as subsequently following activities. Simultaneously, subsidence depth was quantified from fluoroscope films. A mixed model (significance level: 0.05) was established to relate subsidence risk to implant geometries and patients' activities. RESULTS: With this new test method, simulating everyday activities provoked clinically relevant subsidence schemes. Generally, severe everyday activities caused deeper subsidence which resulted in increased ROM. Subsidence of lateral end pieces was remarkably less pronounced which was accompanied by a smaller ROM in flexion-extension and higher motion possibilities in axial rotation (p = 0.05). CONCLUSION: In this study, a new biomechanical test method was developed that simulates physiologic activities to examine implant subsidence. It appears that the highest risk of subsidence occurs most when lifting heavy weights, and into the ventral part of the caudal vertebra. The results indicate that lateral end pieces may better prevent from implant subsidence because of the additional cortical support. Generally, patients that are treated with a VBR should avoid activities that create high loading on the spine.

Development of a two-part biomaterial adhesive strategy for annulus fibrosus repair and ex vivo evaluation of implant herniation risk.

Intervertebral disc (IVD) herniation causes pain and disability, but current discectomy procedures alleviate pain without repairing annulus fibrosus (AF) defects. Tissue engineering strategies seal AF defects by utilizing hydrogel systems to prevent recurrent herniation, however current biomaterials are limited by poor adhesion to wetted tissue surfaces or low failure strength resulting in considerable risk of implant herniation upon spinal loading. Here, we developed a two-part repair strategy comprising a dual-modified (oxidized and methacrylated) glycosaminoglycan that can chemically adsorb an injectable interpenetrating network hydrogel composed of fibronectin-conjugated fibrin and poly (ethylene glycol) diacrylate (PEGDA) to covalently bond the hydrogel to AF tissue. We show that dual-modified hyaluronic acid imparts greater adhesion to AF tissue than dual-modified chondroitin sulfate, where the degree of oxidation is more strongly correlated with adhesion strength than methacrylation. We apply this strategy to an ex vivo bovine model of discectomy and demonstrate that PEGDA molecular weight tunes hydrogel mechanical properties and affects herniation risk, where IVDs repaired with low-modulus hydrogels composed of 20kDa PEGDA failed at levels at or exceeding discectomy, the clinical standard of care. This strategy bonds injectable hydrogels to IVD extracellular matrix proteins, is optimized to seal AF defects, and shows promise for IVD repair.

Measuring the neutral zone of spinal motion segments: Comparison of multiple analysis methods to quantify spinal instability.

PURPOSE: Neutral zone (NZ) parameters in spinal biomechanics studies are sensitive to spinal instability, disc degeneration, and repair. Multiple methods in the literature quantify NZ, yet no consensus exists on applicability and comparability of methods. This study compares five different NZ quantification methods using two different load-deflection profiles. METHODS: Rat caudal and lumbar motion segments were tested in axial rotation to generate load-deflection curves with profiles exhibiting prominent distinction between elastic and NZ regions (ie, triphasic) and profiles that did not (ie, viscoelastic). NZ was quantified using five methods: trilinear, double sigmoid (DS), zero load, stiffness threshold (ST), and extrapolated elastic zone. Absolute agreement and consistency of NZ parameters were assessed using intraclass correlation (ICC), Bland-Altman analyses, and analysis of variance. RESULTS: For triphasic profiles, NZ magnitude exhibited high consistency (methods correlate but differ in absolute values), and only some methods exhibited agreement. For viscoelastic profiles, NZ magnitude showed limited consistency and no absolute agreement. NZ stiffness had high agreement and consistency across most methods and profiles. For triphasic profiles, the linear NZ regions for all methods were not well-described by a linear fit yet for viscoelastic profiles all methods characterized a linear NZ region. CONCLUSION: This NZ comparison study showed surprisingly limited agreement and consistency among NZ parameters with approximately 5% to 100% difference depending on the method and load-deflection profile. Nevertheless, the DS and ST methods appeared to be most comparable. We conclude that most NZ quantification methods cannot be applied interchangeably, highlighting a need to clearly state NZ calculation methods. Future studies are required to identify which methods are most sensitive to disc degeneration and repair in order to identify a "best" method.

