Background/Aims: The use of endoscopic intervention (EI) for acute biliary pancreatitis (ABP) remains controversial because the severity of biliary obstruction/cholangitis/pancreatitis is not reflected in the indications for early EI (EEI). Methods: A total of 148 patients with ABP were included to investigate 1) the differences in the rate of worsening cholangitis/pancreatitis between the EEI group and the early conservative management (ECM) group, especially for each severity of cholangitis/pancreatitis, and 2) the diagnostic ability of imaging studies, including endoscopic ultrasound (EUS), to detect common bile duct stones (CBDSs) in the ECM group. Results: No differences were observed in the rate of worsening cholangitis between the EEI and ECM groups, regardless of the severity of cholangitis and/or the existence of impacted CBDSs. Among patients without impacted CBDSs and moderate/severe cholangitis, worsening pancreatitis was significantly more frequent in the EEI group (18% vs. 4%, p=0.048). In patients in the ECM group, the sensitivity and specificity for detecting CBDSs were 73% and 98%, respectively, for EUS, whereas the values were 13% and 92%, respectively, for magnetic resonance cholangiopancreatography. Conclusions EEI should be avoided in the absence of moderate/severe cholangitis and/or impacted CBDSs because of the high rate of worsening pancreatitis. EUS can contribute to the accurate detection of residual CBDSs, for the determination of the need for elective EI.

Methods: Volunteers over 50 years of age underwent radiographic analysis. Radiographic parameters including pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), thoracic kyphosis, and sagittal vertical axis (SVA) were measured. The the three Scoliosis Research Society-Schwab sagittal modifiers (PT, SVA, PI–LL) were categorized and the KL grade was assessed. Differences in spinopelvic parameters and Oswestry Disability Index (ODI) scores among KL grades were evaluated. Results: A total of 396 volunteers (160 men, 236 women; mean age, 74.4 years) were analyzed. PI–LL and PT in KL4 were significantly higher compared to that in the other KL grades. However, there were no significant group differences in SVA. In women, but not in men, higher frequencies of the worst modifier grade (++) were observed for PI–LL and PT in the KL3 and KL4 groups compared to those for the other KL grades. In women, the ODI score in KL4 was worse compared to that in the other KL grades. Conclusions Individuals over 50 years of age with severe knee osteoarthritis had poor lumbo-pelvic sagittal alignment. Moreover, the progression severity of knee osteoarthritis had more impact onstronger relationship with lumbo-pelvic malalignment and disability-related low back pain in women than in men.

Methods: The subjects were 473 volunteers. They were divided into two groups (activity and non-activity) according to participation or non-participation in sporting activities using a self-filled questionnaire. The evaluation items were height, weight, grip strength, bone density, Hospital Anxiety and Depression Scale (HADS) score, standing radiographic parameters, PRO (evaluated by EuroQol-5 dimension [EQ-5D], Oswestry Disability Index [ODI]), and NDI. Results: There were 101 males in the non-activity group and 69 in the activity group and 178 females in the non-activity group and 125 in the activity group. For the males, the evaluation items with significant influence were cervical lordosis (non-activity group:activity group, 17°:22°) and T1 slope minus cervical lordosis (10°:6°, p <0.05). For the females, the evaluation items with significant influence were sagittal vertical axis (28:14 mm), HADS (10.4:8.4), EQ-5D (0.79:0.86), ODI (17:12), and NDI (12:9, p <0.01). HADS and PRO in the females were significantly correlated with the EQ-5D (−0.40), ODI (0.43), and NDI (0.55). Conclusions Males who participated in sporting activities had better cervical spine alignment but no effect on PRO. Females with sporting activities had better spinal global alignment and less mental stress. It is suggested that sporting activity in females might be associated with PRO because HADS highly correlates with PRO.

