Clinical study of preoperative skeletal muscle mass as a predictor of physical performance recovery following palliative surgery for spinal metastases.

BACKGROUND: Surgical treatment of spinal metastases has been associated with high morbidity and mortality in patients with sarcopenia based on low skeletal muscle mass. We assessed physical performance using the Eastern Cooperative Oncology Group performance status scale and the Barthel Index on the 30th day after palliative surgery for spinal metastases and investigated the effectiveness of surgery according to sarcopenia assessed by skeletal muscle mass. METHODS: We retrospectively analyzed 78 consecutive patients with thoracic and lumbar spinal metastases who underwent palliative surgery. The value of the area of the psoas major muscle at the L3 level normalized by the vertebral area was divided into first, middle, and third tertiles. Clinical variables were compared by tertile. Variables affecting the 30-day good performance status were investigated with univariate and multivariate analyses. RESULTS: The 30-day morbidity rates were 50%, 38.5%, and 15.4% by tertile. The 30-day mortality rate was 2%; all were in the first tertile. Good preoperative performance status scores were seen in 15.4% of first and 50% of third tertile patients. Postoperatively, the performance status improved in all groups, with 30.8%, 65.4%, and 92.3% by tertile. Multivariate regression analysis revealed that a good preoperative performance status (OR: 15.50, 95% CI: 1.610-149.00, P < 0.05) and the value of the area of the psoas major muscle at the L3 level normalized by the vertebral area not in the first tertile (OR: 0.22, 95% CI: 0.06-0.82, P < 0.05) were significant predictors of a good postoperative 30-day performance status. CONCLUSIONS: A good preoperative performance status and exclusion from the first tertile were clinical factors predicting a good postoperative 30-day performance status. In patients with large psoas muscle mass (third tertile), a good 30-day performance status can be expected after surgery, suggesting that surgery in this population should be pursued aggressively.

Myositis Ossificans of the Psoas Major Muscle After XLIF With Preoperative Administration of Romosozumab: A Case Report.

CASE: A 62-year-old woman receiving romosozumab for 3 months underwent extreme lateral interbody fusion (XLIF) for lumbar degenerative spondylolisthesis. From 1 week after surgery, she experienced gradually increasing pain from the right groin to the front of the thigh. Examination revealed ossifying myositis in bilateral psoas major muscles. Etidronate treatment was initiated, improving pain after 4 days. Computed tomography showed lesion disappearance by 3 months after surgery. CONCLUSION: We report a rare case of myositis ossificans in bilateral psoas major muscles following XLIF surgery, possibly influenced by intraoperative manipulation and romosozumab treatment. Etidronate administration may be effective, as with heterotopic ossification.

Factors leading to open revision surgery after trans-sacral canal plasty for lumbar spine disease.

Trans-sacral canal plasty (TSCP) is a minimally invasive lumbar spine surgery under local anaesthesia. TSCP is expected to be effective regardless of whether the patient has had previous surgery. However, there are cases in which open revision surgery is required after TSCP. This study aimed to identify risk factors for open revision surgery after TSCP in order to determine surgical indications and limitations. A retrospective case-control study was conducted in patients who underwent TSCP for lumbar spine disease. Data of 112 patients were analysed. During an observation period of 7-23 months, 34 patients (30.4%) required open revision surgery and 78 (69.6%) did not. The following patient background characteristics were investigated: age, sex, body mass index (BMI), diagnosis, history of spine surgery and the institution where the surgery was performed. Comorbidities were scored using the Elixhauser Comorbidity Index. Preoperative imaging parameters were investigated, including the lesion level (L4/5, L5/S1, other), presence of intervertebral instability, dural sac area, presence of bony stenosis and presence of epidural lipoma. Multivariate analysis revealed that intervertebral instability (odds ratio 2.56, confidence interval 1.00-6.51, p = 0.046) and a narrow dural sac area (odds ratio 0.98, confidence interval 0.97-0.99, p = 0.002) were significant risk factors for open revision surgery after TSCP.

