Outbreak of Invasive Serratia marcescens among Persons Incarcerated in a State Prison, California, USA, March 2020-December 2022.

Serratia marcescens is an environmental gram-negative bacterium that causes invasive disease in rare cases. During 2020-2022, an outbreak of 21 invasive Serratia infections occurred in a prison in California, USA. Most (95%) patients had a history of recent injection drug use (IDU). We performed whole-genome sequencing and found isolates from 8 patients and 2 pieces of IDU equipment were closely related. We also identified social interactions among patients. We recovered S. marcescens from multiple environmental samples throughout the prison, including personal containers storing Cell Block 64 (CB64), a quaternary ammonium disinfectant solution. CB64 preparation and storage conditions were suboptimal for S. marcescens disinfection. The outbreak was likely caused by contaminated CB64 and propagated by shared IDU equipment and social connections. Ensuring appropriate preparation, storage, and availability of disinfectants and enacting interventions to counteract disease spread through IDU can reduce risks for invasive Serratia infections in California prisons.

Clinical features of double seronegative ocular myasthenia gravis.

PURPOSE: To clarify the clinical features of patients with Double seronegative (DS) ocular myasthenia gravis (OMG). METHODS: Sixty-one patients diagnosed with DS OMG at the Department of Ophthalmology, Hyogo Medical University Hospital over a 5-year period from 2017 were included. Patients were classified into three groups based on the initial examination findings: group P (ptosis alone), group M (ocular motility disorder alone), and group PM (combination of both). We retrospectively reviewed the patients and clarified their clinical features. RESULTS: There were 32 males and 29 females, with a mean age of 49.8 ± 20.9:1-82 years. Twenty-one patients (34.4%) were in group P, 23 (37.7%) in group M, and 17 (27.8%) in group PM. The proportion of males (73.9%) was significantly higher in group M compared with the other two groups. The diagnosis was proven by detection of neuromuscular junction (NMJ) disorder in 73.8%, oral pyridostigmine trial test in 13.1%, and eight patients (13.1%) in group M were diagnosed after surgical treatment. The clinical symptoms were resolved by oral pyridostigmine treatment in 54.1% of cases. CONCLUSION: About 30% of patients with DS OMG had no obvious NMJ disorder, and an oral pyridostigmine trial test was necessary to diagnose these patients. Although DS OMG is often considered as the mildest form of MG, its prognosis is not optimistic and it requires aggressive therapeutic intervention. TRIAL REGISTRATION: Trial registration number: 202104-750, "2016/4/18," retrospectively registered.

[Analysis of Preventive Cases Using Resilience Engineering in Radiotherapy Department].

PURPOSE: Resilience engineering is the ability of a system to adjust its own functions and maintain the required behavior in the face of changes and disturbances, and resilience potential is a necessary requirement. We aimed to clarify the relationship between resilience potential and error prevention cases. METHOD: Based on the error cases reported in our department, we aggregated the relationship with resilience potential for each radiation treatment process. RESULT: As a result of tabulating the relationship, we were able to recognize and prevent errors by taking preventive measures from past cases. On the other hand, in cases that slipped through the check mechanism, errors were discovered because of a sense of discomfort in unusual situations, and some error cases could be prevented by increasing the resilience potential. CONCLUSION: This study found that preparation, observation, coping, and utilization of past experiences are related to resilience potential in preventive cases.

Comparison of head tilt test between sagging eye syndrome and acquired unilateral trochlear nerve palsy.

