Nationwide multicenter study on adverse events associated with a patency capsule: Additional survey of appropriate use of patency capsule study.

BACKGROUND AND AIM: The PillCam patency capsule (PC) without a radio frequency identification tag was released to preclude retention of the small bowel capsule endoscope (CE) in Japan in 2012. We conducted a multicenter study to determine tag-less PC-related adverse events (AEs). METHODS: We first conducted a retrospective survey using a standardized data collection sheet for the clinical characteristics of PC-related AEs among 1096 patients collected in a prospective survey conducted between January 2013 and May 2014 (Cohort 1). Next, we retrospectively investigated additional AEs that occurred before and after Cohort 1 within the period June 2012 and December 2014 among 1482 patients (Cohort 2). RESULTS: Of the 2578 patients who underwent PC examinations from both cohorts, 74 AEs occurred among 61 patients (2.37%). The main AEs were residual parylene coating in 25 events (0.97%), PC-induced small bowel obstruction, suspicious of impaction, in 23 events (0.89%), and CE retention even after patency confirmation in 10 events (0.39%). Residual parylene coating was significantly associated with Crohn's disease (P < 0.01). Small bowel obstruction was significantly associated with physicians with less than 1 year of experience handling the PC and previous history of postprandial abdominal pain (P < 0.01 and P < 0.03, respectively). CE retention was ascribed to erroneous judgment of PC localization in all cases. CONCLUSIONS: This large-scale multicenter study provides evidence supporting the safety and efficiency of a PC to preclude CE retention. Accurate PC localization in patients without excretion and confirmation of previous history of postprandial abdominal pain before PC examinations is warranted (UMIN000010513).

Cysts of the ligamentum flavum are often linked to ischemic conditions: A morphological study.

"Cysts of the ligamentum flavum (cysts-LF)" is the term for non-neoplastic cystic lesion involving LF. The aim of the present study was to elucidate the histopathological characteristics and pathogenesis of "cysts-LF". Herein, we defined cysts-LF as spinal cysts containing degenerative LF components. From archival cases, we investigated 18 symptomatic cysts-LF surgically removed from 18 patients (13 males and five females; median age 68.5 years [range, 42-86 years]). The elastic fibers of LF components in the wall were separated and/or torn, and cyst walls were accompanied by chondroid metaplasia (17 cases), myxoid changes (13 cases), ossification (11 cases), amyloid deposits (14 cases), hemosiderosis (six cases), granular/smudgy calcification (four cases), synovial cell linings (three cases), and severe inflammatory infiltrates (one case). These histologic features of our cysts-LF were shared by previously reported "cysts-LF." Fourteen cysts-LF demonstrated vascular stenosis/occlusion, and eight showed thick hyalinized vessels, suggesting local circulatory insufficiency. Eight cases (44%) exhibited lipomembranous fat necrosis, accompanied by hyalinized vascular changes (p = 0.003). Ischemic conditions were observed in nearly half of the present cysts-LF, and may be one of the main contributing factors for the formation of cysts-LF, via degeneration and cystic changes in the LF.

Does the presence of preoperative neck pain impact clinical outcomes after posterior decompression in patients with cervical ossification of the posterior longitudinal ligament?: Retrospective multicenter cohort study.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To evaluate how preoperative neck pain influences clinical outcomes following posterior decompression for cervical ossification of the posterior longitudinal ligament (OPLL). SETTING: Fourteen medical institutions in Japan. METHODS: We enrolled 90 patients with cervical OPLL who underwent posterior decompression and were followed for a minimum of two years. We collected demographic data, medical history, and imaging findings. Patients were divided into two groups based on preoperative neck pain presence (Pre-op. neck pain (-) and (+) groups), and their outcomes were compared. RESULTS: There were no significant differences in patient demographics between the Pre-op. neck pain (-) and (+) groups. Both groups showed similar distributions of ossification types and K-line positivity. Perioperative complications were comparable between the two groups. Radiographic analysis revealed no significant differences in C2-7 angles or cervical range of motion, pre- and postoperatively. Both groups demonstrated significant improvement in postoperative Japanese orthopedic association (JOA) scores, but there were no significant differences in scores or recovery rates. In the Pre-op. neck pain (-) group, factors associated with appearance of postoperative neck pain included pre- and postoperative lower JOA scores and larger C2-7 angles in neutral and extension positions. CONCLUSIONS: It emerges that lower pre- and postoperative JOA scores or larger C2-7 angles in neutral and extension positions predispose to postoperative neck pain even in those patients without preoperative neck pain. Therefore, this is worth discussing at the time of consenting patients for surgical decompression and fixation.

