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Acute myeloid leukemia (AML) cells are highly dependent on oxidative phosphorylation and the mitochondrial dynamics regulated by fusion-related genes MFN1, MFN2, and OPA1 and fission-related genes DNM1L and MFF. An analysis of previously published gene expression datasets showed that high expression of MFF was significantly associated with poor prognosis in patients with AML. Based on this finding, we investigated the impact of mitochondrial dynamics in AML. Transduction of shRNA against fission-related genes, DNM1L and MFF, inhibited growth and increased the mitochondrial area in AML cell lines. Extracellular flux analysis showed that deletion of mitochondrial dynamic regulators reduced mitochondrial respiration without significantly affecting glycolysis, except in shDNM1L-transfected cells. Immunodeficient NOG mice transplanted with DNM1L- or MFF-knockdown AML cells survived significantly longer than controls. Treatment of AML cell lines with Mdivi-1, which inhibits the DRP1 encoded by DNM1L, inhibited cell proliferation and oxidative phosphorylation. Our results show that mitochondrial dynamics play an important role in AML, and provide novel biological insights. The inhibition of mitochondrial dynamics induces unique mitochondrial alterations, which may be explored as a potential therapeutic target in AML., (© 2024. Japanese Society of Hematology.)

Obesity and diabetes are major risk factors for cardiovascular diseases. Zucker fatty diabetes mellitus (ZFDM) rats are novel animal model of obesity and type 2 diabetes. We have recently reported that blood pressure in ZFDM-Lepr fa/fa (Homo) rats was normal, while blood adrenaline level and heart rate were lower than those in control ZFDM-Lepr fa/+ (Hetero) rats. Here, we compared the reactivity in isolated mesenteric artery between Hetero and Homo rats. Contraction induced by phenylephrine was increased, while relaxation induced by isoprenaline was decreased in Homo rats at 21-23 weeks old compared with those in Hetero rats. The mRNA expression for α 1A but not β 2 adrenoreceptor in Homo rats was increased. Nitric oxide (NO)-mediated relaxation induced by acetylcholine was decreased, while the mRNA expression for endothelial NO synthase (eNOS) was rather increased in mesenteric artery from Homo rats. These findings for the first time revealed that in Homo rats with reduced plasma adrenaline, blood pressure could be maintained by enhancing vascular contractility induced by adrenaline through the increased α 1 adrenoceptor expression and the attenuated β 2 adrenoceptor signaling. Additionally, NO-mediated endothelium-dependent relaxation is impaired perhaps due to eNOS dysfunction, which might also contribute to maintain the blood pressure in Homo rats., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: Endoscopic submucosal dissection (ESD) is a specific procedure that uses an electrosurgical knife for en-bloc resectioning large tumors. However, no study has examined the effect of ESD on the defecation function of patients with rectal tumors. We aimed to investigate the potential effects caused by ESD by analyzing changes in the morphology and movement of the anorectum pre- and post-ESD., Methods: This prospective observational study included 11 patients with anorectal tumors who underwent ESD between April 2020 and February 2022. Pre-ESD assessments included anorectal manometry and defecography. Post-ESD assessments were conducted 2 months later, including anorectal manometry, defecography, and proctoscopy for ulcer and stenosis evaluation., Results: The median patient age was 73 years, including seven males and four females. Eight patients (73%) had a tumor in the lower rectum, and the extent of resection was less than 50% of the rectal lumen. Resection reached the dentate line in six cases (55%). In the patients with post-ESD mucosal defects involving the dentate line, the median of functional anal canal length significantly decreased from (3.4 cm pre-ESD to 2.8 cm post-ESD, p  = 0.04). Defecography revealed one case with incomplete evacuation (<50%) and incontinence post-ESD. Interestingly, patients with pre-existing rectoceles noted resolution of lesions post-ESD. None of the patients reported daily constipation or fecal incontinence., Conclusions: While rectal ESD is unlikely to cause significant real-world defecation difficulties, alterations in rectal and anal canal morphology and function may occur if the dentate line is involved in the resection range.

Purpose: This study aimed to evaluate a novel technique for cell tracking by visualising the activity of the human sodium/iodide symporter (hNIS) after transplantation of hNIS-expressing multilayered cell sheets in a rat model of chronic myocardial infarction., Methods: Triple-layered cell sheets were generated from mouse embryonic fibroblasts (MEFs) derived from mice overexpressing hNIS (hNIS-Tg). Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery in F344 athymic rats, and a triple-layered MEFs sheets were transplanted to the infarcted area two weeks after surgery. To validate the temporal tracking and kinetic analysis of the transplanted MEFs sheets, sequential cardiac single-photon emission computed tomography (SPECT) examinations with a 99m TcO 4 - injection were performed. The cell sheets generated using MEFs of wild-type mice (WT) served as controls., Results: A significantly higher amount of 99m TcO 4 - was taken into the hNIS-Tg MEFs than into WT MEFs (146.1 ± 30.9-fold). The obvious accumulation of 99m TcO 4 - was observed in agreement with the region where hNIS-Tg MEFs were transplanted, and these radioactivities peaked 40-60 min after 99m TcO 4 - administration. The volume of distribution of the hNIS-Tg MEF sheets declined gradually after transplantation, implying cellular malfunction and a loss in the number of transplanted cells., Conclusion: The reporter gene imaging with hNIS enables the serial tracking and quantitative kinetic analysis of cell sheets transplanted to infarcted hearts., (© 2024. The Author(s).)

Background: Previous studies have recognized the potential of the Vertebral Bone Quality (VBQ) score for predicting fractures. However, these studies often have lacked longitudinal perspectives and have not focused on community populations. Our study aimed to enhance the predictive capacity of the VBQ score by investigating its correlation with new vertebral fractures (NVFs) that were detected 11 years later in a community-based cohort and by developing a comprehensive prediction model., Methods: This study was a population-based study conducted in the Minami-Aizu area in Fukushima Prefecture, Japan. One hundred and thirty participants voluntarily underwent T1-weighted magnetic resonance imaging (MRI) of the lumbar spine in 2004 and 2015. VBQ scores were ascertained from the 2004 scans. NVFs that occurred between 2004 and 2015 were detected based on a ≥20% reduction in vertebral height on the midsagittal sections of the MRI. Other predictors that were considered included age, sex, body mass index, smoking history, heart disease, cerebrovascular disease, respiratory disease, and existing vertebral fractures (EVFs). A logistic regression analysis was conducted., Results: The logistic regression analysis indicated that the VBQ score, age, sex, and EVFs were significant predictors of NVFs. The prediction model showed an area under the curve of 0.84, suggesting excellent discriminatory power. The calibration capacity was confirmed using the Hosmer-Lemeshow test., Conclusions: The VBQ score was significantly correlated with the long-term incidence of NVFs in a community population. The prediction model exhibited satisfactory discrimination and calibration capacities, highlighting the use of the VBQ score as a potential tool for long-term prediction of NVFs., Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A657)., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Objective: Osteoarthritis is linked to dementia, but no longitudinal studies have established this connection. This prospective cohort study from the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) aimed to determine if knee osteoarthritis (KOA) independently predicts dementia in adults aged 65 and above., Methods: Participants were classified by the Kellgren-Laurence scale into no/minimal KOA (grades 0 and I) and definitive KOA (grade II or higher). We analyzed dementia incidence from 2009 to 2015 using long-term care insurance data, adjusting for age, sex, vascular risks, depressive symptoms, and activity levels., Results: Out of 1089 participants (58.9% female, average age 72.5), 72.0% had definitive KOA. Dementia occurrence was significantly higher in the definitive group (8.4%) compared to the no/minimal group (3.0%) ( p < 0.001). A log-rank test and Cox regression analysis confirmed these findings, showing an adjusted hazard ratio of 2.29 (confidence interval: 1.12-4.68) for dementia in those with definitive KOA., Conclusions: These results suggest that KOA is a significant risk factor for dementia, highlighting the importance of addressing contributing factors in KOA patients to potentially slow the progression of dementia.

