The Outcome of Molecularly Targeted Therapy after Surgical Treatment of Spinal Metastasis.

The aim of this study was to investigate outcomes of molecularly targeted therapy after surgical treatment of spinal metastasis. Participants comprised 164 patients who underwent surgical treatment of spinal metastasis, divided according to whether molecularly targeted therapy was performed. We compared survival, local recurrence of metastasis detected by imaging, the disease-free interval, relapses of neurological deterioration, and the ability to walk between groups. Molecularly targeted drugs were administered to 39 patients after surgery (TT group) and were not administered to 125 patients (non-TT group). Median survival was significantly longer in the TT group (1027 days) than in the non-TT group (439 days, p < 0.01). Local recurrence occurred in 25 patients in the non-TT group and 10 patients in the TT group. The disease-free interval did not differ between groups. Neurological deterioration was observed in three patients in the non-TT group and no patients in the TT group. The ability to walk was preserved in 97.6% of patients in the TT group and 88% of patients in the non-TT group (p = 0.12). In conclusion, molecularly targeted drugs improve survival in patients with spinal metastasis but do not alter local control of metastatic tumors.

Correlation Between Gait and Life Expectancy in Patients with Spinal Metastases.

BACKGROUND: Metastatic epidural spinal cord compression (MESCC) may lead to walking disability. The effect of regaining gait ability on the life expectancy of cancer patients is still unknown. To explore this issue, we evaluated the effect of gait ability recovery in nonambulatory patients after treatment for a metastatic spinal tumor. METHODS: In total, 105 patients who underwent surgery for MESCC between January 2006 and December 2016 and survived longer than 3 months were enrolled. All the patients were nonambulatory because of the MESCC and had undergone posterior decompression and fixation with intraoperative radiotherapy. At postoperative month 3, patients who had regained their gait ability were categorized as ambulatory and those who had not were categorized as nonambulatory. Age, sex, prognosis score (modified Bauer score), preoperative and postoperative Frankel grade scores, tumor origin site, Charlson comorbidity index, and survival time were compared between the groups. RESULTS: Seventy-two patients regained gait ability at postoperative month 3, and 33 patients did not. The modified Bauer score did not differ between the groups (P = 0.08); therefore, the presumptive life expectancy of the groups before treatment was not biased. The median survival time was significantly longer in the ambulatory group (610 days) than that in the nonambulatory group (181 days, P < 0.05). CONCLUSIONS: Patients who regained their gait ability after treatment for MESCC tended to live longer than those who did not, indicating that recovery of gait ability by patients with cancer is associated with improved life expectancy.

Electron beam intraoperative radiotherapy for metastatic epidural spinal cord compression: a prospective observational study.

To assess the additional effects of intraoperative radiotherapy (IORT) with decompression surgery and adjuvant external beam radiotherapy (EBRT) for metastatic epidural spinal cord compression (MESCC). This single-arm institutional prospective observational study recruited patients between June 2017 and March 2020 and included those with symptoms of spinal cord compression owing to metastases, who were diagnosed using MRI. Patients with radiation-sensitive primary tumors and those who could not tolerate surgery were excluded. The treatment protocol comprised decompression surgery and electron beam IORT of 20 Gy in a single fraction followed by EBRT of 30 Gy in 10 fractions. The primary endpoints included the 1-year local failure rate and ambulatory functions. The study was closed in May 2019 owing to changes in treatment policies at our institution. Twenty patients were registered between June 2017 and May 2019. Although all patients completed surgery and IORT, 2 did not receive postoperative EBRT. Patients most commonly had colorectal cancer (4 patients), followed by thyroid cancer, renal cell carcinoma, lung cancer, breast cancer, sarcomas, and other cancers (3, 3, 2, 2, 2, and 4 patients, respectively). The median follow-up duration was 16 months (range 2-30 months); the 1-year local failure rate was 16%. On comparing ambulatory functions pre-treatment and at 1 year after treatment, improvement, no change, and worsening were observed in 3, 9, and 0 patients, respectively. This study's findings suggest that decompression surgery and IORT followed by EBRT are effective in achieving local control and maintaining ambulation in patients with MESCC.

Incidence of Unrecognized Incidental Durotomy during Surgery for Malignant Spinal Tumor.

