Recent publications
Purpose
To report a case of bilateral choroidal osteoma successfully treated with subscleral sclerectomy for secondary serous retinal detachment (SRD).
Observations
A 52-year-old Japanese woman first diagnosed with Vogt-Koyanagi-Harada disease and treated with steroids for 9 years was referred to our clinic. SRD in both eyes recurred frequently and was uncontrolled with adalimumab subcutaneous injections and oral cyclosporine, in addition to steroids. A yellowish-to-orange, slightly elevated subretinal lesion was observed superior to the macular and inferotemporal regions of the right eye and superior to the macular and temporal regions of the left eye without any inflammation. Swept-source optical coherence tomography (OCT) revealed SRD in the fovea and a mass under the retinal pigment epithelium (RPE) in the macular area of both eyes. Indocyanine green angiography (ICGA) demonstrated hypocyanescence corresponding to the mass area under the RPE, with dilation of the dominant vortex veins. Ultrasonography revealed a hyperechogenic mass in the posterior wall of both eyes with deeper acoustic shadows, and computed tomography (CT) detected calcifications in the posterior wall of both eyes. A bilateral choroidal osteoma was diagnosed, and the superior SRD of her left eye increased toward the fovea without any evidence of choroidal neovascularization during follow-up. Therefore, subscleral sclerectomy (4 × 4 mm² sclerectomy under the scleral flap) was performed at three sites at the equators in the upper temporal, upper nasal, and lower temporal quadrants of her left eye. Immediately after surgery, SRD resolved dramatically. As the foveal SRD of her right eye also increased after two months, the same surgery was performed, and it worked successfully.
Conclusions and Importance
Choroidal osteoma can cause severe SRD that cannot be controlled with medication. Although further studies are needed, subscleral sclerectomy may be an effective treatment for the resolution of subretinal fluid secondary to choroidal osteoma by improving choroidal circulation congestion.
During the initial diagnosis of superficial esophageal squamous cell carcinoma, a 70‐year‐old man was treated with endoscopic submucosal dissection (ESD). Two years after the first ESD, follow‐up endoscopy revealed that the extent of hyperkeratosis gradually expanded over the following 4 years; however, biopsies conducted only detected Candida mycelia and no cancer at that time and every 6 months for 4 years. Despite initiating fluconazole treatment for persistent Candida esophagitis 6 years after the first ESD, the lesions did not resolve, and the second ESD was performed 6 years after the first ESD, which revealed squamous cell carcinoma. This case highlights that esophageal cancer should be considered when localized, hyperkeratotic Candida esophagitis is unresponsive to antifungal treatments, especially with a history of esophageal cancer or high‐risk factors such as drinking alcohol and smoking.
Purpose
To investigate the age-related changes in magnetic resonance imaging (MRI) findings of lobular endocervical glandular hyperplasia (LEGH) during long-term follow-up.
Materials and methods
This multicenter study included 91 patients who underwent preoperative MRI and had a histopathological diagnosis of LEGH, atypical LEGH, or adenocarcinoma in situ (AIS) with LEGH after surgical resection. Thirty patients underwent follow-up MRIs at intervals of more than 3 months. According to the age and menopausal status, patients were categorized into four groups: group A, 31–40 years; group B, 41–50 years (premenopausal); group C, more than 50 years (premenopausal); group D, postmenopausal. Differences in the MRI findings (size and morphological pattern) were compared among the four groups.
Results
The lesion volume was the largest in group C and smallest in group D, showing a statistically significant difference ( p < 0.05). The typical cosmos pattern was seen in 60.0% of group A, 62.2% of group B, 75.0% of group C, and 29.2% of group D. The cosmos pattern was significantly less frequent in postmenopausal patients compared to premenopausal patients ( p < 0.05). During follow-up, five of 12 individuals in group A exhibited the typical cosmos pattern. Among the seven individuals who did not initially show the cosmos pattern, two later developed the typical cosmos pattern. No changes in the lesion pattern were observed in participants in their 40 s up to the premenopausal 50 s. From the premenopausal 50 s to the postmenopausal period, the cosmos pattern changed to a microcystic pattern in one case of atypical LEGH.
