Motion Capture-based 3-dimensional Measurement of Range of Motion in Patients Undergoing Cervical Laminoplasty.

STUDY DESIGN: A prospective study. OBJECTIVE: To measure 3-dimensional cervical range of motion (ROM) by noninvasive optical tracking-based motion-capture technology in patients undergoing laminoplasty, and to elucidate the postoperative effects of laminoplasty on cervical mobility. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty is a motion-sparing decompression surgery for degenerative cervical myelopathy. Unlike cervical laminectomy and fusion, the true postoperative impact of laminoplasty on neck motion has not been well studied. METHODS: Participants comprised 25 patients undergoing double-door cervical laminoplasty for degenerative cervical myelopathy in a single center. Maximum flexion/extension, left/right rotation, and left/right side bending were recorded using the motion-capture device preoperatively and 3 months postoperatively. ROMs in 3 orthogonal axes were calculated. Preoperative differences in C2-7 Cobb angles on lateral flexion/extension x-rays were also measured as the radiologic ROM to assess reliability. Preoperative and 1-year postoperative Japanese Orthopaedic Association score, Neck Disability Index [NDI], and Euro-QOL were recorded, and correlations with ROMs were assessed. RESULTS: Preoperative mean (±SD) ROMs for flexion/extension, rotation, and side bending were 90±17, 107±16, and 53±17 degrees, respectively. Although radiologic sagittal ROM measurement showed a smaller range than motion capture, averaging 36±13 degrees, a moderate to strong correlation between radiologic and motion capture values was observed (R=0.57, P=0.003). Preoperative NDI showed a negative correlation with coronal ROM (rho=-0.547, P=0.02). Postoperative ROM showed a significant reduction in rotation (95±16 degrees, P=0.002) but not in flexion/extension or side bending. CONCLUSIONS: Three-dimensional motion-capture analysis allowed reliable measurement of cervical ROM. Rotational ROM was significantly reduced after laminoplasty, showing that cervical kinematics are still significantly altered.

A new surgical method to treat intracanal lumbar disc herniation using the unilateral biportal endoscopic transforaminal approach: patient series.

BACKGROUND: Unilateral biportal endoscopic lumbar discectomy (UBELD) is a new minimally invasive spine surgery. The purpose of this study is to describe a new surgical method to treat intracanal lumbar disc herniation (LDH) using the unilateral biportal endoscopic transforaminal approach (UBE-TFA). The first 15 patients who had undergone UBELD for single-level LDH were included in this study. Operative time, intraoperative blood loss, postoperative stay, and intraoperative complications were recorded. The Oswestry Disability Index (ODI), numeric rating scale (NRS) score for leg pain, and modified MacNab criteria were assessed at 3 months postoperatively. OBSERVATIONS: The mean operative time was 52.0 ± 13.8 minutes. The mean intraoperative blood loss was 10.5 ± 10.2 mL. The mean postoperative stay was 1.1 ± 0.3 days. There were no complications. The postoperative mean ODI was significantly improved from 44.9 ± 14.4 to 7.7 ± 11.2 at the final follow-up (p < 0.001). There was a significant decrease in the postoperative mean NRS score for leg pain, from 6.1 ± 1.9 to 0.8 ± 1.3 at the final follow-up (p < 0.001). Based on the modified MacNab criteria, good to excellent results were obtained in 86.7% of the patients. LESSONS: We considered UBELD-TFA as not only one of the promising surgical methods for UBELD, but also a new surgical implementation of the TFA.

Bone Turnover Markers in Patients With Ossification of the Posterior Longitudinal Ligament in the Thoracic Spine.

