Four-Level Cervical Disc Arthroplasty.

BACKGROUND: Multilevel anterior cervical discectomy and fusion inevitably yields a higher chance of pseudarthrosis or require more reoperations than single-level procedures. Therefore, multilevel cervical disc arthroplasty (CDA) could be an alternative surgery for cervical spondylosis, as it (particularly 3- and 4-level CDA) could preserve more functional motility than single-level disc diseases. This study aimed to investigate the clinical and radiological outcomes of 4-level CDA, a relatively infrequently indicated surgery. METHODS: The medical records of consecutive patients who underwent 4-level CDA were retrospectively reviewed. These highly selected patients typically had multilevel disc herniations with mild spondylosis. The inclusion criteria were symptomatic cervical spondylotic myelopathy, radiculopathy, or both, that were medically refractory. The clinical outcomes were assessed. The radiographic outcomes, including global and individual segmental range of motion (ROM) at C3-7, and any complications were also analyzed. RESULTS: Data from a total of 20 patients (mean age: 56 ± 8 years) with an average follow-up of 34 ± 20 months were analyzed. All patients reported improved clinical outcomes compared with that of preoperation, and the ROMs at C3-7 were not only preserved but also trended toward an increase (35 ± 8 vs 37 ± 10 degrees, pre- vs postoperation, P = 0.271) after the 4-level CDA. However, global cervical alignment remained unchanged. There was one permanent C5 radiculopathy, but no other neurological deteriorations or any reoperations occurred. CONCLUSION: For these rare but unique indications, 4-level CDA yielded clinical improvement and preserved segmental motility with low rates of complications. Four-level CDA is a safe and effective surgery, maintaining the ROM in patients with primarily disc herniations and mild spondylosis. CLINICAL RELEVANCE: For patients with mild spondylosis, whose degeneration at the cervical spine is not so severe, CDA is more suitable.

Assessing Range of Motion Gap in Circumferential Surgery for Cervical Myelopathy due to Ossification of the Posterior Longitudinal Ligament.

OBJECTIVE: Only a few studies have investigated the gap range of motion (gROM) in cervical myelopathy or deformity caused by ossification of the posterior longitudinal ligament (OPLL). The aim of this study is to investigate the correlation between the individual gROM and the postoperative clinical outcomes of patients with OPLL. METHODS: Consecutive patients of cervical myelopathy caused by OPLL were analyzed retrospectively. The clinical outcomes were evaluated using Visual Analogue Scale scores of the neck and arm pain and the Japanese Orthopaedic Association scores. Radiologic measurements included flexion ROM (fROM), which was defined as the difference of cervical lordosis in flexion and neutral positions, extension ROM (eROM), defined as the difference between neutral and extension positions, and gROM, defined as the difference between fROM and eROM. Patients were grouped by the values of gROM, and comparisons of all outcomes were made between the groups. RESULTS: A total of 42 patients underwent surgery. The patients with greater gROM did not differ from those with smaller gROM by demographic characteristics. During follow-up (mean 45.8 months), both groups had similar improvements, but the C5 palsy rates were higher in the greater gROM group than in the smaller gROM group (71% and 22%, P < 0.05). CONCLUSIONS: Simultaneous circumferential decompression and fixation is an effective surgical option for patients with cervical myelopathy caused by OPLL. A higher rate of postoperative C5 palsy was observed in the patients with greater gROMs after surgery, although all patients presented with similar clinical improvements.

Comparison of intraoperative cone-beam CT versus preoperative fan-beam CT for navigated spine surgery: a prospective randomized study.