Background/aims: Treatment using tumor necrosis factor-α (TNF-α) inhibitors is one of the risk factors for active tuberculosis (TB) in patients with Crohn's disease (CD). Biologics, such as ustekinumab (UST) and vedolizumab (VDZ), are less likely to cause opportunistic infections. However, large-scale studies for active TB and biologics other than TNF-α inhibitors are limited. We aimed to investigate the association between biologics and active TB utilizing a Japanese medical claims database., Methods: We analyzed retrospectively the association of the risk of active TB development with treatment using TNF-α inhibitors and other biologics (UST and VDZ) in patients with CD using the Japanese Medical Data Vision (MDV) database between April 2008 and June 2022. The durations of each biologic and biologic-free treatment were calculated for each patient. Univariate and multivariate analyses were performed using the Cox proportional hazards model, with the utilization of biologics considered as time-dependent covariates., Results: We included 28,811 patients with CD in MDV database. Finally, 17,169 patients were analyzed. In total, 7,064 patients were categorized as biologic-naïve, while 10,105 were classified as biologic-experienced. Seventeen patients developed active TB, including 7 on infliximab, 5 on adalimumab, and 5 on no biologics. None of the patients treated with UST and VDZ developed active TB. Multivariate analysis suggested that TNF-α inhibitors were the risk factors for active TB (hazard ratio, 3.66; P= 0.020)., Conclusions: TNF-α inhibitors, but not UST or VDZ, are risk factors for active TB in Japanese patients with CD.

A bioinspired semisynthesis of human-interleukin-6 bearing N-glycan at Asn143 (143glycosyl-IL-6) was performed by intentional glycosylation effects and protein folding chemistry for regioselective peptide-backbone activation. 143Glycosyl-IL-6 is a genetically coded cytokine, but isolation was difficult owing to a tiny amount. IL6-polypeptide (1-141-position) with an intentionally inserted cysteine at 142-position was expressed in E. coli. The expressed polypeptide was treated with a chemical folding process to make a specific helices bundle conformation through native two-disulfide bonds (43-49 and 72-82). Utilizing the successfully formed free-142-cysteine, sequential conversions using cyanation of 142-cysteine, hydrazinolysis, and thioesterification created a long polypeptide (1-141)-thioester. However, the resultant polypeptide-thioester caused considerable aggregation owing to a highly hydrophobic peptide sequence. After the reduction of two-disulfide bonds of polypeptide (1-141)-thioester, an unprecedented hydrophilic N-glycan tag was inserted at the resultant cysteine thiols. The N-glycan tags greatly stabilized polypeptide-thioester. The subsequent native chemical ligation and desulfurization successfully gave a whole 143glycosyl-IL-6 polypeptide (183-amino acids). Removal of four N-glycan tags and immediate one-pot in vitro folding protocol efficiently produced the folded 143glycosyl-IL-6. The folded 143glycosyl-IL-6 exhibited potent cell proliferation activity. The combined studies with molecular dynamics simulation, semisynthesis, and bioassays predict the bioactive conformation of latent 143glycosyl-IL-6., (© 2024 Wiley‐VCH GmbH.)

A 27-year-old man had ulcerative colitis (UC) 1 year prior and underwent a colectomy and two-stage ileal pouch-anal anastomosis for medically refractory UC 6 months ago. He visited our department with epigastric pain and discomfort, increased stool frequency, and bloody diarrhea. Esophagogastroduodenoscopy revealed continuous diffuse friable mucosa, erosions, and edema in the duodenum, and pouchoscopy revealed multiple ulcers and purulent mucus adhesions. Based on endoscopic and pathological findings, the patient was diagnosed with duodenitis associated with UC and pouchitis, for which he received oral prednisolone (40 mg/day) and ciprofloxacin. The frequency of stools and occurrence of bloody diarrhea reduced, and epigastric pain and discomfort improved after 2 weeks. However, when prednisolone was discontinued, the symptoms worsened, albumin level decreased, and C-reactive protein level increased. Following this, we administered a 20 mg prednisolone sodium phosphate enema once daily, and the patient's symptoms improved. However, the symptoms relapsed when the enema was discontinued. Assuming that the patient had steroid-dependent duodenitis associated with UC and pouchitis, we initiated upadacitinib. His symptoms improved within a few days, and biomarkers returned to normal after 1 month. Nine months after initiating the upadacitinib treatment, endoscopic remission was achieved in the mucosa of the duodenum and pouch. The patient has been in clinical remission for 1 year without any adverse events., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Purpose: This study aimed to examine the prognostic impact of concomitant pH-regulating drug use in patients with epidermal growth factor receptor (EGFR)-mutation-positive non-small-cell lung cancer (NSCLC) receiving EGFR-tyrosine kinase inhibitors (TKIs)., Methods: We conducted a nationwide retrospective cohort study and reviewed clinical data of consecutive patients with NSCLC treated with the first-line EGFR-TKIs in 46 hospitals between April 2010 and March 2020. Cox regression analyses were conducted to examine the differences in overall survival (OS) between patients treated with and without concomitant pH-regulating drugs, including potassium-competitive acid blockers (P-CABs), proton pump inhibitors (PPIs), and H 2 -receptor antagonists (H 2 RAs)., Results: A total of 758 patients were included in the final dataset, of which 307 (40%) were administered concomitant pH-regulating drugs while receiving frontline EGFR-TKIs. After adjusting for basic patient characteristics, patients administered gefitinib, erlotinib, afatinib, and osimertinib with concomitant pH-regulating drugs had lower OS than those without concomitant pH-regulating drugs, with hazard ratios of 1.74 (with a 95% confidence interval of 1.34-2.27), 1.33 (0.80-2.22), 1.73 (0.89-3.36), and 5.04 (1.38-18.44), respectively. The 2-year OS rates of patients receiving gefitinib with or without concomitant pH-regulating drugs were 65.4 and 77.5%, those for erlotinib were 55.8 and 66.6%, and those for afatinib were 63.2 and 76.9%, respectively. The 1-year OS rates of patients receiving osimertinib with or without concomitant pH-regulating drugs were 88.1% and 96.9%, respectively., Conclusion: In addition to the first-generation EGFR-TKIs, the second- and third-generation EGFR-TKIs also resulted in OS deterioration in patients with EGFR mutation-positive NSCLC when used concurrently with pH-regulating drugs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases.

Introduction: Excessive bothersome belching is clinically problematic and the Rome IV classification categorizes belching disorders as gastroduodenal disorders., Methods: A total of 10,000 Japanese adults participated in this web-based survey. We aimed to examine the prevalence of belching disorders and their characteristics., Results: Belching disorders were found in 151 (1.5%) adults. The presence of reflux esophagitis, thyroid diseases, gastroesophageal reflux disease, functional dyspepsia, full eaters, or a small or large number of mastication was significantly associated with an increased odds ratio of belching disorders., Discussion: A detailed epidemiology of belching disorders in adults was clarified., (Copyright © 2024 by The American College of Gastroenterology.)

Competing Interests: Competing interests: None declared.