Substantial mismatch of skeletal maturity assessment between Risser sign and Simplified Skeletal Maturity Scale/Thumb Ossification Composite Index in patients with adolescent idiopathic scoliosis.

BACKGROUND: Recently, hand skeletal maturity systems such as the Simplified Skeletal Maturity Scale (SSMS) or Thumb Ossification Composite Index (TOCI) have been introduced to attempt to prospectively predict the occurrence of peak height velocity (PHV) in adolescents. This study aims to compare the frequency of the mismatch in estimation of HV between Risser sign (RS) and SSMS/TOCI stages in adolescent idiopathic scoliosis (AIS) patients. METHODS: One hundred thirty-three female patients with AIS were included. The mean age of the patients was 13.1 years. A whole spine and hand X-rays were obtained to establish skeletal maturity stage according to RS, SSMS, and TOCI systems. A mismatch resulting in overestimation (MOE) with RS compared to SSMS/TOCI was defined as the combination of RS 3-4/SSMS 3-5 or RS 3-4/TOCI 4-6, whereas a mismatch resulting in underestimation (MUE) with RS and SSMS/TOCI was defined as RS 0-1/SSMS 6-8 or RS 0-1/TOCI 7-8. Height velocity (HV) was compared between MOE/non-MOE and MUE/non-MUE groups. RESULTS: Between RS and SSMS, the rates of the MOE and MUE groups were 4.3% and 1.7%, respectively. Between RS and TOCI, rates were 2.8% and 1.7%, respectively. With the combination of RS and SSMS stages, an estimate of HV of 5.6 cm/year in the MOE group was significantly larger than that of 2.7 cm/year in the non-MOE group, and 3.7 cm/year in the MUE group was significantly smaller than 6.9 cm/year in the non-MUE group. Likewise, with the combination of RS and TOCI stages, an estimate of HV of 5.8 cm/year in the MOE group was significantly greater that of 2.7 cm/year in the non-MOE group, and 3.7 cm/year in the MUE group was significantly smaller than 6.9 cm/year in the non-MUE group. CONCLUSIONS: These findings support the use of SSMS/TOCI as the standard for assessing HV and skeletal maturity in patients with AIS.

Postoperative Spinal Subdural Extra-arachnoid Hygroma Because of Trauma: Resolution with Lumbar Puncture: A Case Report.

CASE: A 73-year-old woman, after spinal surgery, presented with symptomatic spinal subdural extra-arachnoid hygroma (SSEH) because of a fall on the third postoperative day. The hygroma was diagnosed by magnetic resonance imaging (MRI). Lumbar puncture was performed under local anesthesia, after which the leg pain disappeared immediately. MRI obtained immediately after puncture and 1 week later confirmed disappearance of the hygroma. CONCLUSION: Although dural transection is mentioned in most of the reports on treatment of symptomatic postoperative SSEH, we were able to treat this entity by epidural puncture. In the absence of paraplegia or cystorectal disturbance, puncture can be an effective and minimally invasive treatment option.

Retroperitoneal Hematoma Due to Drainage Tube Insertion in Extreme Lateral Interbody Fusion: A Case Report.

CASE: A 73-year-old woman presented with degenerative kyphoscoliosis. Radiographs revealed sagittal and coronal imbalance with lumbar spinal stenosis. Extreme lateral interbody fusion (XLIF) was performed in the first stage of 2-stage surgery, and a closed-suction drainage tube was placed in the retroperitoneal cavity. Postoperatively, there was massive bleeding through the tube. Contrast-enhanced computed tomography revealed lumbar artery injury, which required emergency arterial embolization. CONCLUSION: Placing a drainage tube in the retroperitoneal cavity during XLIF surgery can help detect complications such as intestinal and ureteral injuries, the lumbar artery within the lumbar muscle can be injured during drain placement.

