A genome-wide association study identified PTPN2 as a population-specific susceptibility gene locus for primary biliary cholangitis.

BACKGROUND AIMS: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-non-specific) and non-shared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC. APPROACH RESULTS: Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was identified as a novel PBC susceptibility gene locus through a GWAS and subsequent genome-wide meta-analysis involving 2,181 cases and 2,699 controls from the Japanese population (GWAS-lead variant: rs8098858, p=2.6×10-8). In-silico and in-vitro functional analyses indicated that the risk allele of rs2292758, which is a primary functional variant, decreases PTPN2 expression by disrupting Sp1 binding to the PTPN2 promoter in T follicular helper cells (Tfh) and plasmacytoid dendritic cells (pDCs). Infiltration of PTPN2-positive T-cells and pDCs were confirmed in the portal area of the PBC-liver by immunohistochemistry. Furthermore, transcriptomic analysis of PBC-liver samples indicated the presence of a compromised negative feedback loop in-vivo between PTPN2 and IFNG in patients carrying the risk allele of rs2292758. CONCLUSIONS: PTPN2, a novel susceptibility gene for PBC in the Japanese population, may be involved in the pathogenesis of PBC via an insufficient negative feedback loop caused by the PTPN2 risk allele of rs2292758 in IFN signaling. This suggests that PTPN2 could be a potential molecular target for PBC treatment.

Prognosis of patients with liver cirrhosis: A multi-center retrospective observational study.

AIM: Despite advances in the management of liver diseases and changes in the etiology of cirrhosis, few studies have updated the prognosis of cirrhosis. This study aimed to clarify the recent prognosis of cirrhosis and identify risk factors for death. METHODS: In this retrospective observational study by the Hepatic Disease Network of the National Hospital Organization in Japan, chart reviews were performed to follow patients with cirrhosis beginning in 2011. We conducted Kaplan-Meier survival time analyses stratified by Child-Pugh classification and albumin-bilirubin grade. Cox regression analysis was used to identify risk factors for death. RESULTS: We identified 444 eligible patients from 25 hospitals, including 303 (68%), 110 (25%), and 31 (7%) patients with Child-Pugh classes A, B, and C, respectively. Hepatitis C virus infection was the cause of cirrhosis for 63% of the patients. The 1-year and 5-year cumulative survival rates of patients with Child-Pugh classes A, B, and C were 90% and 61%, 78% and 42%, and 65% and 25%, respectively. The 1-year and 5-year cumulative survival rates of patients with albumin-bilirubin grades 1, 2, and 3 were 98% and 80%, 91% and 56%, and 58% and 23%, respectively. Cirrhosis classification (Child-Pugh and albumin-bilirubin), age, liver cancer, and untreated esophageal varices were associated with increased hazard of death. CONCLUSIONS: Little improvement was observed in the prognosis of cirrhosis compared with previous reports, and the prognosis of Child-Pugh class C cirrhosis remained poor. Untreated esophageal varices were identified as a risk factor for death.

Choroidal vessel density in unilateral hyperopic amblyopia using en-face optical coherence tomography.

BACKGROUND: Structural changes of the choroid, such as choroidal thickening, have been indicated in amblyopic eyes with hyperopic anisometropia as compared to fellow or healthy eyes. The purpose of the present study was to investigate choroidal vascular density (CVD) in children with unilateral hyperopic amblyopia. METHODS: This study included 88 eyes of 44 patients with unilateral amblyopia due to hyperopic anisometropia with or without strabismus and 29 eyes of 29 age-matched normal controls. The CVD of Haller's layer was quantified from en-face images constructed by 3-dimensional swept-source optical coherence tomography images flattened relative to Bruch's membrane. The analysis area was a 3 × 3-mm square of macula after magnification correction. Relationships between CVD and other parameters [best-corrected visual acuity (BCVA), refractive error and subfoveal choroidal thickness (SFCT)] were investigated, and CVDs were compared between amblyopic, fellow, and normal control eyes. RESULTS: Mean CVD was 59.11 ± 0.66% in amblyopic eyes, 59.23 ± 0.81% in fellow eyes, and 59.29 ± 0.74% in normal control eyes. CVD showed a significant positive relationship with SFCT (p = 0.004), but no relationships with other parameters. No significant differences in CVD were evident among amblyopic, fellow, and normal control eyes after adjusting for SFCT (p = 0.502). CONCLUSIONS: CVD was unrelated to BCVA, and CVD did not differ significantly among amblyopic, fellow and normal control eyes. These results suggest that the local CVD of Haller's layer is unaffected in unilateral hyperopic amblyopic eyes.