Background: Long-leg frontal radiographs of the lower extremities are used to assess knee osteoarthritis. Given the three-dimensional (3D) nature of alignment changes in osteoarthritis, postural alterations in the femur and tibia extend beyond the coronal plane (in-plane) to include the transverse and sagittal planes (out-of-plane). This study investigates the impact of these out-of-plane factors on in-plane knee alignment parameters observed in frontal radiographs., Methods: A total of 97 osteoarthritic knees in women were examined. Using a 3D-to-two-dimensional (2D) image matching technique, we evaluated the 3D postures of the femur and tibia in the standing position as viewed from frontal radiographs in the world coordinate system. Statistical analyses were conducted to explore associations between these 3D postures and 2D alignment parameters obtained from frontal radiographs under identical conditions., Findings: The femur exhibited a medial inclination of 2.7°, a posterior inclination of 3.9°, and an internal rotation of 4.2°, whereas the tibia showed a lateral inclination of 6.4°, an anterior inclination of 6.7°, and an internal rotation of 6.7°. Both coronal and rotational postures of femur and tibia influenced the hip-knee-ankle angle, mechanical axis percentage, and medial proximal tibial angle. However, only coronal factors of tibia impacted tibial joint line obliquity relative to the floor., Interpretation: Attention should be paid to the potential impact of the out-of-plane postures of the femur and tibia on parameters assessed in plain frontal radiographs of the lower extremities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Study Design: We conducted a retrospective review of data from patients who underwent surgical treatment for lumbosacral radiculopathy., Objective: To assess the effectiveness of the foot tapping test (FTT) in evaluating lower limb motor function in patients with lumbosacral radiculopathy pre- and post-surgery., Summary of Background Data: Lumbosacral radiculopathy is becoming increasingly common in aging populations. Despite standard treatments, paralysis often leads to incomplete postoperative recovery, necessitating early detection and interventions., Methods: We enrolled individuals who underwent surgery for lumbosacral radiculopathy at our facility between 2009 and 2020. Patients with a history of lumbar surgeries, dialysis, rheumatoid arthritis, and transitional vertebrae were excluded. The FTT score was measured by having the sole of the foot tap as many times as possible for 10 s while keeping the heel in contact with the floor. The L4, L5, and S1 groups were assigned using the scores on the side of the radiculopathy, and the control group was assigned using the scores on the intact side. Data were analyzed using Dunnett's test for group comparisons and paired t-tests for pre-post-surgery comparisons., Results: Of the 522 eligible patients, 80 (159 nerve roots, one patient with hemi-prosthetic leg) were analyzed. The preoperative FTT scores in the L4 and L5 groups were significantly lower than those in the control group, indicating functional impairment. One year post-surgery, all groups showed improvements in FTT scores, with the L5 group exhibiting significant improvements compared to the control; this was supported by the results of sensitivity analyses considering the effects of paralysis and pain., Conclusion: The FTT is a valuable tool for the early detection of lower limb motor dysfunction in lumbosacral radiculopathy, particularly for L5 nerve root impairment, where it aids in timely surgical intervention and may improve postoperative outcomes and quality of life., Competing Interests: Conflict of Interest and Source of Funding: The authors have no relevant financial relationships to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The management of intractable secondary pneumothorax poses a considerable challenge as it is often not indicated for surgery owing to the presence of underlying disease and poor general condition. While endobronchial occlusion has been employed as a non-surgical treatment for intractable secondary pneumothorax, its effectiveness is limited by the difficulty of locating the bronchus leading to the fistula using conventional techniques. This report details a case treated with endobronchial occlusion where the combined use of transbronchoscopic oxygen insufflation and a digital chest drainage system enabled location of the bronchus responsible for a prolonged air leak, leading to the successful treatment of intractable secondary pneumothorax., Case Presentation: An 83-year-old male, previously diagnosed with chronic hypersensitivity pneumonitis and treated with long-term oxygen therapy and oral corticosteroid, was admitted due to a pneumothorax emergency. Owing to a prolonged air leak after thoracic drainage, the patient was deemed at risk of developing an intractable secondary pneumothorax. Due to his poor respiratory condition, endobronchial occlusion with silicone spigots was performed instead of surgery. The location of the bronchus leading to the fistula was unclear on CT imaging. When the bronchoscope was wedged into each subsegmental bronchus and low-flow oxygen was insufflated, a digital chest drainage system detected a significant increase of the air leak only in B5a and B5b, thus identifying the specific location of the bronchus leading to the fistula. With the occlusion of those bronchi using silicone spigots, the air leakage decreased from 200 mL/min to 20 mL/min, and the addition of an autologous blood patch enabled successful removal of the drainage tube., Conclusion: The combination of transbronchoscopic oxygen insufflation with a digital chest drainage system can enhance the therapeutic efficacy of endobronchial occlusion by addressing the problems encountered in conventional techniques, where the ability to identify the leaking bronchus is dependent on factors such as the amount of escaping air and the location of the fistula., (© 2024. The Author(s).)

Background: The current 3D-iFlow application can only measure the arrival time of contrast media through intensity values. If the flow rate could be estimated by 3D-iFlow, patient-specific hemodynamics could be determined within the scope of normal diagnostic management, eliminating the need for additional resources for blood flow rate estimation., Objective: The aim of this study is to develop and validate a method for measuring the flow rate by data obtained from 3D-iFlow images - a prototype application in Four-dimensional digital subtraction angiography (4D-DSA)., Methods: Using phantom model and experimental circuit with circulating glycerin solution, an equation for the relationship between contrast media intensity and flow rate was developed. Applying the equation to the aneurysm phantom models, the derived flow rate was evaluated., Results: The average errors between the derived flow rate and setting flow rate became larger when the glycerin flow and the X-rays from the X-ray tube of the angiography system were parallel to each other or when the measurement point included overlaps with other contrast enhanced areas., Conclusion: Although the error increases dependent on the imaging direction and overlap of contrast enhanced area, the developed equation can estimate the flow rate using the image intensity value measured on 3D-iFlow based on 4D-DSA.