Transsacral Canal Plasty for Decompression of Lumbar Spinal Stenosis in a Patient With Epidural Lipomatosis: A Case Report.

CASE: A 58-year-old man presented with lumbar spinal stenosis due to epidural lipomatosis. He underwent transsacral canal plasty (TSCP), in a manner similar to epidural adhesiolysis, which can be performed under local anesthesia. His leg pain improved dramatically in the year after surgery. Furthermore, magnetic resonance images during this time show neural decompression by reduction of the amount of epidural fat. CONCLUSION: TSCP was found not only to relieve pain but also to achieve neural decompression in this patient with spinal canal stenosis caused by lumbar epidural lipomatosis. This is the first report to demonstrate the usefulness of TSCP for spinal epidural lipomatosis.

A Simplified Skeletal Maturity Scale and Thumb Ossification Composite Index to Assess Skeletal Maturity and Predict Height Velocity in Japanese Females with Adolescent Idiopathic Scoliosis.

INTRODUCTION: Since Little et al. first reported that peak height velocity (PHV) could be described as a reliable clinical marker for the prediction of remaining growth and curve progression of adolescent idiopathic scoliosis (AIS) in clinical practice, much attention has been paid to PHV as a possible predictor of curve progression in patients with AIS. However, PHV itself is only identified retrospectively, so its value is not available at the first outpatient clinic visit. Using the simplified skeletal maturity scale (SSMS) and the thumb ossification composite index (TOCI) staging systems, this study aims to assess skeletal maturity and predict height velocity (HV) in Japanese female patients with AIS. METHODS: This study involved 95 female patients with AIS, ranging from 9 to 17 years old. A standing AP radiograph of the entire spine and a hand radiograph were retrospectively obtained to establish the skeletal maturity stage in accordance with the SSMS and TOCI systems. Height measurements were recorded at each visit; HV was calculated as the height change (cm) divided by the time interval (years). RESULTS: The TOCI stage rating increased identically to the SSMS stage rating increase. The chi-square test showed that there was a significant correlation between the two scoring systems (χ2=720.4). The Cramer V correlation also demonstrated a very strong correlation (Cramer V=0.62). Regarding the relationship between HV and each SSMS and TOCI stage, HV decreased as SSMS and TOCI stages increased. η 2 equaled to 0.67 in both groups and displayed a strong correlation between HV and SSMS and TOCI stages. CONCLUSIONS: These findings suggest that evaluation of the rate of HV using these radiological assessments is of supreme importance for determining the status of pubertal maturity and predicting the remaining amount of adolescent growth at the outpatient clinic visit.

Overexpression of the c-fos gene perturbs functional maturation of M1 cells into macrophages.

Expression of the proto-oncogene c-fos is induced in normal myelopoiesis. However, functions of c-Fos in the process of differentiation towards macrophages are still controversial. To explore the functions, we used the murine myeloblastic leukemia cell line M1. Stimulation of M1 cells with bacterial LPS promotes their terminal differentiation into functional macrophages. Overexpression of c-fos in M1 cells dramatically increased sensitivity of the cells for LPS-induced differentiation and generation of morphologically differentiated cells. However, the overexpression did not modulate phagocytotic functions, surface expression of macrophage markers such as CD16/CD32 (Fcgamma Receptor) and CD54 (ICAM-1), and expression of lysozyme, esterase and c-fms mRNA. Surprisingly, induction of the MHC class II expression on M1 cells after stimulation was inhibited by the overexpression. Expression of CIITA, as an essential transcription factor for the expression, was also reduced in the M1 cells. These results suggest that overexpression of c-fos in differentiating M1 cells perturbs their functional maturation.

A role for c-fos/activator protein 1 in B lymphocyte terminal differentiation.