Evaluation of Significance Maps and the Analysis of the Longitudinal Time Course of the Macular Ganglion Cell Complex Thicknesses in Acquired Occipital Homonymous Hemianopia Using Spectral-domain Optical Coherence Tomography.

The present study was performed to evaluate the ganglion cell complex (GCC) thickness as well as the significance map and analyse the time course of the change in GCC thickness in patients with homonymous hemianopia due to posterior cerebral artery (PCA) territory stroke using spectral-domain optical coherence tomography. This study included 40 control subjects and 11 patients with unilateral PCA territory stroke. The GCC parameters were quantified using a custom-built software programme. The GCC data, centred on the macula, was divided vertically into hemianopic and unaffected sides. GCC parameters were calculated using an average of those from both eyes. The relationship between the GCC parameters and the time after stroke was determined by regression analyses. The GCC parameters in the hemi-retinae corresponding to the affected hemifields significantly differed between the hemianopes and the control group. The area under the receiver operating characteristics curve of the GCC significance map areas was significantly high. A regression analysis revealed a significant relationship between the time after stroke and both the GCC significance map areas (r = 0.791, p = .004) and GCC thickness (r = -0.736, p = .010) on the hemianopic side. The GCC parameters on the hemianopic side were reduced in patients with acquired occipital homonymous hemianopia, and the reduction was slowly progressive probably due to transsynaptic retrograde degeneration of the retinal ganglion cells. A significance map analysis provides additional OCT parameters that could be used to investigate the effect of retrogeniculate lesions on the inner retina of patients.

Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population.

A previous genome-wide association study (GWAS) performed in 963 Japanese individuals (487 primary biliary cholangitis [PBC] cases and 476 healthy controls) identified TNFSF15 (rs4979462) and POU2AF1 (rs4938534) as strong susceptibility loci for PBC. In this study, we performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls), and combined the results with the previous data. This GWAS, together with a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls), identified PRKCB (rs7404928) as a novel susceptibility locus for PBC (odds ratio [OR] = 1.26, P = 4.13 × 10-9). Furthermore, a primary functional variant of PRKCB (rs35015313) was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.

Foveal avascular zone and macular vessel density after correction for magnification error in unilateral amblyopia using optical coherence tomography angiography.

BACKGROUND: To investigate the area of foveal avascular zone (FAZ) and macular vessel density (VD) after correction for magnification error in unilateral amblyopia using optical coherence tomography angiography (OCTA). METHODS: Participants comprised 15 patients with unilateral amblyopia due to anisometropia with or without strabismus (mean age, 9.8 ± 3.4 years; range, 6-17 years). OCTA images were obtained by using spectral-domain OCT with angiography software. The OCTA scanning protocol used was 3 × 3-mm volume scan centered on the fovea. OCTA images were corrected for magnification errors using individual axial length (AL), and an adjusted 2.3 × 2.3-mm square was derived as a region of interest. The FAZ area and VD in both superficial capillary plexus (SCP) and deep capillary plexus (DCP) layers, foveal minimum thickness (FMT) were assessed using built-in OCTA software and ImageJ software (NIH, Bethesda, MD). RESULTS: LogMAR in the amblyopic eyes was significantly poorer than that of the fellow eye (p < 0.001). AL was significantly shorter in the amblyopic eye than in the fellow eye (p < 0.001). FAZ area of SCP in amblyopic eyes was significantly smaller than that of fellow eyes (p < 0.001). No significant differences were seen in FAZ area of DCP, VD of SCP, VD of DCP, and FMT between amblyopic and fellow eyes (p = 0.07, 0.43, 0.55, and 0.25, respectively). CONCLUSIONS: Our present study after magnification error correction found smaller FAZ area of SCP in the amblyopic eye compared with the fellow eyes, but there was no significant difference in the macular VD between the amblyopic and fellow eyes.