Drug-induced acute renal failure (ARF) is a public health concern that hinders optimal drug therapy. However, pathological mechanisms of drug-induced ARF remain to be elucidated. Here, we show that a pathological process of drug-induced ARF is mediated by proinflammatory cross-talk between kidney tubular cells and macrophages. Both polymyxin B and colistin, polypeptide antibiotics, frequently cause ARF, stimulated the ERK and NF-κB pathways in kidney tubular cells, and thereby upregulated M-CSF and MCP-1, leading to infiltration of macrophages into the kidneys. Thereafter, the kidney-infiltrated macrophages were exposed to polypeptide antibiotics, which initiated activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. Interestingly, blockade of the NLRP3 activation clearly ameliorated the pathology of ARF induced by polypeptide antibiotics, suggesting that a combination of the distinct cellular responses to polypeptide antibiotics in kidney tubular cells and macrophages plays a key role in the pathogenesis of colistin-induced ARF. Thus, our results provide a concrete example of how drugs initiate ARF, which may give insight into the underlying pathological process of drug-induced ARF., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Background and Aim: Nonsteroidal anti-inflammatory drugs (NSAIDs) damage the small intestine via neutrophil infiltration driven by the mucosal invasion of enterobacteria. The antimicrobial function of neutrophils is partially dependent on neutrophil extracellular traps (NETs). Excessive NET formation has been associated with several inflammatory diseases. Here, we aimed to investigate the role of NETs in NSAID-induced small intestinal damage using human samples and an experimental mouse model., Methods: Human small intestine specimens were obtained from NSAID users during double-balloon enteroscopy. Wild-type, protein arginine deiminase 4 (PAD4) knockout, and antibiotic-treated mice were administered indomethacin to induce small intestinal injury. The expression of NET-associated proteins, including PAD4, citrullinated histone H3 (CitH3), cell-free DNA, and myeloperoxidase (MPO), was evaluated., Results: The double-positive stained area with CitH3 and MPO, which is specific for neutrophil-derived extracellular traps, was significantly high in the injured small intestinal mucosa of NSAID users. In a mouse model, small intestinal damage developed at 6 h after indomethacin administration, accompanied by increased mRNA levels of interleukin-1β and keratinocyte chemoattractant and elevated NET-associated protein levels of PAD4, CitH3, and MPO in small intestine and serum levels of cell-free DNA. Both genetic deletion and pharmacological inhibition of PAD4 attenuated this damage by reducing the mRNA expression of inflammatory cytokines and NET-associated proteins. Furthermore, mice pretreated with antibiotics showed resistance to indomethacin-induced small intestinal damage, with less NET formation., Conclusion: These results suggest that NETs aggravate NSAID-induced small intestinal injury. Therefore, NET inhibition could be a potential treatment for NSAID-induced small intestinal injury., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Study Design: This was a descriptive study through secondary analysis of aggregated data., Purpose: This study aimed to describe changes in women's membership in the Japanese Society for Spine Surgery and Related Research (JSSR) for orthopedic surgery and the Neurospinal Society of Japan (NSJ) for neurosurgery over the past decade and make predictions for the future., Overview of Literature: Although the ratio of women physicians in the field of spine surgery is known to be low worldwide, there is a lack of detailed surveys in Japan., Methods: We sent emails to the JSSR and NSJ secretariats to verify membership information (gender and age) from 2013 to 2022. Using ordinary least squares, we projected the years it would take for the JSSR and NSJ to achieve a gender diversity ratio of 30%., Results: In 2013, the percentage of women in JSSR and NSJ was 2.3% and 2.7%, respectively. However, after 2018, the percentage of women in NSJ will be higher than in JSSR, rising to 2.7% in JSSR and 4.7% in NSJ by 2022. It would require 101 years for the NSJ and more than 1,000 years for the JSSR to realize 30% gender diversity., Conclusions: JSSR and NSJ have low percentages of women. Improving gender diversity is an important issue for both societies, and they may collaborate on finding a good solution. Both the JSSR and NSJ societies need to actively address gender diversity and become more attractively represented in society for the next generation of spine surgeons., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Morimoto et al.)

We used standardized detection ratio to evaluate the quality of nasal upper gastrointestinal endoscopy screening for the secondary prevention of gastric cancer, and examined the gastric cancer risk in the era of total Helicobacter pylori ( H. pylori ) eradication. We performed 21,931 upper gastrointestinal endoscopies, 77 subjects were diagnosed with gastric cancer. Of these, 28 had gastric cancer after H. pylori eradication, 47 had gastric cancer with H. pylori -positive or others, and 2 had H. pylori -negative gastric cancer. The Standardized detection ratios for men and women were 5.33 and 4.82, respectively. Multivariable logistic regression analyses performed exclusively on first endoscopy subjects, excluding H. pylori -negative gastric cancer, revealed that smoking was a risk factor for developing gastric cancer (adjusted odds ratio, 3.31; 95% confidence interval, 1.65-6.64; p  = 0.001). A statistically significant interaction was found between daily alcohol consumpption and H. pylori eradication on gastric cancer development ( p  = 0.005). In conclusion, relatively high standardized detection ratio values suggest that an appropriate endoscopic diagnosis of gastric cancer should be performed during a medical check-up. Smoking is a risk factor for developing gastric cancer, and continued alcohol consumption suggests a possible risk for developing gastric cancer after H. pylori eradication., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2024 JCBN.)