Reliable skeletal maturity assessment for an AIS patient cohort: external validation of the proximal humerus ossification system (PHOS) and relevant learning methodology.

STUDY DESIGN: Validation of classification system. OBJECTIVES: To externally validate the Proximal Humerus Ossification System (PHOS) as a reliable skeletal maturity scoring system and to assess the learning curve associated with teaching the procedure to individuals of varying levels of experience. BACKGROUND: Assessment of skeletal maturity is essential for treatment decisions in Adolescent Idiopathic Scoliosis (AIS). PHOS is a five-stage system that uses the proximal humeral physis in assessing skeletal maturity and has been shown to reliably grade skeletal age leading up to and beyond peak growth age (PGA). This system is advantageous in the AIS patient, as it is often captured in standard scoliosis films. METHODS: A medical student, an orthopedic surgery resident (PGY-2), spine fellow, and experienced scoliosis surgeon in his 25th year in practice were given a three-slide PHOS learning module. Each participant rated 100 X-rays on two separate occasions, separated by 1 week. Intra- and inter-observer reliability, as well as cross-institutional reliability, were calculated using intraclass correlation coefficients (ICC) with 95% confidence intervals [CI95]. RESULTS: Average intra-observer reliability ICC between scoring sessions was 0.94 [0.92, 0.96] and inter-observer reliability by level of training were 0.94 [0.91, 0.96], 0.93 [0.9, 0.95], 0.94 [0.91, 0.96], 0.96 [0.94, 0.97] for the medical student, PGY-2, fellow, and attending, respectively. Reliability across institutions was 0.99 [0.98, 0.99]. Combined rating observations (n = 400) showed 82% exact matches, as well as 17% and 1% mismatches by 1 and 2 stages, respectively. Similar to the PHOS developers, we found PHOS stage 3 to occur immediately after PGA. CONCLUSION: PHOS is easily learned and employed by raters with varying levels of training. It comprises a five-stage system to reliably measure bone age leading up to PGA and thereafter. This new system relies on visualization of the proximal humerus, which is readily available on standard scoliosis X-rays. LEVEL OF EVIDENCE: Level III.

Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model.

Tissue engineering repair of annulus fibrosus (AF) defects has the potential to prevent disability and pain from intervertebral disc (IVD) herniation and its progression to degeneration. Clinical translation of AF repair methods requires assessment in long-term large animal models. An ovine AF injury model was developed using cervical spinal levels and a biopsy-type AF defect to assess composite tissue engineering repair in 1-month and 12-month studies. The repair used a fibrin hydrogel crosslinked with genipin (FibGen) to seal defects, poly(trimethylene carbonate) (PTMC) scaffolds to replace lost AF tissue, and polyurethane membranes to prevent herniation. In the 1-month study, PTMC scaffolds sealed with FibGen herniated with polyurethane membranes. When applied alone, FibGen integrated with the surrounding AF tissue without herniation, showing promise for long-term studies. The 12-month long-term study used only FibGen which showed fibrous healing, biomaterial resorption and no obvious hydrogel-related complications. However, the 2 mm biopsy punch injury condition also exhibited fibrotic healing at 12 months. Both untreated and FibGen treated groups showed equivalency with no detectable differences in histological grades of proteoglycans, cellular morphology, IVD structure and blood vessel formation, biomechanical properties including torque range and axial range of motion, Pfirrmann grade, IVD height, and quantitative scores of vertebral body changes from clinical computed tomography. The biopsy-type injury caused endplate defects with a high prevalence of osteophytes in all groups and no nucleus herniation, indicating that the biopsy-type injury requires further refinement, such as reduction to a slit-type defect that could penetrate the full depth of the AF without damaging the endplate. Results demonstrate translational feasibility of FibGen for AF repair to seal AF defects, although future study with a more refined injury model is required to validate the efficacy of FibGen before translation.

Comparative biomechanical study of a new transpedicular vertebral device and vertebroplasty for the treatment or prevention of vertebral compression fractures.