STUDY DESIGN: A prospective, single-center, observational study. OBJECTIVE: To explore the association between serum levels of bone turnover markers and ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine. SUMMARY OF BACKGROUND DATA: The relationship between bone turnover markers, such as N-terminal propeptide of type I procollagen (PINP) or tartrate-resistant acid phosphate 5b (TRACP-5b), and OPLL has previously been examined. However, the correlation between these markers and thoracic OPLL, which is more severe than cervical-only OPLL, remains unclear. METHODS: This prospective study included 212 patients from a single institution with compressive spinal myelopathy and divided them into those without OPLL (Non-OPLL group, 73 patients) and those with OPLL (OPLL group, 139 patients). The OPLL group was further subdivided into cervical OPLL (C-OPLL, 92 patients) and thoracic OPLL (T-OPLL, 47 patients) groups. Patients' characteristics and biomarkers related to bone metabolism, such as calcium, inorganic phosphate (Pi), 25-hydroxyvitamin D, 1α,25 dihydroxyvitamin D, PINP, and TRACP-5b, were compared between the Non-OPLL and OPLL groups, as well as the C-OPLL and T-OPLL groups. Bone metabolism biomarkers were also compared after adjusting for age, sex, body mass index, and the presence of renal impairment using propensity score-matched analysis. RESULTS: The OPLL group had significantly lower serum levels of Pi and higher levels of PINP versus the Non-OPLL group as determined by propensity score-matched analysis. The comparison results between the C-OPLL and T-OPLL groups using a propensity score-matched analysis showed that T-OPLL patients had significantly higher concentrations of bone turnover markers, such as PINP and TRACP-5b, compared with C-OPLL patients. CONCLUSIONS: Increased systemic bone turnover may be associated with the presence of OPLL in the thoracic spine, and bone turnover markers such as PINP and TRACP-5b can help screen for thoracic OPLL.

Does surgical site infection affect patient-reported outcomes after spinal surgery? A multicenter cohort study.

BACKGROUND: Surgical site infections are common in spinal surgeries. It is uncertain whether outcomes in spine surgery patients with vs. without surgical site infection are equivalent. Therefore, we assessed the effects of surgical site infection on postoperative patient-reported outcomes. METHODS: We enrolled patients who underwent elective spine surgery at 12 hospitals between April 2017 and February 2020. We collected data regarding the patients' backgrounds, operative factors, and incidence of surgical site infection. Data for patient-reported outcomes, namely numerical rating scale, Neck Disability Index/Oswestry Disability Index, EuroQol Five-Dimensional questionnaire, and 12-Item Short-Form Health Survey scores, were obtained preoperatively and 1 year postoperatively. We divided the patients into with and without surgical site infection groups. Multivariate logistic regression analyses were performed to identify the risk factors for surgical site infection. Using propensity score matching, we obtained matched surgical site infection-negative and -positive groups. Student's t-test was used for comparisons of continuous variables, and Pearson's chi-square test was used to compare categorical variables between the two matched groups and two unmatched groups. RESULTS: We enrolled 8861 patients in this study; 74 (0.8 %) developed surgical site infections. Cervical spine surgery and American Society of Anesthesiologists physical status classification ≥3 were identified as risk factors; microendoscopy was identified as a protective factor. Using propensity score matching, we compared surgical site infection-positive and -negative groups (74 in each group). No significant difference was found in postoperative pain or dysesthesia of the lower back, buttock, leg, and plantar area between the groups. When comparing preoperative with postoperative pain and dysesthesia, statistically significant improvement was observed for both variables in both groups (p < 0.01 for all variables). No significant differences were observed in postoperative outcomes between the matched surgical site infection-positive and -negative groups. CONCLUSIONS: Patients with surgical site infections had comparable postoperative outcomes to those without surgical site infections.

Quality of Life and Postoperative Satisfaction in Patients with Benign Extramedullary Spinal Tumors: A Multicenter Study.