Upregulation of the Long Noncoding RNA HULC by Hepatitis C Virus and Its Regulation of Viral Replication.

BACKGROUND: Many long noncoding RNAs (lncRNAs) have important roles in biological processes. The lncRNA HULC was found to be upregulated in human hepatoma tissues. HULC is thought to be involved in multiple steps of hepatoma development and progression; however, the relationship between HULC and hepatitis C virus (HCV) infection, which is a leading cause of hepatoma, remains unclear. METHODS: We examined the effect of HCV replication on HULC expression and the underlying mechanism using cell culture systems. Subsequently, we tested the effect of HULC suppression and overexpression on HCV replication. Finally, we examined the impact of HCV eradication on HULC expression using human liver tissue and blood samples. RESULTS: HCV replication increased HULC expression in cell cultures. A promoter assay showed that an HCV nonstructural protein, NS5A, increased HULC transcription. HULC suppression inhibited HCV replication; conversely, its overexpression enhanced HCV replication. These effects on HCV replication seemed to occur by the modification of HCV translation. Measurements from human liver and blood samples showed that HCV eradication significantly reduced HULC levels in the liver and blood. CONCLUSIONS: HCV infection increases HULC expression in vitro and in vivo. HULC modulates HCV replication through an HCV internal ribosome entry site-directed translation step.

Oral Corticosteroids Impair Mucin Production and Alter the Posttransplantation Microbiota in the Gut.

INTRODUCTION: Gut microbiota alterations cause inflammation in patients with ulcerative colitis (UC). Fecal microbiota transplantation (FMT) enables manipulating the microbiota's composition, but the mechanisms underlying colonization of the posttransplantation microbiota are poorly understood. METHODS: In this open-label, nonrandomized study, the FMT efficacy and changes in the gut microbiota were evaluated in 8 UC patients with mild-to-moderately active endoscopic colonic lesions. Compositional changes in the fecal and mucosal microbiotas between donors and recipients were examined via 16S rRNA-based sequencing. To investigate the effects of oral corticosteroids on microbiota colonization, FMT was performed in germ-free prednisolone (PSL)-administered mice to examine the factors determining colonization. RESULTS: Four UC patients achieved clinical remission (CR) after FMT, and 3 also achieved endoscopic remission. The fecal microbiotas of the CR patients changed similar to those of the donors after FMT. The mucin-coding gene, MUC2, was less expressed in the colons of the PSL-dependent patients than in the PSL-free patients. In the mice, PSL treatment decreased the fecal mucin production and altered the posttransplantation fecal microbiota composition. Adding either exogenous mucin or the mucin secretagogue, rebamipide, partially alleviated the PSL-induced dysbiosis of the gut microbiota. Administering rebamipide with FMT from healthy donors relieved inflammation in mice with Enterococcus faecium-induced colitis. CONCLUSION: Colonic mucin controlled the gut microbiota composition, and oral corticosteroid treatment modified the gut microbiota partly by reducing the colonic mucin.

Influence of anticoagulants on the risk of delayed bleeding after gastric endoscopic submucosal dissection: a multicenter retrospective study.

