An analysis of information segregation in parallel streams of a multi-stream convolutional neural network.

Visual information is processed in hierarchically organized parallel streams in the primate brain. In the present study, information segregation in parallel streams was examined by constructing a convolutional neural network with parallel architecture in all of the convolutional layers. Although filter weights for convolution were initially set to random values, color information was segregated from shape information in most model instances after training. Deletion of the color-related stream decreased recognition accuracy of animate images, whereas deletion of the shape-related stream decreased recognition accuracy of both animate and inanimate images. The results suggest that properties of filters and functions of a stream are spontaneously segregated in parallel streams of neural networks.

A case of secondary pseudohypoaldosteronism that presented as poor weight gain.

Key clinical message: Pseudohypoaldosteronism (PHA) carries a good prognosis if treated early and appropriately, but some cases can have life-threatening events. We underscored the need to consider secondary PHA as one of the differential diagnoses of hyponatremia and hyperkalemia in infancy. Abstract: Pseudohypoaldosteronism (PHA) type 1 has two classifications; the primary type, caused by genetic abnormalities that develop during neonatal and infancy periods, and the secondary type, caused by urinary tract malformation and urinary tract infection. Secondary PHA, if treated early and appropriately, has a good prognosis; however, some cases can present life-threatening events. Therefore, early diagnosis is crucial. We present a case of early infancy secondary PHA presented with marked hyponatremia and poor weight gain. The patient's growth and development improved with secondary PHA treatment. Here, were demonstrated the value of prompt action against infection and electrolyte imbalance and the importance of imaging for diagnosis, and underscore the need to consider secondary PHA as a differential diagnoses of hyponatremia and hyperkalemia in infancy. However further studies, including basic research, to elucidate the diseases pathology is warranted.

Probability of normal tissue complications for hematologic and gastrointestinal toxicity in postoperative whole pelvic radiotherapy for gynecologic malignancies using intensity-modulated proton therapy with robust optimization.

This retrospective treatment-planning study was conducted to determine whether intensity-modulated proton therapy with robust optimization (ro-IMPT) reduces the risk of acute hematologic toxicity (H-T) and acute and late gastrointestinal toxicity (GI-T) in postoperative whole pelvic radiotherapy for gynecologic malignancies when compared with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated X-ray (IMXT) and single-field optimization proton beam (SFO-PBT) therapies. All plans were created for 13 gynecologic-malignancy patients. The prescribed dose was 45 GyE in 25 fractions for 95% planning target volume in 3D-CRT, IMXT and SFO-PBT plans and for 99% clinical target volume (CTV) in ro-IMPT plans. The normal tissue complication probability (NTCP) of each toxicity was used as an in silico surrogate marker. Median estimated NTCP values for acute H-T and acute and late GI-T were 0.20, 0.94 and 0.58 × 10-1 in 3D-CRT; 0.19, 0.65 and 0.24 × 10-1 in IMXT; 0.04, 0.74 and 0.19 × 10-1 in SFO-PBT; and 0.06, 0.66 and 0.15 × 10-1 in ro-IMPT, respectively. Compared with 3D-CRT and IMXT plans, the ro-IMPT plan demonstrated significant reduction in acute H-T and late GI-T. The risk of acute GI-T in ro-IMPT plan is equivalent with IMXT plan. The ro-IMPT plan demonstrated potential clinical benefits for reducing the risk of acute H-T and late GI-T in the treatment of gynecologic malignances by reducing the dose to the bone marrow and bowel bag while maintaining adequate dose coverage to the CTV. Our results indicated that ro-IMPT may reduce acute H-T and late GI-T risk with potentially improving outcomes for postoperative gynecologic-malignancy patients with concurrent chemotherapy.