Retinal Nerve Fiber Layer and Peripapillary Capillary Density Reduction Detected Using Optical Coherence Tomography Enface Images and Angiography in Optic Tract Syndrome.

In a patient with an optic tract syndrome, we describe the loss of retinal nerve fiber layer and retinal microvasculature using enface and optical coherence tomography angiography image analyses.

Usefulness of semiquantitative PCR-Invader assay for selecting candidates for daclatasvir plus asunaprevir combination therapy among patients with hepatitis C virus genotype 1b.

AIMS: PCR-Invader is a highly sensitive assay for detecting non-structural protein 5A (NS5A) resistance-associated variants (RAVs) of hepatitis C virus (HCV). Here, we validated the accuracy of the semiquantitative PCR-Invader (SQ-PI) assay compared to direct sequencing (DS) for identifying NS5A RAVs, and we evaluated the treatment efficacy of daclatasvir plus asunaprevir (DCV + ASV) for patients judged to be non-positive for NS5A RAVs by SQ-PI. METHODS: Detection rates of NS5A RAVs by SQ-PI and DS were compared for 204 patients with HCV genotype 1b. Patients with non-positive results for NS5A RAVs by SQ-PI were treated by DCV + ASV, and the efficacy of this treatment was examined. RESULTS: All samples judged as negative for NS5A RAVs by SQ-PI were similarly judged by DS. However, 29.7% of samples judged as negative for Y93H by DS were judged as weakly positive or positive by SQ-PI. Among 108 patients who were judged as negative by SQ-PI and treated by DCV + ASV, rates of sustained virologic response at 24 weeks (SVR24) were 96.3% in intention-to-treat analysis and 99.0% in patients who completed treatment. Among patients who were weakly positive for Y93H on SQ-PI, the SVR24 rate was 95.0% (19/20). This rate was 100% (78/78) in patients who were negative for Y93H on SQ-PI and completed treatment. CONCLUSION: Treatment efficacy of DCV + ASV was extremely high among patients who were non-positive for NS5A RAVs on SQ-PI, especially for patients with negative results.

Effect of amblyopia treatment on choroidal thickness in hypermetropic anisometropic amblyopia using swept-source optical coherence tomography.

BACKGROUND: Recent studies using optical coherence tomography (OCT) have indicated that choroidal thickness (CT) in the anisometropic amblyopic eye is thicker than that of the fellow and normal control eyes. However, it has not yet been established as to how amblyopia affects the choroid thickening. The purpose of the present study was to investigate the effect of amblyopia treatment on macular CT in eyes with anisometropic amblyopia using swept-source OCT. METHODS: Thirteen patients (mean age: 6.2 ± 2.4 years) with hypermetropic anisometropic amblyopia were included in this study. Visual acuity (VA), axial length (AL), and CT were measured at the enrollment visit and at the final visit, after at least 6 months of treatment. CT measurements were corrected for magnification error and were automatically analyzed using built-in software and divided into three macular regions (subfoveal choroidal thickness (SFCT), center 1 mm, and center 6 mm). A one-way analysis of covariance using AL as a covariate was performed to determine whether CT in amblyopic eyes changed after amblyopia treatment. RESULTS: The average observation period was 22.2 ± 11.0 months. After treatment, VA (logMAR) improvement in the amblyopic eyes was 0.41 ± 0.19 (p < 0.001). SFCT, center 1 mm CT, and center 6 mm CT were significantly thicker in the amblyopic eyes compared with the fellow eyes both before and after treatment (p < 0.05 for all comparisons). There were no significant changes in SFCT, center 1 mm CT, or center 6 mm CT before and after treatment in the amblyopic (p = 0.25, 0.21, and 0.84, respectively) and fellow (p = 0.75, 0.84, and 0.91, respectively) eyes. The correlation between changes in logMAR versus changes in CT after treatment was not significant. CONCLUSIONS: Although VA in amblyopic eyes was significantly improved after treatment, the choroid thickening of anisometropic amblyopic eyes persisted, and there was no significant change found in the CT after the treatment. Our findings suggest that thickening of the CT in amblyopia is not directly related to visual dysfunction.