BACKGROUND AND AIMS: Delayed bleeding after gastric endoscopic submucosal dissection (ESD) in patients receiving anticoagulants remains an unpreventable adverse event. Although direct-acting oral anticoagulants (DOACs) have superior efficacy in preventing thromboembolism, their effects on the occurrence of delayed bleeding remain unclear. This study aimed to elucidate the clinical effect of DOACs on delayed bleeding after gastric ESD. PATIENTS AND METHODS: We retrospectively examined 728 patients who received anticoagulants and were treated for gastric neoplasms with ESD in 25 institutions across Japan. Overall, 261 patients received DOACs, including dabigatran (92), rivaroxaban (103), apixaban (45) and edoxaban (21), whereas 467 patients were treated with warfarin. RESULTS: Delayed bleeding occurred in 14% of patients taking DOACs, which was not considerably different in patients receiving warfarin (18%). Delayed bleeding rate was significantly lower in patients receiving dabigatran than in those receiving warfarin and lower than that observed for other DOACs. Multivariate analysis showed that age ≥ 65, receiving multiple antithrombotic agents, resection of multiple lesions and lesion size ≥ 30 mm were independent risk factors, and that discontinuation of anticoagulants was associated with a decreased risk of bleeding. In multivariate analysis among patients taking DOACs, dabigatran therapy was associated with a significantly lower risk of delayed bleeding. CONCLUSIONS: The effects of DOACs on delayed bleeding varied between agents, but dabigatran therapy was associated with the lowest risk of delayed bleeding. Switching oral anticoagulants to dabigatran during the perioperative period could be a reasonable option to reduce the risk of delayed bleeding after gastric ESD.

Safety and efficacy of sorafenib followed by regorafenib or lenvatinib in patients with hepatocellular carcinoma.

AIM: Sequential administration of sorafenib followed by regorafenib or lenvatinib is effective against advanced hepatocellular carcinoma (HCC). In this study, we compared the safety profiles and anti-tumor effects of sequential sorafenib and regorafenib or lenvatinib therapy in patients with HCC. METHODS: We investigated adverse events, treatment responses and dose intensities in patients with HCC who were consecutively treated with sorafenib followed by regorafenib or lenvatinib at the individual level. RESULTS: Each group included 20 patients. The safety profiles of regorafenib and sorafenib were similar. The severity of hypophosphatemia, palmar-plantar erythrodysesthesia syndrome, and decreased neutrophil counts associated with regorafenib or sorafenib was similar in 12 patients. Conversely, the incidences and grades of adverse events differed between sorafenib and lenvatinib treatment. The anti-tumor effects of regorafenib and lenvatinib compared with sorafenib were significantly different for each patient. The response to treatment and progression-free survival were comparable for regorafenib and lenvatinib. The median relative dose intensities during the first 56 days of regorafenib and lenvatinib treatment were 83.6 and 80.0%, respectively. CONCLUSIONS: Similar adverse events were experienced by patients during consecutive treatment with sorafenib and regorafenib, which was not observed during treatment with sorafenib and lenvatinib. The obtained safety profile of sorafenib provided meaningful insights for selecting sequential therapy for patients with advanced HCC.

Non-adherence to Medications in Pregnant Ulcerative Colitis Patients Contributes to Disease Flares and Adverse Pregnancy Outcomes.

