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Purpose Halos are a chief source of patient dissatisfaction after multifocal intraocular lens (IOL) implantation. The primary purpose of this study was to investigate the influence of age, postoperative refraction, and pre- and postoperative pupil size on postoperative halo size with a trifocal diffractive IOL (AcrySof IQ PanOptix) and extended depth-of-focus (EDOF) IOL (TECNIS Symfony) to determine whether these factors could predict postoperative halo size. Patients and Methods This single-center, open-label study conducted between October 2018 and April 2020 in Yokosuka, Japan included 160 patients: 80 with PanOptix and 80 with Symfony IOLs. Size and intensity of the halos were examined binocularly using a computer-based simulator (Eyeland Design Network GmbH) and scored from 0 (minimum) to 10 (maximum) at 1, 3, and 6 months postoperatively, along with the change in each variable for both IOLs. The respective correlations of halo size with age, postoperative refraction, pre- and postoperative pupil size, and discomfort level due to the halo were also investigated 6 months postoperatively. Results Halo size and intensity were significantly mitigated between 1, 3, and 6 months postoperatively. Throughout the observation period, halo size was significantly larger with PanOptix than with Symphony (P < 0.05), and halo intensity was significantly higher with Symphony than with PanOptix (P < 0.05). The pre- and postoperative pupil size correlated positively with halo size, while age and postoperative refraction were negatively correlated, for both IOLs. Conclusion Understanding the features and predictive preoperative factors of halos in different types of multifocal IOLs may be useful in improving patient satisfaction.

Introduction Understanding the relationship between postoperative intraocular lens (IOL) shift and refractive change is crucial for the accuracy of predicted postoperative refraction (PPR). We assessed the relationships between different IOL fixation methods, haptic designs, and several metrics. Methods Single-center, open-label study which included 69 eyes. We preoperatively measured the anterior chamber depth (ACD), lens thickness (LT), axial length (AL), and PPR. AcrySof IQ (n = 27) and FineVision (n = 24) were fixed in the bag, and FEMTIS (n = 18) was fixed in capsulorhexis. At 1 day, 1 week, and 1 month postoperatively, we checked the IOL position and refraction and compared the IOL shift, refraction change, and the margin of error of the predicted PPR (PR-PPR difference). We also analyzed the correlation between postoperative and preoperative variables. Results FEMTIS showed the highest stability in terms of IOL shift and refraction. The in-the-bag-fixated IOLs showed a significant forward shift between 1 day and 1 week postoperatively. There were significant differences in the PR-PPR difference between the IOLs. ACD and AL showed significant positive correlations, and LT showed a significant negative correlation with IOL shift and change in PR between 1 day and 1 week, but not between 1 week and 1 month postoperatively. Conclusion The relationship between postoperative IOL shift and refraction change varied according to IOLs with different haptic types. Capsulorhexis fixation may be more stable than in-the-bag fixation. Furthermore, preoperative ACD, LT, and AL may be useful factors to predict IOL shift, change in PR, and to a lesser extent the degree of the margin of error in clinical practice. Our findings may improve the accuracy of PPR and refractive outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00390-x.

Introduction This study investigated the effect of rebamipide on discrepancies in the power and axis of astigmatism between two intra-patient keratometric measurements in patients with dry eyes. Methods Fifty-eight dry eyes (with a short tear breakup time [TBUT] of less than 5 s) were analyzed. Patients with dry eye were treated with 2% rebamipide ophthalmic suspension (group R) or Mytear® artificial tear ophthalmic solution (group M) for 4 weeks. TBUT and corneal higher-order aberrations (HOAs) were evaluated at baseline and 4 weeks after treatment. Astigmatism power and axis were measured twice during both evaluations, at 5-min intervals. Baseline and post-treatment measurements were compared. Changes in TBUT and HOAs, and intra-patient discrepancies in astigmatism power and axis measurements were evaluated. Results HOAs showed significant positive correlations with intra-patient differences in astigmatism power and axis (P, Plain Language Summary This study investigated the effect of rebamipide on discrepancies in power and axis of astigmatism between two intra-patient keratometric measurements in patients with dry eyes. Short tear break-up time and corneal high-order aberrations were evaluated at baseline and 4 weeks after treatment. Astigmatism power and axis were measured twice at both evaluations. Baseline and post-treatment measurements were compared, and changes in short tear break-up time and high-order aberrations, as well as intra-patient discrepancies in astigmatism power and axis measurements, were evaluated. High-order aberrations at baseline showed significant positive correlations with intra-patient differences in astigmatism power and axis. Rebamipide significantly improved the corneal surface condition and significantly reduced intra-patient discrepancies in astigmatism power and axis measurements. Rebamipide may improve the accuracy of intraocular lens power calculations in dry eyes, particularly when toric intraocular lenses are implanted. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00368-9.

A thrombosed giant aneurysm of the V1 and V2 segments of the vertebral artery (VA) is rare. Therefore, there is controversy regarding its optimal treatment. A case of a symptomatic giant VA aneurysm located in the V1 to V2 segments on the left treated successfully by endovascular trapping of the VA is reported. A 68-year-old woman presented with swelling in the left anterior neck. Computed tomography angiography (CTA) showed a giant aneurysm measuring 47 × 58 × 47 mm3 in the left neck. Ten days after her first visit, she presented with sudden onset of left anterior neck pain. Repeated CTA showed a partial thrombus in the aneurysm. Angiography showed two thrombosed giant aneurysms located in the V1 to V2 segments of the left VA. After endovascular trapping for the aneurysms, the anterior neck pain resolved and the aneurysm gradually shrank. This case demonstrates that endovascular surgery is better than open surgery because it is less invasive. When performing endovascular treatment, trapping will be an alternative strategy for a symptomatic giant thrombotic aneurysm of the V1 and V2 segments of the VA if the patient can tolerate ischemia.