Conclusions
LEGH increases in volume with age until menopause, along with an increasing frequency of the typical cosmos pattern in MRI. However, after menopause, both the volume of the lesion and frequency of the typical cosmos pattern decrease.
Fontan-associated liver disease leads to liver cirrhosis and hepatocellular carcinoma, worsening patient prognosis. Although the Model of End-Stage Liver Disease Excluding International Normalized Ratio score correlates with disease severity, precise prediction methods remain elusive. The hepatic computed tomography (CT) attenuation is used to assess steatohepatitis, which may offer insight into disease progression. This study aimed to determine the usefulness of hepatic CT attenuation values in assessing Fontan-associated liver disease progression. All post-Fontan patients with >20 years’ follow-up data between 1980 and 2021 were reviewed. We set five regions of interest with a 20-mm-diameter circle in the peripheral region of the liver to obtain minimum, maximum, mean, and standard deviation of the CT attenuation values, which were adjusted to those of the aorta. The impact of hepatic CT attenuation values on cirrhosis development was evaluated. Cox regression revealed significant associations between adjusted minimum (hazard ratio: 0.01 [0.00–0.02, p < 0.01), adjusted maximum (hazard ratio: 159 [4.34–5831, p < 0.01]), and standard deviation (hazard ratio: 1.89 [1.29–2.76, p < 0.01]) and Model of End-Stage Liver Disease Excluding International Normalized Ratio score (hazard ratio: 1.2 [1.02–1.43, p = 0.03]) with cirrhosis. In cirrhosis cases, the adjusted minimum value exhibited significant longitudinal alteration prior to cirrhosis ( p < 0.01), whereas Model of End-Stage Liver Disease Excluding International Normalized Ratio scores remained stable. The hepatic CT attenuation values were associated with cirrhosis development and the longitudinal changes are more sensitive than the Model of End-Stage Liver Disease Excluding International Normalized Ratio score.
Rapid assessment of severity is crucial for timely intervention and improved patient outcomes in heatstroke (HS). However, existing biomarkers are limited in their accuracy and accessibility in ER settings. A prospective pilot study was conducted to assess urinary liver fatty acid-binding protein (L-FABP) levels using a point-of-care testing (POCT) upon HS. Severity was estimated using initial Sequential Organ Failure Assessment (SOFA) scores, and outcomes were measured using modified Rankin Scale (mRS) scores. In 78 severe HS patients, semi-quantitative L-FABP measurements were performed in ER and patients were divided as P-group (positive group, L-FABP ≧ 12.5 ng/mL on POCT) and N-group (negative group: L-FABP < 12.5ng/mL, on POCT). urinary L-FABP concentrations were also measured on admission, with a median concentration of 48.3 ng/mL. The positive correlation was observed between urinary L-FABP concentration and pulse rate (r = 0.300, P < 0.01) and lactate (r = 0.259, P < 0.01). The POCT of L-FABP showed promise in predicting severity, as indicated by higher concentrations in patients with higher initial SOFA scores. Furthermore, the comparison between semi-quantitative POCT measurements and urine concentrations of L-FABP measured by enzyme-linked immunosorbent assay (ELISA) revealed significant differences among three POCT groups (POC Range < 12.5 ng/ml, 12.6–100 ng/ml, and 55 > 100 ng/ml, P = 0.001). Additionally, patients in the POCT positive group had significantly worse outcomes at discharge compared to the negative group, although this difference diminished over time. The study demonstrates the feasibility and potential utility of POCT for initial L-FABP in estimating severity in HS patients. This rapid and accessible testing method may aid in early field triage and intervention, ultimately improving patient outcomes in the management of HS.