Objective: Maternal embryonic leucine zipper kinase (MELK) is receiving an attention as a therapeutic target in various types of cancers. In this study, we aimed to evaluate the prognostic significance of MELK expression in ovarian cancer using clinical samples, and assessed the efficacy of a small molecule MELK inhibitor, OTS167, using patient-derived ovarian cancer cells as well as cell lines. Methods: Expression levels of MELK in 11 ovarian cancer cell lines were confirmed by western blotting. Inhibitory concentration of OTS167 was determined by colorimetric assay.MELK messenger RNA (mRNA) expression was evaluated in 228 ovarian cancer patients by quantitative polymerase chain reaction. Growth inhibition of OTS167 was also evaluated using freshly-isolated primary ovarian cancer cells including spheroid formation condition. Results: MELK mRNA expression was significantly higher in ovarian cancer than in normal ovaries (p<0.001), and high MELK mRNA expression was observed in patients with advanced stage, positive ascites cytology and residual tumor size. Patients with high MELK mRNA expression showed shorter progression-free survival (p=0.001). Expression of MELK was also confirmed in 10 of 11 ovarian cancer cell lines tested, and the half maximal inhibitory concentration of MELK inhibitor, OTS167, ranged from 9.3 to 60 nM. Additionally, OTS167 showed significant growth inhibitory effect against patient-derived ovarian cancer cells, regardless of their tumor locations, histologic subtypes and stages. Conclusions We demonstrated MELK as both a prognostic marker and a therapeutic target for ovarian cancer using clinical ovarian cancer samples. MELK inhibition by OTS167 may be an effective approach to treat ovarian cancer patients.

STUDY DESIGN: Cross-sectional cohort study.PURPOSE: This study aimed to investigate the relationship between hypertension and spino-pelvic sagittal alignment in middle-aged and elderly individuals.OVERVIEW OF LITERATURE: Positive global sagittal alignment is associated with poor health-related quality of life. Hypertension is associated with tissue microcirculation disorders of the skeletal muscle. We hypothesized that hypertension may be involved in positive global sagittal alignment.METHODS: In this institutional review board-approved study, 655 participants (262 men and 393 women; mean age, 72.9 years; range, 50–92 years) who underwent musculoskeletal screening in Toei town, Aichi, Japan were included. Whole spine and pelvic radiographs were taken, and radiographic parameters (thoracic kyphosis, lumbar lordosis, pelvic tilt, sacral slope, pelvic incidence, and sagittal vertical axis [SVA]) were measured using an image-analysis software. Hypertension was assessed using the standard criteria. The study participants were divided into three subgroups as per age (50–64 years, 65–74 years, and ≥75 years). We examined the differences in the radiographic parameters of those with and without hypertension in each age subgroup.RESULTS: In each age subgroup, there was no significant difference in the age and sex of those with and without hypertension. SVA was significantly shifted forward in the hypertension group than in the non-hypertension group in those aged 50–64 years old (32.4 mm vs. 16.0 mm, p=0.018) and in those aged 65–74 years old (42.7 mm vs. 30.6 mm, p=0.012). There was no significant difference between the hypertension and non-hypertension groups in terms of the alignment of the lumbar and thoracic spine in all the subgroups. In multivariate analysis, hypertension was a significant independent factor of forward-shifted SVA (standardized beta 0.093, p=0.015).CONCLUSIONS: This study showed that hypertension was associated with forward-shifted global sagittal alignment.
Aged ; Animals ; Cohort Studies ; Female ; Humans ; Hypertension ; Incidence ; Japan ; Kyphosis ; Lordosis ; Male ; Mass Screening ; Microcirculation ; Multivariate Analysis ; Muscle, Skeletal ; Quality of Life ; Spine