Expression of B lymphocyte-induced maturation protein 1 (Blimp-1) transcription factor is essential for promoting B cell differentiation into plasma cells. However, a critical transcription factor for Blimp-1 expression in activated B cells is unclear. When splenic B cells were stimulated with CD40 ligand (CD40L) and IL-4, terminal differentiation was induced in the B cells from c-fos transgenic (H2-c-fos) mice but barely in those from control littermates and from c-fos-deficient mice. AP-1 family and Blimp-1 mRNAs were transiently induced in the control B cells, and overexpression of c-Fos induced a sufficient amount of Blimp-1 for terminal differentiation in the H2-c-fos B cells. When normal and c-fos-deficient B cells were stimulated with LPS, a sufficient amount of Blimp-1 for terminal differentiation was induced in those B cells. However, expression of c-fos/AP-1 family mRNAs in LPS-stimulated normal B cells was similar to that of normal B cells stimulated with CD40L and IL-4. EMSA and chromatin immunoprecipitation assays using the AP-1-binding DNA sequence in the murine Blimp-1 promoter region demonstrated that AP-1-binding activity in nuclear protein of LPS-stimulated normal B cells was prolonged more than that in normal B cells stimulated with CD40L and IL-4. Furthermore, the percentage of CD138(+) B cells within germinal center B cells in the spleen and the number of Ab-forming cells in the bone marrow of H2-c-fos mice was larger than that of control mice 12 days after immunization. Thus, although c-Fos is not essential for Blimp-1 expression, c-Fos/AP-1 positively regulates Blimp-1 expression and terminal differentiation of activated B cells.

Dominant-negative effect of the c-fos family gene products on inducible NO synthase expression in macrophages.

Activation of murine peritoneal macrophages or the macrophage cell line RAW264 with IFN-gamma and bacterial lipopolysaccharide promotes a transient up-regulation of c-fos family gene expression following inducible NO synthase (iNOS) production. Since introduction of a double mutation into the two AP-1-binding sites in the iNOS promoter region reduced the promoter activity to 25% of the authentic one in activated RAW264 cells, the induced c-Fos/AP-1 may promote iNOS expression in activated macrophages. Surprisingly, overexpression of c-fos in activated macrophages completely suppressed the production of iNOS, but not that of IL-6 and IL-1beta. The regulatory effect was also observed by overexpression of c-fos, c-jun or fosB on the promoter activity as deduced from transfection experiments. However, the mutation of AP-1-binding sites in the promoter region did not abrogate the regulatory effect of c-fos and the effect of c-fos was diminished by co-transfection with c-jun, but not with fosB, suggesting no relation between the regulatory effect and a c-Fos/AP-1 complex. Expression of NF-IL6 (C/EBPbeta), whose gene product can make a non-functional heterodimer with c-Fos family proteins, was transiently induced in activated macrophages. Overexpression of NF-IL6 in activated RAW264 cells augmented iNOS promoter activity and reduced the regulatory effect of c-fos overexpression. Thus, overproduction of c-Fos family proteins acts as a dominant-negative-type regulator on iNOS expression in activated macrophages.

GL7 defines the cycling stage of pre-B cells in murine bone marrow.

We have identified a novel subset of early B lineage cells in the mouse bone marrow (BM) by GL7 expression on cell surface. GL7(+)B220(low) BM cells have a large cell size and are CD43(-to low), CD95(-), Sca-1(-), I-A(low), IgM(-) and IgD(-), suggesting that they are large pre-B cells. These BM cells express lambda5 and VpreB but not terminal deoxytransferase (TdT) and Bcl-2, and approximately 50 % of them are in cell cycle. This fraction was not detected in BM cells of Rag-1-deficient and Scid mice, supporting that GL7(+)B220(low) BM cells belong to fraction C' and D according to Hardy's criteria or to an early large pre-B-II fraction according to Melchers-Rolink's criteria. Furthermore, GL7(+)B220(low) BM cells can differentiate into IgM(+) immature B cells in co-culture with stromal cells. These results suggest that B lymphocytes pass through the GL7(+) pre-B cell stage during differentiation in the BM. Thus, GL7 is the critical marker to define the proliferation stage of large pre-B cells.