INTRODUCTION: Cerebral spinal fluid leak from durotomy is a well-known risk with spinal surgeries. The aim of this study is to identify the incidence of unrecognized incidental durotomy during posterior surgery for spinal metastases and its risk factors. METHODS: Participants comprised 75 patients who underwent posterior spine surgery for spinal metastases between January 2012 and December 2016. Cases with apparent durotomy noticed intraoperatively were excluded. Unrecognized durotomy was diagnosed as the presence of wide subcutaneous fluid retention on magnetic resonance imaging at least 3 months postoperatively. For comparison, 50 patients who underwent cervical laminoplasty due to cervical spondylotic myelopathy were examined using the same method. We also examined correlations between occurrence of durotomy and patient characteristics such as age, type of tumor, location of tumor (ventral or dorsal), extent of tumor, and history of radiotherapy before surgery. RESULTS: Unrecognized durotomy occurred in 21 cases of spinal metastasis (26.7%) and in 1 case of cervical spondylotic myelopathy (2%), representing a significant difference between groups. Age, type of tumor, location of tumor, extent of tumor, and history of radiotherapy before surgery did not correlate significantly with occurrence of durotomy. No local trouble was observed in durotomy cases, except in one case with subcutaneous local infection. CONCLUSIONS: The incidence of unrecognized incidental durotomy is significantly higher during surgery for spinal metastases than that during surgery for degenerative disease.

Publisher Correction: Fgf10 is essential for limb and lung formation.

In the version of the paper initially published, Fig. 5a was inadvertently duplicated and presented as both Fig. 5a and 5f, and the correct image for Fig. 5f was omitted. Images of the original and corrected figure panels are shown in the correction notice.

Novel Compound Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease Patients and Healthy Volunteers.

BACKGROUND: TP0463518 is a novel hypoxia-inducible factor prolyl hydroxylase inhibitor developed to aid in the treatment of anemia associated with chronic kidney disease (CKD) and is expected to increase erythropoietin (EPO) derived from liver. Two phase I studies were conducted in healthy volunteers (HV) and CKD patients undergoing hemodialysis (i.e., HD patients) or those not undergoing dialysis (i.e., ND patients). METHODS: Pharmacokinetics, pharmacodynamics, and safety profiles of TP0463518 were assessed. Forty HV received single oral doses of TP0463518 at 3, 6, 11, 20, and 36 mg or placebo. Twenty ND patients received single doses of TP0463518 at 1, 6, and 11 mg and 9 HD patients received TP0463518 at 1 and 11 mg doses. To identify the source organ of EPO, glycosylation patterns were determined using percentage migrated isoform (PMI) values. RESULTS: Declining renal function slowed elimination of TP0463518 and increased the mean AUC0-∞. ∆Emax of serum EPO in 11-mg groups of HV, ND patients, and HD patients were 24.37 ± 11.37, 201.57 ± 130.34, and 1,324.76 ± 1,189.24 mIU/mL respectively. A strong correlation was -observed between logarithm conversions of ∆Emax and AUC0-∞ with correlation coefficients of 0.945. PMI values of blood after TP0463518 administration were elevated to similar or higher levels in comparison with those of umbilical cord blood, which mainly contains liver-derived EPO. CONCLUSIONS: TP0463518 induced dose-dependent EPO production, mainly derived from the liver in HV and CKD patients. These results suggest that TP0463518 is a new strategy for treating anemia in CKD, which can be used regardless of renal functions.

Clinical study of splint therapeutic efficacy for the relief of temporomandibular joint discomfort.

PURPOSE: This study aimed to evaluate the relationship between displacement of the mandibular condyle/disc due to occlusal splint insertion with splint therapy and changes in discomfort of the temporomandibular joint (TMJ), and to clarify the relationships between the outcomes over time of temporomandibular discomfort and TMJ magnetic resonance imaging (MRI) findings at the initiation of splint therapy. MATERIALS AND METHODS: A total of 75 patients admitted to hospital with discomfort around the TMJ were evaluated. A visual analogue scale for TMJ discomfort was administered during visits for approximately 3 months following the initiation of splint therapy. At the start of splint therapy, magnetic resonance imaging (MRI) was performed with and without splint insertion, and condyle and disc movements were evaluated. Disc balance, disc position and function, disc configuration, joint effusion, osteoarthritis, and bone marrow were evaluated. Linear regression and multiple regression analyses were used to clarify relationships between changes in discomfort and the factors evaluated. RESULTS: There was no significant correlation between TMJ discomfort and condyle/disc movement with splint insertion. TMJ discomfort was significantly relieved by splint therapy regardless of temporomandibular MRI findings. Unilateral anterior disc displacement and marked or extensive joint effusion fluid were significantly improved with splint therapy. CONCLUSION: Discomfort tended to remit with splint therapy regardless of temporomandibular MRI findings. Improvement of TMJ discomfort appears more likely to occur in patients with unilateral anterior disc displacement and with an apparent organic disorder, such as a joint effusion.

