Tony Hartwig

Terminally Differentiated CD8+ T Cells Negatively Affect Bone Regeneration in Humans

A subset of T cells inhibits bone regeneration in humans. No Bones About It Sticks and stones may break your bones, but immune cells will not hurt you, at least if Reinke et al. have anything to say about it. The immune system seems to have a hand in everything these days, and bone repair is no exception. T cells have been implicated in modulating bone fracture repair, even in the absence of infection. Reinke et al. take these studies into patients and find that delayed fracture healing correlated with a subset of T cells—terminally differentiated effector memory CD8+ T (TEMRA) cells. The authors examined the number of CD8+ TEMRA cells over time and found that the difference in CD8+ TEMRA cell number in patients with delayed healing reflected the individual’s immune profile, or lifelong response to infection, rather than a more acute, fracture-related event. They specifically found these cells in fracture hematoma, one of the earliest stages of fracture healing. They then took these studies into mice and found that the absence of CD8+ T cells improved bone regeneration, whereas adding CD8+ T cells impaired fracture healing. This mechanistic link supported their association in patients and suggests that these CD8+ TEMRA cells may be targeted or serve as markers for intervention in patients with delayed bone fracture healing. There is growing evidence that adaptive immunity contributes to endogenous regeneration processes: For example, endogenous bone fracture repair is modulated by T cells even in the absence of infection. Because delayed or incomplete fracture healing is associated with poor long-term outcomes and high socioeconomic costs, we investigated the relationship between an individual’s immune reactivity and healing outcome. Our study revealed that delayed fracture healing significantly correlated with enhanced levels of terminally differentiated CD8+ effector memory T (TEMRA) cells (CD3+CD8+CD11a++CD28−CD57+ T cells) in peripheral blood. This difference was long lasting, reflecting rather the individual’s immune profile in response to lifelong antigen exposure than a post-fracture reaction. Moreover, CD8+ TEMRA cells were enriched in fracture hematoma; these cells were the major producers of interferon-γ/tumor necrosis factor–α, which inhibit osteogenic differentiation and survival of human mesenchymal stromal cells. Accordingly, depletion of CD8+ T cells in a mouse osteotomy model resulted in enhanced endogenous fracture regeneration, whereas a transfer of CD8+ T cells impaired the healing process. Our data demonstrate the high impact of the individual adaptive immune profile on endogenous bone regeneration. Quantification of CD8+ TEMRA cells represents a potential marker for the prognosis of the healing outcome and opens new opportunities for early and targeted intervention strategies.

Minimally invasive TLIF leads to increased muscle sparing of the multifidus muscle but not the longissimus muscle compared with conventional PLIF—a prospective randomized clinical trial

BACKGROUND CONTEXT An overload of the paravertebral muscles after surgical intervention is suggested to be the major cause of postoperative pain. In cross-sectional area analyses, increased atrophy of the multifidus muscle (MF) after conventional open versus minimally invasive posterior lumbar interbody fusion (PLIF) has been described. The three-dimensional characteristics of the paravertebral muscles and separate evaluation of the longissimus muscle (LS) have not been addressed in analyses thus far. PURPOSE The purpose of the present study was to compare the MF and LS volume atrophy and fatty degeneration between single-level minimally invasive transforaminal lumbar interbody fusion (miTLIF) and conventional midline approach-based PLIF (coPLIF) of L4/L5 or L5/S1 at the index and superior adjacent segments. DESIGN This was a prospective, randomized, controlled, non-blinded study. PATIENT SAMPLE Fifty patients with single-level segment degeneration (Pfirrmann ≥III and Modic ≥3) of L4/L5 or L5/S1 not requiring decompression were randomly assigned to two groups. OUTCOME MEASURES Paraspinal lumbar residual muscle tissue volume, change in the relative fat content of MF and LS at the index and superior adjacent segments, and clinical parameters, including a visual analogue scale (VAS) for low back pain and the Oswestry Disability Questionnaire (ODI) were the outcome measures in this study. METHODS Twenty-five patients were treated with miTLIF, and the remaining patients were treated with coPLIF (both with transpedicular fixation). Clinical scoring was performed preoperatively and at 1 week and 12 months postoperatively, and computed tomography was performed at the latter two follow-ups. RESULTS The LS damage at the index segment was similar in both groups (3% greater fat content increase in the coPLIF vs. the miTLIF group, p=.032), whereas MF atrophy and degeneration were increased (p<.001) in the coPLIF group. At the adjacent segment, muscle atrophy and increased fatty infiltration (p<.05) were minimal in both muscles but were similar in both groups. Visual analogue scale and ODI scores improved (p<.001), without differences between the groups. CONCLUSIONS The muscle damage after miTLIF was inferior to that after coPLIF; spatially, however, the muscle sparing was predominantly attributed to the MF and, surprisingly, not to the LS.