Malignant progression of grade I meningioma with a long latency period is rare. We experienced grade II/III meningiomas with refractoriness and recurrence from grade I meningiomas through multiple surgeries. Three patients with atypical/anaplastic meningioma experienced long-latent recurrence after initial surgery for grade I (meningothelial) meningioma without following adjuvant radiotherapy were included in the present study. Histological findings of the initial tumors in all cases (case 1, 2, and 3) revealed meningothelial meningioma with 1%, 5%, and 0.1% MIB-1 positive cells, respectively. Surprisingly, magnetic resonance imaging (MRI) detected a recurrent tumor 2, 12, and 12 years after the initial operation, respectively. Case 1 was atypical meningioma after third recurrence, and case 2 and 3 were anaplastic meningioma after second and third recurrence, respectively. The patient in case 2 received adjuvant radiotherapy. In case 2, the tumor recurred intracranial and distant metastasis to the lung with huge substantial pleural effusion was detected. To investigate the pathogenesis of malignant progression from benign to malignant meningioma, CD163/CD68 expression by immunohistochemically and FOXM1 mRNA expression by RT-PCR were compared using surgical specimens from initial and recurrent tumors in all three patients. The ratio of CD163/CD68 positivity and FOXM1 mRNA expression were increased in recurrent tumors compared with matched initial tumors. CD163 and FOXM1 expression levels were induced even in recurrent grade I meningioma, suggesting that macrophage polarization and pro-mitotic transcriptional factor might be associated with clinical behavior of meningioma and be useful as a prediction marker for malignant progression. Careful long-term follow-up is important for early diagnosis of malignant progression in meningiomas, even if grade I meningioma is completely resected. Development of a multidisciplinary approach including radiation and novel molecular targeted therapy is expected for recurrent and malignant meningiomas.

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.

Pseudomonas aeruginosa (P. aeruginosa) infection is one of the major causes of keratitis. However, effective prophylactic and therapeutic vaccines against P. aeruginosa keratitis have yet to be developed. In this study, we explored the use of P. aeruginosa membrane vesicles (MVs) as a prophylactic vaccine as well as the use of immune sera derived from P. aeruginosa MV-immunized animals as a treatment for P. aeruginosa corneal infections in C57BL/6 mice., C57BL/6 mice were intramuscularly immunized with P. aeruginosa MVs; the mouse corneas were then scarified and topically infected with several P. aeruginosa strains, followed by determination of corneal clinical score and corneal bacterial load. Next, immune sera derived from P. aeruginosa MV-immunized ICR mice were administered intraperitoneally to naïve C57BL/6 mice, followed by topical P. aeruginosa challenge. Finally, the immune sera were also used as a topical treatment in the mice with established P. aeruginosa corneal infections., P. aeruginosa-specific IgG and IgA antibodies induced by intramuscular immunization were detected not only in the sera but also in the eye-wash solution. Both active and passive immunization significantly inhibited P. aeruginosa corneal infection. Finally, topical treatment with immune sera in the mice with established P. aeruginosa corneal infections notably decreased the corneal clinical score and corneal bacterial load., P. aeruginosa keratitis can be attenuated by vaccination of P. aeruginosa MVs and topical application of P. aeruginosa MV-specific immune sera.

Purpose To identify novel susceptibility loci for high myopia. Design Genome-wide association study (GWAS) followed by replication and meta-analysis. Participants A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls). Methods We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. Main Outcome Measures We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. Results We identified 9 loci with genome-wide significance (P Conclusions The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.

A 68-year-old man with senile cataract underwent femtosecond laser-assisted cataract surgery (FLACS) in his left eye. Only anterior capsulotomy and lens fragmentation were planned with a femtosecond laser. Docking of the patient interface and anterior capsulotomy were completed without any complications. During the lens fragmentation process, the patient could not resist the temptation to squeeze his eyes shut, which caused excessive pressure from the eyelids. As the procedure proceeded, a bubble was formed at the edge of the patient interface and became increasingly larger. In addition, wrinkles in the conjunctiva were observed. As the lens fragmentation was approaching the final stage, the surgeon was reluctant to release the foot pedal to stop the laser emission. Finally, the patient interface lost adhesion to the cornea. Owing to the high repetition rate of the laser, the laser beam slipped into the corneal layers. Under an operating microscope, a grid-pattern laser beam trace was observed in the peripheral part of the cornea. As posterior capsule rupture occurred during the lens removal process, IOL insertion was no longer a suitable option. Therefore, scleral fixation of the implanted intraocular lens was performed without any unexpected events. One year postoperatively, the laser beam trace in the corneal layers could still be identified by slit-lamp examination. Nonetheless, since the laser beam trace was limited to the peripheral part of the cornea, and there was no damage to the central cornea, the visual acuity was 20/20. FLACS has significant benefits, especially in challenging cases of cataract surgery, and has well-established built-in safeguards for complications. However, this case study indicates the possibility of a suction break during laser emission and the preoperative risk factors. It demonstrates that recognizing the signs of suction break is necessary to avoid misplacement of the laser beam on the corneal layers.

Background We have reported an extremely rare case of a frontal convexity tumor diagnosed as IgG4-related disease (IgG4-RD) with unique neuroradiological images. Case Description A 64-year-old man with a history of monoclonal gammopathy of undetermined significance and conservative treatment had presented with a left facial spasm. Computed tomography showed a high-density round tumor with perifocal edema in the right frontal convexity. Magnetic resonance imaging demonstrated unique findings, including low signal intensity on T1- and T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images, with slight gadolinium enhancement. The tumor was totally removed via right frontal craniotomy. It had been located in the subdural space, was not adherent to the dura, and was less vascular than meningiomas. Histological investigation demonstrated plasma cells that were strongly positive for IgG4 and contained κ and λ light chains at a ratio of 1.5:1. The serum IgG4 level was elevated. The tumor met the diagnostic criteria for IgG4-RD. The patient was followed up for 3 years during postoperative adjuvant steroid therapy. The steroid therapy was discontinued, and during the next 4 years, neither tumor recurrence nor symptoms were observed. Conclusion Intracranial IgG4-RD with smoldering monoclonal gammopathy of undetermined significance is extremely rare. We reviewed the differential diagnosis of plasma cell granuloma and plasmacytoma, therapeutic implications, and clinical outcomes. Complete resection of a conspicuous and solitary IgG4-RD lesion in the frontal convexity is simple and could provide a cure with less-aggressive adjuvant therapy.

Posterior capsule opacification (PCO) is the most common cause of deterioration of vision and contrast sensitivity and glare after cataract surgery. Neodymium (Nd): yttrium aluminum garnet (YAG) laser capsulotomy is an effective and standard procedure to treat these symptoms. The incidence rate of PCO requiring Nd:YAG laser treatment varies and depends on published studies, ranging from 2.2% to 10.0%. Although Nd:YAG laser treatment is largely safe, it still has complications, such as transient increase of intraocular pressure, anterior uveitis, intraocular lenses pitting, cystoid macula edema, endophthalmitis, and retinal detachment. We encountered a rare complication related to Nd:YAG laser treatment, where the laser accidentally hits the cornea. This occurred because the PCO was mistaken for the corneal layers during the laser procedure. This report presents the 3-year post-treatment process, and the findings herein may help raise the awareness of the possibility of this rare complication and provide measures for its treatment.