PURPOSE: To investigate the distinction between sagging eye syndrome (SES group) and acquired unilateral trochlear nerve palsy (Trochlear group) in the Bielschowsky head tilt test (BHTT). METHODS: Fifteen patients in the SES group (mean age 74.6 ± 5.2 years) and 14 patients in the Trochlear group (55.2 ± 15.9 years) visited the Department of Ophthalmology, Hyogo Medical University Hospital between November 2016 and October 2022 for treatment of their diplopia. Eye position was measured with the alternate prism cover test, and values for fixation of the dominant eye, or unaffected eye, were used. Cyclodeviation was measured with the synoptophore and the Glaucoma Module Premium Edition of the SPECTRALIS optical coherence tomography. In the BHTT, eye position was measured in three head postures: primary position (PP), head tilt to the side with hypertropia (Hyper), and head tilt to the side with hypotropia (Hypo). The differences in vertical deviation between PP and Hyper (Hyper - PP), PP and Hypo (PP - Hypo) and Hyper - Hypo were measured and compared. RESULTS: Vertical deviation in primary position was 7.3 ± 4.5 PD in the SES group and significantly larger (17.1 ± 8.4 PD) in the Trochlear group (p = 0.002). The vertical deviation in Hyper was significantly larger in the Trochlear group with 7.7 ± 4.7 PD and 22.1 ± 9.4 PD, respectively (p < 0.001), whereas the that in Hypo was not significantly different between the two groups with 6.5 ± 3.4 PD and 8.4 ± 6.6 PD, respectively (p = 0.725). The SES group showed no significant difference according to the 3 head postures (p = 0.311), while the Trochlear group showed a significantly different with smaller mean values in vertical deviation in Hypo (p < 0.001). The difference in the vertical deviation for the 3 head postures was the largest in Hyper - Hypo (1.7 ± 2.1 PD and 13.6 ± 7.1 PD, respectively), and the accuracy of SES was at the cutoff value of 6 PD, and it was considered not to be SES if the value was 6PD or higher. The accuracy of SES determination was 100% sensitivity and 100% specificity, and the area under the curve was 1.0. CONCLUSION: The difference in Hyper - Hypo in the BHTT may be the most useful index in differentiating SES from acquired unilateral trochlear nerve palsy; if the difference was more than 6 PD, the probability of SES was very low.

Large Community Outbreak of Legionnaires Disease Potentially Associated with a Cooling Tower - Napa County, California, 2022.

Legionnaires disease is a serious infection acquired by inhalation of water droplets from human-made building water systems that contain Legionella bacteria. On July 11 and 12, 2022, Napa County Public Health (NCPH) in California received reports of three positive urinary antigen tests for Legionella pneumophila serogroup 1 in the town of Napa. By July 21, six Legionnaires disease cases had been confirmed among Napa County residents, compared with a baseline of one or two cases per year. NCPH requested assistance from the California Department of Public Health (CDPH) and CDC to aid in the investigations. Close temporal and geospatial clustering permitted a focused environmental sampling strategy of high-risk facilities which, coupled with whole genome sequencing results from samples and investigation of water system maintenance, facilitated potential linking of the outbreak with an environmental source. NCPH, with technical support from CDC and CDPH, instructed and monitored remediation practices for all environmental locations that tested positive for Legionella. The investigation response to this community outbreak illustrates the importance of interdisciplinary collaboration by public health agencies, laboratory support, timely communication with the public, and cooperation of managers of potentially implicated water systems. Timely identification of possible sources, sampling, and remediation of any facility testing positive for Legionella is crucial to interrupting further transmission.

Serratia marcescens Outbreak at a Correctional Facility: Environmental Sampling, Laboratory Analyses and Genomic Characterization to Assess Sources and Persistence.

Serratia marcescens is an environmental bacterium and clinical pathogen that can cause an array of infections. We describe an environmental sampling and comparative genomics approach used to investigate a multi-year outbreak of S. marcescens at a correctional facility. Whole genome sequencing analysis revealed a predominant cluster of clonally related S. marcescens from nine patient cases and items associated with illicit drug use. Closely related strains found among items associated with case-patient cells and diluted Cell Block 64 (CB64), a quaternary ammonium disinfectant, and Break Out (BO), a multipurpose cleaner, highlighted their role as environmental reservoirs for S. marcescens in this outbreak. Comparative genomic analysis suggested outbreak strains were both persistent (identical strains found over long periods and in multiple locations of the correctional facility) and diverse (strains clustered with multiple global samples from NCBI database). No correlation was found between antimicrobial resistance (AMR) genes of outbreak strains; NCBI strains have more AMR genes. Principal component analysis (PCA) of virulence factors associated with persistence and infectivity indicated variation based on phylogroups, including the predominant cluster; identifiable variations among environmental versus clinical strains were not observed. Identification of multiple distinct genetic groups highlights the importance of putting epidemiological genomic studies in a proper genetic context.