Short-Term Outcomes of 3 Monthly intravitreal Faricimab On Different Subtypes of Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the efficacy and safety of faricimab injections for treatment-naïve neovascular age-related macular degeneration (nvAMD) patients, including subtypes and pachychoroid phenotypes, and identify predictive factors for visual outcomes. Methods: nvAMD patients were prospectively recruited, receiving three monthly faricimab (6 mg) injections. Best-corrected visual acuity (BCVA) two months after the last injection (month 4) was compared between subtypes, and between pachychoroid neovasculopathy (PNV) and non-PNV eyes. Regression analysis determined factors influencing month 4 BCVA. Results: The study involved 23 patients (12 typical AMD [tAMD], 10 polypoidal choroidal vasculopathy [PCV], 1 retinal angiomatous proliferation [RAP]). Eleven exhibited PNV phenotype. Significant BCVA (P = 4.9 × 10-4) and central retinal thickness (CRT) (P = 1.3 × 10-5) improvements were observed post-faricimab treatment. The therapy demonstrated favourable results for both tAMD and PCV eyes, and non-PNV and PNV eyes. Faricimab achieved dry macula in 77.3% of eyes, with subretinal fluid resolution in most cases, although intraretinal fluid (IRF) often persisted. Multivariable analysis identified external limiting membrane (ELM) presence and IRF as BCVA contributors at month 4. Conclusion: Faricimab demonstrated significant effectiveness and safety in treatment-naïve nvAMD patients, particularly for PCV and PNV eyes. ELM presence and IRF is predictive of visual outcomes.

MACULAR CHORIORETINAL ATROPHY AND VISUAL OUTCOMES IN RANIBIZUMAB- OR AFLIBERCEPT-TREATED MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To investigate the predictors of macular chorioretinal atrophy, consisting of patchy atrophy (PA) at the macula and choroidal neovascularization (CNV)-related macular atrophy (CNV-MA), during treatment with ranibizumab or aflibercept for myopic CNV (mCNV) and its impact on visual outcomes. METHODS: This retrospective study included 82 eyes with treatment-naïve mCNV who were treated with pro re nata injections of ranibizumab or aflibercept. RESULTS: Nine eyes (11.0%) presented with macular PA at baseline (PA group), and 73 eyes (89.0%) did not (non-PA group). VA improved during the first year in the non-PA group; a similar trend was noted in the PA group until 3 months after initial treatment. This improvement was maintained until 24 months ( P < 0.001) in the non-PA group, but not in the PA group. In the PA group, macular chorioretinal atrophy progressed faster ( P < 0.0001), and CNV-MA was more frequent during the 2 years of treatments ( P = 0.04). Even non-PA group eyes sometimes developed CNV-MA (42% at Month 24) if they had a larger CNV and thinner subfoveal choroidal thickness at baseline, resulting in poorer visual prognosis ( P < 0.01). CONCLUSION: Macular PA at baseline was a risk factor for CNV-MA development and was associated with poor visual outcomes.

Ongoing impacts of childhood-onset glomerular diseases during young adulthood.

BACKGROUND: Childhood-onset glomerular disease often requires ongoing treatment and follow-up into adulthood. However, few studies have analyzed the associated impact and distress experienced by patients with this condition during the transition from childhood to adolescence and adulthood. METHODS: At three facilities, we recruited patients who developed idiopathic nephrotic syndrome or IgA nephropathy during childhood and were at least 18 years old at the time of study entry. Among them, a questionnaire-based survey was administered to patients who consented to participate, and the results were analyzed in conjunction with clinical information. RESULTS: Data from a total of 38 patients were analyzed. Of these patients, 15 had idiopathic nephrotic syndrome and 23 had IgA nephropathy. The age of transition from pediatrics to the adult medicine department was correlated with the number of recurrences. Many patients also reported being significantly affected by exercise restrictions and physical decline associated with their diseases and medications. Various impacts, including distress, affected decision-making regarding higher education, with patients engaging in higher education at a significantly higher rate compared with the regional average (66.7% vs. 46.9%, p = 0.028). CONCLUSION: We analyzed the impact of childhood-onset glomerular disease and distress during the transition period from pediatric to adult care. This study highlighted the significant impact of medications and exercise restrictions on patients' decisions regarding higher education. Future prospective studies will be needed to examine patients' distress in more detail and establish management approaches to enhance patient quality of life.

Prevalence and Incidence of Strabismus by Age Group in Japan: A Nationwide Population-Based Cohort Study.

