Development of a score model to predict long-term prognosis after community-onset pneumonia in older patients.

BACKGROUND AND OBJECTIVE: The identification of factors associated with long-term prognosis after community-onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model. METHODS: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected. RESULTS: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial-resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2. CONCLUSION: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered.

Efficacy and safety of lascufloxacin for nursing- and healthcare-associated pneumonia: A single-arm, open-label clinical trial.

BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.

Uveitis associated with immune checkpoint inhibitors or BRAF/MEK inhibitors in patients with malignant melanoma.

The objective of this study was to evaluate the frequency and characteristics of uveitis associated with immune checkpoint inhibitors (ICIs) or BRAF/MEK inhibitors (B/MIs) in patients with malignant melanoma. Patients diagnosed with malignant melanoma who underwent radical or local resection for malignant melanoma, regardless of clinical stage or postoperative adjuvant therapy, at Hiroshima University Hospital from January 2015 to June 2021 were enrolled in a retrospective cohort. The medical records of patients were collected to estimate the prevalence of ocular adverse events. The clinical characteristics of patients who developed uveitis were reviewed. Among 152 patients, 54 and 12 were treated with ICIs and B/MIs, respectively. Four patients developed uveitis; 1 in the ICI group and 3 in the B/MI group, while there were no uveitis cases among patients who did not receive ICIs or B/MIs. Three patients had Vogt-Koyanagi-Harada disease-like findings. Uveitis was improved by steroid therapy with or without oncological treatment interruption. Oncological treatment could be resumed. Patients with melanoma treated with ICIs or B/MIs had a higher risk of uveitis compared with those who did not receive them. Oncological treatment could be resumed in all patients who developed uveitis.

Head-to-head comparison of three chelates reveals DOTAGA promising for 225 Ac labeling of anti-FZD10 antibody OTSA101.

To select the most suitable chelate for 225 Ac radiolabeling of the anti-FZD10 antibody OTSA101, we directly compared three chelates: S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), 2,2',2″-(10-(1-carboxy-4-((4-isothiocyanatobenzyl)amino)-4-oxobutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (p-SCN-Bn-DOTAGA), and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-N-hydroxysuccinimide ester (DO3A-NHS-ester). We evaluated the binding affinity of the chelate-conjugated OTSA101 antibodies, as well as the labeling efficiency and stability in murine serum of 225 Ac-labeled OTSA101 as in vitro properties. The biodistribution, intratumoral distribution, absorbed doses, and therapeutic effects of the chelate-conjugated OTSA101 antibodies were assessed in the synovial sarcoma mouse model SYO-1. Of the three conjugates, DOTAGA conjugation had the smallest impact on the binding affinity (p < 0.01). The labeling efficiencies of DOTAGA-OTSA101 and DO3A-OTSA101 were 1.8-fold higher than that of DOTA-OTSA101 (p < 0.01). The stabilities were similar between 225 Ac-labeled DOTA-OTSA101, DOTAGA-OTSA101, and DO3A-OTSA101in serum at 37 and 4°C. The dosimetric analysis based on the biodistribution revealed significantly higher tumor-absorbed doses by 225 Ac-labeled DOTA-OTSA101 and DOTAGA-OTSA101 compared with 225 Ac-DO3A-OTSA101 (p < 0.05). 225 Ac-DOTAGA-OTSA101 exhibited the highest tumor-to-bone marrow ratio, with bone marrow being the dose-limiting tissue. The therapeutic and adverse effects were not significantly different between the three conjugates. Our findings indicate that among the three evaluated chelates, DOTAGA appears to be the most promising chelate to produce 225 Ac-labeled OTSA101 with high binding affinity and high radiochemical yields while providing high absorbed doses to tumors and limited absorbed doses to bone marrow.

Orbital fibrous capsule formation with abscess found 3 years after penetrating injury from a wooden chopstick.

Intraorbital wooden foreign bodies are sometimes difficult to diagnose because of nonspecific clinical manifestations and diversity of imaging characteristics. We herein report a case involving a 72-year-old woman with a history of trauma induced by a coated wooden chopstick 3 years prior. Two years after the incident, computed tomography (CT) scan revealed an intraorbital mass that was initially diagnosed as an intraorbital hemangioma. The patient presented with hyperemia, impairment of ocular movement, and optic neuropathy in her right eye. Magnetic resonance imaging (MRI) showed granulation tissue and an abscess around a foreign body, which was compressing the eyeball. Surgical extraction of the foreign body was performed, leading to resolution of symptoms. The depiction of wooden foreign bodies by imaging is complicated and affected by several factors, increasing the risk of delayed diagnosis. To avoid permanent sequelae, MRI might be helpful because its imaging capabilities are superior to those of CT.