OBJECTIVE: This prospective randomized study aimed to investigate the accuracy, radiation exposure, and surgical workflow optimization of a novel intraoperative spinal navigation system using preoperative fan-beam (FB) CT versus the classic intraoperative cone-beam (CB) CT in patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: In this two-arm, single-center, randomized study, the authors evaluated the safety and clinical outcomes of a novel navigation system for pedicle screw placement in spine surgery. RESULTS: The accuracy of pedicle screw placement in the experimental group (FB group) was 94.38%, while it was 94.55% in the control group (CB group). Notably, the intraoperative radiation exposure to patients in the FB CT group (mean 0.361 ± 0.261 mSv) was significantly lower than that in the CB CT group (mean 6.526 ± 13.591 mSv) (p < 0.0001). Furthermore, the intraoperative preparation time for screw placement in the FB group (mean 10.6 ± 5.62 minutes) was significantly lower than that in the CB group (mean 17.6 ± 5.59 minutes) (p = 0.0004). No significant differences were observed for blood loss during surgery, total radiation exposure to surgeons, mean time for inserting a single pedicle screw, revision surgery rate, patients' reported outcomes, and length of postoperative hospital stay between the two groups. Significant differences were observed for intraoperative radiation exposure to patients and the preparation time for pedicle screw placement. CONCLUSIONS: The preoperative FB CT-based intraoperative spinal navigation system demonstrated comparable accuracy and safety when compared with the intraoperative CB CT-based system. Moreover, the FB CT-based system had a shorter time for screw placement and reduced intraoperative radiation exposure to patients. These findings support the potential benefits of adopting this novel navigation system to enhance surgical precision and reduce radiation-related risks in MIS-TLIF procedures.

Cervical disc arthroplasty for magnetic resonance-evident cervical spondylotic myelopathy: comparison with anterior cervical discectomy and fusion.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is a standard surgical approach for cervical spondylotic myelopathy (CSM) caused by disc herniations. Although cervical disc arthroplasty (CDA) has become, in the past decade, a viable alternative to ACDF in selected patients, the differences among patients with CSM treated with CDA and ACDF remain elusive. The effectiveness of motion preservation devices in CSM is also unclear. METHODS: Adult patients who underwent 1- or 2-level CDA or ACDF between 2007 and 2021 were retrospectively reviewed. Patients whose preoperative T2-weighted MRI demonstrated increased intramedullary signal intensity (IISI) were included and analyzed for the following: comparison of the length of IISI on pre- and postoperative MR images as well as range of motion (ROM) at the indexed levels between the CDA and ACDF groups. Measurement for clinical outcomes included the visual analog scale (VAS) of the arm and neck, the Neck Disability Index, and modified Japanese Orthopaedic Association scores. Perioperative clinical data were also compared between the two groups. RESULTS: A total of 122 patients were allocated to the CDA group and 108 to the ACDF group, with mean follow-ups of 46.6 and 39.0 months, respectively. Patients in the CDA group were younger than those in the ACDF group (47.64 ± 12.40 vs 61.73 ± 12.25 years, p < 0.001) (mean ± SD). The ACDF group had more 2-level surgery compared to the CDA group (p = 0.002). Both groups had significant regression of IISI on postoperative MRI compared to that of preoperative imaging (CDA: 1.23 ± 0.84 to 0.28 ± 0.39 cm; ACDF: 1.07 ± 0.60 to 0.37 ± 0.42 cm; both p < 0.001). The decrease in the length of IISI was similar between the two groups (p = 0.058). The postoperative ROM was well preserved in the CDA group (superior to ACDF, which yielded minimal ROM postoperatively). Both the CDA and ACDF groups demonstrated improvement in Neck Disability Index and modified Japanese Orthopaedic Association scores at 24 months postoperatively. The CDA group had significant improvements on VAS scores, whereas the improvement did not reach significance for the ACDF group at 24 months postoperatively. CONCLUSIONS: Significant shortening of IISI on T2-weighted MRI was demonstrated after both CDA and ACDF. At 24 months postoperatively, all clinical outcomes demonstrated improvement after both strategies, except that the VAS score was not significantly improved for ACDF. Therefore, CDA is a safe and effective option for patients with MR-evident CSM.

5,6-Dichloro-1-ß-D-ribofuranosylbenzimidazole (DRB) induces apoptosis in breast cancer cells through inhibiting of Mcl-1 expression.