The autonomic nervous system plays critical roles in maintaining homeostasis in humans, directly regulating inflammation by altering the activity of the immune system. The cholinergic anti-inflammatory pathway is a well-studied neuroimmune interaction involving the vagus nerve. CD4-positive T cells expressing β2 adrenergic receptors and macrophages expressing the alpha 7 subunit of the nicotinic acetylcholine receptor in the spleen receive neurotransmitters such as norepinephrine and acetylcholine and are key mediators of the cholinergic anti-inflammatory pathway. Recent studies have demonstrated that vagus nerve stimulation, ultrasound, and restraint stress elicit protective effects against renal ischemia-reperfusion injury. These protective effects are induced primarily via activation of the cholinergic anti-inflammatory pathway. In addition to these immunological roles, nervous systems are directly related to homeostasis of renal physiology. Whole-kidney three-dimensional visualization using the tissue clearing technique CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) has illustrated that renal sympathetic nerves are primarily distributed around arteries in the kidneys and denervated after ischemia-reperfusion injury. In contrast, artificial renal sympathetic denervation has a protective effect against kidney disease progression in murine models. Further studies are needed to elucidate how neural networks are involved in progression of kidney disease.
Acetylcholine ; Arteries ; Autonomic Nervous System ; Cholinergic Neurons ; Homeostasis ; Humans ; Immune System ; Inflammation ; Kidney Diseases ; Kidney ; Macrophages ; Nervous System ; Neurotransmitter Agents ; Norepinephrine ; Optogenetics ; Physiology ; Receptors, Adrenergic ; Receptors, Nicotinic ; Reperfusion Injury ; Spleen ; Sympathectomy ; Sympathetic Nervous System ; T-Lymphocytes ; Ultrasonography ; Vagus Nerve ; Vagus Nerve Stimulation

STUDY DESIGN: A retrospective study. PURPOSE: To investigate the incidence of iliac screw loosening with a two-rod vs. multi-rod construct and the effect on clinical and radiographic outcomes after surgery for adult spinal deformity (ASD). OVERVIEW OF LITERATURE: Multi-rod construct is useful for preventing rod fracture in ASD surgery. However, limited information is available regarding the incidence of iliac screw loosening after corrective fusion surgery using a multi-rod construct. METHODS: Total 106 patients with ASD (24 men and 82 women; mean age, 68 years) who underwent corrective fusion surgery using bilateral iliac screws and were followed up for at least 1 year were reviewed. The following variables were compared between patients who underwent surgery with a two-rod and multi-rod construct: age, sex, bone mineral density (BMD), fusion level, high-grade osteotomy, L5/S interbody fusion, screw loosening (upper instrumented vertebra [UIV], S1, and iliac), rod fracture, proximal junctional kyphosis, spinopelvic parameters, and Oswestry Disability Index (ODI) score. We also compared patients with and without iliac screw loosening in the multi-rod construct group. RESULTS: Of the 106 patients, 55 underwent surgery with a conventional two-rod construct and 51 with a multi-rod construct (three rods in 16, four rods in 35). Iliac and UIV screw loosening was observed in 24 patients (21%) and 35 patients (33%), respectively. The multi-rod group showed significantly higher incidence of iliac and UIV screw loosening and lower incidence of rod fracture. Patients with iliac screw loosening had a lower BMD than those without screw loosening; however, no significant differences were observed in the spinopelvic parameters or the ODI score. CONCLUSIONS: The use of multi-rod constructs led to a higher incidence of junctional screw loosening than the use of conventional two-rod constructs, especially in patients with osteoporosis. Iliac screw loosening did not affect sagittal alignment or clinical outcome in the short term.
Adult ; Bone Density ; Congenital Abnormalities ; Female ; Humans ; Incidence ; Kyphosis ; Male ; Osteoporosis ; Osteotomy ; Retrospective Studies ; Spine

BACKGROUND/AIMS: Although both radial- and convex-arrayed endoscopic ultrasonography (EUS) scopes are widely used for observational EUS examinations, there have been few comparative studies on their power of visualization. The aim of this study was to evaluate the capability of these EUS scopes for observation of the pancreatobiliary junction. METHODS: The rate of successful visualization of the pancreatobiliary junction was retrospectively compared between a radial-arrayed and a convex-arrayed echoendoscope, from a prospectively maintained database. Study periods were defined as January 2010 to December 2012 for the radial group, and February 2015 to October 2016 for the convex group because the respective scope was mainly used during those periods. RESULTS: During the study period, 1,660 cases with radial EUS and 1,984 cases with convex EUS were recruited. The success rates of observation of the pancreatobiliary junction were 80.0% and 89.5%, respectively (p < 0.0001). CONCLUSIONS: The capability of visualization of the pancreatobiliary junction in observational EUS was found to be better with a convex-arrayed than with a radial-arrayed echoendoscope.
Endosonography ; Prospective Studies ; Retrospective Studies