Clinical presentations of acquired comitant esotropia in 5-35 years old Japanese and digital device usage: a multicenter registry data analysis study.

PURPOSE: To describe clinical presentations of acquired comitant esotropia and digital device use in children, adolescents, and young adults without neurological problems. STUDY DESIGN: Multicenter prospective observational study. METHODS: Patients with acquired comitant esotropia, without intracranial diseases aged 5-35 years at the time of visit, who were seen at pre-registered facilities within 1 year of onset were enrolled. The duration from the onset of symptoms and the time of digital device usage approximately 1 month before onset and their lifestyles were surveyed. Visual acuity, cycloplegic refraction, and strabismus angles were measured. Data were analyzed in three age groups (Child: 5-12 years, Adolescent: 13-18 years, and Young adult: 19-35 years). RESULTS: Between November 2019 and December 2021, 218 patients were enrolled from 55 facilities, and 194 patients (including 62 children, 69 adolescents, and 63 young adults) were analyzed. The child group spent the least amount of time using digital devices (children: 159; adolescents: 210; young adults: 267 min/work day, p < 0.05; (mean time in the same order below) 229, 338, 314 min/holiday, p < 0.05) and had the largest strabismus angle (mean strabismus angle at near: 30, 22, 18 PD, p < 0.01; at far: 28, 26, 21 PD, p<0.05). CONCLUSION: The clinical features of acquired comitant esotropia and hand-held digital device usage differed between children aged ≤ 12 years and older patients. This report gives the current clinical characteristics of young patients with acquired esotropia and digital device usage.

Structure-function relationship between magnetic resonance imaging lesion areas and visual field defects in initial optic neuritis with altitudinal hemianopsia.

PURPOSE: To study the spatial association of magnetic resonance imaging (MRI) contrast enhancement (CE) areas with visual field defect (VFD) asymmetry in initial cases of optic neuritis (ON) with altitudinal hemianopsia (AH) with reference to nonarteritic anterior ischemic optic neuropathy (NAION) with AH. STUDY DESIGN: Multicenter, cross-sectional study. METHODS: The present study comprised 19 ON patients and 20 NAION patients with AH who underwent orbital contrast fat-suppressed MRI. The signal-to-intensity ratio (SIR) was calculated by dividing the maximum CE of the optic nerve by the mean CE of the cerebral white matter in 11 coronal sections at 3-mm intervals from immediately posterior to the eyeball to the optic chiasm. Sections in ON patients with an SIR exceeding the mean plus 2 standard deviations of the SIR at the corresponding section in the NAION group were considered abnormal. The correlation between upper-to-lower CE asymmetry in the maximum SIR section and VFD counterpart was determined. RESULTS: The ON group had significantly higher maximum SIR than that of the NAION group (1.77 ± 0.88 vs. 1.25 ± 0.32; P < .01). Seven of the 19 patients had sections with abnormally high CE extending posteriorly beyond the orbital apex. Significant spatial correspondence was observed between CE and VFD asymmetry (rs = 0.563; P = .015) in the ON group but not in the NAION group (rs = - 0. 048; P = .850). CONCLUSIONS: ON patients with AH frequently show CE even in the intracerebral optic nerve, maintaining a moderate structure-function correspondence.

Quantitative evaluation of blinking in blepharospasm using electrooculogram-integrated smart eyeglasses.