The effective treatment of breast cancer remains a profound clinical challenge, especially due to drug resistance and metastasis which unfortunately arise in many patients. The transcription inhibitor 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB), as a selective inhibitor of cyclin-dependent kinase 9, was shown to be effective in inducing apoptosis in various hematopoietic malignancies. However, the anticancer efficacy of DRB against breast cancer is still unclear. Herein, we demonstrated that administration of DRB to the breast cancer cell line led to the inhibition of cellular proliferation and induction of the typical signs of apoptotic cells, including the increases in Annexin V-positive cells, DNA fragmentation, and activation of caspase-7, caspase-9, and poly (ADP ribose) polymerase (PARP). Treatment of DRB resulted in a rapid decline in the myeloid cell leukemia 1 (Mcl-1) protein, whereas levels of other antiapoptotic proteins did not change. Overexpression of Mcl-1 decreased the DRB-induced PARP cleavage, whereas knockdown of Mcl-1 enhanced the effects of DRB on PARP activation, indicating that loss of Mcl-1 accounts for the DRB-mediated apoptosis in MCF-7 cells, but not in T-47D. Furthermore, we found that co-treatment of MCF-7 cells with an inhibitor of AKT (LY294002) or an inhibitor of the proteasome (MG-132) significantly augmented the DRB-induced apoptosis. These data suggested that DRB in combination with LY294002 or MG-132 may have a greater therapeutic potency against breast cancer cells.

Comparative Study of the Cytokine Profiles of Serum and Tissues from Patients with the Ossification of the Posterior Longitudinal Ligament.

BACKGROUND: The ossification of the posterior longitudinal ligament (OPLL) is one of the contributing factors leading to severe cervical spondylotic myelopathy (CSM). The mechanism causing ossification is still unclear. The current study was designed to analyze the specimens of patients with or without OPLL. METHODS: The study collected 51 patients with cervical spondylosis. There were six serum samples in both the non-OPLL (NOPLL) and OPLL groups. For tissue analysis, there were seven samples in the NOPLL group and five samples in the OPLL group. The specimens of serum and tissue were analyzed by using Human Cytokine Antibody Arrays to differentiate biomarkers between the OPLL and NOPLL groups, as well as between serum and OPLL tissue. Immunohistochemical staining of the ligament tissue was undertaken for both groups. RESULTS: For OPLL vs. NOPLL, the serum leptin levels are higher in the OPLL group, corroborating others' observations that it may serve as a disease marker. In the tissue, angiogenin (ANG), osteopontin (OPN), and osteopro-tegerin (OPG) are higher than they are in the OPLL group (p < 0.05). For serum vs. OPLL tissue, many chemotactic cytokines demonstrated elevated levels of MIP1 delta, MCP-1, and RANTES in the serum, while many cytokines promoting or regulating bone genesis were up-regulated in tissue (oncostatin M, FGF-9, LIF, osteopontin, osteoprotegerin, TGF-beta2), as well as the factor that inhibits osteoclastogenesis (IL-10), with very few cytokines responsible for osteoclastogenesis. Molecules promoting angiogenesis, including angiotensin, vEGF, and osteoprotegerin, are abundant in the OPLL tissue, which paves the way for robust bone growth.

Comparison of Cortical Bone Trajectory to Pedicle-Based Dynamic Stabilization: An Analysis of 291 Patients.

OBJECTIVE: Pedicle-based dynamic stabilization (DS) has gained popularity outside of America. Although pedicle screw (PS) loosening has always been a concern, it is reportedly innocuous. Cortical bone trajectory (CBT) screw is an emerging option with less invasiveness and similar effectiveness to PS in short-segment lumbar fusion. This study aimed to verify the use of CBT for DS by comparing the outcomes between pedicle- and CBT-based DS. METHODS: Consecutive patients with lumbar spondylosis or low-grade spondylolisthesis who underwent 1- or 2-level DS between L3-5 with a minimum follow-up of 24 months were reviewed. Screw loosening was determined by computed tomography and the incidences were compared. RESULTS: A total of 291 patients who underwent Dynesys DS (235 pedicle- and 56 CBT-based, respectively) were compared. The demographics and preoperative conditions were similar. All the clinical outcomes improved at 24-month postoperation, while the CBT-based group had less operation time and blood loss than the pedicle-based group. The rates of screw loosening were lower in the CBT-based (5.4% per screw and 12.5% per patient) than the pedicle-based group (9% per screw and 26.4% per patient). Furthermore, there were no differences in the clinical outcomes and complication profiles. CONCLUSION: The CBT-based DS for 1- or 2-level lumbar degeneration demonstrated equivalent clinical improvement as the pedicle-based DS. The adaption of CBT-based screws for DS could be a less invasive approach (shorter operation time and less blood loss), with lower chances of screw loosening than the conventional PS-based DS.