STUDY DESIGN: Retrospective cohort study using prospectively collected registry data. OBJECTIVE: The purpose of this study is to evaluate health-related quality of life (HRQOL) and postoperative satisfaction in patients with different histotypes of benign extramedullary spinal tumors (ESTs). BACKGROUND: Little is known about how different histotypes influence HRQOL and postoperative satisfaction in EST patients. MATERIALS AND METHODS: Patients undergoing primary benign EST surgery at 11 tertiary referral hospitals between 2017 and 2021 who completed preoperative and 1-year postoperative questionnaires were included. HRQOL assessment included the Physical Component Summary and Mental Component Summary (MCS) of Short Form-12, EuroQol 5-dimension, Oswestry/Neck Disability Index (ODI/NDI), and Numeric Rating Scales (NRS) for upper/lower extremities (UEP/LEP) and back pain (BP). Patients who answered "very satisfied," "satisfied," or "somewhat satisfied" on a seven-point Likert scale were considered to be satisfied with treatment. Student t -tests or Welch's t -test were used to compare continuous variables between two groups, and one-way analysis of variance was used to compare outcomes between the three groups of EST histotypes (schwannoma, meningioma, atypical). Categorical variables were compared using the χ 2 test or Fisher exact test. RESULTS: A total of 140 consecutive EST patients were evaluated; 100 (72%) had schwannomas, 30 (21%) had meningiomas, and 10 (7%) had other ESTs. Baseline Physical Component Summary was significantly worse in patients with meningiomas ( P =0.04), and baseline NRS-LEP was significantly worse in patients with schwannomas ( P =0.03). However, there were no significant differences in overall postoperative HRQOL or patient satisfaction between histology types. Overall, 121 (86%) patients were satisfied with surgery. In a subgroup analysis comparing intradural schwannomas and meningiomas adjusted for patient demographics and tumor location with inverse probability weighting, schwannoma patients had worse baseline MCS ( P =0.03), ODI ( P =0.03), NRS-BP ( P <.001), and NRS-LEP ( P =0.001). Schwannoma patients also had worse postoperative MCS ( P =0.03) and NRS-BP ( P =0.001), with no significant difference in the percentage of satisfied patients ( P =0.30). CONCLUSIONS: Patients who underwent primary benign EST resection had a significant improvement in HRQOL postoperatively, and ~90% of these patients reported being satisfied with their treatment outcomes one year after surgery. EST patients may exhibit a relatively lower threshold for postoperative satisfaction compared with patients undergoing surgery for degenerative spine conditions.

Adaptation and Limitations of painDETECT Questionnaire Score Approach Before and After Posterior Cervical Decompression Surgery.

BACKGROUND: The painDETECT questionnaire (PDQ) is one of the available screening tools for neuropathic pain (NeP), with a cut-off score of 13. This study aimed to investigate changes in PDQ scores in patients undergoing posterior cervical decompression surgery for degenerative cervical myelopathy (DCM). METHODS: Patients with DCM undergoing cervical laminoplasty or laminectomy with posterior fusion were recruited. They were asked to complete a booklet questionnaire including PDQ and Numerical Rating Scales (NRS) for pain at baseline and one year after surgery. Patients with a preoperative PDQ score ≥13 were further investigated. RESULTS: A total of 131 patients (mean age = 70.1 years; 77 male and 54 female) were analyzed. After posterior cervical decompression surgery for DCM, mean PDQ scores decreased from 8.93 to 7.28 (P = 0.008) in all patients. Of the 35 patients (27%) with preoperative PDQ scores ≥13, mean PDQ changed from 18.83 to 12.09 (P < 0.001). Comparing the NeP improved group (17 patients with postoperative PDQ scores ≤12) with the NeP residual group (18 patients with postoperative PDQ scores ≥13), the NeP improved group showed less preoperative neck pain (2.8 vs. 4.4, P = 0.043) compared to the NeP residual group. There was no difference in the postoperative satisfaction rate between the two groups. CONCLUSIONS: Approximately 30% of patients exhibited preoperative PDQ scores ≥13, and about half of these patients demonstrated improvements to below to the cut-off value for NeP after posterior cervical decompression surgery. The PDQ score change was relatively associated with preoperative neck pain.

Noninvasive Skin Autofluorescence of Advanced Glycation End Products for Detecting Ossification of the Posterior Longitudinal Ligament in the Thoracic Spine.