Adverse events during CT colonography for screening, diagnosis and preoperative staging of colorectal cancer: a Japanese national survey.

OBJECTIVES: To retrospectively evaluate the frequencies and magnitudes of adverse events associated with computed tomographic colonography (CTC) for screening, diagnosis and preoperative staging of colorectal cancer. METHODS: A Japanese national survey on CTC was administered by use of an online survey tool in the form of a questionnaire. The questions covered mortality, colorectal perforation, vasovagal reaction, total number of examinations, and examination procedures. The survey data was collated and raw frequencies were determined. Fisher's exact test was used to determine differences in event rates between groups. RESULTS: At 431 institutions, 147,439 CTC examinations were performed. No deaths were reported. Colorectal perforations occurred in 0.014% (21/147,439): 0.003% (1/29,823) in screening, 0.014% (13/91,007) in diagnosis and 0.028% (7/25,330) in preoperative staging. The perforation risk was significantly lower in screening than in preoperative staging CTC procedures (p = 0.028). Eighty-one per cent of perforation cases (17/21) did not require emergency surgery. Vasovagal reaction occurred in 0.081% (120/147,439): 0.111% (33/29,823) in screening, 0.088% (80/91,007) in diagnosis and 0.028% (7/25,330) in preoperative staging. CONCLUSIONS: The risk of colorectal perforation and vasovagal reaction in CTC is low. The frequency of colorectal perforation associated with CTC is least in the screening group and greatest in the preoperative-staging group. KEY POINTS: • The colorectal perforation rate during preoperative-staging CTC was 0.028 %. • The perforation rates for screening and diagnosis were 0.003 % and 0.014 %, respectively. • The perforation risk is significantly lower in screening than in preoperative staging. • Eighty-one per cent of perforation cases did not require emergency surgery. • Use of an automatic colon insufflator can reduce the risk of bowel perforation.

Evaluation of the role of splint therapy in the treatment of temporomandibular joint pain on the basis of MRI evidence of altered disc position.

OBJECTIVE: To clarify whether altering temporomandibular joint (TMJ) condyle and disc positions by occlusal splint (splint) therapy relieves TMJ pain and to determine whether splint therapy facilitates improvement of the ranges of condyle and articular disc motions. STUDY DESIGN: A total of 150 joints of 75 patients admitted with TMJ pain/discomfort were evaluated. A visual analog scale for TMJ pain was administered during visits following the start of splint treatment. At the start of splint treatment, MRI was performed with/without splint insertion, after which condyle/disc movements were evaluated. Disc position and function, disc configuration, joint effusion, osteoarthritis, and the bone marrow were evaluated. Pearson's correlation coefficients, linear regression, and multiple regression analyses were used for statistical analysis. RESULTS: Splint-related anterior movement of the condyle was related to TMJ pain. With a biconvex disc and/or bone marrow abnormality, splint treatment was ineffective for reducing TMJ pain. CONCLUSION: Splint therapy was not likely to be successful for any kind of TMJ abnormalities, such as bone marrow abnormalities and/or a biconvex disc appearance on MRI.

Prevalence of temporomandibular disorders among junior high school students who play wind instruments.

OBJECTIVES: This study investigated whether playing wind instruments has adverse effects on musculoskeletal functions among junior high school students who play in music clubs. MATERIAL AND METHODS: The study included 210 junior high school students (35 boys, 175 girls) belonging to 1 of 4 different school clubs that practiced playing wind instruments more than 6 days/week. The mean age of the participants was 14 years. The study was performed using a questionnaire survey and an electromyographic examination of jaw and cervical muscle activities during playing wind instruments. RESULTS: The prevalence of temporomandibular disorders (TMD) among the children playing woodwind (WW) or brass wind (BW) instruments was higher than in those playing non-wind (NW) instruments. Long duration of playing WW with a reed mouthpiece or BW with a small mouthpiece was suggested to affect the incidence of TMD, which was more marked in girls than in boys, irrespective of height or weight. Muscle activity in the masseter muscle during playing an instrument was significantly higher in the BW with a small mouthpiece group than in the NW group (p < 0.05). In cervical muscles, muscle activity of both the sternocleidomastoid and trapezius muscles was higher during playing BW than in the case of other instruments, and activity in the sternocleidomastoid muscle was significantly higher in the BW with a small mouthpiece group than in the case of other instrument groups (p < 0.05). CONCLUSIONS: Playing wind instruments may have adverse effects on musculoskeletal functions among junior high school students playing in music clubs as compared with playing NW instruments. The prevalence of TMD among the students playing wind instruments was higher than in those playing other instruments. Long duration of playing those instruments affects musculoskeletal function, and this effect is more marked in girls than in boys, irrespective of height or weight.