PURPOSE The aim of this study was to compare the influence of pupil dilation on power calculation formulas for third- (Hoffer Q, SRK/T) and fourth- (Haigis, Holladay3) generation intraocular lens (IOL) between monofocal and multifocal IOLs. DESIGN Retrospective, comparative study. METHODS We analyzed 280 eyes (162 monofocal, 118 multifocal; mean patient age: 72.9 ± 7.7 years; 41.25% male). Anterior chamber depth (ACD) and lens thickness (LT) were measured. Predicted postoperative refraction (PPR) and recommended IOL power were calculated using third- and fourth-generation formulas pre- and post-dilation. We evaluated the mean absolute change (MAC) in PPR, change in recommended IOL power per formula, and mean change in ACD and LT between pre- and post-dilation, for both monofocal and multifocal IOLs. RESULTS ACD and LT showed significant changes post-dilation. The MAC in PPR was significantly higher with fourth-generation formulas than that with third-generation formulas, for both IOLs, and more so for multifocal IOLs. For both IOLs, the PPR change correlated positively with ACD changes, but negatively with LT changes, for fourth-generation formulas. Multifocals correlated significantly stronger with LT than monofocals. When using fourth-generation formulas post-dilation, the recommended IOL power changed more frequently in multifocals than in monofocals, although not significantly. CONCLUSIONS Pupil dilation did not influence third-generation formula calculations for both IOL types, but did affect PPR and recommended IOL power when using fourth-generation formulas, and more so for multifocals. Considering pupil dilation effects on monofocal and multifocal parameters is vital for accurate IOL calculation.

We analyzed clinical cutoffs for defining computed tomography (CT) methods for sarcopenia and examined the prognostic value of CT for allogeneic hematopoietic stem cell transplantation (allo-HCST) outcomes of patients with myeloid malignancy. One hundred twenty-five adult patients with acute myeloid leukemia and myelodysplastic syndrome who underwent first allo-HSCT between 2000 and 2017 were included. Sarcopenia was assessed using CT-based skeletal muscle index (SMI) and mean muscle attenuation at L3. A statistical difference in SMI was confirmed between sarcopenia (n = 52) and nonsarcopenia (n = 73) patients. There were no significant correlations of muscularity with age, performance status, or other characteristics of HSCT. After 2 years, overall survival (OS) was 43.5% and 70.1%, disease-free survival was 52.9% and 68.6%, nonrelapse mortality (NRM) was 20.8% and 8.4%, incidence of acute GVHD (≥ grade 2) was 38.8% and 39.1%, that of chronic GVHD was 53.2% and 37.3%, and median duration of hospitalization was 88 days and 74 days (P = 0.026), respectively, in the sarcopenia and nonsarcopenia groups. Multivariate analysis showed that presence of sarcopenia is a novel adverse factor for high NRM and poor OS. Pretransplant CT-defined sarcopenia is correlated with decreased OS, increased NRM, and prolonged hospitalization.

ObjectiveThe causality and pathogenic mechanism of microbiome composition remain elusive in many diseases, including autoimmune diseases such as rheumatoid arthritis (RA). This study aimed to elucidate gut microbiome’s role in RA pathology by a comprehensive metagenome-wide association study (MWAS).MethodsWe conducted MWAS of the RA gut microbiome in the Japanese population (ncase=82, ncontrol=42) by using whole-genome shotgun sequencing of high depth (average 13 Gb per sample). Our MWAS consisted of three major bioinformatic analytic pipelines (phylogenetic analysis, functional gene analysis and pathway analysis).ResultsPhylogenetic case–control association tests showed high abundance of multiple species belonging to the genus Prevotella (e.g., Prevotella denticola) in the RA case metagenome. The non-linear machine learning method efficiently deconvoluted the case–control phylogenetic discrepancy. Gene functional assessments showed that the abundance of one redox reaction-related gene (R6FCZ7) was significantly decreased in the RA metagenome compared with controls. A variety of biological pathways including those related to metabolism (e.g., fatty acid biosynthesis and glycosaminoglycan degradation) were enriched in the case–control comparison. A population-specific link between the metagenome and host genome was identified by comparing biological pathway enrichment between the RA metagenome and the RA genome-wide association study results. No apparent discrepancy in alpha or beta diversities of metagenome was found between RA cases and controls.ConclusionOur shotgun sequencing-based MWAS highlights a novel link among the gut microbiome, host genome and pathology of RA, which contributes to our understanding of the microbiome’s role in RA aetiology.

Patient: Male, 42-year-old Final Diagnosis: Traumatic posterior cerebral artery aneurysm Symptoms: Deterioration of mental status and disorientation Medication: — Clinical Procedure: Parent artery occlusion by endovascular approach Specialty: Neurosurgery Objective: Unusual clinical course Background: Subdural hematoma (SDH) caused by traumatic intracranial aneurysm (TICA) is rare. TICAs are known to rupture easily, resulting in a high morbidity and mortality rate. Therefore, accurate diagnosis and treatment are crucial for preserving life. We describe a case of delayed SDH in the setting of posterior cerebral artery (PCA) aneurysm. Case Report: A 42-year-old man presented with sustained head injury from a traffic accident, and was being followed-up conservatively for traumatic SDH and subarachnoid hemorrhage. Three weeks after the head trauma, the patient developed a sudden deterioration of mental status and disorientation. Computed tomography revealed de novo SDH at the cerebellar tentorium. Computed tomography angiography and magnetic resonance imaging demonstrated TICA in the PCA. The patient was diagnosed with SDH due to a ruptured PCA aneurysm at the quadrigeminal segment. To avoid SDH growth due to re-rupture of the aneurysm, parent artery occlusion was subsequently performed with no complications. The patient was discharged home 2 months after endovascular treatment, with moderate disability. Follow-up angiography 2 years after the operation showed no recanalization, and the patient had returned to work. Conclusions: TICA in the PCA can cause tentorial SDH with or without the presence of subarachnoid hemorrhage. Routine cerebrovascular assessment is crucial for head trauma with hematoma adjacent to the cerebellar tentorium. Parent artery occlusion via an endovascular procedure is an alternative treatment for TICA in the PCA that is less invasive than other approaches.

Passenger lymphocyte syndrome (PLS) is a specific subtype of graft versus host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) characterized by an immune-mediated hemolysis caused by donor-derived B cells. However, precise nature of PLS has not been well characterized due to its rarity. We herein report two cases of PLS following ABO-incompatible HSCT whose clinical course and dynamics of anti-ABO allo-antibody and blood type conversion were closely examined. Both cases demonstrated acute hemolysis upon engraftment, and the presence of high titer allo-antibody against recipients' red blood cells (RBCs) helped us to reach the diagnosis of PLS. Hemolysis in both cases showed spontaneous improvement with prednisolone and supportive therapy including transfusion and fluid support. In one case with blood type O, the patient recursively developed PLS in the second and the third HSCT from ABO-mismatch donors, leading to a hypothesis that original blood type O may serve as a background for acute elevation of serum anti-ABO antibody and therefore a risk for developing PLS in multiple ABO-incompatible HSCTs. When hemolysis is noted following ABO-incompatible HSCTs, PLS should be considered and measurement of anti-ABO antibodies is warranted.