STUDY DESIGN: A single-center prospective observational study. OBJECTIVE: The aim was to clarify the usefulness of assessing advanced glycation end products (AGEs) by noninvasive skin autofluorescence in patients with ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: AGE accumulation is associated with various systemic disorders, including aging, diabetes mellitus, and obesity. AGEs have also been associated with OPLL, but their assessment by noninvasive skin autofluorescence has not been yet studied in these patients. MATERIALS AND METHODS: We enrolled patients with degenerative spinal spondylosis and divided them into non-OPLL and OPLL groups. The OPLL group was further subdivided into cervical OPLL (C-OPLL) and thoracic OPLL (T-OPLL) groups. We compared patients' characteristics, serum laboratory data (i.e. hemoglobin A1c, total cholesterol, creatinine, and estimated glomerular filtration rate), and the skin autofluorescence intensity of AGEs (the AGE score) between the non-OPLL and OPLL groups and among the non-OPLL, C-OPLL, T-OPLL groups. Finally, the association of the AGE score with the presence of C-OPLL or T-OPLL was assessed by multinomial logistic regression. RESULTS: Among the 240 eligible patients, 102 were in the non-OPLL group and 138 were in the OPLL group (92 with C-OPLL and 46 with T-OPLL). We observed no significant difference in the AGE score between the non-OPLL and OPLL groups, but when comparing the score among the non-OPLL, C-OPLL, and T-OPLL groups, we found that the T-OPLL group had a significantly higher AGE score. The results of multinomial regression analysis showed that a higher AGE score was significantly associated with T-OPLL (odds ratio: 1.46; 95% CI: 1.01-2.11; P=0.044). CONCLUSION: The AGE score determined by noninvasive skin autofluorescence could help to screen for OPLL in the thoracic spine.

Surgical outcomes between posterior decompression alone and posterior decompression with fusion surgery among patients with Meyerding grade 2 degenerative spondylolisthesis: a multicenter cohort study.

BACKGROUND: Whether lumbar decompression with fusion surgery is effective against Meyerding grade 2 degenerative spondylolisthesis (DS) is unknown. Therefore, the current study aimed to compare the surgical outcomes between posterior decompression alone and posterior decompression with fusion surgery among patients with grade 2 DS with central canal stenosis. METHODS: This retrospective cohort study included prospectively registered patients (n = 3863) who underwent surgery for degenerative lumbar spinal canal stenosis at nine high-volume spine centers from April 2017 to July 2019. Patients with grade 2 DS and central canal stenosis were included in the analysis. Patients with radiculopathy, including foraminal stenosis, degenerative scoliosis, and concomitant anterior spinal fusion, and those with a previous history of lumbar surgery were excluded. The participants were divided into the decompression alone group (group D) and decompression with fusion surgery group (group F). Data about patient-reported outcomes, including Numeric Rating Scale (low back pain, leg pain, leg numbness, and foot numbness), Oswestry Disability Index, EuroQol Five-Dimensional questionnaire, and 12-Item Short-Form Health Survey scores, were obtained preoperatively and 2 years postoperatively. RESULTS: In total, 2354 (61%) patients, including 42 (1.8%) with grade 2 DS (n = 18 in group D and n = 24 in group F), completed the 2-year follow-up. Group D had a higher proportion of female patients than group F. However, the two groups did not significantly differ in terms of other baseline demographic characteristics. Group D had a significantly shorter surgical time and lower volume of intraoperative blood loss than group F. Postoperative patient-reported outcomes did not significantly differ between the two groups, although the preoperative degree of low back pain was higher in group F than in group D. The slip degree of group D did not worsen during the follow-up period. CONCLUSION: The surgical outcomes were similar regardless of the addition of fusion surgery among patients with grade 2 DS. Decompression alone was superior to decompression with fusion surgery as it was associated with a lower volume of intraoperative blood loss and shorter surgical time.