The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis.

The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities between CD4+ T cells in the spinal cord and their counterparts in the small intestine. Furthermore, we unveil a synergistic relationship between the microbiota, particularly enriched with the tryptophan metabolism gene EC:1.13.11.11, and intestinal cells. This symbiotic collaboration results in the biosynthesis of kynurenic acid (KYNA), which modulates the recruitment and aggregation of GPR35-positive macrophages. Subsequently, a robust T helper 17 (Th17) immune response is activated, ultimately triggering the onset of EAE. Conversely, modulating the KYNA-mediated GPR35 signaling in Cx3cr1+ macrophages leads to a remarkable amelioration of EAE. These findings shed light on the crucial role of microbial-derived tryptophan metabolites in regulating immune responses within extraintestinal tissues.

D-amino Acids Ameliorate Experimental Colitis and Cholangitis by Inhibiting Growth of Proteobacteria: Potential Therapeutic Role in Inflammatory Bowel Disease.

BACKGROUND & AIMS: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression. METHODS: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model. RESULTS: The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains. CONCLUSIONS: D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.

Downregulation of chemokine receptor 9 facilitates CD4+CD8αα+ intraepithelial lymphocyte development.

Intestinal intraepithelial lymphocytes (IELs) reside in the gut epithelial layer, where they help in maintaining intestinal homeostasis. Peripheral CD4+ T cells can develop into CD4+CD8αα+ IELs upon arrival at the gut epithelium via the lamina propria (LP). Although this specific differentiation of T cells is well established, the mechanisms preventing it from occurring in the LP remain unclear. Here, we show that chemokine receptor 9 (CCR9) expression is low in epithelial CD4+CD8αα+ IELs, but CCR9 deficiency results in CD4+CD8αα+ over-differentiation in both the epithelium and the LP. Single-cell RNA sequencing shows an enriched precursor cell cluster for CD4+CD8αα+ IELs in Ccr9-/- mice. CD4+ T cells isolated from the epithelium of Ccr9-/- mice also display increased expression of Cbfß2, and the genomic occupancy modification of Cbfß2 expression reveals its important function in CD4+CD8αα+ differentiation. These results implicate a link between CCR9 downregulation and Cbfb2 splicing upregulation to enhance CD4+CD8αα+ IEL differentiation.

Two Cases of Atopic Dermatitis Patients With Scleral Perforation After Recurrent Scleritis Induced by Scleral-Sutured Posterior Chamber Intraocular Lens Implantation.

This report describes two cases of atopic dermatitis patients with scleral perforation after recurrent scleritis induced by suture exposure after scleral-sutured posterior chamber intraocular lens (PC-IOL) implantation. The first patient was a 41-year-old man (case 1), and the second was a 46-year-old man (case 2). Both had a history of atopic dermatitis and scleral-sutured intraocular lens (IOL) implantation. Scleritis recurred at the suture site after scleral-sutured IOL implantation in both patients. Although the scleritis was controlled by topical and/or systemic anti-inflammatory drugs, the sclera was perforated in both cases because of exposure of the suture knots (after seven years in case 1 and after 11 years in case 2). In case 1, the superotemporal IOL haptic was also exposed over the conjunctiva, and in case 2, the ciliary body was incarcerated in the scleral hole with deformation of the pupil superonasally. Considering that there were no signs of severe intraocular inflammation, surgical intervention was performed in both cases. In case 1, IOL repositioning was performed with oral prednisolone cover at a dosage of 15 mg/day, starting two weeks prior to the surgery. The steroid dosage was gradually tapered off until two months after the surgery. In case 2, the scleral patch underwent without IOL extraction, and no steroid or immunosuppression cover was administered. There was no recurrence of scleritis after surgery in either case, and visual acuity was preserved in both cases. The scleral perforation that occurred after scleral-sutured IOL implantation in these patients was thought to be the result of recurrent scleritis caused by suture exposure and chronic mechanical irritation by a suture knot. The scleritis subsided without removal of the IOL by moving the suture site of the IOL haptic and covering the suture with a scleral flap or patch graft.

IL-15-producing splenic B cells play pathogenic roles in the development of autoimmune hepatitis.

