Use of the sagittal Cobb* angle to guide the rod bending in the treatment of thoracolumbar fractures: a retrospective clinical study.

BACKGROUND: Pedicle screw fixation is a well-established technique for thoracolumbar fracture. A large number of studies have shown that the bending angle of the connecting rod has a significant correlation with the postoperative spinal stability. However, no studies have confirmed an objective indicator to guide the bending angle of the connecting rod during the operation. Our study aims to define a sagittal Cobb* angle to guide the bending angle of the connecting rod during surgery. METHODS: The frontal and lateral X-ray films in 150 cases of normal thoracolumbar spine were included to measure the normal spinal sagittal Cobb* angle in each segment. The patients who underwent single segment thoracolumbar fractures and pedicle screw internal fixation surgery were included. The radiological parameters included lumbar lordosis (LL), thoracic kyphosis (TK), pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), and sacral slope (SS) were measured. The incidence of adjacent segment degeneration (ASD) 2 years after surgery was measured. RESULTS: The average values of normal sagittal Cobb* angle in each segment were - 5.196 ± 3.318° (T12), 2.279 ± 3.324° (L1), 7.222 ± 2.798° (L2), and 12.417 ± 11.962° (L3), respectively. The LL in the three groups was 35.20 ± 9.12°, 46.26 ± 9.68°, and 54.24 ± 15.31°, respectively. Compared with the normal group, there were significant differences in group A and group C, respectively (p < 0.05). The results were similar in the parameters of TL, PT, and SS. The incidences of SVA > 50 mm in group A, group B, and group C were 23.33%, 12.50%, and 19.23%, respectively. The parameter of PI in three groups was 41.36 ± 12.69, 44.53 ± 15.27, and 43.38 ± 9.85°, respectively. The incidences of ASD in group A, group B, and group C 2 years after surgery were 21.67%, 13.75%, and 17.95%, respectively. CONCLUSIONS: The study confirmed that the sagittal Cobb* angle can be used as a reference angle for bending rods. When the bending angle of the connecting rod is 4 to 8° greater than the corresponding segment sagittal Cobb* angle, the patient's spinal sagittal stability is the best 2 years after the operation.

Extradural Contralateral C7 Nerve Root Transfer in a Cervical Posterior Approach for Treating Spastic Limb Paralysis: A Cadaver Feasibility Study.

STUDY DESIGN: Anatomic study in nine fresh-frozen cadavers. OBJECTIVE: To confirm the anatomical feasibility of transferring the extradural ventral roots (VRs) and dorsal roots (DRs) of contralateral C7 nerves to those of the ipsilateral C7 nerves respectively through a cervical posterior approach. SUMMARY OF BACKGROUND DATA: The contralateral C7 nerve root transfer technique makes breakthrough for treating spastic limb paralysis. However, its limitations include large surgical trauma and limited indications. METHODS: Nine fresh-frozen cadavers (four females and five males) were placed prone, and the feasibility of exposing the bilateral extradural C7 nerve roots, separation of the extradural C7 VR and DR, and transfer of the VR and DR of the contralateral C7 to those of the ipsilateral C7 on the dural mater were assessed. The pertinent distances and the myelography results of each specimen were analyzed. The acetylcholinesterase (AChE) and antineurofilament 200 (NF200) double immunofluorescent staining were preformed to determine the nerve fiber properties. RESULTS: A cervical posterior midline approach was made and the laminectomy was performed to expose the bilateral extradural C7 nerve roots. After the extradural C7 VR and DR are separated, the VR and DR of the contralateral C7 have sufficient lengths to be transferred to those of the ipsilateral C7 on the dural mater. The myelography results showed that the spinal cord is not compressed after the nerve anastomosis. The AChE and NF200 double immunofluorescent staining showed the distal ends of the contralateral C7 VRs were mostly motor nerve fibers, and the distal ends of the contralateral C7 DRs were mostly sensory nerve fibers. CONCLUSION: Extradural contralateral C7 nerve root transfer in a cervical posterior approach for treating spastic limb paralysis is anatomically feasible. LEVEL OF EVIDENCE: 5.

Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients.

BACKGROUND: Cachexia is a multifactorial syndrome that is highly prevalent in advanced cancer patients and leads to progressive functional impairments. The classification of cachexia stages is essential for diagnosing and treating cachexia. However, there is a lack of simple tools with good discrimination for classifying cachexia stages. Therefore, our study aimed to develop a clinically applicable cachexia staging score (CSS) and validate its discrimination of clinical outcomes for different cachexia stages. METHODS: Advanced cancer patients were enrolled in our study. A CSS comprising the following five components was developed: weight loss, a simple questionnaire of sarcopenia (SARC-F), Eastern Cooperative Oncology Group, appetite loss, and abnormal biochemistry. According to the CSS, patients were classified into non-cachexia, pre-cachexia, cachexia, and refractory cachexia stages, and clinical outcomes were compared among the four groups. RESULTS: Of the 297 participating patients, data from 259 patients were ultimately included. Based on the CSS, patients were classified into non-cachexia (n = 69), pre-cachexia (n = 68), cachexia (n = 103), and refractory cachexia (n = 19) stages. Patients with more severe cachexia stages had lower skeletal muscle indexes (P = 0.002 and P = 0.004 in male and female patients, respectively), higher prevalence of sarcopenia (P = 0.017 and P = 0.027 in male and female patients, respectively), more severe symptom burden (P < 0.001), poorer quality of life (P < 0.001 for all subscales except social well-being), and shorter survival times (P < 0.001). CONCLUSIONS: The CSS is a simple and clinically applicable tool with excellent discrimination for classifying cachexia stages. This score is extremely useful for the clinical treatment and prognosis of cachexia and for designing clinical trials.

Incidence of interstitial pneumonitis in non-Hodgkin's lymphoma patients receiving immunochemotherapy with pegylated liposomal doxorubicin and rituximab.

Pneumonitis is a rare but severe and potentially fatal adverse effect in chemotherapy of lymphoma. This study is aimed to investigate the incidence of interstitial pneumonitis in non-Hodgkin's lymphoma (NHL) patients receiving immunochemotherapy with pegylated liposomal doxorubicin and rituximab. Lymphoma patients were retrospectively reviewed, and eligible patients were included in this study. According to the chemotherapy regimens, patients were classified in four groups: combination of vincristine, cyclophosphamide, doxorubicin, and prednisone (CHOP group) with rituximab (RCHOP group) and combination of vincristine, cyclophosphamide, pegylated liposomal doxorubicin and prednisone (CDOP group) with rituximab (RCDOP group). Incidence and severity of interstitial pneumonitis were compared among the four groups. Among 757 patients reviewed, 207 patients were included in final analysis. Thirteen patients developed chemotherapy-induced interstitial pneumonitis, and the mean cycle of chemotherapy before the onset of pneumonitis was 4. Incidence rates of pneumonitis were 0, 1.8, 17.4, and 21.1% in CHOP, RCHOP, CDOP, and RCDOP groups, respectively (p < 0.001). The mean grades of pneumonitis were 0, 2, 2.5, and 3 in four groups, respectively (p < 0.001). After adjustment of confounders, chemotherapy regimens (OR 3.491, 95% CI 1.527-7.981, p = 0.003) and neutropenia in previous cycles (OR 2.186, 95% CI 1.281-3.731, p = 0.004) were independently associated with the incidence of pneumonitis. Interstitial pneumonitis should be highlighted in NHL patients who received more than 4 cycles of RCDOP chemotherapy regimen, especially in those who had grade 4 neutropenia in the previous cycles of chemotherapy.

Evaluation of changes in lumbar neuroforaminal dimensions in symptomatic young adults using positional MRI.