TM5614, an Inhibitor of Plasminogen Activator Inhibitor-1, Exerts an Antitumor Effect on Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is triggered by t(9;22)(q34;q11.2) translocation, leading to the formation of the BCR-ABL1 fusion gene. Although the development of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has dramatically improved the prognosis of CML, the disease could often relapse, presumably because leukemic stem cell fraction of CML (CML-LSC) may reside in specific niches, and also acquire an ability to resist the cytotoxic agents. Recently a study indicated that pharmacological inhibition of plasminogen activator inhibitor-1 (PAI-1, also known as SERPINE1) would cause detachment of CML-LSCs from their niche by inducing maturation of membrane-type matrix metalloprotease-1 (MT1-MMP), leading to increased susceptibility of CML-LSCs against TKIs. However, the direct antitumor effect of PAI-1 inhibition in CML remains unclear. Because PAI-1 mRNA expression was lower in CML cell line (K562) than bone marrow mononuclear cells derived from CML patients, we established K562 cell clones stably expressing exogenous PAI-1 (K562/PAI-1). We found that TM5614 treatment significantly suppressed cell proliferation and induced apoptosis in K562/PAI-1 cells, accompanied by increased activity of Furin protease, which is a known target of PAI-1. Besides processing mature MT1-MMP, Furin is in charge of cleaving the NOTCH receptor to form a heterodimer before exporting it to the cell surface membrane. In K562/PAI-1 cells, TM5614 treatment increased NOTCH1 intracellular domain (NICD) protein expression as well as NOTCH1 target of HEY1 mRNA levels. Finally, forced expression of either Furin or NICD in K562/PAI-1 cells significantly inhibited cell proliferation and induced apoptosis. Collectively, PAI-1 inhibition may have an antitumor effect by modulating the Furin/NICD pathway.

Treatment of restenosis after lumbar decompression surgery: decompression versus decompression and fusion.

OBJECTIVE: The aim of this study was to compare perioperative complications and postoperative outcomes between patients with lumbar recurrent stenosis without lumbar instability and radiculopathy who underwent decompression surgery and those who underwent decompression with fusion surgery. METHODS: For this retrospective study, the authors identified 2606 consecutive patients who underwent posterior surgery for lumbar spinal canal stenosis at eight affiliated hospitals between April 2017 and June 2019. Among these patients, those with a history of prior decompression surgery and central canal restenosis with cauda equina syndrome were included in the study. Those patients with instability or radiculopathy were excluded. The patients were divided between the decompression group and decompression with fusion group. The demographic characteristics, numerical rating scale score for low-back pain, incidence rates of lower-extremity pain and lower-extremity numbness, Oswestry Disability Index score, 3-level EQ-5D score, and patient satisfaction rate were compared between the two groups using the Fisher's exact probability test for nominal variables and the Student t-test for continuous variables, with p < 0.05 as the level of statistical significance. RESULTS: Forty-six patients met the inclusion criteria (35 males and 11 females; 19 patients underwent decompression and 27 decompression and fusion; mean ± SD age 72.5 ± 8.8 years; mean ± SD follow-up 18.8 ± 6.0 months). Demographic data and perioperative complication rates were similar. The percentages of patients who achieved the minimal clinically important differences for patient-reported outcomes or satisfaction rate at 1 year were similar. CONCLUSIONS: Among patients with central canal stenosis who underwent revision, the short-term outcomes of the patients who underwent decompression were comparable to those of the patients who underwent decompression and fusion. Decompression surgery may be effective for patients without instability or radiculopathy.

Relative Risks and Benefits of Crossing the Cervicothoracic Junction During Multilevel Posterior Cervical Fusion: A Multicenter Cohort.

OBJECTIVE: To compare the clinical and radiographic outcomes and complications in patients undergoing multilevel posterior cervical fusion surgery, ending at C7 or crossing the cervicothoracic junction (CTJ). METHODS: A total of 96 patients undergoing multilevel posterior cervical fusion surgery ending at C7, T1, or T2 were screened. The patients who fulfilled the inclusion criteria were divided into 2 groups based on the lower instrumented vertebra (LIV) level: group C7 (ending at C7) and group T1-T2 (crossing the CTJ). The radiographic and clinical outcomes were compared between the 2 groups, and the risk factors for instrument failure at LIV were investigated. RESULTS: In total, 73 patients (76%) completed at least 1 year follow-up and divided into group C7 (n = 43) and group T1-T2 (n = 30). Preoperative and postoperative radiographic parameters, the Japanese Orthopaedic Association score, and patient-reported outcomes were not significantly different between the 2 groups. Significantly longer surgical time, increased blood loss, and higher incidence rates of perioperative or postoperative complications were noted in group T1-T2. On the other hand, the incidence of instrument failures at LIV was significantly higher in group C7. Multivariate analysis showed that ending at C7, skipping screw insertion at the proximal vertebra adjacent to LIV, and a large postoperative cervical sagittal vertical axis (>40 mm) were risk factors for instrument failure at LIV. CONCLUSIONS: Crossing the CTJ during multilevel posterior cervical fusion surgery reduced instrument failures at LIV, but increased the surgical invasiveness and perioperative and postoperative complications.