Relative Afferent Pupillary Defects in Homonymous Visual Field Defects Caused by Stroke of the Occipital Lobe Using Pupillometer.

Relative afferent pupillary defects (RAPD) may be detected in patients with occipital lobe lesions. However, no previous report has used an objective technique to record the abnormal pupillary light reflex in such cases. Therefore, we measured the pupillary light reflex objectively in 15 patients with homonymous visual field defects (HVFD) due to occipital stroke using a new pupillometer. This study detected significantly smaller and slower pupillary light reflexes in the contralateral eyes than in the other eyes, which is equivalent to the presence of RAPD in patients with HVFDs caused by retrogeniculate lesions using an objective technique. Our results confirmed those of the previous reports using the swinging flashlight test more objectively.

Macular retinal and choroidal thickness in unilateral amblyopia using swept-source optical coherence tomography.

BACKGROUND: To investigate macular retinal and choroidal thickness in amblyopic eyes compared to that in fellow and normal eyes using swept-source optical coherence tomography (SS-OCT). METHODS: This study examined 31 patients with hyperopic anisometropic amblyopia (6.9 ± 3.8 years, mean ± standard deviation), 15 patients with strabismic amblyopia without anisometropia (7.9 ± 4.2 years), and 24 age-matched controls (7.8 ± 3.3 years). Retinal and choroidal thickness was measured by 3D scans using SS-OCT. A 6-mm area around the fovea was automatically analyzed using the Early Treatment Diabetic Retinopathy Study map. The thickness from SS-OCT was corrected for magnification error using individual axial length, spherical refraction, cylinder refraction, and corneal radius. Retinal thickness was divided into the macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL+IPL), ganglion cell complex (GCC), and the inner limiting membrane to the retinal pigment epithelium (ILM-RPE) thickness. Retinal and choroidal thickness was compared among amblyopic, fellow, and normal eyes. RESULTS: In both amblyopia groups, there was no significant difference in the mRNFL, GCL+IPL, and GCC thicknesses among the amblyopic, fellow, and control eyes. In the anisometropic amblyopia group, choroidal thickness (subfovea, center 1 mm, nasal and inferior of the inner ring, nasal of the outer ring, and center 6 mm) of amblyopic eyes were significantly greater than that of fellow and normal eyes. In contrast, none of the choroidal thicknesses were significantly different among the investigated eyes in the strabismic amblyopia group. CONCLUSIONS: We found no significant difference in inner retinal thickness in patients with unilateral amblyopia. Although there were significant differences in choroidal thickness with hyperopic anisometropic amblyopia, there was no significant difference for the strabismic amblyopia. The discrepancy in choroidal thickness between the two types of amblyopia may be due to both differences in ocular size and underlying mechanism.

A novel method to reduce noise in electroretinography using skin electrodes: a study of noise level, inter-session variability, and reproducibility.