Evaluation of dose reduction and image quality in CT colonography: comparison of low-dose CT with iterative reconstruction and routine-dose CT with filtered back projection.

OBJECTIVE: To prospectively evaluate the radiation dose and image quality comparing low-dose CT colonography (CTC) reconstructed using different levels of iterative reconstruction techniques with routine-dose CTC reconstructed with filtered back projection. METHODS: Following institutional ethics clearance and informed consent procedures, 210 patients underwent screening CTC using automatic tube current modulation for dual positions. Examinations were performed in the supine position with a routine-dose protocol and in the prone position, randomly applying four different low-dose protocols. Supine images were reconstructed with filtered back projection and prone images with iterative reconstruction. Two blinded observers assessed the image quality of endoluminal images. Image noise was quantitatively assessed by region-of-interest measurements. RESULTS: The mean effective dose in the supine series was 1.88 mSv using routine-dose CTC, compared to 0.92, 0.69, 0.57, and 0.46 mSv at four different low doses in the prone series (p < 0.01). Overall image quality and noise of low-dose CTC with iterative reconstruction were significantly improved compared to routine-dose CTC using filtered back projection. The lowest dose group had image quality comparable to routine-dose images. CONCLUSIONS: Low-dose CTC with iterative reconstruction reduces the radiation dose by 48.5 to 75.1% without image quality degradation compared to routine-dose CTC with filtered back projection. KEY POINTS: • Low-dose CTC reduces radiation dose ≥ 48.5% compared to routine-dose CTC. • Iterative reconstruction improves overall CTC image quality compared with FBP. • Iterative reconstruction reduces overall CTC image noise compared with FBP. • Automated exposure control with iterative reconstruction is useful for low-dose CTC.

Colonic distention at CT colonography: randomized evaluation of both IV hyoscine butylbromide and automated carbon dioxide insufflation.

OBJECTIVE: The purpose of this article is to evaluate the efficacy of IV hyoscine butylbromide as a bowel relaxant and automated carbon dioxide insufflation in CT colonography in terms of colonic distention and perceived burden. SUBJECTS AND METHODS; Two hundred twenty-four participants were randomly allocated to one of four groups: control (no bowel relaxant and IV saline placebo before CT colonography with manual carbon dioxide insufflation), hyoscine butylbromide (IV hyoscine butylbromide before examination with manual carbon dioxide insufflation), automated (no bowel relaxant before examination with automated carbon dioxide insufflation), and combined (hyoscine butylbromide before examination with automated carbon dioxide insufflation). The degree of colonic distention on a 4-point scale, examination time, and participants' satisfaction, as measured by their responses to a questionnaire, were assessed. RESULTS: The mean distention grades of all the colonic segments and both positions were 3.22 in the control group, 3.28 in the hyoscine butylbromide group, 3.77 in the automated group, and 3.74 in the combined group. Compared with manual carbon dioxide insufflation, automated carbon dioxide insufflation significantly improved the clinical adequacy of colonic distention and shortened examination time. No statistically significant difference was seen in the clinical adequacy of distention between participants who received hyoscine butylbromide and those who did not, or in examination time. Overall, the participants' experiences were not different. CONCLUSION: Colonic distention was statistically significantly improved by automated carbon dioxide insufflation, but not by the administration of hyoscine butylbromide. The participants' tolerance was similar in each group.

Effect of listening to music and essential oil inhalation on patients undergoing screening CT colonography: a randomized controlled trial.