BACKGROUND: Adherence to medications is important to maintain disease under control and to prevent complications in pregnant patients with ulcerative colitis (UC). To evaluate the incidence of non-adherence during pregnancy and its effect on relapse and pregnancy outcomes, we conducted a multicenter prospective study using a patient self-reporting system without physician interference. METHODS: Sixty-eight pregnant UC women were recruited from 17 institutions between 2013 and 2019. During the course of pregnancy, questionnaires were collected separately from patients and physicians, to investigate the true adherence to medications, disease activity, and birth outcomes. Multivariable logistic regression analysis was performed to identify the risk factors for the relapse or adverse pregnancy outcomes. RESULTS: Of 68 pregnancy, 15 adverse pregnancy outcomes occurred in 13 patients. The rate of self-reported non-adherence was the greatest to mesalamines in the first trimester, which was significantly higher than physicians' estimate (p = 0.0116), and discontinuation was observed in 42.1% of non-adherent group. Logistic regression analysis revealed non-adherence as an independent risk factor for relapse [odds ratio (OR) 7.659, 95% CI 1.928-30.427, p = 0.038], and possibly for adverse pregnancy outcome (OR 8.378, 95% CI 1.350-51.994, p = 0.023). Among the subgroup of patients treated with oral mesalamine alone, the non-adherence was confirmed to be an independent risk factor for relapse (p = 0.002). CONCLUSION: Non-adherence to mesalamine was underestimated by physicians in pregnant UC patients and contributed to disease relapse and possibly on pregnancy outcomes. Preconceptional education regarding safety of medications and risk of self-discontinuation is warranted.

Evaluation of the efficacy and safety of salvage photodynamic therapy by talaporfin sodium for cervical esophageal cancers and lesions larger than 3 cm.

BACKGROUND: Salvage photodynamic therapy with talaporfin sodium has a high local control rate for esophageal cancer after definitive chemoradiotherapy. The eligibility criteria for photodynamic therapy include the absence of invasion to the cervical esophagus and a 3 cm maximum longitudinal lesion length. There is little evidence regarding the efficacy and safety of lesions outside the eligibility criteria. This retrospective cohort study evaluated the efficacy and safety of photodynamic therapy of such lesions. METHODS: Patients with consecutive lesions between February 2016 and May 2020 (n = 36) were enrolled. The local complete response rates and adverse events were compared between patients with cervical and non-cervical lesions and those with lesions larger and smaller than 3 cm. RESULTS: The local complete response rate was 77.8% and was significantly lower in cervical than in non-cervical lesions (20.0% vs 80.6%, p = 0.005). Esophageal stricture, laryngeal pain, and fever were significantly higher in the cervical than in the non-cervical lesion group; however, the detected adverse events were up to grade 2. Laser exposure dose was high in lesions larger than 3 cm (median, 650 vs 400 J; p < 0.001). No significant differences in local complete response rates and adverse effects were noted. One case involving a lesion larger than 3 cm needed balloon dilations for esophageal stricture. CONCLUSIONS: Although salvage esophageal photodynamic therapy was effective for local control with acceptable safety after definitive chemoradiotherapy failure, photodynamic therapy toward cervical lesions had a statistically lower local complete response rate. Lesions larger than 3 cm may be considered treatable.

Comparative analysis of liver functional reserve during lenvatinib and sorafenib for advanced hepatocellular carcinoma.

AIM: Most patients with advanced hepatocellular carcinoma (HCC) have underlying chronic liver disease, which potentially deteriorated the liver functional reserve that often affects the patients' clinical course. We investigated and compared the changes in liver functional reserve during lenvatinib or sorafenib therapy in patients with advanced HCC. METHODS: We prospectively collected medical information about patients with advanced HCC with a Child-Pugh score of 5-7 to compare the liver functional reserve during treatment in those who were treated with lenvatinib or sorafenib. We also evaluated the effect of the change in the liver functional reserve on patients' outcome. Moreover, we analyzed the contributing factors for maintaining the liver functional reserve during treatment. RESULTS: Patients were treated with lenvatinib (n = 45) or sorafenib (n = 157). Forty-five patients in the lenvatinib group and 135 patients in the sorafenib group were selected through a propensity score matching analysis. More patients treated with lenvatinib had a Child-Pugh score that was maintained or improved after 4 and 12 weeks compared with those treated with sorafenib (P = 0.048, P = 0.036, respectively). Lenvatinib was identified as one of the variables that was associated with maintaining Child-Pugh scores. Multivariate analysis revealed that a worsened Child-Pugh score after 4 weeks was an independent unfavorable predictive factor for overall survival. CONCLUSIONS: More patients treated with lenvatinib for advanced HCC maintained their liver functional reserves compared with those treated with sorafenib. Maintaining the liver functional reserve contributed to better outcomes for patients with advanced HCC.