To determine the feasibility of recording reproducible electroretinograms (ERGs) with skin electrodes using a new ERG system. Seventeen healthy volunteers were studied. The dark-adapted, bright-flash ERGs were recorded with a new ERG recording system (LE-4000, Tomey, Nagoya, Japan) in which the stimulus alternated between the eyes every 15 s, and each eye was stimulated eight times. The active skin electrode was placed on the lower eyelids of both eyes. The voltage changes of the non-stimulated eye were subtracted from that of the stimulated eye to try to increase the signal-to-noise ratio for eight stimulus cycles. The noise levels were measured from 12 subjects with and without the subtraction steps. ERGs were also recorded on five different days from five subjects, and the coefficient of variation (CV) and the intra-class correlation coefficients (ICCs) were calculated. The noise level without the subtraction step was 18.4 ± 8.4 µV, and it was significantly reduced to 13.8 ± 4.0 µV with the subtraction step (P = 0.001). Reproducible ERGs were obtained from each subject, and the average CV for the five subjects was 6.1 % for the a-wave amplitude, 7.7 % for the b-wave amplitude, and 7.7 % for the sum of the oscillatory potential (OP) amplitude. The ICC was 0.76 for the a-wave amplitude, 0.68 for the b-wave amplitude, and 0.72 for the sum of the OPs amplitude. These findings indicate that our new ERG recording methods shows noise reduction and good reproducibility with low inter-session variability even with skin electrodes.

Sectoral analysis of the retinal nerve fiber layer thinning and its association with visual field loss in homonymous hemianopia caused by post-geniculate lesions using spectral-domain optical coherence tomography.

PURPOSE: To report a sectoral analysis of circumpapillary retinal nerve fiber layer (cpRNFL) thinning and its association with visual field loss using spectral-domain optical coherence tomography (SD-OCT) in patients with homonymous hemianopia following acquired post-geniculate visual pathway damage. PATIENTS AND METHODS: Seven patients with homonymous hemianopia due to unilateral acquired post-geniculate visual pathway lesions were studied. The average duration from the onset of brain lesions to the initial visit was 49.8 months. Forty-nine normal control subjects without visual field defects, as confirmed using a Humphrey visual field analyzer, were also enrolled. Measurement of the cpRNFL thickness was performed at the initial visit and 24 months using SD-OCT (RTVue-100® OCT). The cpRNFL thickness was divided into eight sectors (superior temporal: ST, temporal upper: TU, temporal lower: TI, inferior temporal: IT, inferior nasal: IN, nasal lower: NL, nasal upper: NU, superior nasal: SN). The eye on the same side as the occipital lobe lesions was defined as the ipsilateral eye, and the eye on the opposite side was defined as the contralateral eye. RESULTS: The average cpRNFL thickness in the homonymous hemianopic eyes was significantly reduced as compared with that seen in the normal controls, except for the ipsilateral eyes at the initial visit. Four of the eight sectors of the cpRNFL thickness in the homonymous hemianopic eyes were significantly reduced compared with that noted in the normal controls. In the ipsilateral eyes, the cpRNFL thickness in the ST, TU, TL, and IT sectors was significantly reduced at both the initial visit and 24 months. In the contralateral eyes, the cpRNFL thickness in the TU, TL, IT, and SN sectors was significantly reduced at both the initial visit and 24 months. The reduction of the quadrantic cpRNFL thickness significantly correlated with some of the visual field parameters, in accordance with the structure-function relationship. In the contralateral eyes, the T and I quadrant cpRNFL thickness correlated with the mean deviation and hemianopic field total deviation at 24 months. In the ipsilateral eyes, the S, T, and I quadrant cpRNFL thickness correlated with mean deviation. However, there were no correlations between the cpRNFL thickness and visual field parameters at the initial visit. CONCLUSIONS: A reduction of the cpRNFL thickness corresponding to the hemianopic visual field loss due to acquired post-geniculate visual pathway lesions was detected using SD-OCT, and the change was more evident at 24 months than at the initial visit. The latter finding suggests that this change is, at least partially, caused by transsynaptic retrograde degeneration.