BACKGROUND: A comparative study was performed between a novel transpedicular implant (V-STRUT©, Hyprevention, France) and vertebroplasty. This study aims to assess the biomechanical efficacy of this implant in resurrecting and fortifying the osteoporotic vertebra following a vertebral body fracture. METHODS: A total of 17 vertebrae from 3 human osteoporotic spine segments (T9-L5) were selected. Vertebral compression fractures were generated by eccentric compressive loading until a height reduction of 25%. Then the vertebrae were either fixed using vertebroplasty technique (control group; n = 8) or implanted with V-STRUT© implant combined with bone cement (device group; n = 9). A new compressive loading was performed in the same conditions. Maximal load and stiffness, as well as total energy to fracture were measured. FINDINGS: Fracture force and energy to fracture were both increased either after V-STRUT© implantation or vertebroplasty compared to when the initial fracture was generated. Mean increase percentage between the initial value and the post-treatment value for each parameter were +77% vs +39% regarding fracture load and +126% vs +99% for energy to fracture, for the device group vs vertebroplasty group respectively. No pedicle fractures were observed in both groups, nor implant breaking or bending in the device group. INTERPRETATION: These results show the ability of V-STRUT© combined with bone cement to reinforce the vertebral body strength, with an at least equivalent biomechanical performance as vertebroplasty. Further clinical investigation needs to be undertaken to demonstrate any clinical superiority of V-STRUT© over vertebroplasty.

Peripheral injury alters schooling behavior in squid, Doryteuthis pealeii.

Animals with detectable injuries are at escalated threat of predation. The anti-predation tactic of schooling reduces individual predation risk overall, but it is not known how schooling behavior affects injured animals, or whether risks are reduced equally for injured animals versus other school members. In this laboratory study we examined the effects of minor fin injury on schooling decisions made by squid. Schooling behavior of groups of squid, in which one member was injured, was monitored over 24h. Injured squid were more likely to be members of a school shortly after injury (0.5-2h), but there were no differences compared with sham-injured squid at longer time points (6-24h). Overall, the presence of an injured conspecific increased the probability that a school would form, irrespective of whether the injured squid was a member of the school. When groups containing one injured squid were exposed to a predator cue, injured squid were more likely to join the school, but their position depended on whether the threat was a proximate visual cue or olfactory cue. We found no evidence that injured squid oriented themselves to conceal their injury from salient threats. Overall we conclude that nociceptive sensitization after injury changes grouping behaviors in ways that are likely to be adaptive.

Hypoxic culture conditions induce increased metabolic rate and collagen gene expression in ACL-derived cells.

There has been substantial effort directed toward the application of bone marrow and adipose-derived mesenchymal stromal cells (MSCs) in the regeneration of musculoskeletal tissue. Recently, resident tissue-specific stem cells have been described in a variety of mesenchymal structures including ligament, tendon, muscle, cartilage, and bone. In the current study, we systematically characterize three novel anterior cruciate ligament (ACL)-derived cell populations with the potential for ligament regeneration: ligament-forming fibroblasts (LFF: CD146(neg) , CD34(neg) CD44(pos) , CD31(neg) , CD45(neg) ), ligament perivascular cells (LPC: CD146(pos) CD34(neg) CD44(pos) , CD31(neg) , CD45(neg) ) and ligament interstitial cells (LIC: CD34(pos) CD146(neg) , CD44(pos) , CD31(neg) , CD45(neg) )-and describe their proliferative and differentiation potential, collagen gene expression and metabolism in both normoxic and hypoxic environments, and their trophic potential in vitro. All three groups of cells (LIC, LPC, and LFF) isolated from adult human ACL exhibited progenitor cell characteristics with regard to proliferation and differentiation potential in vitro. Culture in low oxygen tension enhanced the collagen I and III gene expression in LICs (by 2.8- and 3.3-fold, respectively) and LFFs (by 3- and 3.5-fold, respectively) and increased oxygen consumption rate and extracellular acidification rate in LICs (by 4- and 3.5-fold, respectively), LFFs (by 5.5- and 3-fold, respectively), LPCs (by 10- and 4.5-fold, respectively) as compared to normal oxygen concentration. In summary, this study demonstrates for the first time the presence of three novel progenitor cell populations in the adult ACL that demonstrate robust proliferative and matrix synthetic capacity; these cells may play a role in local ligament regeneration, and consequently represent a potential cell source for ligament engineering applications. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:985-994, 2016.