STUDY DESIGN: Large cohort study. PURPOSE: To clarify spinal sagittal alignment and health-related quality of life (HRQOL) according to sex in volunteers aged >50 years with cervical deformity (CD). OVERVIEW OF LITERATURE: Adult spinal deformities, especially those associated with lumbosacral lesions, are more frequent in females; however, CD is observed to a greater extent in males. METHODS: We divided 656 volunteers (263 males, 393 females; age, 50–89 years [mean, 73 years]) as follows: males with CD (CDM; 82 patients); males without CD (NCDM, 181); females with CD (CDF, 36); and females without CD (NCDF, 357). CD was defined as C2–7 sagittal vertical axis (SVA) ≥40 mm. We measured pelvic tilt (PT), pelvic incidence minus lumbar lordosis (PI−LL), thoracic kyphosis, T1 slope, cervical lordosis, C7 SVA, and C2–7 SVA. HRQOL was evaluated using EuroQOL five dimensions questionnaire (EQ-5D). RESULTS: In CDM, NCDM, CDF, and NCDF groups, the respective parameters were as follows: PT: 15°, 14°, 26°, and 21°; PI−LL: 7°, 5°, 16°, and 10°; C2–7 SVA: 49, 24, 46, and 20 mm; C7 SVA: 61, 40, 75, and 47 mm; and EQ-5D: 0.82, 0.88, 0.78, and 0.81. PT and PI−LL were significantly greater in the CDF group than in the NCDF group (p < 0.05) but were not significantly different between CDM and NCDM groups. The CDF group already showed deterioration of spinopelvic alignment, although it was maintained in the CDM group. EQ-5D in showed significantly greater deterioration the CDM group than in the NCDM group; deterioration of lumbopelvic parameters had less influence in males (p < 0.05). CONCLUSIONS: Sagittal spinal deformity may have different mechanisms in males and females. The deterioration of spinal sagittal alignment in males may originate from the cervical spine, and CD may be associated with HRQOL.
Adult ; Animals ; Cohort Studies ; Congenital Abnormalities* ; Female* ; Humans ; Incidence ; Kyphosis ; Lordosis ; Male* ; Quality of Life* ; Sex Characteristics ; Spine ; Volunteers

STUDY DESIGN: Retrospective case series. PURPOSE: To investigate the relationship between tumor location and clinical characteristics. OVERVIEW OF LITERATURE: Hemangioblastoma is a rare disease that develops in the central nervous system. Magnetic resonance imaging (MRI) is useful to evaluate hemangioblastomas. Hemangioblastoma's location is designated as intramedullary, intramedullary+extramedullary, or extramedullary by MRI. METHODS: We analyzed 11 patients who underwent surgery for spinal hemangioblastoma. Using T1 contrast axial MRI data, the cases were divided into three groups (intramedullary, intramedullary+extramedullary, and extramedullary). Patient demographics, MRI findings, and preoperative neurological status were analyzed and compared for each group. RESULTS: The average age of patients with intramedullary, intramedullary+extramedullary, and extramedullary hemangioblastoma was 34.0, 64.4, and 67.5 years, respectively. Patients in the intramedullary hemangioblastoma group were younger than the other groups. Extramedullary cases had a smaller syrinx compared to the other groups. CONCLUSIONS: Age may play an important role in the hemangioblastoma tumor location and the subsequent diagnosis by an MRI.
Central Nervous System ; Demography ; Diagnosis ; Hemangioblastoma* ; Humans ; Magnetic Resonance Imaging ; Rare Diseases ; Retrospective Studies