IL-28B variant as a predictor in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy.

BACKGROUND AND AIM: Single-nucleotide polymorphisms (SNPs) of the interleukin-28B (IL-28B) gene are associated with the effectiveness of interferon therapy for chronic hepatitis C infection. Whether the IL-28B genotype affects the course of treatment and the outcomes of patients with advanced hepatocellular carcinoma (HCC) is unknown. METHODS: We detected the IL-28B SNP (rs8099917) using TaqMan PreDesigned SNP Genotyping Assays to assess the effects of the IL-28B genotype on treatment efficacy and prognosis of patients with advanced HCC treated with hepatic arterial infusion chemotherapy (HAIC) between September 2003 and January 2015. RESULTS: The study included 154 patients who received HAIC to treat advanced HCC, among which 27 (17.5%) had the minor genotype, IL-28B rs8099917 TG or GG, and the others had the major genotype, IL-28B rs8099917 TT. The objective response rates of patients with the minor or major genotype were 51.9% and 29.1% (P = 0.022), respectively. Multivariate analysis revealed that the minor genotype remained associated with the response to HAIC (odds ratio, 2.620; P = 0.026). The median overall survival of patients with major or minor genotypes was 14.1 and 16.9 months, respectively, and the overall survival of patients with the major genotype was significantly shorter than that of patients with the minor genotype (P = 0.027). Multivariate analysis revealed that the major genotype was an independent, unfavorable prognostic factor (hazard ratio, 1.720; P = 0.024). Consistent results were obtained in selected populations after propensity score matching analysis. CONCLUSIONS: The IL-28B SNP (rs8099917) will serve as a useful predictor of the outcomes of patients with advanced HCC treated with HAIC.

Analysis of the impact of spinopelvic radiographic parameters on the severity of cervical spondylotic myelopathy.

BACKGROUND: The correlation between spinal radiographic parameters and severity of cervical spondylotic myelopathy (CSM) is controversial. This study aimed to investigate the associations between spinal radiographic parameters and CSM severity, as well as between cervical and other spinopelvic radiographic parameters. METHODS: Patients diagnosed with CSM (N = 118; 77 men) at our hospital from March 2013 to February 2017 were included. The patients' demographic data and the following radiographic parameters were investigated: cervical lordosis (CL), C2-C7 sagittal vertical axis (C2-C7 SVA), T1 slope, thoracic kyphosis, lumbar lordosis, pelvic incidence, sacral slope, pelvic tilt, and sagittal vertical axis (SVA). Cervical cord compression ratio (CCCR) was evaluated on sagittal magnetic resonance imaging. The Japanese Orthopaedic Association (JOA) scoring system was used for clinical evaluation. Correlation analyses were performed among the clinical and radiographic parameters. RESULTS: The JOA score had the strongest correlation with SVA (r = -0.46, p < 0.01), followed by CCCR (r = -0.33, p < 0.01), CL (r = -0.29, p < 0.01), T1 slope (r = -0.29, p = 0.01), and C2-C7 SVA (r = -0.20, p = 0.03). Multivariate linear regression analysis revealed a model predicting the JOA score; JOA = 13.6 - 0.24 × SVA - 4.2 × CCCR (r = 0.51, p < 0.01). Although there was no significant correlation between the cervical and lumbopelvic radiographic parameters, the sequential correlation among the investigated spinopelvic parameters was identified. CONCLUSIONS: CSM severity worsened with spinal malalignment, such as a larger SVA. Though lumbopelvic radiographic parameters did not significantly impact cervical alignment and CSM severity, the sequential correlations among cervical-thoracic-lumbopelvic radiographic parameters were observed. Therefore, SVA is the most relevant radiographic parameter for CSM, but we cannot preclude the possibility that lumbopelvic alignment also affects cervical alignment and CSM severity.