Background & Aims: B-cell depletion therapy with an anti-CD20 is an effective treatment strategy for patients with refractory autoimmune hepatitis (AIH). However, the mechanisms underlying B-cell action are unclear. Methods: Herein, we used the adeno-associated virus IL-12 model, in which hepatic IL-12 expression triggers liver injuries characteristic of AIH. We also analysed the clinical samples of patients with AIH. Results: B-cell depletion using anti-CD20 or splenectomy was found to improve liver functions and decrease the cytotoxic CD8+ T-cell (cytotoxic T lymphocyte [CTL]) count in the liver. This improvement was reversed by the adoptive transfer of splenic B cells derived from AAV IL-12-treated mice to splenectomised mice as it caused the hepatic CTL count to increase. RNA-sequencing analysis identified IL-15 as a key factor in pathogenic B cells, which promotes CTL expansion and subsequent migration to the liver via the CXCL9/CXCR3 axis. Indeed, IL-15 neutralisation ameliorated hepatitis by suppressing splenic and hepatic CTLs in vivo. The close distribution of B220+ B cells and CD8+ T cells in the spleen of AIH mice suggested mutual interactions. Mechanistically, IFNγ and CD40L/CD40 signalling were indispensable for the expression of IL-15 in B cells, and in vitro co-culture experiments revealed that splenic CD40L+CD8+ T cells promoted IL-15 production in B cells, which led to CTL expansion. In patients with AIH, high serum IL-15 concentration and IL-15+ B-cell counts, positively correlating with serum alanine aminotransferase levels, support translation and potential therapeutic targeting in human AIH. Conclusions: This investigation elucidated the roles of IL-15-producing splenic B cells that occur in concert with pathogenic CD8+ T cells during the development of AIH. Impact and Implications: IL-15-producing B cells were shown to exacerbate experimental AIH via cytotoxic T lymphocyte expansion. CD40L+CD8+ T cells promoted IL-15 expression in B cells, indicating the mutual interaction of both cells. High serum IL-15 concentrations, IL-15+ B-cell counts, and CD40L+IL-15Rα+CD8+ T-cell counts were confirmed in the blood of patients with AIH.

Faricimab for Diabetic Macular Edema in Patients Refractory to Ranibizumab or Aflibercept.

Background and Objectives: Faricimab is the first intravitreal injection of vascular endothelial growth factor-A and angiopoietin-2 bispecific monoclonal antibody. Here, we evaluate the functional and anatomical outcomes of faricimab treatment in patients with diabetic macular edema (DME) that was refractory to ranibizumab or aflibercept. Materials and Methods: We performed a retrospective, observational, consecutive-case study of patients who had DME that was refractory to treatment with ranibizumab or aflibercept and were treated with faricimab between July 2022 and January 2023 under a pro re nata regimen. All the participants were followed for ≥4 months after the initiation of faricimab. The primary outcome was a recurrence interval of ≥12 weeks, and the secondary outcomes were the changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: We analyzed 18 eyes of 18 patients. The mean recurrence interval of previous anti-VEGF injection was 5.8 ± 2.5 weeks, which was significantly extended to 10.8 ± 4.9 weeks (p = 0.0005) by the switch to faricimab. Eight patients (44.4%) achieved a recurrence interval of ≥12 weeks. A history of subtenon injection of triamcinolone acetonide (p = 0.0034) and the presence of disorganization of the retinal inner layers (p = 0.0326) were found to be significantly associated with a recurrence interval of <12 weeks. The mean BCVAs were 0.23 ± 0.28 logMAR and 0.19 ± 0.23 logMAR, and the mean CMTs were 473.8 ± 222.0 µm and 381.3 ± 219.4 µm at baseline and 4 months, respectively, but these changes were not statistically significant. None of the patients experienced serious adverse events. Conclusions: Faricimab may extend the treatment interval for patients with DME that is refractory to ranibizumab or aflibercept. DME previously treated with the subtenon injection of triamcinolone acetonide or associated with disorganization of the retinal inner layers may be less likely to be associated with a longer recurrence interval after switching to faricimab.

Incidence and pre/post-treatment risk factors of glaucoma in Vogt-Koyanagi-Harada disease.

PURPOSE: To investigate the incidence and pre/post-treatment risk factors of glaucoma in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: Data regarding secondary glaucoma were collected from the medical records of patients with VKH disease who were followed up at the uveitis service at Hiroshima University for more than 6 months. We examined the incidence of glaucoma and pre/post-treatment risk factors for glaucoma in patients with VKH disease. RESULTS: Forty-nine patients with VKH disease were included in this study (31 women and 18 men). The mean age at onset was 50.4 ± 15.4 years and the mean length of follow-up was 40.7 ± 25.5 months. The most common initial treatment was pulse intravenous corticosteroid therapy (89.8%). Fifteen patients developed secondary glaucoma during follow-up. The median time of glaucoma onset from VKH development was 4.5 months (range 0-44 months). Disc swelling type as a pre-treatment factor (p = 0.089, hazard ratio = 7.268), worse final best corrected visual acuity (p = 0.099, odds ratio = 1.545), and cataract progression (p = 0.076, odds ratio = 7.886) as post-treatment factors showed trends for glaucoma development. The patients who progressed to the chronic recurrent stage had more complications including glaucoma. CONCLUSION: Secondary glaucoma occurred in more than 30% of patients with VKH disease. The factors that showed a trend toward glaucoma development may reflect an association with delayed treatment initiation and prolonged ocular inflammation.