Smart eyeglasses with an integrated electrooculogram (EOG) device (JINS MEME ES_R®, JINS Inc.) were evaluated as a quantitative diagnostic tool for blepharospasm. Participants without blepharospasm (n = 21) and patients with blepharospasm (n = 19) undertook two voluntary blinking tests (light and fast) while wearing the smart eyeglasses. Vertical (Vv) and horizontal (Vh) components were extracted from time-series voltage waveforms recorded during 30 s of the blinking tests. Two parameters, the ratio between the maximum and minimum values in the power spectrum (peak-bottom ratio, Fourier transform analysis) and the mean amplitude of the EOG waveform (peak amplitude analysis) were calculated. The mean amplitude of Vh from light and fast blinking was significantly higher in the blepharospasm group than in the control group (P < 0.05 and P < 0.05). Similarly, the peak-bottom ratio of Vv from light and fast blinking was significantly lower in the blepharospasm group than in the control group (P < 0.05 and P < 0.05). The mean amplitude of Vh and peak-bottom ratio of Vv correlated with the scores determined using the Jankovic rating scale (P < 0.05 and P < 0.01). Therefore, these parameters are sufficiently accurate for objective blepharospasm classification and diagnosis.

Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial.

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

Yearly changes in cases of acute acquired comitant esotropia during a 12-year period.

PURPOSE: The number of patients with acute acquired comitant esotropia (AACE) has been increasing in Japan. The purpose of this study was to investigate the changes in the number and characteristics of patients with AACE examined in our institution during a 12-year period. METHODS: We retrospectively reviewed the medical records of patients with AACE aged < 30 years who suddenly developed diplopia or esotropia and were examined in Hyogo College of Medicine Hospital from January 2008 to December 2021. We investigated the association of the yearly changes in the number of patients with the age category, refractive error category, AACE type, esotropia type, and use or nonuse of smartphones. RESULTS: The total number of patients with AACE was 171, and this number significantly increased each year (Pearson correlation coefficient, 0.9450; p < 0.0001). Significant increases were found among students in junior high school and beyond, patients with myopia, patients with Bielschowsky type AACE, and patients with basic esotropia (p < 0.0001 for all). We compared two age groups, elementary school students and below versus junior high school students and above, and found that the rate of increase was significantly higher in the junior high school students and above (estimate, 1.951; p < 0.0001), and the non-myopia group and myopia group and found that the rate of increase was significantly higher in the myopia group (estimate, 1.891; p < 0.0001). Excessive use of smartphones was confirmed in 82 of 133 patients, and the rate of the increase in the number of patients with AACE was significantly greater among patients with than without excessive use of smartphones (estimate, 1.098; p = 0.0009). CONCLUSION: This study confirmed a significant increase in the number of patients with AACE in recent years. The excessive use of smartphones may be associated with the increase in AACE.

Final efficacy and safety results and biomarker analysis of a phase 2 study of cabozantinib in Japanese patients with advanced renal cell carcinoma.

BACKGROUND: Cabozantinib was established as the standard of care for the treatment of patients with renal cell carcinoma (RCC) whose disease had progressed after vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in the global randomized trial METEOR. A phase 2 study was conducted to bridge the findings in METEOR to Japanese patients. Here, we report a biomarker analysis and update the efficacy and safety results of cabozantinib treatment. METHODS: Japanese patients with RCC who received at least one prior VEGFR-TKI were enrolled and received cabozantinib 60 mg orally once daily. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory analyses included the relationship between plasma protein hepatocyte growth factor (HGF) levels and treatment responses. RESULTS: In total, 35 patients were enrolled. The median treatment duration was 58.3 (range 5.1-131.4) weeks. The objective response rate was 25.7% (90% confidence interval [CI] 14.1-40.6). Kaplan-Meier estimate of median progression-free survival was 11.1 months (95% CI 7.4-18.4). The estimated progression-free survival proportion was 73.1% (95% CI 54.6-85.0) at 6 months. Median overall survival was not reached. Adverse events were consistent with those in METEOR and the safety profile was acceptable. Nonresponders to cabozantinib showed relatively higher HGF levels than responders at baseline. CONCLUSIONS: Updated analyses demonstrate the long-term efficacy and safety of cabozantinib in Japanese patients with advanced RCC after at least one VEGFR-TKI therapy. Responders tended to show lower baseline HGF levels ClinicalTrials.gov Identifier: NCT03339219.