Incidence and Risk Factor of Implant Dislocation After Cervical Disk Arthroplasty: A Retrospective Cohort Analysis of 756 Patients.

BACKGROUND: Implant dislocation after cervical disk arthroplasty (CDA) is obviously a critical complication, but no information about the incidence and associated risk factor has been reported. OBJECTIVE: To investigate the incidence and risk factor of implant dislocation after CDA by a retrospective cohort analysis. METHODS: A retrospective review of a consecutive series of CDA performed between January 2009 and March 2021 at a single institution was conducted. Analyses of chart records and radiological data established the incidence and associated risk factor of implant dislocation after CDA. A Kaplan-Meier survival estimation of implant survival was performed. RESULTS: A total of 756 consecutive patients were included in this analysis. Five patients (0.7%) had a migration and even dropout of the artificial disk. The overall cumulative survival rate of the implant reached approximately 99.3% of the 756 patients. Preoperative kyphosis was significantly related to implant dislocation ( P = .016), with an odds ratio of 15.013. CONCLUSION: The incidence of implant dislocation after CDA is as low as 0.7% or 5/756 patients. Preoperative kyphosis significantly increases the risk of postoperative implant dislocation by a factor of 15. The migrating implants could be revealed on radiographs as early as 0.9 to 1.4 months postoperatively and were revised to anterior cervical diskectomy and fusion within half a year. No new event of implant dislocation occurred half a year postoperatively. The overall cumulative survival rate of the implant reached 99.3% of the 756 patients. In conclusion, CDA remains a safe and reliable procedure.

Nature or nurture: a latent ossification of the posterior longitudinal ligament after atlantoaxial fusion. Illustrative case.

BACKGROUND: The natural history of ossification of the posterior longitudinal ligament (OPLL) remains poorly understood and multiple etiologies have been reported. However, most have focused on the characteristics of the patient rather than alternation of mechanical stress after spinal fusion. OBSERVATIONS: This report describes, for the first time, a de novo OPLL found at the subaxial cervical spine 7 years after an atlantoaxial fusion surgery. A 57-year-old female initially required atlantoaxial arthrodesis for os odontoideum and stenosis that caused myelopathy. The posterior fusion surgery went smoothly without complications and the patient had good recovery of neurological functions. There was no associated instability, trauma, or reoperations during the follow-up. Seven years later, the patient presented with slight neck pain and a newly developed OPLL at C3-4 caudal to the C1-2 fusion construct. LESSONS: Conflicting with the conventional concept that OPLL is common in elderly men with genetic or hormonal factors, or associated spondyloarthropathies, OPLL could develop in women even after solid C1-2 fusion. The adjacent subaxial cervical spine is not free of risks for subsequent development of OPLL and cervical spondylotic myelopathy. This case illustration extends the scope of etiologies of OPLL within the present literature.

Anterior Bone Loss in Cervical Disc Arthroplasty Correlates with Increased Cervical Lordosis.