Background: Cerebellar hemorrhage is rare in children, and its cause is usually vascular disorders such as arteriovenous malformations or hematological disorders. Case Description: A previously healthy 10-year-old girl presented with a loss of consciousness following sudden headache and vomiting. A non-contrast brain computed tomography (CT) scan revealed a massive cerebellar hemorrhage with obstructive hydrocephalus; however, subsequent CT angiography (CTA) showed no vascular abnormalities. An emergency craniotomy was performed to evacuate the hematoma, and histological analysis of the specimen obtained from the tissue surrounding the hematoma revealed a pilocytic astrocytoma (PA). Six months after the ictus, her recovery was scored at 2 on the modified Rankin Scale. Conclusion: PA can be a cause of critical cerebellar hemorrhage. In this case of life-threatening massive hematoma, CTA was useful to exclude a major vascular pathology and to save time.

Objective Visual field defects occasionally occur secondary to tumors in the parietal and the occipital lobes. The aim of this study was to analyze the efficacy of improvement in hemianopsia after surgery for metastatic brain tumors involving or adjacent to the optic radiation (OR). Methods The study included 49 patients with brain metastasis in the parietal and occipital lobes in the present study. Preoperative and postoperative neurological assessments included visual field, Mini-Mental State Examination, and Karnofsky performance scale. Results Of 49 patients, 33 (67.3%) presented with preoperative homonymous hemianopsia. Of these 33 patients, the visual field was improved postoperatively in 17 patients (51.5%). In all patients regardless of preoperative hemianopsia, postoperative visual fields did not deteriorate. Tractography demonstrated that the OR was split by the tumor (n = 6) and fanning of fibers expanded along the lateral side of the tumor (n = 11). All tumors were removed via surgical access toward the medial side of the tumor. Gross total resection was achieved in most tumors in the group with visual improvement (n = 16/17; 94.1%). Improvement in the visual field was attributed to tumor location in the subcortical white matter, removal rate of the tumor, and higher postoperative Karnofsky performance scale score. Conclusions The OR tended to deviate to the lateral side of the tumor in the parieto-occipital junction. The postoperative visual field improved even in cases of an occipital tumor. Based on the present study, total resection via an appropriate surgical route should be considered to preserve the OR, leading to improvement in the postoperative visual field.

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear.Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease.Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24–2.55, P = 0.002) and Calsepa [High-Man (Man2–6)]: 1.56 (1.19–2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001–0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045–0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively].Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE.Trial Registration: This study was registered with the University Hospital Medical Information Network on June 26, 2012 (Clinical trial number: UMIN000011525, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482).

Biological disease-modifying anti-rheumatic drugs (bDMARDs) against pathogenic proinflammatory cytokines and lymphocytes, such as tumour necrosis factor-α (TNF-α), interleukin-6, T cells and B cell...

Aims/introduction The predictive low glucose management (PLGM) system was introduced in March 2018 in Japan. Although there are some reports demonstrating the benefit of PLGM in preventing hypoglycemia, no data are currently available in Japanese patients with type 1 diabetes mellitus (T1DM). The aim of the present study is to evaluate the effect of PLGM with sensor-augmented pump therapy in the prevention of hypoglycemia in Japanese patients. Materials and methods We included 16 patients with T1DM who used the MiniMed®640G system after switching from the MiniMed®620G system. We retrospectively analysed the data of the continuous glucose monitoring system in 1 month after switching to MiniMed®640G. Results The area under the curve (AUC) of hypoglycemia of 180 mg/dL and the duration of hyperglycemia did not change. With the PLGM function, 79.3% of the predicted hypoglycemic events were avoided. Conclusions The hypoglycemia avoidance rate was comparable to those in previous reports. In addition, we demonstrated that PLGM can markedly suppress severe hypoglycemia without deteriorating glycemic control in Japanese T1DM patients. It is necessary to further investigate the effective use of the PLGM feature such as establishing a lower limit and the timing of resumption.

Background Many women experience depressive symptoms during pregnancy and postpartum periods. These depressive symptoms are often accompanied by other inflammatory morbidities present during pregnancy. Tryptophan (TRP) metabolism has attracted considerable attention due to its influence on the onset of depression via induction of inflammation. We examined the changes in plasma levels of TRP metabolites in pregnant women with depressive symptoms during pregnancy and/or the postpartum period. Methods In line with a previous analysis using the Edinburgh Postnatal Depression Scale (EPDS), participants were divided into a non-depressive (ND) group, a postpartum depressive (PD) group, a temporary gestational depressive (TG) group, and a continuous depressive (CD) group. Blood samples were collected before and 1 month after delivery. The concentrations of plasma TRP metabolites were measured using high-performance liquid chromatography (HPLC). Results There are differences in plasma levels of TRP metabolites during pregnancy and postpartum periods between the ND group and the PD group, but not the TG or CD group. In the PD group, plasma levels of kynurenine (KYN) and kynurenic acid (KA), and KYN/TRP and KA/KYN ratio during the pregnancy period were higher and 3-hydroxyanthranilic acid (3HAA) during the postpartum period was lower than those in the ND group. Limitations Histories regarding mood disorders before pregnancy were not assessed. Conclusions The higher plasma levels of KYN and KA, and KYN/TRP and KA/KYN ratio during pregnancy period and lower plasma level of 3HAA during the postpartum period could be useful predictive and diagnostic markers of postpartum depressive symptoms.

A 26-year-old woman with Takayasu's arteritis (TAK) experienced back and neck pain during tocilizumab (TCZ) treatment. The levels of C-reactive protein were normal, and ultrasonography revealed no significant changes. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) showed signal enhancement in the walls of several arteries. Contrast computed tomography showed arterial inflammation in the same lesion. After increasing the dose of prednisolone and TCZ, all signal enhancements decreased and continued to decrease, as observed on days 76 and 132. Thus, DWIBS may be a novel imaging modality for assessing the disease activity of TAK, particularly during follow-up.

Background Anaphylactic reactions to opioids are rare. We report a case of an infant who experienced fentanyl-induced anaphylaxis. Case presentation A 2-month-old male was scheduled to undergo a Blalock-Taussig shunt. Following uneventful anesthetic induction, he experienced profound hypotension and generalized erythema. Anaphylaxis was clinically diagnosed, and he was treated with epinephrine, vasopressin, and fluids. The surgery was canceled, and he was transferred to the intensive care unit after restoration of his hemodynamic status. Intradermal testing was performed for all of the drugs given during the anaphylactic event on postoperative day (POD) 3. The results showed a positive reaction to fentanyl. For the second anesthesia scheduled on POD 5, morphine sulfate was selected as an alternative opioid. Anesthesia was maintained uneventfully with sevoflurane, morphine, and rocuronium. Conclusion Intradermal testing revealed fentanyl anaphylaxis. We were able to manage the patient by using of morphine as an alternative opioid for the subsequent anesthesia.