Attenuation of spontaneous thrombolytic activity measured by the global thrombosis test in male habitual smokers.

Smoking is known as one of the major risk factors for atherothrombotic cardiovascular diseases. We investigated the susceptibility to thrombosis in habitual smokers by using the global thrombosis test (GTT), by which both clot formation and clot lysis activities can be evaluated simultaneously in native blood samples in vitro. Subjects were 139 men participating in a periodic health checkup examination, and an informed consent for the subjects was obtained as a document. Using GTT, occlusion time (OT: the time taken for clot formation in the blood sample) and lysis time (LT: the time taken for lysis of the clot that had been formed) were measured. LT was significantly (p = 0.029) longer in smokers [median with range, 1,794 (1,080-6,000) s (n = 76)] than in nonsmokers [median with range, 1,530 (792-3,800) s (n = 63)], while there was no significant difference in OT between smokers and nonsmokers. In smokers, LT was significantly correlated with daily cigarette consumption but not with Brinkman index. LT measured in nine smokers at 3 months after quitting their habitual smoking was significantly shorter than LT measured before the cessation of smoking. Since prolongation of LT implies existence of thrombogenic tendency, smokers are thought to be more susceptible to thrombosis due to decreased fibrinolytic activity, and no smoking for even a short term may be effective for improving fibrinolytic activity in smokers.

[The influence of sodium hyaluronate solution and artificial tears on higher-order aberrations].

PURPOSE: To investigate the influence of sodium hyaluronate solution (HA) and artificial tears (AT) on higher-order aberrations (HOAs). SUBJECTS AND METHODS: Twenty four eyes of 24 normal subjects and 11 eyes of 11 dry eye patients were examined. Cornea and ocular wavefront aberrations (total, spherical-like and coma-like) were measured with a Hartmann-Shack wavefront aberrometer before and after 0.1% or 0.3% HA, AT. The consecutively obtained data of the cornea and ocular HOAs were analyzed in the central 4-mm diameter for coma-like, spherical-like and total HOAs. Average HOAs, as well as fluctuation index (FI) and stability index (SI) of the HOAs over time were compared between the two groups. RESULTS: In normal subjects, the AVE of all aberration parameters and FI showed an increase depending on viscosity of the HA (p < 0.001). After AT and 0.1% HA treatment the cornea aberration of the dry eye patients changed from a sawtooth pattern to a stable pattern. CONCLUSION: Cornea HOAs decreased, and the optical characteristics showed improvement after AT and 0.1% HA in the dry eye patients. HOAs increased depending on the viscosity of the HA, and optical stability worsened.

[Two cases of optic neuritis in children with rapid thinning of the ganglion cell complex].

BACKGROUND: There are many reports regarding the circumpapillary retinal nerve fiber layer (cpRNFL) in optic neuritis (ON). However, few studies of changes over time in the ganglion cell complex (GCC) have been reported. As far as we know, no studies of such changes in children have been reported. In the present study, we report two patients with pediatric ON in which the time course of GCC and cpRNFL were observed using optical coherence tomography. CASES: Two cases, one 9-year-old boy and one 11-year-old boy. The two patients showed acute visual impairment, relative afferent pupillary defect, and swelling of the optic disc, leading to the diagnosis of ON. Regardless of whether visual function was improved after steroid pulse therapy, thinning of the GCC and cpRNFL progressed rapidly over time. CONCLUSION: Atrophy of the retinal inner layer in the macula occurred soon after the onset of ON. Although the inflammation was reduced after treatment, atrophy of the ganglion cells continuted to progress. GCC thickness measurement in pediatric ON is useful for pathological assessment and followup, because we can detect atrophy of the ganglion cells and retinal nerve fibers soon after onset.

Changes in Choroidal Thickness and Structure Induced by 1% Atropine Instillation in Children With Hyperopic Anisometropic Amblyopia.