Laboratory experiments were conducted using model organisms to elucidate biological phenomena. However, the natural habitats of organisms are inherently more complex than those found in the laboratory. To complement the laboratory experiments, we conducted field observations of the small freshwater fish medaka (Oryzias latipes), widely used as a model organism, to elucidate its ecology and behavior in natural environments. Our results showed that medaka initiated courtship and spawning late at night, much earlier than previously thought. Nocturnal video observations examining spawning time during the breeding season in Gifu, Japan (sunset: 19:00; sunrise: 5:00) revealed the presence of post-spawning medaka females around midnight. Behavioral analysis showed that the medaka was inactive until 23:00, with activity increasing from 0:00 and peaking from 1:00 to 3:00. Furthermore, a significant increase in male courtship was observed between 0:00 and 4:00. These findings provide the first empirical evidence that medaka mating begins significantly earlier than previously reported in the laboratory, as within an hour before or after light onset in the morning. This study highlights the importance of field observations in revealing critical aspects of organismal biology that may be overlooked in laboratory settings.
Immune checkpoint blockade therapy has been successfully applied in clinical settings as a standard therapy for many cancer types, but its clinical efficacy is restricted to patients with immunologically hot tumors. Various strategies to modify the tumor microenvironment (TME), such as Toll-like receptor (TLR) agonists that can stimulate innate immunity, have been explored but have not been successful. Here, we show a mechanism of acquired resistance to combination treatment consisting of an agonist for multiple TLRs, OK-432 (Picibanil), and programmed cell death protein 1 (PD-1) blockade. Adding the TLR agonist failed to convert the TME from immunogenically cold to hot and did not augment antitumor immunity, particularly CD8 ⁺ T cell responses, in multiple animal models. The failure was attributed to the coactivation of innate suppressive cells, such as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) expressing CXCR2, through high CXCL1 production by macrophages in the TME upon OK-432 treatment. A triple combination treatment with OK-432, PD-1 blockade, and a CXCR2 neutralizing antibody overcame the resistance induced by PMN-MDSCs, resulting in a stronger antitumor effect than that of any dual combinations or single treatments. The accumulation of PMN-MDSCs was similarly observed in the pleural effusions of patients with lung cancer after OK-432 administration. We propose that successful combination cancer immunotherapy intended to stimulate innate antitumor immunity requires modulation of unwanted activation of innate immune suppressive cells, including PMN-MDSCs.
The Antarctic midge, Belgica antarctica, is a unique insect endemic to Antarctica. It has a 2-year life cycle, with larvae overwintering in two different instars and adults emerging the following summer. This seasonality is crucial for adaptation to Antarctica’s harsh climates and ephemeral growing seasons; however, the underlying mechanisms remain unclear. We found that, under summer-like conditions, larvae could develop from egg to the fourth-instar larval stage without interruption, but they never pupated. Spontaneous developmental arrest at this stage suggests that they overwinter in obligate diapause, a genetically determined period of dormancy. The winter cold can terminate this diapause, and long-term cold exposure is more effective. Although this species can utilise two alternative cold tolerance strategies with diapause for overwintering, freezing was more successful than cryoprotective dehydration in allowing survival and developmental resumption in our experimental conditions. In contrast, the first three larval instars continued their development under the same conditions as the fourth-instar larvae. Although we do not exclude the possibility of facultative diapause, they likely overwinter in a quiescent state, an immediate developmental arrest in response to adversity, to maximise exploitation of the short Antarctic summer. Diapause and quiescence ensure developmental and reproductive success in this extremophile insect.