Cabozantinib in Japanese patients with advanced hepatocellular carcinoma: Final results of a multicenter phase II study.

AIM: Cabozantinib showed a favorable benefit-risk profile in Japanese patients with advanced hepatocellular carcinoma (HCC) in an open-label, phase II study (NCT03586973). This analysis presents cumulative data to final database lock. METHODS: Patients with previously treated, advanced HCC received cabozantinib 60 mg/day. Progression-free survival (PFS) and tumor response rates in prior-sorafenib and sorafenib-naïve cohorts were assessed by independent radiology committee (IRC) and an investigator. Liver function was evaluated by albumin-bilirubin (ALBI) score. RESULTS: Median cabozantinib exposure was 5.6 months. In the prior-sorafenib cohort (n = 20), median PFS was 7.4 months per IRC assessment and 5.6 months per investigator assessment. In the sorafenib-naïve cohort (n = 14), median PFS was 3.6 and 4.4 months per IRC and investigator assessment, respectively. Six-month PFS rate per IRC and investigator assessment in the prior-sorafenib cohort was 59.8% and 49.5%, respectively, and in the sorafenib-naïve cohort was 16.7% and 35.7%, respectively. Disease control rate by both IRC and investigator assessment was 85.0% in the prior-sorafenib cohort and 64.3% in the sorafenib-naïve cohort. Median overall survival (Kaplan-Meier estimate) was 19.3 and 9.9 months in the prior-sorafenib and sorafenib-naïve cohort, respectively. Mean ALBI score remained relatively constant in patients able to continue treatment. The most frequent adverse events were palmar-plantar erythrodysesthesia syndrome, diarrhea, hypertension, and decreased appetite. No new safety concerns were identified. CONCLUSIONS: Cabozantinib showed efficacy and a manageable safety profile in Japanese patients with advanced HCC.

Pevonedistat in East Asian patients with acute myeloid leukemia or myelodysplastic syndromes: a phase 1/1b study to evaluate safety, pharmacokinetics and activity as a single agent and in combination with azacitidine.

Pevonedistat, the first small-molecule inhibitor of NEDD8-activating enzyme, has demonstrated clinical activity in Western patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). We report findings from a phase 1/1b study in East Asian patients with AML or MDS, conducted to evaluate the safety/tolerability and characterize the pharmacokinetics of pevonedistat, alone or in combination with azacitidine, in this population, and determine the recommended phase 2/3 dose for pevonedistat plus azacitidine. Twenty-three adult patients with very high/high/intermediate-risk AML or MDS were enrolled in Japan, South Korea and Taiwan. All 23 patients experienced at least one grade ≥ 3 treatment-emergent adverse event. One patient in the combination cohort reported a dose-limiting toxicity. Eighteen patients discontinued treatment; in nine patients, discontinuation was due to progressive disease. Three patients died on study of causes considered unrelated to study drugs. Pevonedistat exhibited linear pharmacokinetics over the dose range of 10-44 mg/m2, with minimal accumulation following multiple-dose administration. An objective response was achieved by 5/11 (45%) response-evaluable patients in the pevonedistat plus azacitidine arm (all with AML), and 0 in the single-agent pevonedistat arm. This study showed that the pharmacokinetic and safety profiles of pevonedistat plus azacitidine in East Asian patients were similar to those observed in Western patients as previously reported. The recommended Phase 2/3 dose (RP2/3D) of pevonedistat was determined to be 20 mg/m2 for co-administration with azacitidine 75 mg/m2 in Phase 2/3 studies, which was identical to the RP2/3D established in Western patients.Trial registration: clinicaltrials.gov: NCT02782468 25 May 2016. https://clinicaltrials.gov/ct2/show/NCT02782468.