Zonulopathy is a major concern if found during cataract surgery as it can cause further complications. Such complications may occur during continuous curvilinear capsulorhexis (CCC), lens fragmentation and intraocular lens (IOL) implantation. Femtosecond laser-assisted cataract surgery (FLACS) devices, such as the LenSX (Alcon Laboratories) are advantageous because they can detect the area and largest point of zonulopathy via anterior segment optical coherent tomography (AS-OCT) before the manual part of the procedure. CCC and lens fragmentation can also minimize further zonular stress. A symmetrical CCC is ideal for IOL implantation in the sulcus with optic capture. In the present study, we did not detect significant zonular dehiscence preoperatively in either of the eyes of our 68-year-old patient when using AS-OCT (CASIA2 Tomey). However, LenSx AS-OCT revealed zonular dehiscence in both eyes, perioperatively. We created CCC and lens fragmentation without causing stress to the zonules. In the subsequent manual part of procedure, we found zonular dehiscence in the same area as indicated by LenSx AS-OCT, which extended to approximately 200° in the right eye and 180° in the left. After lens fragmentation by LenSx, we successfully removed the lens without further zonular dialysis. However, zonular dialysis (>180°) in the right eye was too large to insert an IOL, either in the capsule or the sulcus. Therefore, we performed scleral IOL implantation. In the left eye, we avoided using capsular tension ring (CTR) for IOL placement to avoid further iatrogenic damage to the zonule. Instead, an IOL was inserted into the sulcus with optic capture to reduce the possibility of further stress to the zonula and phimosis. Post-surgically, the patient regained good eyesight in both eyes. This case illustrates the advantages of FLACS in addressing zonulopathy. The consistent creation of CCC and lens fragmentation by FLACS may increase success rates, even in unexpectedly challenging cases.

Background High mobility group box 1 (HMGB1) protein plays a key role in triggering inflammatory responses in many diseases. Our previous study showed that HMGB1 is found upstream of secondary damage in traumatic brain injury (TBI). We found that anti-HMGB1 monoclonal antibody (mAb) effectively decreased acute brain damage, including the disruption of the blood-brain barrier, brain edema, and neurologic dysfunction. This effect of anti-HMGB1 mAb lasts for at least 1 week. In this study, we explored subacute effects of anti-HMGB1 mAb after TBI. Methods TBI was induced in rats by fluid percussion. Anti-HMGB1 mAb or control mAb was given intravenously after TBI. Histochemical staining, plasma levels of HMGB1, motor activity and memory, and video electroencephalography monitoring were evaluated 2 weeks after fluid percussion injury. Results Anti-HMGB1 mAb remarkably attenuated accumulation of activated microglia in the rat cortex in the ipsilateral hemisphere after TBI. Anti-HMGB1 mAb also prevented neuronal death in the hippocampus in the ipsilateral hemisphere after TBI. Treatment of rats with anti-HMGB1 mAb inhibited HMGB1 translocation and suppressed impairment of motor function. The beneficial effects of anti-HMGB1 mAb on motor and cognitive function persisted for 14 days after injury. Treatment with anti-HMGB1 mAb also had positive effects on electroencephalography activity. Conclusions The beneficial effects of anti-HMGB1 mAb continued during the subacute postinjury phase, suggesting that anti-HMGB1 mAb may prevent cognitive dysfunction after TBI.

Purpose: To investigate whether variants in the ARMC9 gene encoding KU-MEL-1 are associated with Vogt-Koyanagi-Harada (VKH) disease in a Japanese population.Methods: We recruited 380 Japane...

It is important to distinguish foramen magnum arachnoiditis (FMA) from Chiari malformation (CM) before surgery because the operative strategies for these diseases differ. In the current study, we compared pretreatment magnetic resonance imaging (MRI) of FMA with CM and investigated the MRI findings useful to differentiate between these diseases. We retrospectively reviewed patients with FMA or CM aged ≥ 18 years who underwent surgeries at our institution between 2007 and 2019. The morphologies of the syrinx, neural elements, and posterior cranial fossa were preoperatively evaluated with MRI. We used the receiver operating characteristic (ROC) curve for the fourth ventricle-to-syrinx distance (FVSD). Ten patients with FMAs and 179 with CMs were included. FVSD in the FMA group was significantly shorter than that in the CM group (7.5 mm [IQR, 2.8–10 mm] in FMA vs. 29.9 mm [IQR, 16.3–52.9 mm] in CM, p

Objectives No large-scale registration study has comprehensively evaluated the activities of daily living (ADL) in patients with Behçet’s disease. Methods The Japanese government provided us with a dataset of confirmed or suspected Behçet’s disease cases derived from ongoing national registration. ADL were categorized and analysed into four categories in patients who satisfied the International Criteria for Behçet’s Disease. Results Data from 2960 patients (men 38.9%, women 61.1%; median age 39 years) were assessed. While 1767 patients (59.7%) had normal ADL, the others had impaired ADL comprising limited but not assisted [n = 1058 (35.7%)], partially assisted [n = 116 (3.9%)] and fully assisted [n = 19 (0.6%)]. Logistic regression analysis showed that chronic ocular lesions [odds ratio (OR) 1.85 (95% CI 1.46, 2.35), P Conclusion Ocular lesions, neurological manifestations and arthritis affected ADL. Patients with ocular lesions or neurological manifestations more frequently required physical assistance.

Obesity is a major public health problem worldwide owing to the substantial increase in risk of metabolic diseases. Hypoxia-inducible factors (HIFs) regulate transcriptional responses to hypoxic stress. DNA methylation in the CpG sites of intron 1 of HIF3A is associated with body mass index in the whole blood and adipose tissue. This study investigates the correlation between DNA methylation of HIF3A and parameters of obesity, including thickness of visceral (VAT) and subcutaneous adipose tissues, in the general Japanese population. Participants (220 men and 253 women) who underwent medical examination were enrolled in this cross-sectional study. We used pyrosequencing to quantify DNA methylation (CpG sites of cg16672562, cg22891070, and cg27146050) in HIF3A. DNA methylation of HIF3A was only different in women. Multiple regression analysis showed that DNA methylation level at cg27146050 was associated with thickness of VAT in women. DNA methylation level at cg27146050 also correlated with body mass index and percentage of body fat in women after excluding smokers and non-smokers who quit smoking with the last 5 years. DNA methylation in the CpG site (cg27146050) of HIF3A correlated with parameters of obesity in Japanese women.