In Japan, cancer screening is conducted under a variety of umbrellas, i.e., via population-based screening, occupational health checkups, insured medical care, and personal medical checkups. Quality control assessment of cancer screenings is conducted by national and local governments only for population-based screenings. The purpose of this study was to clarify the status of women receiving cervical and breast cancer screenings in Japan by any of these means. As a model associated with occupational screenings, we surveyed female employees and male employees’ spouses of Sunstar, Inc., a Japanese subsidiary of an international corporation. The number of valid responses collected from March to July 2023 was 345. Among those who had cancer screening either regularly or irregularly, 66% (89/134) and 56% (47/84), respectively, received cervical and breast cancer screenings more frequently than every two years, the prescribed interval for population-based screening. Our survey revealed that a small number of women are routinely receiving cervical and breast cancer screenings more frequently than appropriate, suggesting a need to provide better information to screening consumers and providers on what constitutes appropriate screening schedules. Our survey also revealed that there is no governmental management entity for opportunistic screenings, so the status among female employees and male employee’s spouses of a company, Sunstar, Inc. is unclear.
Introduction
Current mitral annuloplasty rings fail to restrict the anteroposterior distance while allowing dynamic mitral annular changes. We designed and manufactured a mitral annuloplasty ring that demonstrated axis-specific, selective flexibility to meet this clinical need. The objectives were to evaluate ex vivo biomechanics of this ring and to validate the annular dynamics and safety after ring implantation in vivo.
Methods
Healthy human mitral annuli (n = 3) were tracked, and motions were isolated. Using the imaging data, we designed and manufactured our axis-specific mitral annuloplasty ring. An ex vivo annular dilation model was used to compare hemodynamics and chordal forces after repair using the axis-specific, rigid, and flexible rings in five porcine mitral valves. In vivo, axis-specific (n = 6), rigid (n = 6), or flexible rings (n = 6) were implanted into male Dorset sheep for annular motion analyses. Five additional animals receiving axis-specific rings survived for up to 6 months.
Results
Here we show the axis-specific, rigid, and flexible rings reduced regurgitation fraction to 4.7 ± 2.7%, 2.4 ± 3.2%, and 17.8 ± 10.0%, respectively. The axis-specific ring demonstrated lower average forces compared to the rigid ring (p = 0.046). Five animals receiving axis-specific rings survived for up to 6 months, with mitral annular motion preserved in vivo. Mature neoendocardial tissue coverage over the device was found to be complete with full endothelialization in all animals.
Conclusions
The axis-specific mitral annuloplasty ring we designed demonstrates excellent capability to repair mitral regurgitation while facilitating dynamic mitral annular motion. This ring has tremendous potential for clinical translatability, representing a promising surgical solution for mitral regurgitation.
Purpose: Human flourishing is a multidimensional concept that encompasses happiness and life satisfaction (happiness), mental and physical health (health), meaning and purpose (purpose), character and virtue (character), and close social relationships (social), which are characterized by comprehensive well-being. This cross-sectional study investigated the association of oral health, number of remaining teeth, and prosthesis use with multidimensional flourishing.
Methods: Data was sourced from the 2022 wave of the Japan Gerontological Evaluation Study, a population-based survey of independent individuals aged 65 years or older. This study utilized multilevel linear regression with multiple imputations. The covariates included sex, age, income, education, marital status, smoking status, diabetes history, instrumental activities of daily living, and depressive symptoms.
Results: This study included 87,201 participants with a mean age of 74.87 years [standard deviation (SD)=6.30], and mean±SD composite flourishing index of 6.77±1.64. Multilevel multivariable regression showed that individuals with dental prostheses or more teeth had a higher flourishing index. Among individuals without dental prostheses, those with >20 teeth showed a composite flourishing index of 0.34 units higher (95% confidence interval (95% CI): 0.26-0.42, P < 0.001) than those with 0-9 teeth. Among those with 0-9 teeth, individuals with dental prostheses showed 0.21 (95% CI: 0.12-0.29, P < 0.001) higher units compared to those without prostheses. The interaction analysis showed that dental prosthesis use was significantly associated with higher indices, especially among those with fewer teeth.
Conclusions: Teeth and prostheses were independently associated with multidimensional flourishing. Using dental prostheses may enhance multidimensional flourishing among individuals with fewer remaining teeth.