Development of novel diagnostic system for pancreatic cancer, including early stages, measuring mRNA of whole blood cells.

Pancreatic ductal adenocarcinoma (PDAC) is the most life-threating disease among all digestive system malignancies. We developed a blood mRNA PDAC screening system using real-time detection PCR to detect the expression of 56 genes, to discriminate PDAC from noncancer subjects. We undertook a clinical study to assess the performance of the developed system. We collected whole blood RNA from 53 PDAC patients, 102 noncancer subjects, 22 patients with chronic pancreatitis, and 23 patients with intraductal papillary mucinous neoplasms in a per protocol analysis. The sensitivity of the system for PDAC diagnosis was 73.6% (95% confidence interval, 59.7%-84.7%). The specificity for noncancer volunteers, chronic pancreatitis, and patients with intraductal papillary mucinous neoplasms was 64.7% (54.6%-73.9%), 63.6% (40.7%-82.8%), and 47.8% (26.8%-69.4%), respectively. Importantly, the sensitivity of this system for both stage I and stage II PDAC was 78.6% (57.1%-100%), suggesting that detection of PDAC by the system is not dependent on the stage of PDAC. These results indicated that the screening system, relying on assessment of changes in mRNA expression in blood cells, is a viable alternative screening strategy for PDAC.

Danaparoid sodium-based anticoagulation therapy for portal vein thrombosis in cirrhosis patients.

BACKGROUND: Portal vein thrombosis (PVT) is a common complication of cirrhosis. However, in patients with PVT and cirrhosis, there is no clear evidence supporting effective treatment modalities. In this study, we examined the effectiveness and safety of anticoagulation therapy using danaparoid sodium for PVT in patients with cirrhosis. METHODS: This retrospective study assessed 52 cirrhotic patients with PVT treated with danaparoid sodium for 2 weeks between November 2008 and September 2018. The primary outcome measure was the post-treatment status of PVT assessed by reduction in thrombus volume and safety of the therapeutic intervention. PVT status was evaluated with contrast-enhanced computed tomography (CECT). All patients received 1250 units of danaparoid sodium twice daily by intravenous injection for 14 days. Patients on antithrombin III (AT-III) combination therapy were additionally administered 1500 units of AT-III on days 1-5 and days 8-12. Effectiveness was evaluated by CECT from between days 13 and 18. The secondary outcome measure was the prognosis of PVT. RESULTS: All patients showed reduction in PVT volume without complications. Return of plasma AT-III level to > 70% during the treatment period contributes to ≥75% reduction of PVT volume. The prognosis in PVT patients depends on hepatic reserve capacity. When limited to Child-Pugh B and C liver cirrhosis patients, a ≥ 75% reduction of PVT volume improved the prognosis. CONCLUSIONS: Danaparoid sodium-based anticoagulation therapy was effective and safe for PVT in patients with cirrhosis. Return of plasma AT-III level to the normal range during the treatment period contributes to reduction of PVT volume. A reduction of ≥75% in PVT volume may improve the prognosis of Child-Pugh B and C decompensated cirrhosis patients with PVT.

TH17 cells mediate inflammation in a novel model of spontaneous experimental autoimmune lacrimal keratoconjunctivitis with neural damage.