Background Despite the surge in the number of cataract surgeries, there is limited information available regarding the influence of pupil dilation on predicted postoperative refraction and its comparison with recommended various intraocular lens power calculated using the different parameters. We used three different IOL power calculation formulas: Barrett Universal II (Barrett) (5-variable formula), Haigis (3-variable formula), and SRK/T (2-variable formula), in order to investigate the potential effect of pupil dilation on the predicted postoperative refraction (PPR) and recommended intraocular lens (IOL) power calculation. Methods This retrospective study included 150 eyes. All variables were measured and calculated using a ZEISS IOL Master 700. The following variables were measured before and after dilation: anterior chamber depth (ACD), lens thickness (LT), white-to-white (WTW). PPR and recommended IOL power were calculated by Barrett, Haigis, and SRK/T IOL calculation formulas. The change in each variable before and after dilation, and the correlations between all changes were analyzed using the Wilcoxon signed-rank test and the Spearman’s rank-order correlation test, respectively. Results The mean absolute change (MAC) in PPR before and after dilation was found to be highest in the Barrett formula. Significant differences were found between each MAC (P P P P P = 0.022). The recommended IOL power determined using Barrett and Haigis changed before and after dilation in 23.3 and 19.3% cases respectively, while SRK/T showed no change. Conclusions In terms of PPR and recommended IOL power, pupil dilation influenced mostly the Barrett formula. Given the stronger correlation between the changes in PPR when using Barrett and the changes in ACD, LT, and WTW, changes in ACD, LT, and WTW significantly affect how dilation influences the Barrett formula. Determining how dilation influences each formula and other variables is key to improving the accuracy of IOL calculations.

Rapid recurrence of a pilocytic astrocytoma with anaplastic transformation is extremely rare. The case of an elderly patient with a cerebellar pilocytic astrocytoma with anaplastic transformation during short-term follow-up is reported.An 83-year-old woman presented initially with dizziness and a gait deviation to the right. Magnetic resonance imaging demonstrated a homogeneously enhanced mass in the right cerebellar hemisphere, and the tumor was subtotally removed by right suboccipital craniotomy. Histologic examination showed that the tumor cells contained eosinophilic cytoplasm and spindle-shaped processes with Rosenthal fibers and eosinophilic granular bodies, diagnosed as a typical pilocytic astrocytoma (PA). The MIB-1 index was1%. The patient did not receive postoperative adjuvant radiation and chemotherapy. Two months after surgery, magnetic resonance imaging showed growth of the residual tumor adjacent to the fourth ventricle, causing obstructive hydrocephalus. She underwent surgery again, and the tumor was totally removed. Histologic findings showed mitotic cells and increased cellularity compared with the primary tumor, which was compatible with anaplastic transformation of PA with a MIB-1 index of 50%. Postoperatively, she was observed with best supportive care without postoperative adjuvant therapy. Nine months after the second operation, she died due to tonsillar herniation and obstructive hydrocephalus caused by a recurrent tumor. An autopsy was performed.It is extremely rare, as in the present case, that a cerebellar PA in an elderly patient recurs rapidly with anaplastic transformation, despite deferred postoperative adjuvant therapy including radiation and chemotherapy. A novel molecular-targeted therapy is needed for anaplastic PA showing aggressive biological behavior.

Background 5-Aminolaevulinic acid (5ALA) is a precursor of the strong sensitizer protoporphyrin IX (PpIX) in the heme synthesis pathway. We conducted aclinical trial designed to evaluate the efficacy and safety of 5ALA photodynamic therapy (PDT) using a light-emitting diode (LED) in patients with cervical intraepithelial neoplasia (CIN). Methods Data for 51 CIN patients who underwent 5ALA-PDT between 2012 and 2017 were prospectively analysed. After a 20 % 5ALA jelly formulation was topically applied to the cervix, the region was irradiated with red light at approximately 633 nm to excite PpIX for treatment. We estimated outcomes by cytology, pathology, and human papilloma virus (HPV) testing after PDT. Results Patients underwent two PDT sessions at one-week intervals during outpatient treatment and achieved favourable results without photosensitivity and severe adverse events. Over a long follow-up period, 96.1 % of all patients showed some positive effects, including approximately 70 % with a complete response (CR), 10 % with a partial response, and 15 % with downgrades. The HPV clearance rate in patients with CR was 79.4 %. Recurrence occurred in five patients who mostly remained HPV-positive after PDT. Conclusions Based on our study, topical 5ALA-PDT using an LED light source potentially represents a safe treatment for CIN on an outpatient basis.

Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.

Background: We assessed the accuracy and tendency of the VERION image-guided system (Alcon) and the intra-ocular lens (IOL) Master 700 (Zeiss), by comparing mean refractive shift (MRS) of predicted post-operative refraction (PPR), mean absolute error (MAE) of PPR, recommended IOL power (RIP) and K-value before and after optimizing the IOL-constant in VERION, to show the importance of optimization.Methods: This retrospective study involved 72 eyes. K-value was measured with both biometers. Axial length (AL) and anterior chamber depth (ACD) measured by the IOL Master were applied to the VERION because it cannot measure these variables. The User group for Laser Interference Biometry (ULIB) IOL-constant for the IOL Master was applied to the VERION before optimizing the IOL constant, since no such official measure was established for it. MRS of PPR, MAE of PPR, RIP and K-value as measured by both biometers were compared before and after optimizing the IOL-constant in the VERION. Finally, correlations between the MRS, MAE, RIP, and K-value were analyzed in the VERION. The Wilcoxon signed-rank test was used for analysis.Results: Compared to the IOL Master, K-value was significantly higher in the VERION. Prior to optimization, MRS of PPR showed a significant myopic shift in the VERION, and MAE of PPR was significantly higher. Additionally, RIP in the VERION was significantly lower. After optimization, there were no significant differences in the MRS of PPR and RIP between the VERION and IOL Master. MAE of PPR in the IOL Master was significantly higher than in the VERION. No significant correlations were found between MRS and MAE of PPR and RIP with K-value in the VERION. Conclusions: Before optimization, the VERION was less reliable in MRS, MAE and RIP than the IOL Master. However, after optimization, the difference in MRS and RIP between the two devices became insignificant. This study indicates that optimization of IOL-constant in the VERION is vital. After optimization, the VERION is more accurate in PPR than the IOL Master.