Digital 3-dimensional analysis of the paravertebral lumbar muscles after circumferential single-level fusion.

Study Design A retrospective controlled cohort study was performed for postoperative 3-dimensional muscle evaluation. Objective Our aim was to establish a method for spatially continuous 3-dimensional analysis of the lumbar paravertebral muscles after instrumented circumferential single-level fusion. Summary of Background Data Paravertebral muscle degeneration is thought to contribute to postoperative low back pain. Previous analysis methods did not regard on implant associated artifacts and on the multisegmental 3-dimensional character of the paravertebral muscles. Methods At 1 week and 12 months postoperatively, thin slice computed tomography scans of the lumbar paravertebral muscles were digitally analyzed and compared for 20 patients with chronic low back pain owing to monosegmental degenerative disc disease ≥ Modic II° and high intensity zones at L4/5. Tissue-specific regions of all slices were determined for automated calculation of fat and muscle volume, and localization of fatty degenerated areas in a 3-dimensional computer reconstruction model. Results All computed tomography scans were successfully digitally reconstructed and evaluated. A significant decrease of paravertebral muscle volume and an increase in volume fraction of fatty degeneration was observed at 12 months (Vmuscle 127.4±28.5 cm3, V%fat 48.67±3.63%) compared with 1 week postoperatively (Vmuscle 217.4±34.2 cm3, V%fat 12.57±2.28%). Fat tissue areas were most often located close to the spinal processes and anterolateral, close to the transverse processes. Conclusion We established a 3-dimensional image analysis method for evaluating postoperative changes in the lumbar paravertebral muscles of patients, after circumferential single-level fusion, consistently accounting for implant-associated artifacts. We were able to demonstrate volume atrophy and an increase of fatty degeneration after 12 months compared with 1 week postoperatively.

[Arthroscopic correction of extra-articular subspinal impingement in the hip joint].

ZusammenfassungWir beschreiben den Fall eines symptomatischen extraartikulären Subspine-Impingements am Hüftgelenk, hervorgerufen durch den pathologischen Kontakt zwischen einer hypertrophen Spina iliaca anterior inferior (SIAI) und dem ventralen Schenkelhals. Die Untersuchung eines 28-jährigen Patienten mit rechtsseitigen belastungsabhängigen Leistenschmerzen und positivem Impingementtest zeigte im Röntgen und CT eine Hypertrophie der SIAI mit Ausdehnung nach kaudal. Bei positivem Infiltrationstest erfolgte die arthroskopische partielle Resektion der SIAI, woraufhin der Patient eine verbesserte und nahezu schmerzfreie Hüftgelenkbeweglichkeit zeigte.AbstractWe report the case of symptomatic extra-articular subspinal impingement in the hip joint caused by a pathological contact between the anterior inferior iliac spine (AIIS) and the femoral neck. A 28-year-old patient presented with activity-related inguinal pain on the right side and a positive anterior impingement test in the clinical examination. Radiological examinations revealed a hypertrophic AIIS with caudal extension below the acetabulum. After a positive injection test confirmed the AIIS as the origin of the pain, arthroscopic correction with partial resection of the AIIS was performed resulting in significant pain relief and improved range of motion.We report the case of symptomatic extra-articular subspinal impingement in the hip joint caused by a pathological contact between the anterior inferior iliac spine (AIIS) and the femoral neck. A 28-year-old patient presented with activity-related inguinal pain on the right side and a positive anterior impingement test in the clinical examination. Radiological examinations revealed a hypertrophic AIIS with caudal extension below the acetabulum. After a positive injection test confirmed the AIIS as the origin of the pain, arthroscopic correction with partial resection of the AIIS was performed resulting in significant pain relief and improved range of motion.

Arthroskopische Korrektur des extraartikulären Subspine-Impingements am Hüftgelenk