Diabetes is associated with greater leg pain and worse patient-reported outcomes at 1 year after lumbar spine surgery.

Although patients with diabetes reportedly have more back pain and worse patient-reported outcomes than those without diabetes after lumbar spine surgery, the impact of diabetes on postoperative recovery in pain or numbness in other regions is not well characterized. In this study, the authors aimed to elucidate the impact of diabetes on postoperative recovery in pain/numbness in four areas (back, buttock, leg, and sole) after lumbar spine surgery. The authors retrospectively reviewed 993 patients (152 with diabetes and 841 without) who underwent decompression and/or fixation within three levels of the lumbar spine at eight hospitals during April 2017-June 2018. Preoperative Numerical Rating Scale (NRS) scores in all four areas, Oswestry Disability Index (ODI), and Euro quality of life 5-dimension (EQ-5D) were comparable between the groups. The diabetic group showed worse ODI/EQ-5D and greater NRS scores for leg pain 1 year after surgery than the non-diabetic group. Although other postoperative NRS scores tended to be higher in the diabetic group, the between-group differences were not significant. Diabetic neuropathy caused by microvascular changes may induce irreversible nerve damage especially in leg area. Providers can use this information when counseling patients with diabetes about the expected outcomes of spine surgery.

Skipping Pedicle Screw Insertion Into Infected Vertebra is a Risk Factor for Revision Surgery for Pyogenic Spondylitis in the Lower Thoracic and Lumbar Spine.

BACKGROUND: Surgical intervention for pyogenic spondylitis is indicated when conservative treatment fails and biomechanical instability persists. Whether to insert pedicle screws into all vertebrae, including the most erosive vertebrae, or whether to skip 1 vertebra in pedicle screw insertion remains controversial. METHODS: A single-institution retrospective cohort study was conducted in consecutive patients with pyogenic spondylitis in the lower thoracic and lumbar spine (T9-S1) between January 2008 and December 2016. The patients were treated with interbody fusion plus posterior stabilization using pedicle screws and were divided into 2 groups as follows: (1) patients in whom 1 vertebra, usually the most erosive, was skipped in pedicle screw insertion (Group Skipping) and (2) pedicle screw insertion into all vertebrae (Group All). Patients' operation data were evaluated, and clinical outcomes were compared between the 2 groups. There were no significant differences between the 2 groups in terms of age, sex, past histories, blood loss, operation time, the presence of abscesses, or operative approach. RESULTS: The length of fixation was greater by 1 vertebral level in the Group Skipping than in the Group All, and the rate of revision surgery for pseudarthrosis was higher in the Group Skipping than in the Group All (P = .02). There was no statistically significant difference between the 2 groups in terms of the mean segmental lordotic angle or Barthel Index. CONCLUSIONS: Skipping pedicle screw insertion for pyogenic spondylitis in posterior fixation led to an increased number of fixed vertebrae and may be a risk factor for revision surgery for pseudarthrosis. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: The insertion of short pedicle screws at the infected vertebra can prevent early treatment failure and increase the biomechanical stability of construct.

Flow Cytometry-Based Photodynamic Diagnosis with 5-Aminolevulinic Acid for the Detection of Minimal Residual Disease in Multiple Myeloma.