OBJECTIVE: To prospectively evaluate the effect of listening to music and inhaling aroma oil on patients undergoing screening computed tomography colonography. MATERIALS AND METHODS: Two hundred and twenty four participants were randomly allocated to one of the four groups including: (1) combined music and aroma, (2) music alone, (3) aroma alone, and (4)control. The visual analog scale for pain and a questionnaire were used for subjective outcomes. We also used a pre-test­post-test design to compare the differences in blood pressure and heart rate as objective outcomes. RESULTS: There were no statistical differences between the control group and other groups in the visual analog scale or changes in heart rate. Changes in blood pressure were similar. Participants reported good overall experiences. There were no differences in terms of overall satisfaction, pain rating, willingness to repeat the computed tomography colonography procedure in the future, or preference between colonoscopy and computed tomography colonography. More participants using music and/or aroma requested music and/or aroma during the next computed tomography colonography (P < 0.0001). CONCLUSION: Although audio and olfactory intervention had little effect on perceived pain or discomfort and vital signs, participants who listened to music and inhaled aroma during the computed tomography colonography preferred music and aroma during the next computed tomography colonography.

Effects of repeated tooth pulp stimulation on concentrations of plasma catecholamines, corticosterone, and glucose in rats.

In this study, we examined whether tooth pulp stimulation (TPS) affects the stress responses in anesthetized rats. As for stress response indices, we monitored changes in the concentrations of plasma catecholamines (CAs) (adrenaline, noradrenaline, and dopamine), corticosterone (CS), and glucose (Glu). We observed that repeated TPS attenuated plasma adrenaline, dopamine, CS, and Glu levels compared with those of sham-TPS. After administering naloxone, an opioid antagonist, repeated TPS reversed the decreases in plasma CAs, CS, and Glu. These findings showed that the effects of repeated TPS may be mediated by endogenous opioid administration. Our findings suggest that repeated TPS can induce stress-analgesia and that an endogenous descending pain modulation system exists.

Comparison of joint pain in patients diagnosed with and without articular disc displacement without reduction based on the Research Diagnostic Criteria for Temporomandibular Disorders.

OBJECTIVE: We compared joint pain (JP) in patients diagnosed with and without articular disc displacement without reduction (ADD) based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and identified the characteristics of each JP. STUDY DESIGN: Fifty-eight patients with restricted mouth opening and pain in temporomandibular joint (TMJ) and with a magnetic resonance imaging diagnosis of ADD were selected. Diagnosis of ADD + JP and nonADD + JP was made with the use of the RDC/TMD. RESULTS: A multiple regression analysis of the data disclosed a positive correlation between range of motion on maximum assisted mouth opening and visual analog scale (VAS) (severity of JP) in the ADD + JP group, and between chronic pain grade (CPG) and VAS in the nonADD + JP group. A significant difference was observed between ADD + JP and nonADD + JP groups in CPG; CPG was higher in the nonADD + JP than in the ADD + JP group. CONCLUSIONS: It is suggested that JP related and unrelated to ADD can indicate different types of disease.

Causes of persistent joint pain after arthrocentesis of temporomandibular joint.

PURPOSE: The present study was undertaken to elucidate the factors responsible for the failure of arthrocentesis to cure persistent joint pain in patients with nonreducing articular disc displacement in the temporomandibular joint (TMJ). PATIENTS AND METHODS: Thirty-six patients with internal derangement of the TMJ were selected. Magnetic resonance imaging was used to examine the configuration and position of the articular discs, cortical changes, and bone marrow abnormalities in the condyle and the presence of joint effusion. Arthrocentesis was then performed, and the patients were followed for 6 weeks. The results were then classified as poor or improved. RESULTS: The effects of arthrocentesis did not depend on the configuration of the disc, disc position and motion, or bone marrow abnormalities. Joints with no or minimal amounts of joint effusion achieved a good response to arthrocentesis. Joints with erosive cortical changes of the condyle were less responsive to arthrocentesis. CONCLUSION: Persistent joint pain after arthrocentesis is generally associated with extensive amounts of joint effusion or erosive cortical changes of the condyle.

Visible fluorescence spectroscopy of single proteins at liquid-helium temperature.

Fluorescence spectroscopy of single proteins at liquid-helium temperatures reveals a relation between structural dynamics and biological functions of the proteins. The technical difficulties in detecting visible fluorescence are chromatic aberration and optical background. They were overcome by a new optical design using reflective optics and employing two-photon excitation. The fluorescence spectrum of single green-fluorescent proteins taken at a temperature of 1.5 K makes a distinction between different metastable conformations that last for tens of seconds.