Study Design: Retrospective cohort study., Objectives: To compare the frequency of complications and outcomes between patients with ossification of the posterior longitudinal ligament (OPLL) of the cervical spine and those with cervical spondylotic myelopathy (CSM) who underwent anterior surgery., Summary of Background Data: Anterior cervical spine surgery for OPLL is an effective surgical procedure; however, it is complex and technically demanding compared with the procedure for CSM. Few reports have compared postoperative complications and clinical outcomes after anterior surgeries between the 2 pathologies., Methods: Among 1434 patients who underwent anterior cervical spine surgery at 3 spine centers within the same spine research group from January 2011 to March 2021, 333 patients with OPLL and 488 patients with CSM were retrospectively evaluated. Demographics, postoperative complications, and outcomes were reviewed by analyzing medical records. In-hospital and postdischarge postoperative complications were investigated. Postoperative outcomes were evaluated 1 year after the surgery using the Japanese Orthopaedic Association score., Results: Patients with OPLL had more comorbid diabetes mellitus preoperatively than patients with CSM ( P <0.001). Anterior cervical corpectomies were more often performed in patients with OPLL than in those with CSM (73.3% and 14.5%). In-hospital complications, such as reoperation, cerebrospinal fluid leak, C5 palsy, graft complications, hoarseness, and upper airway complications, occurred significantly more often in patients with OPLL. Complications after discharge, such as complications of the graft bone/cage and hoarseness, were significantly more common in patients with OPLL. The recovery rate of the Japanese Orthopaedic Association score 1 year postoperatively was similar between patients with OPLL and those with CSM., Conclusion: The present study demonstrated that complications, both in-hospital and after discharge following anterior spine surgery, occurred more frequently in patients with OPLL than in those with CSM., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aim: The albumin to fibrinogen ratio (AFR) has been identified as a promising prognostic marker for some malignancies. The aim of the present study was to evaluate the clinical impact of AFR in esophageal cancer patients who received curative resection., Patients and Methods: The present study included 123 patients who underwent curative treatment for esophageal cancer between 2005 and 2020. The prognosis and clinicopathological parameters were compared between patients with high and low AFRs., Results: The overall survival (OS) stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed when using a pretreatment AFR of 1.23. When comparing the patient backgrounds between the high-AFR (AFR ≥12.3) and low-AFR (AFR<12.3) groups, significant differences were noted in the pathological T status. The high-AFR group had significantly higher OS rates at 3 years (70.8%) and 5 years (59.3%) after surgery in comparison to the low-AFR group (46.6% and 37.4%, respectively). Univariate and multivariate analyses for OS showed that the AFR was a significant prognostic factor. In addition, when comparing the site of first recurrence, a marginally significant difference was noted in hematological recurrence., Conclusion: The AFR is a significant risk factor in patients with esophageal cancer, holding promise as a valuable prognostic factor., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Periostin, an extracellular matrix protein closely related to mechanical stress, inflammation, and ageing, has been implicated in intervertebral disc degeneration (IVDD) in basic research. However, it has not been examined in clinical cases. This study aimed to evaluate the association between IVDD severity and serum periostin concentration as well as to analyse potential associations between IVDD and clinical and demographic factors., Methods: This retrospective cohort study included 198 patients who underwent lumbar disc herniation and lumbar canal stenosis between January 2020 and December 2022. The severity of IVDD was evaluated using the Pfirrmann grading, whereas serum periostin levels were measured using ELISA kits. Clinical demographics, including age, sex, body mass index, comorbidities, psoas muscle index, and spinal disease, were also recorded., Results: This study demonstrated a significant correlation between high serum periostin levels and IVDD severity, as indicated by a high cumulative Pfirrmann score. Serum periostin levels were identified as an independent risk factor for IVDD in a multivariate regression model. Correlation analysis showed a correlation between periostin levels and Pfirrmann grade at each lumbar level (ρ = 0.458-0.550, p < 0.001) and a strong correlation with cumulative Pfirrmann score (ρ = 0.690, p < 0.001)., Conclusion: The higher the serum periostin level, the higher the cumulative Pfirrmann score. Multivariate analysis showed that serum periostin was an independent risk factor for IVDD. Periostin levels may be a clinically suitable and useful biomarker for diagnosing IVDD, estimating disease progression and activity, providing prognostic information, and evaluating treatment options., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Few epidemiological studies have evaluated associations between lumbar facet joint (LFJ) osteoarthritis (OA) and comorbidities. This study aimed to investigate the prevalence of LFJ OA in a Japanese community population and associations between LFJ OA and underlying diseases, including lower extremity OA., Methods: This epidemiological cross-sectional study evaluated LFJ OA in 225 Japanese community residents (81 males, 144 females; median age, 66 years) using magnetic resonance imaging (MRI). LFJ OA from L1-L2 to L5-S1 was evaluated using a 4-grade classification. Associations between LFJ OA and comorbidities were examined using multiple logistic regression analyses adjusting for age, sex, and body mass index., Results: Prevalences of LFJ OA were 28.6% at L1-L2, 36.4% at L2-L3, 48.0% at L3-L4, 57.3% at L4-L5, and 44.2% at L5-S1. Males were significantly more likely to have LFJ OA at several spinal levels (L1-L2 45.7% vs 18.9%, p < 0.001; L2-L3 46.9% vs 30.6%, p < 0.05; L4-L5 67.9% vs 51.4%, p < 0.05). LFJ OA was present in 50.0% of residents <50 years old, 68.4% at 50-59 years old, 86.3% at 60-69 years old, and 85.1% at ≥70 years old. Multiple logistic regression analysis showed no associations between LFJ OA and comorbidities., Conclusions: The prevalence of LFJ OA as evaluated by MRI was >85% at ≥60 years old and highest at the L4-L5 spinal level. Males were significantly more likely to have LFJ OA at several spinal levels. Comorbidities were not associated with LFJ OA., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: Hypertension is one of the major risk factors for renal failure and cardiovascular diseases, and is caused by various abnormalities including the contractility of blood vessels. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which mimic human type 2 diabetes, are frequently used to study obesity-induced insulin resistance (IR) and hypertension. Human omentin-1 is one of the recently identified adipocytokines. We previously demonstrated that human omentin-1 not only caused vasodilation in rat isolated blood vessels, but also prevented inflammatory responses, a possible mechanism relating IR, in human vascular endothelial cells. Taken together, we hypothesized that human omentin-1 may reduce obesity-induced IR and hypertension in OLETF rats., Methods: OLETF rats were intraperitoneally administered with human omentin-1 for 7 days., Results: Human omentin-1 had no influence on overweight, hyperglycemia, urinary glucose extraction, hyperinsulinemia, and systemic IR in OLETF rats. Human omentin-1 decreased systolic blood pressure in OLETF rats. The measurement of isometric contraction revealed that human omentin-1 had no influence on the agonist-induced contractile and relaxant responses in isolated thoracic aorta from OLETF rats. However, the relaxant response mediated by human insulin was converted into the contractile response in thoracic aorta from OLETF rats, which was prevented by human omentin-1. The Western blotting revealed that human omentin-1 improved the decrease in endothelial nitric oxide synthase activation in isolated thoracic aorta from OLETF rats., Conclusion: In summary, we for the first time revealed that human omentin-1 partly reduces vascular IR and thereby inhibits hypertension in OLETF rats., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Diffuse idiopathic skeletal hyperostosis (DISH) frequently occurs in the spine, resulting in unstable fractures. Treating thoracolumbar fractures in patients with DISH is often difficult because the anterior opening of the vertebral body is exacerbated by dislocation in the prone position, making reduction difficult. In this study, we introduced a novel skull clamp-assisted positioning (SAP) technique. The patient is placed in a supine position with a skull clamp used in cervical spine surgery before surgery to prevent the progression of dislocation and to restore the patient's position. Using this method, the mean difference in local kyphosis angle improved from -2.9 (±8.4)° preoperatively to 10.9 (±7.7)° postoperatively. Furthermore, posterior displacement decreased from a preoperative mean of 5.5 (±4.3) mm to 0.3 (±0.7) mm postoperatively. Complications such as neurological sequelae, implant fracture, and surgical site infection were not observed through one year of postoperative follow-up. SAP may decrease invasiveness and complications. Longer-term studies and larger sample sizes are needed to establish long-term efficacy and benefits.

Objective: To investigate on three-dimensional (3D) fusion images the apposition of low-profile visualized intraluminal support (LVIS) stents in intracranial aneurysms after treatment and assess inter-rater reliability., Materials and Methods: Records of all patients with unruptured intracranial aneurysms who were treated with the LVIS stent were retrospectively accessed and included in this study. Two neurosurgeons evaluated the presence of malapposition between the vessel walls and the stent trunk (crescent sign) and the vessel wall and the stent edges (edge malappostion) on 3D fusion images. These images were high-resolution cone-beam computed tomography images of the LVIS stent fused with 3D-digital subtraction angiography images of the vessels. Associations between malapposition and aneurysm location were assessed by Fisher's exact test, and inter-rater agreement was estimated using Cohen's kappa statistic., Results: Forty consecutive patients were included. In all patients, 3D fusion imaging successfully visualized the tantalum helical strands and the closed-cell structure of the nitinol material of the low-profile visualized intraluminal support. A crescent sign was observed in 27.5 % and edge malapposition in 47.5 % of the patients. Malapposition was not significantly associated with location ( p  = 0.23 crescent sign, p  = 0.07 edge malapposition). Almost perfect ( κ  = 0.88) and substantial ( κ  = 0.76) agreements between the two raters were found for the detection of crescent signs and edge appositions, respectively., Conclusions: 3D fusion imaging provided clear visualization of the LVIS stent and parent arteries, and could detect malapposition with excellent inter-rater reliability. This technique may provide valuable guidance for surgeons in determining postoperative management., Competing Interests: K.O. is an employee of Siemens Healthcare. The other authors declare no conflicts of interest., (© 2024 The Authors.)

Background: To investigate factors that have an impact on the risk of falls and determine whether radiographic knee osteoarthritis (KOA) is a factor involved in falls independent of knee pain, psychological factors, and physical function., Methods: A cross-sectional analysis was conducted on 1083 subjects for the 2009 Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study (LOHAS). A logistic regression analysis was performed to examine the relationship between radiographic KOA and fall history., Results: Fall history was significantly associated with the severity of knee pain. Compared to subjects with no knee pain, the odds ratio (OR) was 1.53 times higher in the subjects with mild knee pain (95% confidence interval [CI]: 1.04-2.25), 1.69 times higher in those with moderate knee pain (95%CI: 1.03-2.79), and 2.98 times higher in those with severe knee pain (95%CI: 1.67-5.30). In subjects with depression, the OR was 1.91 (95%CI: 1.25-2.92), and in those with decreased mobility, the OR was 1.70 (95%CI: 1.08-2.69). Age, gender, knee crepitus, BMI, OLST, and sleeping pill use were not significantly associated with fall risk. In a multivariate analysis, radiographic KOA severity was not significantly associated with fall risk (OR 0.81, 95%CI 0.44-1.50 in mild OA; OR 1.10, 95%CI 0.57-2.14 in severe OA)., Conclusion: Knee pain, decreased mobility, and depression, but not the radiographic KOA severity, were significantly associated with a fall risk. Regardless of the individual's radiographic KOA severity, the risk of falls may be reduced by treating his/her knee pain, mobility problems, and/or psychological factors., (© 2024. The Author(s).)