OBJECTIVE: Although cervical disc arthroplasty (CDA) has reportedly been associated with similarly low incidences of complications to anterior cervical discectomy and fusion, the phenomenon of anterior bone loss (ABL) is unique to CDA and has only recently gained notice. This study thus aimed to investigate the incidence of ABL and its correlation with cervical alignment post-operation. METHODS: Consecutive patients who received CDA for herniated disc or spondylosis were retrospectively reviewed. The development and extent of ABL was detected by comparison of preoperative and postoperative serial images for the relative position of the anterior vertebral body with the CDA devices and graded into 3 levels: grade 1 (minor bone loss), grade 2 (anterior portion of the vertebral body without exposure of the artificial disc), and grade 3 (anterior portion of the vertebral body with exposure of the device). RESULTS: A total of 41 patients were analyzed with a mean follow-up of 24.1 months. Under serial radiologic examinations during follow-up, all patients (41 of 41 = 100%) had bone loss of various degrees, with grade 3 ABL the most common (30 of 41 = 73.1%). There were 8 and 3 patients who had grades 2 and 1 ABL, respectively. The changes of the Cobb angle (ΔCobb) trended towards higher grades of ABL. CONCLUSIONS: During the mean follow-up of 2 years, ABL was a common radiologic finding. More than half of the patients (26 of 41, 63.4%) in the series gained cervical lordosis (ΔCobb >0) after CDA. These patients with increased cervical lordosis (ΔCobb >0) after CDA had higher grades of ABL.

Exercise effects on fatigue in breast cancer survivors after treatments: A systematic review and meta-analysis.

AIM: The aim of this study is to explore the effects of exercise interventions by type, duration and intensity of exercise for fatigue in breast cancer survivors who had completed their treatment. BACKGROUND: Most studies found that exercise has valuable outcomes for cancer survivors. This meta-analysis comprehensively summarizes the benefits of exercise intervention for fatigue in breast cancer patients who had completed their adjuvant treatments. METHODS: We conducted a meta-analysis on randomized control trials published during 1 January 2000 through 31 December 2019, from PubMed, Cochrane Library databases, EMBASE, Medline (ProQuest), CINAHL, PsycINFO, Chinese Electronic Periodical Service and Wan Fan Data with prespecified searching criteria. Breast cancer patients earlier than stage IIIc and completing adjuvant treatments were included, and the effects of exercise on fatigue were investigated. RESULTS: Nine randomized controlled trials (RCTs) were included (N = 581). Patients receiving exercise interventions showed reduced fatigue comparing with those without exercise. Exercise with low-moderate intensity, 20 min/day, three times per week and lasting up to 12 weeks had a significant effect on reducing fatigue for breast cancer survivors. CONCLUSION: Our study suggested that exercise interventions can reduce fatigue for this group of cancer survivors. The duration and intensity of exercise intervention could be prescribed for this specific group of cancer patients as a basic requirement to handle their reported fatigue.

Cortical Bone Trajectory-Based Dynamic Stabilization.

BACKGROUND: Cortical bone trajectory (CBT) screws have demonstrated similar biomechanical strength and fusion rates as conventional pedicle screws for short-segment lumbar fusion. However, very few studies have verified the viability of CBT screws in dynamic stabilization. In the present study, we compared the clinical outcomes of CBT-based Dynesys dynamic stabilization (CBT-DDS) with standard minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). METHODS: Consecutive patients who had undergone CBT-DDS or MI-TLIF at L4-L5 or L3-L5 were retrospectively reviewed. All the radiological and clinical outcomes were compared between the 2 groups. The patient-reported outcomes included the visual analog scale scores for back and leg pain, Japanese Orthopaedic Association scores, and Oswestry disability index. The pre- and postoperative radiological evaluations were also reviewed. RESULTS: A total of 60 patients (20 patients in the CBT-DDS and 40 in the MI-TLIF groups) were analyzed. The MI-TLIF group had required a longer operation time (P = 0.010) than the CBT-DDS group but had had a similar estimated blood loss (P = 0.484). The perioperative complications, including screw loosening, wound infection, and radiculopathy, were similar in both groups (P > 0.05 for all). The degree of decreased range of motion after surgery was similar between the 2 groups (P = 0.781), and no pseudarthrosis developed in the MI-TLIF group. CONCLUSIONS: Because the clinical and radiological outcomes of CBT-DDS were similar to those of MI-TLIF in patients with L4-L5 or L3-L5 spondylosis and spondylolisthesis, CBT-DDS appears to be a viable and effective alternative to MI-TLIF, with a shorter operation time and similarly limited segmental motility.

Measurement of Deformity at the Craniovertebral Junction: Correlation of Triangular Area and Myelopathy.