PURPOSE: To investigate the changes of lumbar neural foramina size during dynamic motion using positional MRI. METHODS: Two hundred and fifty neural foramina from 50 patients were analyzed. Lumbar foraminal height, width, and area parameters from L1 to S1 were evaluated for changes in extension, neutral, and flexion positions on T2 parasagittal positional MRI images, and were correlated to lumbar angular motion. One-way analysis of variance (ANOVA) and post hoc analysis were used to examine the differences between levels and positions. RESULTS: Compared to the neutral position, almost all lumbar foraminal parameters (height, width at inferior level, and area) increased in flexion and decreased in extension at all levels, except for L5-S1 foraminal width at superior and middle levels. The foraminal height and area in all lumbar segments except L5-S1 increased as the lumbar angular motion changed from extension to flexion in <40° group. The foraminal width increased significantly at L3-4 and L4-5 among all groups. CONCLUSION: Lumbar foraminal dimensions increased in flexion compared to neutral and extension positions. Lumbar angular motion contributed to the changes of foraminal height and area at most of the segments, while it affected foraminal width only at L3-4 and L4-5. This information can be useful in the understanding of patient symptoms and the correlation with the imaging studies with dynamic foraminal stenosis. Furthermore, data from our study may help with patient positioning for foraminal injections or endoscopic surgery.

Differences in Symptom Burden Among Cancer Patients With Different Stages of Cachexia.

CONTEXT: Cancer patients with cachexia may suffer from significant burden of symptoms and it can severely impair patients' quality of life. However, only few studies have targeted the symptom burden in cancer cachexia patients, and whether the symptom burden differed in different cachexia stages is still unclear. OBJECTIVES: The aims of this study were to evaluate the symptom burden in cancer cachexia patients and to compare the severity and occurrence rates of symptoms among cancer patients with non-cachexia, pre-cachexia, cachexia, and refractory cachexia. METHODS: Advanced cancer patients (n = 306) were included in this cross-sectional study. Patients were divided into four groups, based on the cachexia stages of the international consensus. The M.D. Anderson Symptom Inventory added with eight more cachexia-specific symptoms were evaluated in our patients. Differences in symptom severity and occurrence rates among the four groups were compared using one-way ANOVA or Kruskal-Wallis test analyses. RESULTS: Lack of appetite, disturbed sleep, fatigue, lack of energy, and distress were the symptoms with highest occurrence rates and severity scores in all four groups and were exacerbated by the severity of cachexia stages. After confounders were adjusted for, significant differences were seen in symptoms of pain, fatigue, disturbed sleep, remembering problems, lack of appetite, dry mouth, vomiting, numbness, feeling dizzy, early satiety, lack of energy, tastes/smell changes, and diarrhea. CONCLUSION: This study identified higher symptom burden in cancer patients with cachexia and it increased with the stages of cachexia, which emphasized the importance of screening in multiple co-occurring symptoms for cachexia patients.

Validation of the Chinese version of functional assessment of anorexia-cachexia therapy (FAACT) scale for measuring quality of life in cancer patients with cachexia.

PURPOSE: The assessment of quality of life (QOL) is an important part of cachexia management for cancer patients. Functional assessment of anorexia-cachexia therapy (FAACT), a specific QOL instrument for cachexia patients, has not been validated in Chinese population. The aim of this study was to validate the FAACT scale in Chinese cancer patients for its future use. METHODS: Eligible cancer patients were included in our study. Patients' demographic and clinical characteristics were collected from the electronic medical records. Patients were asked to complete the Chinese version of FAACT scale and the MD Anderson symptom inventory (MDASI), and then the reliability and validity were analyzed. RESULTS: A total of 285 patients were enrolled in our study, data of 241 patients were evaluated. Coefficients of Cronbach's alpha, test-retest and split-half analyses were all greater than 0.8, which indicated an excellent reliability for FAACT scale. In item-subscale correlation analysis and factor analysis, good construct validity for FAACT scale was found. The correlation between FAACT and MDASI interference subscale showed reasonable criterion-related validity, and for further clinical validation, the FAACT scale showed excellent discriminative validity for distinguishing patients in different cachexia status and in different performance status. CONCLUSIONS: The Chinese version of FAACT scale has good reliability and validity and is suitable for measuring QOL of cachexia patients in Chinese population.