Despite the recent advances in cancer treatment, the incidence of patients with spinal metastases continues to grow along with the total number of cancer patients. Spinal metastases can significantly impair activities of daily living (ADL) and quality of life (QOL), compared with other types of bone metastases, as they are characterized with severe pain and paralysis caused by skeletal-related events. Reduced ADL can also lead to treatment limitations as certain anticancer agents and radiation therapy are not compatible treatments; thus, leading to a shorter life expectancy. Consequently, maintaining ADLs in patients with spinal metastases is paramount, and spine surgeons have an integral role to play in this regard. However, neurosurgeon, orthopedic and spinal surgeons in Japan do not have a proactive treatment approach to spinal metastases, which may prevent them from providing appropriate treatment when needed (clinical inertia). To overcome such endemic inertia, it is essential for 1) spine surgeons to understand and be more actively involved with patients with musculoskeletal disorders (cancer locomo) and cancer patients; 2) the adoption of a multidisciplinary approach (coordination and meetings not only with the attending oncologist but also with spine surgeons, radiologists, rehabilitation specialists, and other professionals) to preemptive treatment such as medication, radiotherapy, and surgical treatment; and 3) the integration of the latest findings associated with minimally invasive spinal treatments that have expanded the indications for treatment of spinal metastases and improved treatment outcomes. This heralds a new era in the management of spinal metastases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Morimoto, Toda, Hakozaki, Paholpak, Watanabe, Kato, Tsukamoto, Hirata, Kaneuchi, Tome, Nagamine, Nishida, Katsuya, Matsumoto, Otani, Mawatari and Nikaido.)

Background : In the diagnosis of lumbar spinal stenosis (LSS), finding stenosis with magnetic resonance imaging (MRI) does not always correlate with symptoms such as sciatica or intermittent claudication. We perform decompression surgery only for cases where the levels diagnosed from neurological findings are symptomatic, even if multiple stenoses are observed on MRI. The objective of this study was to examine the time course of asymptomatic stenosis in patients with LSS after they underwent decompression surgery for symptomatic stenosis. Materials and Methods : The participants in this study comprised 137 LSS patients who underwent single-level L4-5 decompression surgery from 2003 to 2013. The dural sac cross-sectional area at the L3-4 disc level was calculated based on preoperative MRI. A cross-sectional area less than 50 mm 2 was defined as stenosis. The patients were grouped, according to additional spinal stenosis at the L3-4 level, into a double group (16 cases) with L3-4 stenosis, and a single group (121 cases) without L3-4 stenosis. Incidences of new-onset symptoms originating from L3-4 and additional L3-4-level surgery were examined. Results : Five years after surgery, 98 cases (72%) completed follow-up. During follow-up, 2 of 12 patients in the double group (16.7%) and 9 of 86 patients in the single group (10.5%) presented with new-onset symptoms originating from L3-4, showing no significant difference between groups. Additional L3-4 surgery was performed for one patient (8.3%) in the double group and three patients (3.5%) in the single group; again, no significant difference was shown. Conclusion : Patients with asymptomatic L3-4 stenosis on preoperative MRI were not prone to develop new symptoms or need additional L3-4-level surgery within 5 years after surgery when compared to patients without preoperative L3-4 stenosis. These results indicate that prophylactic decompression for asymptomatic levels is unnecessary.

Goals: We aimed to examine the response rate to proton pump inhibitors (PPIs) and potassium-competitive acid blockers and the prevalence of topical corticosteroid (TCS) therapy as the second-line treatment for eosinophilic esophagitis (EoE)., Background: Acid-suppressive drugs such as PPIs and potassium-competitive acid blockers are often used to treat EoE. Treatment response is based on outcomes including symptoms, endoscopy, and histology; however, the detailed response rate to PPI/P-CAB is unknown., Study: In total, 236 patients with histologically confirmed EoE who received PPI/P-CAB as the first-line treatment were included. We assessed the symptoms, endoscopic reference score (EREFS), and histology [eosinophils per high-power field (eos/hpf)] 8 weeks after PPI/P-CAB administration. Complete normalization was defined as the disappearance of symptoms, EREFS score 0, or 0-1 eos/hpf, and response as disappearance or improvement of symptoms, EREFS score ≤2, or <15 eos/hpf. The prevalence of TCS therapy in each response group was assessed., Results: Complete normalization was achieved in 25%, 50%, 36%, and 8% of patients for symptoms, endoscopy, histology, and all 3 outcomes, respectively. The response rates were 81%, 87%, 87%, 75%, and 60% for symptoms, endoscopy, histology, and all 3 outcomes, respectively. TCS use was significantly lower (8%) in patients who achieved response of all 3 outcomes than in other groups and was dependent on the number of outcomes with nonresponse., Conclusions: Complete normalization of symptoms, endoscopy, and histology using PPI/P-CAB is uncommon. Based on treatment efficacy by response/nonresponse, TCS was the secondary treatment in cases with an increase in the number of nonresponse outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Lumbar interbody fusion (LIF) is a surgical procedure for treating lumbar spinal stenosis and deformities. It removes a spinal disc and insert a cage or bone graft to promote solid fusion. Extensive research on LIF has been supported by numerous animal studies, which are being developed to enhance fusion rates and reduce the complications associated with the procedure. In particular, the anterior approach is significant in LIF research and regenerative medicine studies concerning intervertebral discs, as it utilizes the disc and the entire vertebral body. Several animal models have been used for anterior LIF (ALIF), each with distinct characteristics. However, a comprehensive review of ALIF models in different animals is currently lacking. Medium-sized and large animals, such as dogs and sheep, have been employed as ALIF models because of their suitable spine size for surgery. Conversely, small animals, such as rats, are rarely employed as ALIF models because of anatomical challenges. However, recent advancements in surgical implants and techniques have gradually allowed rats in ALIF models. Ambitious studies utilizing small animal ALIF models will soon be conducted. This review aims to review the advantages and disadvantages of various animal models, commonly used approaches, and bone fusion rate, to provide valuable insights to researchers studying the spine., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2024 The Japanese Society for Spine Surgery and Related Research.)