A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer.

Cabozantinib inhibits multiple receptor tyrosine kinases, including the TAM kinase family, and may enhance response to immune checkpoint inhibitors. One cohort of the ongoing phase Ib COSMIC-021 study (NCT03170960) evaluating cabozantinib plus the PD-L1 inhibitor atezolizumab in men with metastatic castration-resistant prostate cancer (mCRPC) that has progressed in soft tissue on/after enzalutamide and/or abiraterone treatment for metastatic disease has shown promising efficacy. Here, we describe the rationale and design of a phase III trial of cabozantinib plus atezolizumab versus a second novel hormone therapy (NHT) in patients who have previously received an NHT for mCRPC, metastatic castration-sensitive PC or nonmetastatic CRPC and have measurable visceral disease and/or extrapelvic adenopathy - a population with a significant unmet need for treatment options. Trial Registration Clinical Trial Registration: NCT04446117 (ClinicalTrials.gov) Registered on 24 June 2020.

Death From Primary Amebic Meningoencephalitis After Recreational Water Exposure During Recent Travel to India-Santa Clara County, California, 2020.

BACKGROUND: In February 2020, a man returned to the United States after an 11-day trip to India and died of primary amebic meningoencephalitis (PAM), caused by nasal exposure to the free-living ameba Naegleria fowleri found in warm water. We identified potential exposures, confirmed etiology, and described the molecular epidemiology of the infection. METHODS: We reviewed medical records to describe his clinical course and interviewed his family to determine water exposures. Genotyping was performed on the N. fowleri strain and compared with North American strains through repetitive nonpolymorphic nuclear loci analysis to identify differences. We reviewed N. fowleri strains in the National Center for Biotechnology Information database (GenBank) to determine genotypes present in India. RESULTS: The patient became acutely encephalopathic 3 days after returning; the only known nasal water exposure was at an indoor swimming pool in India 5 days earlier. Cerebrospinal fluid (CSF) testing demonstrated neutrophil-predominant pleocytosis and low glucose, but negative gram stain and culture. CSF microscopy revealed trophozoites; N. fowleri was detected by real-time polymerase chain reaction. Classical genotyping confirmed genotype I, common in the United States and among Indian strains in GenBank. The North American N. fowleri strains and the patient's strain varied at 5 nonpolymorphic loci. CONCLUSIONS: A man died from PAM after likely exposure at a vacation rental pool in India. We recommend including PAM in the differential diagnosis when CSF studies suggest bacterial meningitis but gram stain is negative. Genotyping can advance our understanding of N. fowleri molecular epidemiology and support future investigations.

Intravenous immunoglobulin treatment for steroid-resistant optic neuritis: a multicenter, double-blind, randomized, controlled phase III study.

PURPOSE: To evaluate the efficacy and safety of intravenous "freeze-dried sulfonated human normal immunoglobulin (GGS)" in patients with steroid-resistant optic neuritis (ON). STUDY DESIGN: Multicenter, prospective, double-blind, parallel-group, randomized controlled trial. METHODS: Patients with steroid-resistant acute ON were randomly assigned to receive either intravenous GGS (GGS group) or intravenous methylprednisolone (steroid pulse [SP] group). Visual acuity (logarithm of the minimum angle of resolution [logMAR]), mean deviation (MD) value of the Humphrey Field Analyzer, and critical flicker fusion frequency were measured as efficacy endpoints; adverse events (AEs) were assessed as the safety endpoint. RESULTS: Thirty-two patients (16 patients/group) received the study drugs. The primary endpoint, change in logMAR at week 2 compared to baseline, showed no statistically significant intergroup difference. However, compared with the SP group, change in the GGS group was increasingly indicative of visual improvement, with least squares mean difference of > 0.3 logMAR. On post-hoc analyses, the percentage of patients in the GGS and SP groups with improvement by ≥ 0.3 logMAR at week 2 were 75.0% and 31.3%, respectively. Changes in MD values at week 2 compared to baseline were 9.258  ±  8.296 (mean ± standard deviation) dB and 3.175  ±  6.167 dB in the GGS and SP groups, respectively. These results showed statistically significant intergroup differences (visual acuity improvement, P = 0.032; change in MD values, P = 0.030). No clinically significant AEs were observed. CONCLUSION: Our results suggest that intravenous immunoglobulin could be a safe and efficacious therapeutic option for prompt treatment of steroid-resistant acute ON. TRIAL REGISTRATION: JapicCTI-132080.