At present, only one design is available for trifocal intraocular lens (IOL); unfortunately, this particular design is not suitable for implantation in the sulcus with optic capture when posterior capsule rupture (PCR) occurs. Although three-piece bifocal IOLs can be implanted in the sulcus, this form of IOL can be vulnerable to tilt and decentration, thus causing aberration and photopic phenomena, such as halos and glares. However, visual axis centered optic capture using femtosecond laser-assisted cataract surgery (FLACS) is able to manage such complex operations. In the present study, we implanted a three-piece +4.0 D bifocal IOL into the sulcus of a patient who experienced PCR using optic capture and FLACS following the straightforward implantation of a one-piece trifocal IOL in the other eye. Defocus curves showed that the weakness of the trifocal IOL (nearest distances) was compensated for by the strength of the +4.0 D bifocal IOL, whereas the weakness of the +4.0 D bifocal IOL (middle distance) was compensated for by the strength of the trifocal IOL. Therefore, this combination provided the patient with a wider range of depth of focus. The contrast sensitivity in both eyes was within the normal range. Photopic phenomena were comparable with the bilateral implantation of the trifocal IOL. Anterior segment optical coherence tomography showed that tilt and decentration in the trifocal IOL implanted in the bag was significantly higher than the +4.0 D bifocal IOL implanted in the visual axis centered optic capture. This case showed that the intraindividual implantation of a single-piece trifocal IOL in the bag and a three-piece +4.0 D bifocal IOL in the sulcus, using a combination of optic capture and FLACS, is promising particularly in cases of PCR and can provide a wider range of vision without losing visual quality.

OBJECTIVE Because quantifying glycans with complex structures is technically challenging, little is known about the association of glycosylation profiles with the renal prognosis in diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS In 675 patients with type 2 diabetes, we assessed the baseline urinary glycan signals binding to 45 lectins with different specificities. The end point was a decrease of estimated glomerular filtration rate (eGFR) by ≥30% from baseline or dialysis for end-stage renal disease. RESULTS During a median follow-up of 4.0 years, 63 patients reached the end point. Cox proportional hazards analysis revealed that urinary levels of glycans binding to six lectins were significantly associated with the outcome after adjustment for known indicators of DKD, although these urinary glycans, except that for DBA, were highly correlated with baseline albuminuria and eGFR. Hazard ratios for these lectins were (+1 SD for the glycan index) as follows: SNA (recognizing glycan Siaα2-6Gal/GalNAc), 1.42 (95% CI 1.14–1.76); RCA120 (Galβ4GlcNAc), 1.28 (1.01–1.64); DBA (GalNAcα3GalNAc), 0.80 (0.64–0.997); ABA (Galβ3GalNAc), 1.29 (1.02–1.64); Jacalin (Galβ3GalNAc), 1.30 (1.02–1.67); and ACA (Galβ3GalNAc), 1.32 (1.04–1.67). Adding these glycan indexes to a model containing known indicators of progression improved prediction of the outcome (net reclassification improvement increased by 0.51 [0.22–0.80], relative integrated discrimination improvement increased by 0.18 [0.01–0.35], and the Akaike information criterion decreased from 296 to 287). CONCLUSIONS The urinary glycan profile identified in this study may be useful for predicting renal prognosis in patients with type 2 diabetes. Additional investigation of glycosylation changes and urinary glycan excretion in DKD is needed.

Background Surgical treatment of vertebral artery (VA)-thrombosed giant aneurysms requires achieving both obliteration of the parent artery to prevent bleeding and dome thrombectomy to relieve the brain stem from mass effect. To secure both proximal and distal control of complex VA aneurysms, the contralateral approach to the aneurysm might be a useful alternative, as previously described. We successfully treated a case of VA-thrombosed giant aneurysm in a new, original way by combining craniotomy (ipsilateral and contralateral) and the endovascular technique. Case Description A 48-year-old man presented with a thrombosed giant aneurysm of the right VA compressing the brain stem. Treatment consisted of endovascular proximal ligation of the VA followed by 2-staged craniotomy for complete trapping of the aneurysm and intra-aneurysmal thrombectomy. The VA distal to the aneurysm was obliterated via contralateral craniotomy as only that provided adequate working space. Finally, intra-aneurysmal partial thrombectomy was performed through an ipsilateral craniotomy, which also made possible the obliteration of the eventually dangerous remaining vasa vasorum and additional proximal ligation of the VA. Conclusions Based on pathologic and surgical anatomical characteristics, a combination of an endovascular procedure with 2-staged craniotomy for complete trapping, thrombectomy, and vasa vasorum obliteration could be considered a feasible way to treat VA-thrombosed giant aneurysms located ventral to the brain stem and have their distal neck portions/patent vessel beyond the midline toward the contralateral side.

Objective In systemic lupus erythematosus (SLE), an autoimmune disease associated with multiple organ involvement, the development of lupus nephritis determines prognosis, and arthritis impairs quality of life. Galectin 9 (Gal-9, Lgals9) is a β-galactoside-binding lectin that has been used for clinical application in autoimmune diseases, since recombinant Gal-9, as a ligand for T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), induces apoptosis of activated CD4+TIM-3+ Th1 cells. This study was undertaken to investigate whether deficiency of Lgals9 has beneficial or deleterious effects on lupus in a murine model. Methods Gal-9+/+ and Gal-9-/- female BALB/c mice were injected with pristane, and the severity of arthritis, proteinuria, and levels of autoantibody production were assessed at several time points immediately following injection. At 7 months after pristane injection, renal pathologic features, the severity of joint inflammation, and formation of lipogranulomas were evaluated. Subsets of inflammatory cells in the spleen and peritoneal lavage were characterized, and expression levels of cytokines from peritoneal macrophages were analyzed. Results Lgals9 deficiency protected against the development of immune complex glomerulonephritis, arthritis, and peritoneal lipogranuloma formation in BALB/c mice in this murine model of pristane-induced lupus. The populations of T cell subsets and B cells in the spleen and peritoneum were not altered by Lgals9 deficiency in pristane-injected BALB/c mice. Furthermore, Lgals9 deficiency protected against pristane-induced lupus without altering the Toll-like receptor 7-type I interferon pathway. Conclusion Gal-9 is required for the induction and development of lupus nephritis and arthritis in this murine model of SLE. The results of the current investigation provide a potential new strategy in which antagonism of Gal-9 may be beneficial for the treatment of nephritis and arthritis in patients with SLE through targeting of activated macrophages.