BACKGROUND: Dry eye disease (DED) affects one third of the population worldwide. In prior studies, experimental autoimmune lacrimal keratoconjunctivitis (EALK) induced by desiccating stress in mice has been used as a model of DED. This model is complicated by a requirement for exogenous epithelial cell injury and administration of anticholinergic agents with broad immunologic effects. OBJECTIVE: We sought to develop a novel mouse model of EALK and to demonstrate the responsible pathogenic mechanisms. METHODS: CD4+CD45RBhigh naive T cells with and without CD4+CD45RBlow regulatory T cells were adoptively transferred to C57BL/10 recombination-activating gene 2 (Rag2)-/- mice. The eyes, draining lymph nodes, lacrimal glands, and surrounding tissues of mice with and without spontaneous keratoconjunctivitis were evaluated for histopathologic changes, cellular infiltration, and cytokine production in tissues and isolated cells. Furthermore, the integrity of the corneal nerves was evaluated using whole-tissue immunofluorescence imaging. Gene-deficient naive T cells or RAG2-deficient hosts were evaluated to assess the roles of IFN-γ, IL-17A, and IL-23 in disease pathogenesis. Finally, cytokine levels were determined in the tears of patients with DED. RESULTS: EALK developed spontaneously in C57BL/10 Rag2-/- mice after adoptive transfer of CD4+CD45RBhigh naive T cells and was characterized by infiltration of CD4+ T cells, macrophages, and neutrophils. In addition to lacrimal keratoconjunctivitis, mice had damage to the corneal nerve, which connects components of the lacrimal functional unit. Pathogenic T-cell differentiation was dependent on IL-23p40 and controlled by cotransferred CD4+CD45RBlow regulatory T cells. TH17 rather than TH1 CD4+ cells were primarily responsible for EALK, even though levels of both IL-17 and IFN-γ were increased in inflammatory tissues, likely because of their ability to drive expression of CXC chemokines within the cornea and the subsequent influx of myeloid cells. Consistent with the findings of this model, the tears of patients with DED had increased levels of inflammatory cytokines, including IL-17A and TNF-α. CONCLUSION: We describe a novel model of spontaneous EALK that supports a role for TH17 cells in disease pathogenesis and that will contribute to our understanding of autoimmune lacrimal keratoconjunctivitis in many human eye diseases, including DED.

Application of Hepatocyte Growth Factor for Acute Spinal Cord Injury: The Road from Basic Studies to Human Treatment.

Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018.

Analysis of the liver functional reserve of patients with advanced hepatocellular carcinoma undergoing sorafenib treatment: Prospects for regorafenib therapy.

AIM: This study aimed to investigate liver functional reserves during sorafenib treatment for advanced hepatocellular carcinoma (HCC), to identify predictive factors for maintaining them, and to analyze the proportion of candidates for regorafenib, which has been proven to improve patients' outcomes in the RESORCE trial. METHODS: We retrospectively investigated Child-Pugh scores during and after sorafenib treatment and evaluated their effects on second-line treatment and outcomes of 125 patients with advanced HCC. RESULTS: Pretreatment Child-Pugh A was maintained in 59/90 (65.6%) patients and pretreatment Child-Pugh B was improved to Child-Pugh A in 10/35 (28.6%) patients when sorafenib ceased. A Child-Pugh score = 5 and aspartate amino transferase <40 IU/L before treatment were contributing factors; vascular invasion and cessation of sorafenib due to gastrointestinal or liver-related adverse effects were reverse predictive factors for Child-Pugh A when sorafenib treatment ceased. Significantly more patients with Child-Pugh A when sorafenib treatment ceased received subsequent therapy and achieved better outcomes compared with patients with Child-Pugh B. When sorafenib treatment failed, 45/125 patients (36.0%) fulfilled key inclusion criteria of the RESORCE trial as follows: Child-Pugh A, Eastern Cooperative Oncology Group performance status 0 or 1, tumor progression revealed by imaging, and treatment with ≥400 mg sorafenib for at least 20 of the last 28 days before treatment failure in 56.8%, 84.8%, 73.6%, and 68.0% of patients, respectively. CONCLUSIONS: A comprehensive understanding and management of dynamic changes in liver functional reserve during sorafenib treatment contributed to the efficacy of subsequent therapy (e.g. regorafenib) and to better outcomes for patients with advanced HCC.

Extremely high preoperative C7 slope limits compensatory cervical lordosis after muscle-preserving selective laminectomy.