ZusammenfassungWir beschreiben den Fall eines symptomatischen extraartikulären Subspine-Impingements am Hüftgelenk, hervorgerufen durch den pathologischen Kontakt zwischen einer hypertrophen Spina iliaca anterior inferior (SIAI) und dem ventralen Schenkelhals. Die Untersuchung eines 28-jährigen Patienten mit rechtsseitigen belastungsabhängigen Leistenschmerzen und positivem Impingementtest zeigte im Röntgen und CT eine Hypertrophie der SIAI mit Ausdehnung nach kaudal. Bei positivem Infiltrationstest erfolgte die arthroskopische partielle Resektion der SIAI, woraufhin der Patient eine verbesserte und nahezu schmerzfreie Hüftgelenkbeweglichkeit zeigte.AbstractWe report the case of symptomatic extra-articular subspinal impingement in the hip joint caused by a pathological contact between the anterior inferior iliac spine (AIIS) and the femoral neck. A 28-year-old patient presented with activity-related inguinal pain on the right side and a positive anterior impingement test in the clinical examination. Radiological examinations revealed a hypertrophic AIIS with caudal extension below the acetabulum. After a positive injection test confirmed the AIIS as the origin of the pain, arthroscopic correction with partial resection of the AIIS was performed resulting in significant pain relief and improved range of motion.We report the case of symptomatic extra-articular subspinal impingement in the hip joint caused by a pathological contact between the anterior inferior iliac spine (AIIS) and the femoral neck. A 28-year-old patient presented with activity-related inguinal pain on the right side and a positive anterior impingement test in the clinical examination. Radiological examinations revealed a hypertrophic AIIS with caudal extension below the acetabulum. After a positive injection test confirmed the AIIS as the origin of the pain, arthroscopic correction with partial resection of the AIIS was performed resulting in significant pain relief and improved range of motion.

[Monosegmental anterior lumbar interbody fusion with the SynFix-LR™ device. A prospective 2-year follow-up study].

BACKGROUND With anterior lumbar interbody fusion (ALIF) alone, the morbidity associated with a posterior approach can be avoided. In this study we evaluated the use of a PEEK cage with an integrated angle-stable locking plate (SynFix-LR™). MATERIAL AND METHODS Thirty-two patients with osteochondrosis at L4/5 or L5/S1 were treated with the SynFix-LR™. Follow-up at 0, 3, 6, 9, 12, and 24 months included the Oswestry Disability Index (ODI), visual analog scale (VAS), and questions regarding satisfaction and use of pain medication. The fusion rate was assessed by X-ray and computed tomography (CT) examination. RESULTS A significant reduction of the ODI and VAS was achieved (p<0.05) with a high rate of patient satisfaction. After 2 years, 79% of the patients were able to dispense with long-term use of analgesics. We observed a fusion rate of 93% (X-ray) and 70% (CT) at final follow-up. CONCLUSION The SynFix-LR™ device is a suitable option for the treatment of monosegmental osteochondrosis at L4/5 and L5/S1 with comparable or superior results in comparison to posterior or combined fusion techniques.

Postoperative posterior lumbar muscle changes and their relationship to segmental motion preservation or restriction: a randomized prospective study

OBJECTIVE To date, it remains unclear whether the preservation of segmental motion by total disc replacement (TDR) or motion restriction by stand-alone anterior lumbar interbody fusion (ALIF) have an influence on postoperative degeneration of the posterior paraspinal muscles or the associated clinical results. Therefore, the purpose of the present prospective randomized study was to evaluate the clinical parameters and 3D quantitative radiological changes in the paraspinal muscles of the lumbar spine in surgically treated segments and superior adjacent segments after ALIF and TDR. METHODS A total of 50 patients with chronic low-back pain caused by single-level intervertebral disc degeneration (Pfirrmann Grade ≥ III) and/or osteochondrosis (Modic Type ≤ 2) without symptomatic facet joint degeneration (Fujiwara Grade ≤ 2, infiltration test) of the segments L4-5 or L5-S1 were randomly assigned to 2 treatment groups. Twenty-five patients were treated with a stand-alone ALIF and the remaining 25 patients underwent TDR. For ALIF and TDR, a retroperitoneal approach was used. At 1 week and at 12 months after surgery, CT was used to analyze paraspinal lumbar muscle tissue volume and relative fat content. Residual muscle tissue volume at 12 months and change in the relative fat content were compared between the groups. In addition, clinical parameters (visual analog scale [VAS] for low-back pain and Oswestry Disability Index [ODI] Questionnaire Version 2 for function) were compared. RESULTS Compared with 1 week after surgery, the radiological analysis at 12 months revealed a small decrease in the posterior muscle volume (the mean decrease was < 2.5%), along with a small increase in the relative fat content (the mean increase was < 1.9%), in both groups at the index and superior adjacent segments. At the adjacent segment, the ALIF group presented significantly less muscle tissue volume atrophy and a smaller increase in fat content compared with the TDR group. At final follow-up, the clinical parameters related to pain and function were significantly improved in both groups compared with 1 week postsurgery, but there were no differences between the groups. CONCLUSIONS Motion restriction via stand-alone ALIF and motion preservation via TDR both present small changes in the posterior lumbar paraspinal muscles with regard to volume atrophy or fatty degeneration at the index and superior adjacent segments. Therefore, although the clinical outcome was not affected by the observed muscular changes, the authors concluded that the expected negative influence of motion restriction on the posterior muscles compared with motion preservation does not occur on a clinically relevant level.