Assessing the Correlation Between Visual Acuity and Critical Fusion Frequency in Acute Optic Neuritis Before and After Steroid Therapy.

Background Optic nerve diseases include inflammatory optic nerve diseases such as vasculitis, metabolic optic neuropathy, ischemic optic neuropathy, and optic neuritis. In this study, patients with acute optic neuritis are classified with better and poor visual acuity based on visual acuity after one month of steroid pulse therapy. To determine prognosis, initial visual acuity and critical fusion frequency (CFF) values will be compared with those recorded one month after treatment and at the last visit. Methods Visual acuity and CFF were evaluated one month after the start of treatment in patients diagnosed with acute optic neuritis, and follow-up was available for at least three months at Hiroshima University Hospital. Results All patients received steroid pulse therapy as initial treatment. After one month of treatment, visual acuity and CFF at the last visit were significantly improved in the group with improved visual acuity compared to the group with impaired visual acuity. Conclusions Visual acuity at the initial visit did not affect treatment outcome, and final visual acuity and CFF after one month of treatment for acute optic neuritis were better in patients with better visual acuity. Therefore, visual acuity values one month after treatment initiation may affect treatment outcomes.

Corneal Endothelial Cell Loss after Ciliary Sulcus Placement of Ahmed Glaucoma Valve in Patients with Noninfectious Uveitic Glaucoma.

This study was performed to investigate the corneal endothelial cell density (CECD) reduction and treatment efficacy in patients with uveitic glaucoma treated by the ciliary sulcus placement of the Ahmed glaucoma valve (AGV). This retrospective study included 27 eyes of 27 patients with noninfectious uveitis who underwent the sulcus placement of the AGV. Each patient underwent a clinical assessment including a CECD measurement before surgery and at 3, 6, 9, and 12 months after surgery. The mean CECD was 2431.4 ± 367.5 cells/mm2 at preoperative baseline and 2360.5 ± 391.3 cells/mm2 at 12 months (p = 0.074), with a reduction rate of 2.73 ± 9.29%. The CECD reduction was significantly greater in patients with unilateral uveitis than that with bilateral uveitis. The rate of successful intraocular pressure control was 88% at 12 months, and the number of intraocular pressure-lowering medications was significantly reduced (p < 0.001). The current study showed that the implantation of an Ahmed tube into the ciliary sulcus provided stable intraocular pressure control in patients with glaucoma secondary to noninfectious uveitis, and CECD reduction was moderate in most patients at 12 months.

Localization and movement of Tregs in gastrointestinal tract: a systematic review.

BACKGROUND: The intestine is rich in food-derived and microbe-derived antigens. Regulatory T cells (Tregs) are an essential T-cell population that prevents systemic autoimmune diseases and inhibits inflammation by encountering antigens. Previously, it was reported that the functional loss of Tregs induces systemic inflammation, including inflammatory bowel disease and graft-versus-host disease in human and murine models. However, there is a dearth of information about how Tregs localize in different tissues and suppress effector cells. MAIN BODY: The development of Tregs and their molecular mechanism in the digestive tract have been elucidated earlier using murine genetic models, infectious models, and human samples. Tregs suppress immune and other nonimmune cells through direct effect and cytokine production. The recent development of in vivo imaging technology allows us to visualize how Tregs localize and move in the settings of inflammation and homeostasis. This is important because, according to a recent report, Treg characterization and function are regulated by their location. Tregs located in the proximal intestine and its draining lymph nodes induce tolerance against food antigens, and those located in the distal intestine suppress the inflammation induced by microbial antigens. Taken together, various Tregs are induced in a location-specific manner in the gastrointestinal tract and influence the homeostasis of the gut. CONCLUSION: In this review, we summarize how Tregs are induced in the digestive tract and the application of in vivo Treg imaging to elucidate immune homeostasis in the digestive tract.

Vitreoretinal Lymphoma in a Patient with Rheumatoid Arthritis with a History of Methotrexate-associated Lymphoproliferative Disorders.