PURPOSE: To investigate the effects of 1% atropine eye drops on the choroidal thickness and structure of amblyopic and fellow eyes in children with hyperopic anisometropic amblyopia. METHODS: This study included 16 children with hypermetropic anisometropic amblyopia. All patients received 1% atropine eye drops in both eyes twice a day for 7 days. In the subfoveal choroidal region, choroidal thickness, total choroidal area, luminal area, and stromal area were measured quantitatively using swept-source optical coherence tomography. The choroidal parameters of the amblyopic and fellow eyes were compared between the baseline and atropine conditions. RESULTS: There were no significant differences in all choroidal parameters of the amblyopic eye between baseline and atropine conditions. However, the subfoveal choroidal thickness in the fellow eye was significantly higher for the atropine condition than the baseline condition. This change was accompanied by a significant increase in both the luminal and stromal areas of the choroid. The median differences of subfoveal choroidal thickness between the conditions were larger for the fellow eye (6.46%) than the amblyopic eye (0.26%). CONCLUSIONS: The choroidal structural change induced by 1% atropine instillation was smaller for the amblyopic eye than the fellow eye in children with hyperopic anisometropic amblyopia. Mechanisms of choroidal thickness changes could be inhibited in amblyopic eyes. [J Pediatr Ophthalmol Strabismus. 2023;60(1):39-45.].

[A study of the Arsaprasamanisutra: analysis].

The present paper focuses primarily on a philological and historical study of the Arsaprasamanisutra ("The Sutra of the Tranquilization of Hemorrhoids"). This Sutra is one of the Buddhist scriptures that is characterized by the magico-religious treatment of various diseases, especially by means of "healing spells" (skt. dharani or mantra), as shown by the preliminary survey in our penultimate paper "The Tradition of Healing with Magical Spells as Seen in Buddhist Texts," Journal of the Japan Society of Medical History 55/1 (2009), 77-96. In our last paper "The Tradition of Healing with Magical Spells as Seen in Buddhist Texts (2): A Study of the Arsaprasamanisutra: Edition and Japanese translation" we provided critically edited texts of the Tibetan and Chinese translations accompanied by their Japanese translations with critical notes and annotations. In this paper we analyze the descriptions of hemorrhoids as found in the Sutra in comparison with those illustrated in classical Ayurveda literature, besides a detailed philological examination of the relevant passages available only in the Chinese translation of the Mulasarvastivada-Vinaya. We also offer further observations about the methods and principles for the treatment and healing of hemorrhoids that are attested in Buddhist scriptures, as well as make an overview of the transmission and historical reception of the Arsaprasamanisutra in Japan between the Nara and the Taisho periods.

Photopic negative response recorded with RETeval system in eyes with optic nerve disorders.

Electroretinography (ERG) is used to evaluate the physiological status of the retina and optic nerve. The purpose of this study was to determine the usefulness of ERGs recorded with the RETeval system in diagnosing optic nerve diseases. Forty-eight patients with optic nerve disorders, including optic neuritis, ischemic optic neuropathy, traumatic optic neuropathy, and dominant optic atrophy, and 36 normal control subjects were studied. The amplitudes of the photopic negative response (PhNR) were recorded with the RETeval system without mydriasis. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was determined by optical coherence tomography (OCT). The significance of the correlations between the PhNR and cpRNFLT parameters were determined, and the receiver operating curve (ROC) analyses were performed for the PhNR and cpRNFLT. Patients with optic nerve disorders had significantly smaller PhNRs compared to the control subjects (P = 0.001). The ROC analyses indicated that both PhNR and cpRNFLT had comparable diagnostic abilities of detecting optic nerve disorders with PhNR at 0.857 and cpRNFLT at 0.764. The PhNR components recorded with the RETeval system have comparable diagnostic abilities as the cpRNFLT in diagnosing optic nerve disorders.

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

BACKGROUND: A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. OBJECTIVE: This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. PATIENTS AND METHODS: This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. RESULTS: After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). CONCLUSIONS: ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.