Cabozantinib in Japanese patients with advanced hepatocellular carcinoma: a phase 2 multicenter study.

BACKGROUND: To evaluate the efficacy and safety of cabozantinib in Japanese patients with advanced hepatocellular carcinoma (HCC) who had progressed following one or two lines of systemic therapy including sorafenib. An exploratory evaluation in sorafenib-naïve patients was performed. METHODS: In this open-label, single-arm, phase 2 trial, patients received oral cabozantinib 60 mg once daily. The primary endpoint was progression-free survival (PFS) rate at Week 24. Secondary endpoints included PFS, overall survival (OS), objective response rate (ORR, best response of complete/partial response), disease control rate (DCR, objective response or stable disease) and safety. RESULTS: Thirty-four patients received cabozantinib across 17 centers (prior sorafenib cohort, n = 20; sorafenib-naïve cohort, n = 14). PFS rate at 24 weeks was 59.8% [90% confidence interval (CI) 36.1-77.2%] in the prior sorafenib cohort, 16.7% (90% CI 4.0-36.8%) in the sorafenib-naïve cohort and 40.1% (90% CI 24.8-55.0%) overall. Median PFS was 7.4 months for the prior sorafenib cohort, 3.6 months for the sorafenib-naïve cohort, and 5.6 months overall. OS rate at 6 months was 100.0%, 78.6% and 91.1%, respectively; DCR was 85.0%, 64.3% and 76.5%, respectively. The ORR was 0.0% for both cohorts. All patients required dose modifications due to adverse events, the most common of these were palmar-plantar erythrodysesthesia syndrome and diarrhea. Three patients (8.8%) discontinued due to adverse events other than disease progression. CONCLUSIONS: Cabozantinib 60 mg/day has a favorable benefit/risk profile for Japanese patients with advanced HCC who have previously received one or two lines of systemic anticancer therapy including sorafenib. (Clinical trial registration: NCT03586973).

Effects of cataract surgery in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To investigate the effects of cataract surgery in Japanese patients with neovascular age-related macular degeneration (nAMD). METHODS: The primary endpoint in this prospective, observational study was patient satisfaction at 6 months after cataract surgery in patients with nAMD. Secondary endpoints comprised changes in best-corrected visual acuity (BCVA), M-chart score, central retinal thickness (CRT), AMD status, and number of AMD treatments. All examinations were performed before surgery, and at 1, 3, and 6 months postoperatively. RESULTS: Fifty patients (52 eyes) were included in this study (32 men; mean age, 76.1 ± 7.1 years). Thirty-nine patients (75.0%) reported satisfaction with cataract surgery. BCVA significantly improved at all postoperative timepoints (all p < 0.0001), whereas differences in M-chart scores were not statistically significant. The number of eyes with BCVA ≤ 0.3 logarithm of the minimum angle of resolution (logMAR) increased from 21 to 38; however, CRT did not change. The number of AMD treatments did not change during follow-up. All questionnaire scores showed postoperative improvement. Univariate and multivariate analyses revealed that final BCVA ≤ 0.3 logMAR was significantly associated with patient satisfaction. CONCLUSION: Cataract surgery significantly improved vision in Japanese patients with nAMD, without affecting AMD status. Patients were satisfied with cataract surgery, especially with respect to improvement of distance vision.