Methotrexate (MTX) may induce immunosuppression and facilitate the onset of lymphoproliferative disorders (LPD). Most cases of MTX-LPD occur in patients with rheumatoid arthritis; the incidence is high in Japan. Vitreoretinal lymphoma (VRL) is a rare non-Hodgkin's lymphoma that can masquerade as steroid-resistant chronic uveitis, leading to fatal diagnostic delay. A 68-year-old woman exhibited optic disc swelling and retinal vasculitis causing floaters in the right eye. She was undergoing long-term MTX treatment for rheumatoid arthritis; she previously had been diagnosed with MTX-LPD, which regressed upon discontinuation of MTX. Steroid therapy was ineffective for optic disc swelling and retinal vasculitis; her best-corrected visual acuity decreased to 20/400. Vitreous biopsy revealed VRL, which was successfully treated with high-dose MTX-based systemic chemotherapy and intravitreal injections of MTX. To our knowledge, this is the first case report of VRL in a patient with an autoimmune disease who have a history of MTX-LPD.

Single-cell transcriptomics of human gut T cells identifies cytotoxic CD4+CD8A+ T cells related to mouse CD4 cytotoxic T cells.

Cytotoxic CD4+ T cells (CD4-CTLs) show the presence of cytolytic granules, which include the enzymes granzyme and perforin. The cells have a pathogenic and protective role in various diseases, including cancer, viral infection, and autoimmune disease. In mice, cytotoxic CD4+ T cells express CD8αα+ and reside in the intestine (mouse CD4+CTLs; mCD4-CTLs). The population of cytotoxic CD4+ T cells in the human intestine is currently unknown. Moreover, it is unclear how cytotoxic CD4 T cells change in patients with inflammatory bowel disease (IBD). Here, we aimed to identify cytotoxic CD4+ T cells in the human intestine and analyze the characteristics of the population in patients with IBD using single-cell RNA-seq (scRNA-seq). In CD4+ T cells, granzyme and perforin expression was high in humanMAIT (hMAIT) cells and hCD4+CD8A+ T cell cluster. Both CD4 and CD8A were expressed in hTreg, hMAIT, and hCD4+CD8A+ T cell clusters. Next we performed fast gene set enrichment analysis to identify cell populations that showed homology to mCD4CTLs. The analysis identified the hCD4+CD8A+ T cell cluster (hCTL-like population; hCD4-CTL) similar to mouse CTLs. The percentage of CD4+CD8A+ T cells among the total CD4+ T cells in the inflamed intestine of the patients with Crohn's disease was significantly reduced compared with that in the noninflamed intestine of the patients. In summary, we identified cytotoxic CD4+CD8+ T cells in the small intestine of humans. The integration of the mouse and human sc-RNA-seq data analysis highlight an approach to identify human cell populations related to mouse cell populations, which may help determine the functional properties of several human cell populations in mice.

DRAINAGE RETINOTOMY IS A RISK FACTOR FOR SURGICAL FAILURE AFTER PARS PLANA VITRECTOMY IN PATIENTS WITH PRIMARY UNCOMPLICATED RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To identify risk factors for recurrent retinal detachment after uncomplicated pars plana vitrectomy in patients with primary rhegmatogenous retinal detachment (RRD). METHODS: This single-center retrospective study included patients with primary RRD who underwent 23-gauge and 25-gauge pars plana vitrectomy at Hiroshima University Hospital between January 2016 and May 2021. All patients had ≥3 months of follow-up. Patients were excluded if they had preoperative proliferative vitreoretinopathy worse than Grade C1; giant retinal tears; tractional, exudative, or traumatic retinal detachment; or the use of perfluorocarbon liquid. Factors that influenced RRD treatment outcome and postoperative complications were evaluated. RESULTS: We analyzed 519 eyes of 509 patients who underwent pars plana vitrectomy for primary RRD. The primary and final success rates were 93.8% and 99.8%, respectively. Drainage retinotomy was a risk factor for surgical failure in both multivariate analysis (odds ratio 2.36, 95% confidence interval 1.08-5.15, P = 0.0314) and a propensity score-matching analysis (odds ratio 3.20, 95% confidence interval 1.14-9.04, P = 0.0277). Postoperative epiretinal membrane was associated with drainage retinotomy in multivariate analysis (odds ratio 1.93, 95% confidence interval 1.04-3.57, P = 0.0358). CONCLUSION: The avoidance of drainage retinotomy during small-gauge pars plana vitrectomy in patients with RRD may lead to better surgical success and less frequent epiretinal membrane formation.

Factors associated with low prevalence of Fuchs' uveitis syndrome in Japan.

Aim: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan. Methods: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively. Results: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit. Conclusions: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.