PURPOSE: To investigate the prevalence and incidence of strabismus in the Japanese population by age group and to estimate the subtype proportions. DESIGN: A nationwide population-based cohort study. METHODS: This study investigated the number of cases with previous and new diagnoses of strabismus by age group between 2009 and 2020 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan, which includes almost all (≥95%) medical claims data. We calculated the strabismus prevalence and 1-year incidence in 2019 and analyzed the proportion of each strabismus subtype. RESULTS: The strabismus prevalence was 2.154% (2 709 207/125 708 000; 95% CI, 2.152%-2.157%). It showed a bimodal distribution, with a high proportion in school and old ages (especially ≥75 years). Exotropia, esotropia, and cyclovertical strabismus proportions were 67.3%, 26.0%, and 6.7%, respectively. Cyclovertical strabismus was uncommon in patients aged ≤18 years (1.4%) and more common (10.2%) in those aged >18 years. The strabismus incidence in 2019 was 321 per 100 000 person-years (403 093/125 708 000; 95% CI, 320-322). The annual incidence proportion of cyclovertical strabismus as opposed to whole strabismus subtypes in patients aged >18 years (13.1%) was higher than that in those aged ≤18 years (1.4%). CONCLUSIONS: This is the first nationwide population-based cohort study to demonstrate strabismus's overall prevalence and incidence. The high prevalence of cyclovertical strabismus in adults compared with children may suggest that cyclovertical strabismus is a primarily age-related strabismus. The high prevalence of exotropia may indicate a genetic difference between Japanese and other ethnicities.

Annual trends of ophthalmic surgeries in Japan's super-aged society, 2014-2020: a national claims database study.

This study aimed to analyze the trends and factors influencing the number of ophthalmic surgeries in Japan using the open data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan published by the Ministry of Health, Labour and Welfare. We calculated the number of cataract, glaucoma, and vitreoretinal surgeries, categorized by sex, age, and surgical type, for the fiscal years (FY) 2014 to 2020. The number of cataract surgeries remained stable at approximately 1.45 million cases from FY 2014 to 2018, increased to nearly 1.6 million cases in FY 2019, and decreased to 1.45 million cases in FY 2020. Among glaucoma surgeries, surgical treatments were increased 1.8 times over 7 years, from 33,000 to 60,000 cases. Laser treatment remained steady at around 55,000 cases from FY 2014 to 2017 and then increased to approximately 60,000 cases. The number of vitreoretinal surgeries was increased 1.2 times from FY 2014 to 2019, from 120,000 to 140,000, and decreased to 130,000 by FY 2020. Trends in ophthalmic surgeries over the past 7 years may be influenced by population aging, minimally invasive surgery, and the coronavirus disease pandemic. These findings have implications on surgical decision-making and resource allocation.

Three-dimensional optical coherence tomography to decide on reverse wire technique in bifurcation interventions.

A 79-year-old male with effort angina was admitted to receive optical coherence tomography (OCT)-guided percutaneous coronary intervention for restenosis of an everolimus-eluting stent implanted to the left anterior descending artery (LAD) eight years ago.

Therapeutic effects of faricimab on aflibercept-refractory age-related macular degeneration.

Though vascular endothelial growth factors (VEGF) and other proangiogenic factors, such as angiopoietins (Ang), may be involved in the development of neovascular age-related macular degeneration (nvAMD), only drugs that inhibit the VEGF family are available for the treatment. The newly approved anti-VEGF drug faricimab, which also inhibits Ang-2, is expected to be effective in patients with AMD refractory to conventional anti-VEGF drugs. Therefore, we prospectively investigated the efficacy of faricimab in the treatment of aflibercept-refractory nvAMD. Patients with nvAMD who had been treated with aflibercept in the last year and required bimonthly injections were recruited. 25 eyes showed persistent exudative changes immediately before the faricimab injection (baseline). In these 25 eyes, switching to faricimab did not change visual acuity or central retinal thickness 2 months after the injection; however, 56% of eyes showed reduction or complete absorption of fluid. Notably, 25% of the eyes that showed dry macula at month 2 had no fluid recurrence for up to 4 months. These results indicate that faricimab could benefit some patients with aflibercept-refractory nvAMD.

Three Pediatric Patients with Congenital Nephrogenic Diabetes Insipidus due to AVPR2 Nonsense Mutations and Different Clinical Manifestations: A Case Report.

Congenital nephrogenic diabetes insipidus (CNDI), a rare hereditary disorder, is characterized by the inability of the kidneys to concentrate urine in response to the antidiuretic hormone arginine vasopressin (AVP); as a result, large volumes of unconcentrated urine are excreted. In addition to the clinical manifestations of CNDI, such as dehydration and electrolyte disturbances (hypernatremia and hyperchloremia), developmental delay can result without prompt treatment. In approximately 90% of cases, CNDI is an X-linked disease caused by mutations in the arginine vasopressin receptor 2 (AVPR2) gene. In approximately 9% of cases, CNDI is an autosomal recessive disease caused by mutations in the water channel protein aquaporin 2 (AQP2), and 1% of cases are autosomal dominant. We report a case of CNDI caused by a novel AVPR2 nonsense mutation, c.520C>T (p.Q174X), and cases of siblings in another family who had a different AVPR2 nonsense mutation, c.852G>A (p.W284X). Both cases responded well to treatment with hydrochlorothiazide and spironolactone. If CNDI is suspected, especially in carriers and neonates, aggressive genetic testing and early treatment may alleviate growth disorders and prevent irreversible central nervous system disorders and developmental delay.