Multiple myeloma is the cancer of plasma cells. Along with the development of new and effective therapies, improved outcomes in patients with multiple myeloma have increased the interest in minimal residual disease (MRD) monitoring. However, the considerable heterogeneity of immunophenotypic and molecular markers of myeloma cells has limited its clinical application. 5-Aminolevulinic acid (ALA) is a natural compound in the heme biosynthesis pathway. Following ALA treatment, tumor cells preferentially accumulate porphyrins because of the differential activities of aerobic glycolysis, known as Warburg effect. Among various porphyrins, protoporphyrine IX is a strong photosensitizer; thus, ALA-based photodynamic diagnosis has been widely used in various solid cancers. Here, the feasibility of flow cytometry-based photodynamic detection of MRD was tested in multiple myeloma. Among various human cell lines of hematological malignancies, including K562 erythroleukemia, Jurkat T-cell leukemia, Nalm6 pre-B cell leukemia, KG1a myeloid leukemia, and U937 monocytic leukemia, human myeloma cell line, KMS18, and OPM2 abundantly expressed ALA transporters, such as SLC36A1 and SLC15A2, and 1 mM ALA treatment for 24 h resulted in nearly 100% porphyrin fluorescence expression, which could be competitively inhibited by ALA transport with gamma-aminobutyric acid. Titration studies revealed that the lowest ALA concentration required to achieve nearly 100% porphyrin fluorescence in KMS18 cells was 0.25 mM, with an incubation period of 2 h. Under these conditions, incubation of primary peripheral blood mononuclear cells resulted in only 1.8 % of the cells exhibiting porphyrin fluorescence. Therefore, flow cytometry-based photodynamic diagnosis is a promising approach for detecting MRD in multiple myeloma.

Adaptation and limitation of anterior column reconstruction for pyogenic spondylitis in lower thoracic and lumbar spine.

BACKGROUND: Surgical strategy for pyogenic spondylitis is controversial when vertebral body erosion is severe. Radical debridement and anterior column reconstruction is indicated for the purpose of early ambulatory to prevent secondary complication for long bed rest. However, such aggressive debridement and risk of perioperative complications are trade-off. The purpose of this study was to evaluate the risk factor of poor prognosis after anterior column debridement and reconstruction for pyogenic spondylitis in lower thoracic and lumbar spine. METHODS: We performed a retrospective review of 40 patients diagnosed with pyogenic spondylitis in lower thoracic and lumbar spine who were introduced to our institution due to losing ambulatory ability and underwent anterior column debridement and reconstruction between January 2008 and May 2016. After the patient population was split into a regaining ambulatory group (Group A; n = 23) and a poor prognosis group (Group P; n = 17), we used Fisher exact tests and t-tests as appropriate for univariate analyses to compare patient characteristics and outcomes between the 2 groups. RESULTS: Univariate analysis showed that the significant variables were massive bleeding (>2000 ml) (P < 0.01), Charlson Comorbidity Index ≥3 (P = 0.01), and two-stage surgery needed (P = 0.04). Logistic regression analysis showed that the factors associated with poor prognosis were massive bleeding (Odds Ratio 11.9; 95% confidence interval 1.8 to 119.7; P = 0.04). CONCLUSIONS: Massive bleeding was associated with poor prognosis after debridement followed by anterior column reconstruction for pyogenic spondylitis in lower thoracic and lumbar spine.

Forced FOG1 expression in erythroleukemia cells: Induction of erythroid genes and repression of myelo-lymphoid transcription factor PU.1.

The transcription factor GATA-1-interacting protein Friend of GATA-1 (FOG1) is essential for proper transcriptional activation and repression of GATA-1 target genes; yet, the mechanisms by which FOG1 exerts its activating and repressing functions remain unknown. Forced FOG1 expression in human K562 erythroleukemia cells induced the expression of erythroid genes (SLC4A1, globins) but repressed that of GATA-2 and PU.1. A quantitative chromatin immunoprecipitation (ChIP) analysis demonstrated increased GATA-1 chromatin occupancy at both FOG1-activated as well as FOG1-repressed gene loci. However, while TAL1 chromatin occupancy was significantly increased at FOG1-activated gene loci, it was significantly decreased at FOG1-repressed gene loci. When FOG1 was overexpressed in TAL1-knocked down K562 cells, FOG1-mediated activation of HBA, HBG, and SLC4A1 was significantly compromised by TAL1 knockdown, suggesting that FOG1 may require TAL1 to activate GATA-1 target genes. Promoter analysis and quantitative ChIP analysis demonstrated that FOG1-mediated transcriptional repression of PU.1 would be mediated through a GATA-binding element located at its promoter, accompanied by significantly decreased H3 acetylation at lysine 4 and 9 (K4 and K9) as well as H3K4 trimethylation. Our results provide important mechanistic insight into the role of FOG1 in the regulation of GATA-1-regulated genes and suggest that FOG1 has an important role in inducing cells to differentiate toward the erythroid lineage rather than the myelo-lymphoid one by repressing the expression of PU.1.