Background
Avelumab + axitinib was approved for the treatment of advanced renal cell carcinoma (aRCC) in Japan in December 2019. We report long-term real-world subgroup analyses with first-line avelumab + axitinib in patients with aRCC by International Metastatic RCC Database Consortium (IMDC) risk classification from the J-DART2 study in Japan.
Methods
J-DART2 was a multicenter, noninterventional, retrospective study examining characteristics, treatment patterns, and outcomes in patients with aRCC who started first-line avelumab + axitinib in Japan between December 2019 and October 2022.
Results
Data from 150 patients across 19 sites were analyzed. IMDC risk was favorable in 39 patients (26.0%), intermediate (1 risk factor) in 46 (30.7%), intermediate (2 risk factors) in 36 (24.0%), and poor in 29 (19.3%). Baseline characteristics were generally consistent across IMDC risk subgroups. In subgroups with favorable, intermediate (1 risk factor), intermediate (2 risk factors), and poor risk, median progression-free survival was 31.0, 15.3, 16.4, and 8.1 months; median overall survival (OS) was not reached, but 24-month OS rates were 95.2%, 91.3%, 85.3%, and 57.6%, respectively. Objective response rates were 54.5%, 56.8%, 47.1%, and 54.2%, respectively. High-dose corticosteroid treatment for immune-related adverse events was administered in 5.1%, 8.7%, 8.3%, and 6.9% of patients, respectively.
Conclusion
Subgroup analyses from J-DART2 confirm the long-term real-world effectiveness of first-line avelumab + axitinib across IMDC risk groups in patients with aRCC in Japan. Our findings were consistent with previous analyses by IMDC risk and support the favorable benefit-risk profile of avelumab + axitinib in clinical practice in Japan.
Background
Pyrethroid insecticides are widely used because of their low toxicity in humans. Spray-type pyrethroids are often formulated with kerosene as a carrier solvent, and inhalation of kerosene-containing products can lead to pneumonitis and the formation of lung abscesses. We report a case of chemical pneumonitis resulting in the development of a lung abscess due to the intentional inhalation of pyrethroids.
Case presentation
A man in his 50s in a psychiatric hospital for transient psychotic disorder attempted suicide during an overnight leave from the hospital. He drank sodium hypochlorite, put a nylon bag over his head, and sprayed pyrethroid insecticide inside the bag. He was found collapsed and was transported to our emergency room. On arrival, his SpO2 was 100% on O2 at 10 L/min by mask (100% on room air at ambulance arrival), his circulation was stable, and his Glasgow Coma Scale score was 10 (E1V3M6), which improved to 15 (E4V5M6) in about one hour. A chest computed tomography (CT) scan showed ground-glass shading in both lungs. We diagnosed him as having pneumonia and started antimicrobial therapy. On day 13 of hospitalization, we found multifocal hypo-absorptive areas, and a diagnosis of lung abscess was made based on CT imaging, and antimicrobial therapy was continued. During the hospitalization, he expectorated bloody sputum. A contrast chest CT scan obtained on day 71 of hospitalization showed a pseudoaneurysm in the abscess cavity, for which we performed successful transcatheter coil embolization. On day 77, the abscess was shrinking, and he was transferred to another hospital for continued treatment. However, he again had bloody sputum and was transferred back to our hospital on day 113. Another contrast chest CT scan revealed the formation of a new aneurysm, and on day 114, we successfully performed coil embolization again, and he was transferred back to the other hospital on day 116.
Conclusion
Spray-type pyrethroid insecticides contain the organic solvent kerosene. Inhalation of kerosene has been reported in several cases of chemical pneumonitis leading to lung abscess. Clinicians should pay attention to kerosene contained in insecticides and the circumstances under which they are used. Early recognition and aggressive treatment can likely prevent severe outcomes.