MRI-guided and CT-guided cervical nerve root infiltration therapy: a cost comparison

PURPOSE To evaluate and compare the costs of MRI-guided and CT-guided cervical nerve root infiltration for the minimally invasive treatment of radicular neck pain. MATERIALS AND METHODS Between September 2009 and April 2012, 22 patients (9 men, 13 women; mean age: 48.2 years) underwent MRI-guided (1.0 Tesla, Panorama HFO, Philips) single-site periradicular cervical nerve root infiltration with 40 mg triamcinolone acetonide. A further 64 patients (34 men, 30 women; mean age: 50.3 years) were treated under CT fluoroscopic guidance (Somatom Definition 64, Siemens). The mean overall costs were calculated as the sum of the prorated costs of equipment use (purchase, depreciation, maintenance, and energy costs), personnel costs and expenditure for disposables that were identified for MRI- and CT-guided procedures. Additionally, the cost of ultrasound guidance was calculated. RESULTS The mean intervention time was 24.9 min. (range: 12 - 36 min.) for MRI-guided infiltration and 19.7 min. (range: 5 - 54 min.) for CT-guided infiltration. The average total costs per patient were EUR 240 for MRI-guided interventions and EUR 124 for CT-guided interventions. These were (MRI/CT guidance) EUR 150/60 for equipment use, EUR 46/40 for personnel, and EUR 44/25 for disposables. The mean overall cost of ultrasound guidance was EUR 76. CONCLUSION Cervical nerve root infiltration using MRI guidance is still about twice as expensive as infiltration using CT guidance. However, since it does not involve radiation exposure for patients and personnel, MRI-guided nerve root infiltration may become a promising alternative to the CT-guided procedure, especially since a further price decrease is expected for MRI devices and MR-compatible disposables. In contrast, ultrasound remains the less expensive method for nerve root infiltration guidance.

Die monosegmentale ventrale Spondylodese mit dem SynFix-LR™

BACKGROUND With anterior lumbar interbody fusion (ALIF) alone, the morbidity associated with a posterior approach can be avoided. In this study we evaluated the use of a PEEK cage with an integrated angle-stable locking plate (SynFix-LR™). MATERIAL AND METHODS Thirty-two patients with osteochondrosis at L4/5 or L5/S1 were treated with the SynFix-LR™. Follow-up at 0, 3, 6, 9, 12, and 24 months included the Oswestry Disability Index (ODI), visual analog scale (VAS), and questions regarding satisfaction and use of pain medication. The fusion rate was assessed by X-ray and computed tomography (CT) examination. RESULTS A significant reduction of the ODI and VAS was achieved (p<0.05) with a high rate of patient satisfaction. After 2 years, 79% of the patients were able to dispense with long-term use of analgesics. We observed a fusion rate of 93% (X-ray) and 70% (CT) at final follow-up. CONCLUSION The SynFix-LR™ device is a suitable option for the treatment of monosegmental osteochondrosis at L4/5 and L5/S1 with comparable or superior results in comparison to posterior or combined fusion techniques.

When does intraoperative 3D-imaging play a role in transpedicular C2 screw placement?

INTRODUCTION The stabilization of an atlantoaxial (C1-C2) instability is demanding due to a complex atlantoaxial anatomy with proximity to the spinal cord, a variable run of the vertebral artery (VA) and narrow C2 pedicles. We perfomed the Goel & Harms fusion in combination with an intraoperative 3D imaging to ensure correct screw placement in the C2 pedicle. We hypothesized, that narrow C2 pedicles lead to a higher malposition rate of screws by perforation of the pedicle wall. The purpose of this study was to describe a certain pedicle size, under which the perforation rate rises. PATIENTS AND METHODS In this retrospective study, all patients (n=30) were operated in the Goel & Harms technique. The isthmus height and pedicle diameter of C2 were measured. The achieved screw position in C2 was evaluated according to Gertzbein & Robbin classification (GRGr). RESULTS A statistically significant correlation was found between the pedicles size (isthmus height/pedicle diameter) and the achieved GRGr for the right (p=0.002/p=0.03) and left side (p=0.018/p=0.008). The ROC analysis yielded a Cut Off value for the pedicle size to distinguish between an intact or perforated pedicle wall (GRGr 1 or ≥2). The Cut-Off value was identified for the isthmus height (right 6.1mm, left 5.4mm) and for the pedicle diameter (6.6mm both sides). CONCLUSION The hypothesis, that narrow pedicles lead to a higher perforation rate of the pedicle wall, can be accepted. Pedicles of <6.6mm turned out to be a risk factor for a perforation of the pedicle wall (GRGr 2 or higher). Intraoperative 3D imaging is a feasible tool to confirm optimal screw position, which becomes even more important in cases with thin pedicles. The rising risk of VA injury in these cases support the additional use of navigation.