Effects of inhalation or incubation of oxitropium bromide on diaphragm muscle contractility in mice.

BACKGROUND: Although oxitropium bromide is used clinically as an anticholinergic drug (i.e., parasympathetic antagonist) to relax airway smooth muscle, we examined whether it has or does not have any effects on diaphragm muscle. METHODS: Three treatment sets, an oxitropium bromide inhalation only group, an oxitropium bromide inhalation plus endotoxin injection group (in vivo) and an oxitropium bromide incubation group (in vitro) were studied as to diaphragm muscle contractile properties. RESULTS: Oxitropium bromide inhalation shifted force-frequency curves upward at 2 h after inhalation (p < 0.05) and inhibited the decrease of force-frequency curves due to endotoxin injection in vivo. Incubation with oxitropium bromide of untreated diaphragm muscle and diaphragm muscle injected with endotoxin did not increase the force-frequency curves dose-dependently in vitro; however, it caused both types of muscle to be fatigue resistant. CONCLUSIONS: We speculate that the increment of muscle contractility with the inhalation of oxitropium bromide was induced by the antagonization of musucarinic acetylcholine receptors (mAChR). In addition, the changes of fatigue resistance provoked by oxitropium bromide, which also is speculated to antagonize mAChR, may be beneficial in the treatment of patients with COPD.

Tulobuterol patch maintains diaphragm muscle contractility for over twenty-four hours in a mouse model of sepsis.

Tulobuterol, a sympathomimetic drug used as a transdermal patch, increases normal diaphragm muscle strength. Because diaphragm muscle weakness (i.e. decrease of contraction) is a feature of bronchial asthma and sepsis, we examined the in vitro and in vivo effects of tulobuterol on the contractility of diaphragm muscles prepared from mice treated with endotoxin. We measured contractile parameters of force-frequency curves and twitch kinetics using untreated or treated diaphragm muscles at 0 (E0) and 4 (E4) hours after E. coli endotoxin (20 mg/kg) administration. The force-frequency curve of E4 diaphragm muscle was decreased from that of E0 diaphragm muscle (p < 0.001). E4 diaphragm muscle was incubated in an organ buffer containing 10(-7) or 10(-5) M concentrations of tulobuterol for 1 h (in vitro). The force-frequency curves of both 10(-7) (p < 0.01) or 10(-5) M (p < 0.001) tulobuterol concentrations shifted significantly upward from those of no tulobuterol, indicating that tulobuterol can recover the diaphragm muscle contractility that was decreased by endotoxin. In the in vivo treatment, E0 and E4 diaphragm muscles were analyzed at 0, 12, and 24 h after transdermal tulobuterol treatment. The force-frequency curves of E0 and E4 diaphragm muscles at three time points were not significantly changed each other, indicating that tulobuterol patch restores the muscle contractility. Thus, diaphragm muscle contractility was maintained during 4 h of endotoxin administration with tulobuterol patch for over 24 h. We suggest that this treatment of bronchial asthma may protect against endotoxin contained in inhaled house dust.

Inhalation and incubation with procaterol increases diaphragm muscle contractility in mice.

BACKGROUND: Although procaterol is used clinically as a beta(2)-adrenergic receptor agonist to relax airway smooth muscle, it has not yet been clarified whether procaterol has inotropic effects on respiratory muscles. METHODS: Three intervention groups were investigated: a procaterol inhalation only group; a procaterol inhalation plus endotoxin injection group (in vivo); and a procaterol incubation group (in vitro). The diaphragm muscle in all groups was dissected and measurements of its contractile properties were performed. RESULTS: The effects of procaterol inhalation shifted the force-frequency curves upward at 30 minutes after inhalation, and inhibited the decline of force-frequency curves due to endotoxin injection in vivo. In vitro administration of procaterol resulted in an increase in the force-frequency curves in a dose-dependent manner. CONCLUSIONS: It can be concluded that procaterol has an inotropic effect on the diaphragmatic muscles taken from normal animals as well as on the diaphragm muscles in a septic animal model.