Advanced/metastatic urothelial cancer (a/m UC) still has a poor prognosis despite the recent medical advances. Recent studies demonstrated that fibroblast growth factor receptor (FGFR) gene alterations (GAs) may be driver genes for UC; however, the proportion of UC genetic panel testing in Japan remains low. We clarified the proportion of patients with FGFR2/3 GAs, treatment patterns, and clinical outcomes in a/m UC patients in Japan. This study was a descriptive epidemiological study using the MONSTAR‐SCREEN database, and 138 patients with a/m UC were evaluated. The primary endpoint was the proportion of patients with FGFR2/3 GAs. The secondary endpoints included treatment patterns, clinical outcomes, genomic status before and after treatment, etc. The proportion of FGFR GA‐positive patients in a/m UC was 11.9%. The most common FGFR mutation variant and fusion gene were S249C (4.4%) and FGFR3‐TACC3 fusion (3.7%), respectively. Fifty‐one patients were tested two or more times; a few changes were observed in the FGFR GA status, regardless of the treatment regimen. Co‐occurrence association was observed in FGFR1 with TET2, and in FGFR3 with CHEK2 or MLL2. During the first‐, second‐, and third‐line treatment, median progression‐free survival (PFS) of GA‐positive patients was 7.3, 2.9, and 6.2 months, while for GA‐negative patients, 6.9, 3.1, and 6.9 months, respectively. This study revealed that one in eight a/m UC patients had FGFR2/3 GAs, and a few changes were observed in FGFR GA status before and after treatment. Genetic testing will be beneficial for the selection of appropriate treatments after a diagnosis of a/m UC.
CorneAI, a deep learning model designed for diagnosing cataracts and corneal diseases, was assessed for its impact on ophthalmologists’ diagnostic accuracy. In the study, 40 ophthalmologists (20 specialists and 20 residents) classified 100 images, including iPhone 13 Pro photos (50 images) and diffuser slit-lamp photos (50 images), into nine categories (normal condition, infectious keratitis, immunological keratitis, corneal scar, corneal deposit, bullous keratopathy, ocular surface tumor, cataract/intraocular lens opacity, and primary angle-closure glaucoma). The iPhone and slit-lamp images represented the same cases. After initially answering without CorneAI, the same ophthalmologists responded to the same cases with CorneAI 2–4 weeks later. With CorneAI’s support, the overall accuracy of ophthalmologists increased significantly from 79.2 to 88.8% (P < 0.001). Specialists’ accuracy rose from 82.8 to 90.0%, and residents’ from 75.6 to 86.2% (P < 0.001). Smartphone image accuracy improved from 78.7 to 85.5% and slit-lamp image accuracy from 81.2 to 90.6% (both, P < 0.001). In this study, CorneAI’s own accuracy was 86%, but its support enhanced ophthalmologists’ accuracy beyond the CorneAI’s baseline. This study demonstrated that CorneAI, despite being trained on diffuser slit-lamp images, effectively improved diagnostic accuracy, even with smartphone images.
To investigate the current status of regional disparities in surgical residency training between urban and regional hospitals.
Based on a nationwide online questionnaire survey of newly certified surgical trainees, the responding residents were divided into the following two groups according to the size of the city in which they had trained: the urban city group (UC group; population > 1 million) and the regional city group (RC group; population < 1 million. Surgical education and work environment of the two groups were compared.
The UC group (n = 317, 42%) was characterized by greater post-graduate experience, older age, a higher proportion of female surgeons, and a higher percentage of full-time working partners relative to the RC group (n = 439, 58%). More residents in the UC group were from urban areas, whereas the RC group had more residents from regional areas. No differences were observed in the number of surgeries performed, published papers, opportunities for off-the-job training, or satisfaction with the surgical residency training program. With the exception of higher income in the RC group, no differences were observed for other factors related to the work environment.
There was little regional disparity regarding the impressions of surgical residency training between urban and regional cities, including surgical education and work environment.
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