Objective: The introduction of new-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has afforded promising overall survival outcomes in clinical trials for non-small-cell lung cancer. We aim to investigate the current adoption rate of these agents and the real-world impact on overall survival among institutions., Methods: In a nationwide retrospective cohort study of 46 Tokushukai Medical Group hospitals in Japan, we analyzed clinical data of consecutive patients with non-small-cell lung cancer receiving EGFR-TKIs between April 2010 and March 2020. Univariate and multivariate Cox regression analyses examined the associations between overall survival and patient/tumor-related factors and first-line EGFR-TKIs., Results: A total of 758 patients (58.5% females; median age, 73 years) were included. Of 40 patients diagnosed in 2010, 72.5% received gefitinib, whereas 81.3% of 107 patients diagnosed in 2019 received osimertinib as the first-line EGFR-TKI. With a median follow-up of 15.8 months, the median overall survival was 28.4 months (95% confidence interval, 15.3-31.0). In a multivariate Cox regression analysis, age, body mass index, disease status, EGFR mutational status and first-line epidermal growth factor receptor tyrosine kinase inhibitor were identified as significant prognostic factors after adjusting for background factors including study period, hospital volume and hospital type. The estimated 2-year overall survival rates for gefitinib, erlotinib, afatinib and osimertinib were 70.1% (95% confidence interval 59.7-82.4), 67.8% (95% confidence interval 55.3-83.2), 75.5% (95% confidence interval 64.7-88.0) and 90.8% (95% confidence interval 84.8-97.3), respectively. The median time to treatment failure of gefitinib, erlotinib, afatinib and osimertinib were 12.8, 8.8, 12.0 and 16.9 months or more, respectively., Conclusions: Our real-world data revealed that the swift and widespread utilization of newer-generation EGFR-TKIs in patients with EGFR mutation-positive non-small-cell lung cancer, and that these newer-generation EGFR-TKIs can prolong overall survival regardless of hospital volume or type. Therefore, osimertinib could be a reasonable first choice treatment for these patients across various clinical practice settings., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The deep tendon reflex (DTR) is a more objective indicator than sensory and muscle assessments for lumbar spine disorders. Further, unlike sensory and muscle assessments that require patient cooperation, the DTR can be assessed even in patients with impaired consciousness or cognition. Therefore, DTR assessment with a hammer is an essential neurological test for lumbar spinal diseases. However, despite the usefulness of DTR assessment, few reports have described the significance of increased, diminished, or absent deep lower extremity reflexes in lumbar spine diseases. This review outlines the history of DTR of the lower limbs and describes the techniques, evaluation, and interpretation of DTR for the diagnosis of lumbar spine diseases. The patellar tendon reflex (PTR) was the first parameter of lower extremity DTR identified to have clinical usefulness, followed by the Achilles tendon reflex (ATR), pathological reflexes (Babinski reflex), and reflex enhancement (Jendrassik maneuver). They have now become an integral part of clinical examination. To determine whether an increase or decrease in DTR is pathological, it is necessary to determine left-right differences, differences between the upper and lower extremities, and the overall balance of the limb. There are several critical limitations and pitfalls in interpreting DTRs for lumbar spine diseases. Attention should be paid to examiner and patient factors that make the DTR assessment less objective. When there is a discrepancy between clinical and imaging findings and the level of the lumbosacral nerve root disorder is difficult to diagnose, the presence of a lumbosacral transitional vertebra, nerve root malformation, or furcal nerve should be considered. In addition, assessing the DTR after the gait loading test and standing extension loading test, which induce lumbosacral neuropathy, will help provide a rationale for the diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Morimoto et al.)

Background/aim: The albumin-globulin ratio (AGR) is a useful biomarker for predicting postoperative complications and a poor prognosis in patients with various types of cancer and can be evaluated without invasive testing or surgery. In this study, we aimed to evaluate the usefulness of the AGR in predicting the short- and long-term prognoses of patients with gastric cancer who underwent radical resection at our institution., Patients and Methods: This study is a retrospective cohort analysis in which eligible patients were selected from the medical records of patients who underwent radical resection for gastric cancer at Yokohama City University from 2000 to 2020 and their medical records were reviewed. A total of 240 patients with gastric cancer were classified into high-AGR (>1.57) and low-AGR (≤1.57) groups and their overall survival (OS), recurrence-free survival (RFS), and postoperative complication rates were compared., Results: Of the total 240 patients, 87 were classified into the high AGR group and 153 were classified into the low AGR group; the incidence of postoperative complications in the two groups did not differ to a statistically significant extent (34.4% vs. 39.2%, p=0.491). The long-term findings showed that the 5-year OS and RFS rates were significantly better in the high AGR group [84.0% vs. 64.8% (p=0.005), 80.0% vs. 61.9% (p=0.015), respectively]., Conclusion: Preoperative low AGR is a risk factor for OS and DFS in patients with gastric cancer who undergo surgery. The AGR may be a useful biomarker that can be applied as a prognostic indicator for patients with gastric cancer., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The risk factors for progression of severity of locomotive syndrome (LS) remain unclear., Methods: We conducted a longitudinal observational study of 1148 community-dwelling residents (median age, 68.0 years old; 548 males, 600 females) from 2016 to 2018. LS was assessed by the 25-question Geriatric Locomotive Function Scale (GLFS-25), and total scores of ≤6 points, 7-15 points, 16-23 points, and ≥24 points were diagnosed as non-LS, LS-1, LS-2, and LS-3, respectively. If the LS severity in 2018 was higher than in 2016, the case was defined as progression of LS severity; otherwise, it was defined as non-progressive LS. We compared the age, gender, body mass index, smoking status, alcohol consumption, living situation, car use, chronic musculoskeletal pain, comorbidities, metabolic syndrome, physical activity, and LS severity in 2016 between the progression and non-progression groups. Furthermore, a multivariate logistic regression analysis was performed to elucidate the risk factors for progression of LS severity., Results: Participants in the progression group had a significantly older age, a lower rate of car use, a higher rate of low back pain, a higher rate of hip pain, a higher rate of knee pain, a higher GLFS-25 total score, and a higher rate of LS-2 than those in the non-progression group. The multivariate logistic regression analysis revealed that older age, female gender, higher body mass index (≥25.0 kg/m 2 ), presence of low back pain, and presence of hip pain were risk factors for the progression of LS within two years., Conclusions: To prevent the progression of LS severity, related prophylaxis strategies should be implemented, especially for individuals with the above-mentioned characteristics. Further longitudinal studies with a longer observation period are necessary., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Aim: Recently, change in the neutrophil to lymphocyte ratio (cNLR) has been shown to be a promising prognostic inflammation marker in some malignancies. The aim of the present study was to evaluate the clinical impact of the cNLR in gastric cancer patients who received curative gastrectomy., Patients and Methods: The present study included 450 patients who underwent curative treatment for gastric cancer between 2013 and 2017 at Kanagawa Cancer Center. The cNLR was defined as follows: cNLR = NLR at 1 month after surgery-NLR at 1 week before surgery. The prognosis and clinicopathological parameters of the increased cNLR and decreased cNLR groups were analyzed., Results: The OS stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed using a cutoff value of cNLR at 0.762. When comparing the patient background factors between the increased cNLR (≥ 0.762) and decreased cNLR (< 0.762) groups, there were no significant differences in age, sex, T status, or N status. In the increased cNLR group, the OS rates at 3 and 5 years after surgery were 87.5% and 77.3%, respectively, while those in the decreased cNLR group were 92.8% and 87.3%, which amounted to a statistically significant difference (p = 0.041). The univariate and multivariate analyses of factors associated with OS showed that cNLR was a significant prognostic factor. When the postoperative course was compared between the two groups, the incidence rates of postoperative surgical complications and other-cause death were significantly higher in the increased cNLR group (p = 0.001 and p = 0.005, respectively)., Conclusion: The cNLR is one of the significant risk factors in gastric cancer patients. Our results suggested that the changes of inflammation status during perioperative periods might be a promising prognostic factor for gastrointestinal cancer patients., (© 2023. The Author(s).)