YAP and ERK mediated mechanical strain-induced cell cycle progression through RhoA and cytoskeletal dynamics in rat growth plate chondrocytes.

Yes-associated protein (YAP) and extracellular signal-regulated kinase (ERK) have been considered as key regulators in tissue homeostasis, organ development, and tumor formation. However, the roles of YAP and ERK in the mediating strain mechanosensing in the growth plate cartilage have not been determined. In this study, chondrocytes obtained from the growth plate cartilage of 2-week-old Sprague-Dawley rats were subjected to the mechanical strain with different magnitudes and durations at a frequency of 0.5 Hz. We found that YAP and ERK activation in response to mechanical strain was time and magnitude dependent. Pretreatment with a RhoA inhibitor (C3 toxin) or a microfilament cytoskeleton disrupting reagent (cytochalasin D) could suppress their activation. In addition, activated YAP and ERK were able to induce cell cycle progression by up-regulating the expression of cell cycle-related genes. These results shed new light on the function of YAP and ERK in mechanical strain-promoted growth plate development. Our results also provided evidence that RhoA and cytoskeletal dynamics are required for this mechanotransduction. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1121-1129, 2016.

The effect of electromagnetic fields on the proliferation and the osteogenic or adipogenic differentiation of mesenchymal stem cells modulated by dexamethasone.

Although glucocorticoids provide benefits for inflammation or autoimmune disorders, high-dose and long-term use could cause osteonecrosis or osteoporosis as adverse effect for patients. Electromagnetic field (EMF) treatments have been clinically used for many years to promote fracture healing, but whether EMF can attenuate the deleterious effects of glucocorticoids is not clear. In this study, the effects of different concentrations of dexamethasone (DEX) on proliferation and adipogenic or osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were detected and compared, and the effects of EMF treatment (15 Hz, 1 mT, 4 h/day) on 0.1 µM DEX-modulated BMSCs' proliferation and adipogenic or osteogenic differentiation were investigated. Higher concentrations of DEX (0.1 and 1 µM) inhibited proliferation of BMSCs but promoted expression of adipogenic-related genes, increasing the number of lipid droplets. In the early stage of differentiation, DEX restrained expression of RUNX2 and alkaline phosphatase (ALP), but amplified expression of ALP and osteopontin (OPN) in the late stage. EMF treatment of BMSCs influenced by 0.1 µM DEX inhibited the high expression of adipogenic-related genes, stimulated the expression of RUNX2, ALP, OPN, and osteocalcin, and increased the activity of ALP. EMF exposure augmented the expression of p-ERK, which DEX reduced. After using mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway inhibitor, U0126, the effect of EMF was reduced. In conclusion, EMF exposure accelerates BMSCs proliferation, inhibits adipogenic differentiation, and promotes osteogenic differentiation of BMSCs modulated by DEX, and these effects are mediated at least in part by MEK/ERK signaling pathway.

Hedgehog pathway inhibitor-4 suppresses malignant properties of chondrosarcoma cells by disturbing tumor ciliogenesis.

Chondrosarcoma is a type of malignant bone tumor secreting cartilage-like matrix. In clinical treatment, there is no frequently used drug treatment option except for surgical resection. Hedgehog (HH) pathway is a classical signaling pathway that regulates normal cartilage cell development. In order to detect the role that HH pathway plays in chondrosarcoma, we used immunohistochemistry and found this tumor clearly expressed HH pathway-related proteins. Treatment with HH pathway inhibitor-4 (HPI-4) could significantly decrease human chondrosarcoma cell proliferation, invasion and migration ability. Furthermore, HPI-4 could distinctly disturb HH pathway-mediated ciliogenesis and suppress primary cilia-related protein intraflagellar transport protein IFT88 expression. HH downstream effect molecular GLI2 was restrained to block parathyroid hormone-related protein and affect MAPK/ERK-regulated matrix metalloproteinases (MMP2 and MMP9). These results indicated that activated HH pathway existed in chondrosarcoma and HPI-4 could be a new therapeutic option specific to chondrosarcoma expressing elevated levels of HH pathway.