Neuronal Population Activity in Macaque Visual Cortices Dynamically Changes through Repeated Fixations in Active Free Viewing.

During free viewing, we move our eyes and fixate on objects to recognize the visual scene of our surroundings. To investigate the neural representation of objects in this process, we studied individual and population neuronal activity in three different visual regions of the brains of macaque monkeys (Macaca fuscata): the primary and secondary visual cortices (V1, V2) and the inferotemporal cortex (IT). We designed a task where the animal freely selected objects in a stimulus image to fixate on while we examined the relationship between spiking activity, the order of fixations, and the fixated objects. We found that activity changed across repeated fixations on the same object in all three recorded areas, with observed reductions in firing rates. Furthermore, the responses of individual neurons became sparser and more selective with individual objects. The population activity for individual objects also became distinct. These results suggest that visual neurons respond dynamically to repeated input stimuli through a smaller number of spikes, thereby allowing for discrimination between individual objects with smaller energy.

Widefield choroidal vasculature associated with future condition of subretinal fluid in central serous chorioretinopathy.

Purpose: To examine choroidal angiographic features in the posterior pole associated with resolution or persistency of subretinal fluid (SRF) in eyes with central serous chorioretinopathy (CSC). Design: Observational case series. Methods: Twenty-nine patients with treatment-naïve CSC were divided into two groups based on the presence or absence of SRF 3 months after the initial visit (month 3) without any treatment. Using enhanced depth imaging of widefield swept-source optical coherence tomography, the choroidal thickness (CT), vessel density (VD), and vessel diameter index (VDI) in the superotemporal and inferotemporal subfields on the temporal side of the 18-mm circle from the disc were measured at the initial visit. We calculated the vertical difference in CT and other choroidal angiographic parameters and evaluated their association with the SRF condition at 3 months. Results: The SRF-resolved and SRF-persistent groups included 10 and 19 patients, respectively. At the initial visit, sex, age, axial length, symptom duration, the logarithm of the minimum angle of resolution visual acuity, and foveal thickness were not significantly different between the two groups. The SRF status at month 3 was not associated with the vertical difference in CT and choroidal VD (P = .614, .065, respectively). However, the vertical difference in choroidal VDI was positively associated with the future presence of SRF (P = .017). Conclusions: Vertically asymmetric dilation of choroidal vessels in the posterior pole may be a vasculature feature associated with SRF from CSC and may be a good predictor of future SRF status.

Differences in the Analgesic Effect of Opioids on Pain in Cancer Patients With Spinal Metastases.

Background: Spinal metastasis pain includes both inflammatory and neuropathic pain, and opioids, which have only a µ-opioid receptor-stimulating effect, are generally less effective in neuropathic pain. However, no previous study has been conducted for the comparisons of the efficacy of opioids in treating spinal metastasis pain. Objective: To compare the efficacy of tapentadol and methadone with other opioids for back pain caused by a metastatic spinal tumor. Design: Retrospective cohort study. Setting/Subjects: A total of 274 patients were enrolled, who started a tapentadol extended-release tablet, methadone tablet, hydromorphone extended-release tablet, oxycodone extended-release tablet, or transdermal fentanyl patch for cancer pain due to spinal metastasis in Japan from January 1, 2013 to October 31, 2021. Measurements: The primary endpoint, the difference in the numerical rating scale (NRS) scores before and seven days after each opioid administration, was compared among the five groups. Results: In patients with numbness, a decrease of the NRS score on day seven compared with before starting each opioid was significantly higher in the tapentadol group than those in the hydromorphone, oxycodone, and fentanyl groups and comparable to that in the methadone group. In patients without numbness, no significant differences were observed in decreases of the NRS scores on day seven among the five groups. Conclusions: Tapentadol and methadone may be more effective than hydromorphone, oxycodone, and fentanyl for cancer pain due to spinal metastasis with numbness.

IgA nephropathy associated with Crohn's disease.