Background/aim: This study aimed to evaluate the clinical impact of the Naples Prognostic Score (NPS) in patients with gastric cancer and to clarify the potential of the NPS as a nutritional and inflammation evaluation system., Patients and Methods: This study included 158 patients who underwent curative treatment for gastric cancer between 2005 and 2020. The prognosis and clinical pathological parameters of the high-NPS (NPS >2) and low-NPS (NPS=0, 1) groups were analyzed., Results: The overall survival (OS) rates at 3 and 5 years were 86.7% and 77.7%, respectively, in the low-NPS group and 55.4% and 47.4%, respectively, in the high-NPS group. There were significant differences in OS between the two groups. Uni- and multivariate analyses demonstrated that the NPS was an independent prognostic factor for OS (HR=2.495, 95%CI=1.240-5.451). In addition, the 3- and 5-year recurrence-free survival (RFS) rates were 82.1% and 76.0%, respectively, in the NPS-low group, and 43.8% and 36.6% in the NPS-high group. Univariate and multivariate analyses demonstrated that the NPS was an independent prognostic factor for RFS (HR=2.739, 95%CI=1.509-4.972). When the first site of recurrence was compared between the low-NPS group and high-NPS group, there were significant differences in peritoneal recurrence (8.7% vs. 34.3%, p=0.001) and hematologic recurrence (5.6% vs. 21.9%, p=0.004)., Conclusion: The NPS was a significant prognostic factor in patients with gastric cancer who received curative treatment. The NPS may be a promising biomarker for the treatment and management of gastric cancer., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Gastric cancer is a common cause of cancer death worldwide, especially in East Asia. This study evaluated the impact of preoperative modified Neutrophil-Platelet Score (mNPS) on the survival and recurrence of patients with resectable gastric cancer., Patients and Methods: The study analyzed 168 patients who underwent curative gastrectomy and subsequently received adjuvant treatment for gastric cancer between 2015 and 2021. Univariate and multivariate analyses were performed to identify the risk factors for overall survival (OS) and recurrence-free survival (RFS)., Results: Patients were divided into two groups: 76 patients with an mNPS of 0 were classified into the low-mNPS group, whereas 92 patients with an mNPS of ≥1 were classified into the high-mNPS group. The 3- and 5-year OS rates in the low-mNPS group were 65.6% and 56.2%, respectively, and those in the high-mNPS group were 45.3% and 36.9%, respectively. The difference in OS between the two groups was statistically significant (p=0.007). The 3- and 5-year RFS rates in the low-mNPS group were 45.6% and 38.7%, respectively, whereas those in the high-mNPS group were 33.4% and 28.1%, respectively. The difference in RFS between the two groups was statistically significant (p=0.043). A multivariate analysis showed that the mNPS was a significant independent prognostic factor for OS and RFS., Conclusion: mNPS is a potential prognostic marker for patients with gastric cancer who underwent curative gastrectomy. Higher mNPS values were associated with lower 3- and 5-year OS and RFS rates, indicating a potential correlation between elevated mNPS and worse outcomes., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Recently, change in the C-reactive protein/albumin ratio (CAR) has become a promising prognostic marker in some malignancies. The aim of the present study was to evaluate the clinical impact of change in the CAR in gastric cancer patients who received curative resection., Method: The present study included 458 patients who underwent curative treatment for gastric cancer between 2013 and 2017. The prognosis and clinicopathological parameters were compared between patients who showed a high-change in CAR and those who showed a low-change in CAR., Results: The OS stratified by each clinical factor was compared using a log-rank test, and a significant difference was observed using a 0.05 change in CAR. When the patient background factors were compared between the high-change (change in CAR ≥ 0.05) and low-change (change in CAR < 0.05) groups, the median age, sex ratio, T factor, and N factor were similar. In the low-change group, the OS rates at 3 and 5 years after surgery were 94.1% and 87.6%, respectively, which amounted to a significant difference from the low-change group, with rates of 83.6 and 77.5% in the high-change group. In the low-change group, the RFS rates at 3 and 5 years after surgery were 90.1% and 85.1%, respectively, while those in the high-change group 77.6 and 75.2%. The univariate and multivariate analyses of factors associated with OS and RFS showed that the change in CAR was a significant prognostic factor., Conclusions: The change in CAR is a significant risk factor and promising prognostic factor for gastric cancer patients., (© 2023. The Author(s).)

Competing Interests: The authors have no conflicts of interest to declare.

Purpose: Radium-223 improves overall survival (OS) and reduces skeletal events in patients with bone metastatic castration-resistant prostate cancer (CRPC), but relevant biomarkers are lacking. We evaluated automated bone scan index (aBSI) and circulating tumor cell (CTC) analyses as potential biomarkers of prognosis and activity., Patients and Methods: Patients with bone metastatic CRPC were enrolled on a prospective single-arm study of standard radium-223. 99m Tc-MDP bone scan images at baseline, 2 months, and 6 months were quantitated using aBSI. CTCs at baseline, 1 month, and 2 months were enumerated and assessed for RNA expression of prostate cancer-specific genes using microfluidic enrichment followed by droplet digital polymerase chain reaction., Results: The median OS was 21.3 months in 22 patients. Lower baseline aBSI and minimal change in aBSI (<+0.7) from baseline to 2 months were each associated with better OS ( P = .00341 and P = .0139, respectively). The higher baseline CTC count of ≥5 CTC/7.5 mL was associated with worse OS (median, 10.1 v 32.9 months; P = .00568). CTCs declined at 2 months in four of 15 patients with detectable baseline CTCs. Among individual genes in CTCs, baseline expression of the splice variant AR-V7 was significantly associated with worse OS (hazard ratio, 5.20 [95% CI, 1.657 to 16.31]; P = .00195). Baseline detectable AR-V7 , higher aBSI, and CTC count ≥5 CTC/7.5 mL continued to have a significant independent negative impact on OS after controlling for prostate-specific antigen or alkaline phosphatase., Conclusion: Quantitative bone scan assessment with aBSI and CTC analyses are prognostic markers in patients treated with radium-223. AR-V7 expression in CTCs is a particularly promising prognostic biomarker and warrants validation in larger cohorts.

Background/aim: This study aimed to compare dietary intake (DI) after gastrectomy for gastric cancer between patients with (C group) and without (NC group) postoperative surgical complications., Patients and Methods: This prospective observational study enrolled patients who underwent gastrectomy for gastric cancer. DI was assessed using a food frequency questionnaire with 82 food items (FFQW82) during nutritional counseling before surgery and at one and three months after surgery., Results: A total of 225 patients participated in this study. Of the 225 patients, 193 had no postoperative complications, and 32 had postoperative complications (Clavien-Dindo grade ≥2). The median DI at 1 month postoperatively was 1508 kcal/day in the NC group and 1,470.5 kcal/day in the C group (p=0.175). The median DI at 3 months postoperatively was 1,623 kcal/day in the NC group and 1575 kcal/day in the C group (p=0.473). There was a significant difference between the NC and C groups in the rate of decrease in DI at one month (median: -8.44% vs. -15.37%, p=0.032) and at three months postoperatively (median: -3.58% vs. -6.12%, p=0.038)., Conclusion: There was a statistically significant difference in the rate of decrease in DI after gastrectomy between the C and NC groups at 1 and 3 months postoperatively. Our results suggest that patients with postoperative surgical complications require additional nutritional treatment for decreased DI., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Perioperative inflammation and the nutritional status affect both short- and long-term oncological outcomes in various malignancies. We clarified the clinical impacts of the CRP-albumin-lymphocyte (CALLY) index in patients with esophageal cancer who received curative treatment., Patients and Methods: The present study included 180 patients who underwent curative treatment for esophageal cancer between 2005 and 2020. The prognosis and clinicopathological parameters were compared between a high-fibrinogen group and a low-fibrinogen group., Results: The 3- and 5-year overall survival rates were 50.0% and 42.6%, respectively, in the CALLY index-low group, and 75.9% and 66.6% in the CALLY index-high group. The differences between the two groups were statistically significant (p<0.001). Univariate and multivariate analyses demonstrated that the CALLY index was an independent prognostic factor [hazard ratio=2.310, 95% confidence interval=1.416-3.767, p<0.001]. Similar results were observed in recurrence-free survival. When comparing the details of postoperative surgical complications, there was a significant difference in the incidence of anastomotic leakage. The incidence of anastomotic leakage was 40.2% in the CALLY index-low group, while it was 27.5% in the CALLY index-high group (p=0.030)., Conclusion: The pretreatment CALLY index is one of the independent prognostic factors for esophageal cancer. The CALLY index might become a promising biomarker for the treatment and management of esophageal cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)