Regulation of PTHrP expression by cyclic mechanical strain in postnatal growth plate chondrocytes.

Mechanical loading has been widely considered to be a crucial regulatory factor for growth plate development, but the exact mechanisms of this regulation are still not completely understood. In the growth plate, parathyroid hormone-related protein (PTHrP) regulates chondrocyte differentiation and longitudinal growth. Cyclic mechanical strain has been demonstrated to influence growth plate chondrocyte differentiation and metabolism, whereas the relationship between cyclic mechanical strain and PTHrP expression is not clear. The objective of this study was to investigate whether short-term cyclic tensile strain regulates PTHrP expression in postnatal growth plate chondrocytes in vitro and to explore whether the organization of cytoskeletal F-actin microfilaments is involved in this process. To this end, we obtained growth plate chondrocytes from 2-week-old Sprague-Dawley rats and sorted prehypertrophic and hypertrophic chondrocytes using immunomagnetic beads coated with anti-CD200 antibody. The sorted chondrocytes were subjected to cyclic tensile strain of varying magnitude and duration at a frequency of 0.5 Hz. We found that cyclic strain regulates PTHrP expression in a magnitude- and time-dependent manner. Incubation of chondrocytes with cytochalasin D, an actin microfilament-disrupting reagent, blocked the induction of PTHrP expression in response to strain. The results suggest that short-term cyclic tensile strain induces PTHrP expression in postnatal growth plate prehypertrophic and hypertrophic chondrocytes and that PTHrP expression by these chondrocytes may subsequently affect growth plate development. The results also support the idea that the organization of cytoskeletal F-actin microfilaments plays an important role in mechanotransduction.

Comparative study of the osteogenic differentiation capacity of human bone marrow- and human adipose-derived stem cells under cyclic tensile stretch using quantitative analysis.

Studies comparing the osteogenic differentiation capacity of human bone marrow-derived stem cells (hBMSCs) and human adipose-derived stem cells (hASCs) cultured in osteogenic differentiation medium have been inconclusive. Apart from chemical stimuli, mechanical stimuli have also been shown to be important in bone tissue engineering, which is referred to as functional bone tissue engineering. hBMSCs and hASCs have been shown to be sensitive to both chemical and mechanical stimuli. In an attempt to find a better seed cell in functional bone tissue engineering, we tried to quantify the osteogenic differentiation capacity of hBMSCs and hASCs under both mechanical and chemical stimuli. In this study, hBMSCs and hASCs were isolated from the same volunteers. Cells were cultured in osteogenic differentiation medium with and without exposure to cyclic tensile stretch (CTS). Quantitative measurement of alkaline phosphatase (ALP) activity revealed that the osteogenic differentiation capacity of hBMSCs was similar to that of hASCs in the early phase of differentiation in the CTS-stimulated groups. Quantitative measurement of mineralization showed that the late-phase osteogenic differentiation capacity of the hBMSCs was superior to that of hASCs in the CTS-stimulated groups. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed 5 and 10 days after cell culture. The results of the RT-PCR revealed that the osteogenic differentiation capacity of hASCs was inferior to that of hBMSCs both in the CTS-stimulated and unstimulated groups. All the results showed that both hBMSCs and hASCs were sensitive to CTS during the osteogenic differentiation process. This study compared the osteogenic differentiation capacity of hBMSCs and hASCs in response to mechanical stimulations and has important implications for the use of stem cells in functional bone tissue engineering and regenerative medicine.