The relationship between IgA nephropathy (IgAN) and Crohn's disease was reported. IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure, and up to 50% of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis. However, specific and effective therapeutic strategies are still lacking. In this review, we discuss the possibility of the mechanism involved in IgAN associated with Crohn's disease based on the findings of basic and clinical studies. Although the etiology of IgAN associated with Crohn's disease is not permanent and various factors are thought to be involved, the stabilization of the disease condition of Crohn's disease is believed to help treat IgAN.

Extensive reduction in choroidal thickness after photodynamic therapy in eyes with central serous chorioretinopathy.

We examined the effect of reduced fluence (rf)-photodynamic therapy (PDT) of the macular area on the wide-field choroidal thickness in 20 eyes with central serous chorioretinopathy (CSC) and 20 age- and sex-matched control eyes. The choroidal thickness at the posterior pole was measured before and after rf-PDT, using a grid with inner and outer rings, each divided into superotemporal, inferotemporal, superonasal, and inferonasal quadrants, respectively, making up a total of nine subfields including the central 3 mm ring. Before treatment, all eyes showed wide-field choroidal thickening from the dilated vortex vein ampulla to the fovea, along the course of the vein. After rf-PDT of the macular area, the choroidal thickness significantly decreased, not only in the irradiated macular area but also outside the arcade vessels in all quadrants (p < 0.001 for all inner subfields; p = 0.035 and p = 0.024 for the outer superonasal and inferonasal subfields, respectively; p < 0.001 and p = 0.004 for the outer superotemporal and inferotemporal subfields, respectively). For control eyes, the choroidal thickness did not differ between the initial visit and follow-up 1.2 ± 0.7 months after the initial visit (p > 0.05 for all subfields). These findings provide new insights into the pathogenesis of CSC and explain the reasons for the effectiveness of rf-PDT for this condition.

Evaluation of Cytotoxicity of Hyaluronic Acid/Chitosan/Bacterial Cellulose-Based Membrane.

Novel wound dressing materials are required to non-cytotoxic with a viable cell ratio of above 92%. Herein, the cytotoxicity of hyaluronic acid/chitosan/bacterial cellulose-based (BC(CS/HA)) membranes are evaluated and compared to that of alginate/chitosan/bacterial cellulose-based (BC(CS/Alg)) membranes was investigated. Multilayer membranes with up to ten CS/HA or CS/Alg layers were prepared using the layer-by-layer (LBL) method. Scanning electron microscopy showed that the diameters of the fibers in the BC(CS/Alg) and BC(CS/HA) membranes were larger than those in a BC membrane. The cytotoxicity was analyzed using BALB-3T3 clone A31 cells (mouse fibroblasts, 1 × 104 cells/well). The BC(CS/HA)5 and BC(CS/HA)10 membranes exhibited high biocompatibility, with the cell viabilities of 94% and 87% at 5 d, respectively, compared to just 82% for the BC(CS/Alg)5 and BC(CS/Alg)10 membranes with same numbers of layers. These results suggested that BC(CS/HA)5 is a promising material for wound dressings.

One-Year Outcome of Patients with Chest Pain in the Rule-Out Group According to the 0-Hour/1-Hour Algorithm.

The European Society of Cardiology recommends the 0/1-hour algorithm for risk stratification of patients with suspected non-ST-elevation myocardial infarction as class I, level B; however, there are few reports on the long-term prognosis, resulting in a rule-out group. We aimed to determine whether implementation of the 0-hour/1-hour algorithm is safe and effective in emergency department (ED) patients with possible acute coronary syndrome (ACS) through a 1-year follow-up period. Our study analyzed the 1-year follow-up data from a prospective pre-post study of 1106 ED patients with possible ACS from 4 hospitals in Japan and Taiwan. Patients were 18 years or older. Accrual occurred for 1 year after implementing the 0-1-hour algorithm from November 2014 to December 2018. Overall, 520 patients were stratified into the rule-out group. Major advanced cardiovascular events (all-cause death, acute myocardial infarction [AMI], stroke, unstable angina, and revascularization) at 1-year were determined using data from health records and phone calls. The 0-1-hour algorithm stratified 47.0% of patients in the rule-out group. Over the 1-year follow-up period (follow-up rate = 86.9%), cardiovascular death and subsequent AMI did not occur in the rule-out group. Among the 27 patients who underwent the procedure within 30 days post-index visit, 3 patients (0.7%) had a stroke, 6 patients (1.3%) died of non-cardiovascular cause, and 30 patients (6.7%) underwent coronary revascularization within 1 year. At the 1-year follow-up, implementation of the 0-hour/1-hour algorithm was associated with very low rates of adverse event among patients in the rule-out group.