Objective Various risk factors for recanalization after coil embolization have been reported, but the indications for retreatment of recanalized aneurysms have not been determined. The aim of this study was to identify risk factors indicating the need for retreating recanalization during long-term follow-up (approximately 1 year). Methods A total of 172 unruptured saccular aneurysms in 155 patients treated by initial coil embolization between February 2012 and July 2019 were retrospectively analyzed. Intraluminal thrombosed aneurysms, aneurysms treated with stent assistance, and aneurysms followed without digital subtraction angiography (DSA) were excluded. Recanalization was identified in 31 aneurysms. Recanalized aneurysms (Meyer grade ≥2) were defined as major recanalization (MA); those that worsened to Meyer grade 1 were defined as minor recanalization (MI). Age, sex, aneurysm location, shape, five morphological variables (neck, height, width, dome-to-neck ratio, aspect ratio), aneurysm volume, endovascular technique, immediate Meyer grade, and volume embolization ratio (VER) were compared between MI (n = 18) and MA (n = 13). Predictors of MA were determined using logistic regression and receiver operating characteristic (ROC) curve analyses. Results On multivariate logistic regression analysis, spherical shape (odds ratio (OR) 11.9; 95% confidence interval (CI) 1.28–111) and VER (OR 1.92; 95% CI 1.13–3.28) were independent predictors of MA. On ROC curve analysis, the optimal cut-off value for the VER was 20.8% (sensitivity, 76.9%; specificity, 77.8%). Conclusions Lower VER and non-spherical shape appear to be independent risk factors for progression to MA in recanalized aneurysms, and packing with a VER >20.8% is expected to prevent progression to MA.

This paper focuses on the development and verification of a unified calculation method for estimating the yield of reinforced concrete (RC) beams, columns, and walls deformation considering flexural deformations, shear deformations, and bar slip deformations. Each component of yield deformation is considered independently, and the estimated yield deformation is the sum of these three parts. To verify the accuracy of this method, yield deformation results from a database of experimental results from tests performed in Japan on RC components was compared against those predicted by the proposed methods. The results show that the proposed method provides a reasonable prediction of the yield deformation and show that the proposed method has a better estimate of yield deformation than other previous methods. Sensitivity analysis on the influence of the rigidity reduction rate due to the shear effect, and the anchorage length in the bar slippage calculation, was performed. It was found that the rigidity reduction rate factor could influence the accuracy for walls. The influence of other material and member characteristics are also discussed herein.

Purpose The crystallin beta A4 (CRYBA4) gene variant, rs2009066, was previously reported to be associated with high myopia in a southern Chinese population. In the present study, we investigated whether CRYBA4 variants were associated with high myopia in a Japanese population. Methods We recruited 1,063 Japanese patients with high myopia (spherical equivalent [SE] ≤-9.00 D in both eyes) and 1,009 healthy Japanese subjects (SE >-1.00 D). We genotyped rs2009066 and three tagging single-nucleotide polymorphisms (SNPs), rs16982456, rs2071861, and rs4276, in the CRYBA4 region. Results We did not find any significant association between these four SNPs and high myopia in an allele analysis. However, rs2009066 and rs2071861, which were in strong linkage disequilibrium (LD; r2=0.86), showed a marginal association with high myopia in the recessive genotype model of risk alleles (rs2009066 G allele: P=0.032, odds ratio [OR] =1.31; rs2071861 A allele: P=0.037, OR =1.31). Nevertheless, this association became insignificant after correcting for multiple testing (Pc >0.05). Conclusion This study showed no significant association between CRYBA4 variants and high myopia in a Japanese population. Our findings did not correspond with a previous study. Further genetic studies with other populations are needed to elucidate a potential contribution of the CRYBA4 region in the development of high myopia.

BACKGROUND In our previous study, bevacizumab (Bev), a humanized anti- vascular endothelial growth factor monoclonal antibody, downregulated the expression of programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) immune checkpoint molecules, suppressed the infiltration of immunosuppressing cells such as regulatory T cells (Tregs) and tumor-associated macrophages (TAMs), and induces cytotoxic T lymphocytes (CTL) infiltration. To explore the possibility that inhibition of immunosuppressive cell infiltration and induction of CTL were attributed to not only Bev alone but also radiation (RT) or temozolomide (TMZ), we re-evaluated those alterations in the tumor tissue obtained from patients before and after the treatment using Stupp regimen (RT concomitant with TMZ) without Bev therapy. MATERIALS & METHODS We analyzed 10 tumor tissues from 5 patients with GBMs, which were paired samples of pre- and post- standard chemoradiotherapy (Stupp regimen: RT plus concomitant and adjuvant TMZ). Immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tissue of 10 tumors. The sections were stained with anti-Ki-67, anti-VEGF-A, anti-VEGFR1, anti-VEGFR2, anti-CD34, anti-HIF1 alpha, anti-CA9, anti-nestin, anti-PD-1, anti-PD-L1, anti-CD4, anti-CD8, anti-Foxp3, and anti-CD163 antibodies. All expressions were assessed by authors with blinded clinical information. RESULTS Immunohistochemical analyses demonstrated that the expression levels of immune regulatory molecules such as Foxp3, CD163, PD-1, PD-L1, CD4, and CD8 were not significantly changed after the treatment using the Stupp regimen, compared with combinational usage of Bev. In addition, expressions of VEGF/VEGFR, hypoxic markers, and stem cell marker were not altered before and after Stupp regimen, either. Bev persistently inhibited immune suppressive cells and immune checkpoint molecules via down-regulation of VEGF pathway. In contrast, Stupp regimen did not affect immune regulations and tumor microenvironment. CONCLUSION These results suggested that immunosupportive effect was caused by Bev administration, leading to the novel combinational treatment strategies, in addition to Stupp regimen.

Objectives: To assess the incidence of reactive lymph node hyperplasia (RLH) and the diagnostic characteristics that can help differentiate it from lymphoproliferative disorders (LPD) in patients w...

Background. Tracheostomy is a necessary procedure for patients who require long-term mechanical ventilation support. There are two methods for tracheostomy in current use: surgical tracheostomy (ST) and percutaneous dilational tracheostomy (PDT). In the current study, we retrospectively compared the safety of both procedures performed in our intensive care unit (ICU). Methods. In this study, we enrolled subjects who underwent tracheostomy in our ICU between January 2012 and March 2016. We excluded subjects who were Results. Compared with the ST group, the rate of all complications was lower in the PDT group (13.4% vs. 38.8%, p=0.007). Although the rate of intraoperative complications did not differ between the two groups (3.8% vs. 8.1%, p=0.62), relative to the ST procedure, the PDT procedure was associated with fewer postoperative complications (34.6% vs. 9.6%, p=0.003). Among postoperative complications, accidental removal of the tracheostomy tube and an air leak from the tracheostomy fistula were less frequent in the PDT group than the ST group. Between the two groups, there were no significant differences in their secondary outcomes. Conclusion. This retrospective study indicates that relative to ST, PDT is a safer procedure to be performed in the ICU. Fewer postoperative complications following PDT might be attributed to the small skin incision made during this procedure.