PURPOSE: A high C7 slope induces C2-C7 lordosis to compensate for cervical sagittal balance adjustments. A muscle-preserving selective laminectomy (SL) can maintain this compensation postoperatively. This study evaluated the effect of an extremely high C7 slope on C2-C7 lordotic compensation following SL. METHODS: This study enrolled 151 cervical compressive myelopathy patients who underwent SL. Lateral cervical spine radiographs were taken before surgery and during final follow-up. Patients were divided into extremely high C7 slope (≥ 30°) (EH) and non-high C7 slope (< 30°) (NH) groups and the influence of a high C7 slope on radiological and surgical outcomes was examined. RESULTS: Mean age was higher in group EH (p < 0.001). Preoperatively, patients in group EH had a larger C2-C7 sagittal vertical axis (SVA) (p = 0.001) and greater cervical lordosis (p < 0.001). Although C2-C7 SVA increased after surgery, mean C2-C7 angle of group EH decreased. Mismatches between C7 slope and C2-C7 angle increased for group EH postoperatively (p = 0.015). Postoperative Japanese Orthopedic Association (JOA) score and recovery rate (RR) were slightly lower in group EH (p = 0.001 and p = 0.006, respectively). Multiple linear regression analyses revealed that extremely high C7 slope, not age, affected the RR of JOA score (p = 0.006). CONCLUSIONS: Patients in group EH were older and had highly compensated cervical sagittal alignment preoperatively. They demonstrated postoperative cervical sagittal balance mismatch increases and slightly worse functional recovery. An extremely high C7 slope limited compensatory cervical lordosis following SL. These slides can be retrieved under Electronic Supplementary Material.

Cervical laminectomy of limited width prevents postoperative C5 palsy: a multivariate analysis of 263 muscle-preserving posterior decompression cases.

PURPOSE: Between 2006 and 2010, we performed wide laminectomy (wide LAM) alone, with decompression performed between the bilateral medial margin of the zygapophyseal joints, or double-door laminoplasty (DL) combined with wide LAM for cervical compressive myelopathy (CCM). From 2010, instead of wide LAM and DL, we began to perform narrow LAM, where the laminectomy width was no more than 2-3 mm wider than the spinal cord width (SW). This study aimed to elucidate the risk factors for C5 palsy by reviewing surgical outcomes. METHODS: The clinical features and radiological findings of 263 CCM patients with or without C5 palsy were compared. Risk factors for C5 palsy were assessed using logistic regression analysis. The decompression width (DW) was defined as the laminectomy width or the width between the bilateral medial margins of the bony gutters in DL. RESULTS: Narrow LAM reduced the incidence of C5 palsy from 9.2 to 1.2%. DL was performed more frequently in the C5 palsy group. The difference between the DW and the SW (DW - SW) was significantly greater in the C5 palsy group. Posterior spinal cord shift, aging, and the number of consecutive laminae surgically treated were significantly higher in the C5 palsy group. The diameter of the foramen (DF) at C4/5 was significantly smaller in the C5 palsy patients. The logistic regression analysis revealed that DL, DW - SW, DF, and aging were risk factors for C5 palsy. CONCLUSIONS: Cervical laminectomy of limited width prevented postoperative C5 palsy without compromising the functional recovery.

Acute kidney injury following vomiting and diarrhea after endoscopy in a duodenal gastrinoma patient.

A 51-year-old woman complaining of weakness in the limbs was diagnosed as having a duodenal gastrinoma on performing a further evaluation. Surgical resection was performed with selective arterial calcium injection for localization. During preoperative hospitalization, she experienced recurrent severe vomiting and diarrhea after endoscopy, leading to acute kidney injury. To our knowledge, this is the first report of gastrinoma with post-endoscopy symptom exacerbation. Although the etiology is unknown, the findings in this case suggest that sufficient fluid replacement, sedation, and high-dose proton pump inhibitor administration should be taken into consideration when performing endoscopy in gastrinoma patients.