OBJECTIVE: Diseases of the craniovertebral junction (CVJ) are commonly associated with deformity, malalignment, and subsequent myelopathy. The misaligned CVJ might cause compression of neuronal tissues and subsequently clinical symptoms. The triangular area (TA), measured by magnetic resonance imaging/images (MRI/s), is a novel measurement for quantification of the severity of compression to the brain stem. This study aimed to assess the normal and pathological values of TA by a comparison of patients with CVJ disease to age- and sex-matched controls. Moreover, postoperative TAs were correlated with outcomes. METHODS: Consecutive patients who underwent surgery for CVJ disease were included for comparison to an age- and sex-matched cohort of normal CVJ persons as controls. The demographics, perioperative information, and pre- and postoperative 2-year cervical MRIs were collected for analysis. Cervical TAs were measured and compared. RESULTS: A total of 201 patients, all of whom had pre- or postoperative MRI, were analyzed. The TA of the CVJ deformity group was larger than the healthy control group (1.62 ± 0.57 cm2 vs. 1.01 ± 0.18 cm2, p < 0.001). Moreover, patients who had combined anterior odontoidectomy and posterior laminectomy with fixation had the greatest reduction in the TA (1.18 ± 0.58 cm2). CONCLUSION: In CVJ deformity, the measurement of the cervical TA could indicate the severity of brain stem compression. After surgery, the TA had a varying degree of improvement, which could represent the efficacy of surgery.

Correlation of bone density to screw loosening in dynamic stabilization: an analysis of 176 patients.

Although osteoporosis has negative impacts on lumbar fusion, its effects on screw loosening in dynamic stabilization remain elusive. We aimed to correlate bone mineral density (BMD) with screw loosening in Dynesys dynamic stabilization (DDS). Consecutive patients who underwent 2- or 3-level DDS for spondylosis, recurrent disc herniations, or low-grade spondylolisthesis at L3-5 were retrospectively reviewed. BMD was assessed by the Hounsfield Unit (HU) in vertebral bodies (VB) and pedicles with and without cortical bone (CB) on pre-operative computed tomography (CT). Screw loosening was assessed by radiographs and confirmed by CT. HU values were compared between the loosened and intact screws. 176 patients and 918 screws were analyzed with 78 loosened screws found in 36 patients (mean follow-up: 43.4 months). The HU values of VB were similar in loosened and intact screws (p = 0.14). The HU values of pedicles were insignificantly less in loosened than intact screws (including CB: 286.70 ± 118.97 vs. 297.31 ± 110.99, p = 0.45; excluding CB: 238.48 ± 114.90 vs. 240.51 ± 108.91, p = 0.88). All patients had clinical improvements. In conclusion, the HU values, as a surrogate for BMD, were unrelated to screw loosening in DDS. Therefore, patients with compromised BMD might be potential candidates for dynamic stabilization rather than fusion.

Late complication of cervical disc arthroplasty: heterotopic ossification causing myelopathy after 10 years. Illustrative case.

BACKGROUND: Heterotopic ossification (HO) is a well-documented complication of cervical disc arthroplasty (CDA), although it rarely causes adverse clinical effects. Despite high-grade HO possibly limiting segmental mobility, it is reportedly seldom associated with symptoms. OBSERVATIONS: The authors report a case of a 46-year-old male patient who underwent hybrid CDA and anterior cervical discectomy and fusion for 3-level cervical disc herniation that caused myeloradiculopathy. The surgery was successful; the patient experienced nearly complete recovery postoperatively. The follow-up images, including computed tomography and magnetic resonance imaging scans, showed satisfactory decompression at the indexed levels without residual osteophytes or ossification of the posterior longitudinal ligament. However, 10 years later, the patient presented with symptomatic compressive myelopathy caused by severe HO that prompted a secondary surgery. LESSONS: Although it is generally reported in the literature that HO is clinically innocuous, in this patient, it gradually and progressively developed and caused myelopathy, requiring a secondary surgery. Symptomatic HO can be expected over time, and patients with a high risk of HO deserve long-term follow-up after CDA. Further investigations are warranted to corroborate these risk factors, including multilevel calcified disc herniation, severe spondylosis, and suboptimal placement of the device during primary CDA surgery.