Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease and frequently recurs after kidney transplantation. Recurrent FSGS (rFSGS) is associated with poor allograft and patient outcomes. Bleselumab, a fully human immunoglobulin G4 anti-CD40 antagonistic monoclonal antibody, disrupts CD40-related processes in FSGS, potentially preventing rFSGS. METHODS: A phase 2a, randomized, multicenter, open-label study of adult recipients (aged ≥18 y) of a living or deceased donor kidney transplant with a history of biopsy-proven primary FSGS. The study assessed the efficacy of bleselumab combined with tacrolimus and corticosteroids as maintenance immunosuppression in the prevention of rFSGS >12 mo posttransplantation, versus standard of care (SOC) comprising tacrolimus, mycophenolate mofetil, and corticosteroids. All patients received basiliximab induction. The primary endpoint was rFSGS, defined as proteinuria (protein-creatinine ratio ≥3.0 g/g) with death, graft loss, or loss to follow-up imputed as rFSGS, through 3 mo posttransplant. RESULTS: Sixty-three patients were followed for 12 mo posttransplantation. Relative decrease in rFSGS occurrence through 3 mo with bleselumab versus SOC was 40.7% (95% confidence interval, -89.8 to 26.8; P = 0.37; absolute decrease 12.7% [95% confidence interval, -34.5 to 9.0]). Central-blinded biopsy review found relative (absolute) decreases in rFSGS of 10.9% (3.9%), 17.0% (6.2%), and 20.5% (7.5%) at 3, 6, and 12 mo posttransplant, respectively; these differences were not statistically significant. Adverse events were similar for both treatments. No deaths occurred during the study. CONCLUSIONS: In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed.

Assessment of Mucin-Associated Gene Expression Levels on the Ocular Surface.

The ocular surface is covered with a mucus layer. The mucin-associated genes expressed in the ocular surface cells include MUC1, MUC4, MUC5AC, and MUC16. Impression cytology is useful for collecting specimens from the ocular surface, their histological examination, and measuring mucin-associated gene expression levels. The expression of mucin-associated gene levels was assessed by quantitative polymerase chain reaction. The expression levels of these mucin-associated genes are potential biomarkers for ocular surface diseases, including dry eye disease.

Global Meta-Analysis of Organoid and Organ-on-Chip Research.

Organoids and cells in organ-on-chip platforms replicate higher-level anatomical, physiological, or pathological states of tissues and organs. These technologies are widely regarded by academia, the pharmacological industry and regulators as key biomedical developments. To map advances in this emerging field, a meta-analysis based on a quality-controlled text-mining algorithm is performed. The analysis covers titles, keywords, and abstracts of categorized academic publications in the literature and preprint databases published after 2010. The algorithm identifies and tracks 149 and 107 organs or organ substructures modeled as organoids and organ-on-chip, respectively, stem cell sources, as well as 130 diseases, and 16 groups of organisms other than human and mouse in which organoid/organ-on-chip technology is applied. The meta-analysis illustrates changing diversity and focus in organoid/organ-on-chip research and captures its geographical distribution. The downloadable dataset provided is a robust framework for researchers to interrogate with their own questions.

Rapid detection and diagnosis of herpetic keratitis using quantitative microfluidic polymerase chain reaction system for herpes simplex and varicella-zoster virus DNA: a case series.

BACKGROUND: A microfluidic real-time polymerase chain reaction (PCR) system can rapidly detect the viral DNA in specimens. Detection of herpes simplex virus (HSV) and varicella-zoster virus (VZV) DNA in tears is a useful diagnostic tool for herpes simplex virus keratitis (HSK) and herpes zoster ophthalmicus (HZO). METHODS: In total, 20 patients were included in this cross-sectional study. Among them, 8 patients with infectious epithelial HSK and 12 patients with HZO were included in HSK and HZO groups, respectively. In addition, 8 patients with non-herpetic keratitis and 4 healthy individuals without keratitis were included in the control group. Numbers of HSV and VZV DNA copies in tears of all patients and individuals were evaluated using a microfluidic real-time PCR system. Regarding HSV/VZV DNA test, tear specimens were collected by filter paper method using Schirmer's test paper, and subsequently, DNA was extracted from the filter paper using an automated nucleic acid extractor. Afterward, quantitative PCR was performed using a microfluidic real-time PCR system. RESULTS: From tear collection to real-time PCR result determination, the HSV/VZV DNA test took approximately 40 min. In the HSK group, the sensitivity and specificity of the HSV DNA tests were 100% each. The median value (range) of number of HSV DNA copies for affected eyes was 3.4 × 105 copies/µL (under a lower detection limit of 7.6). In the HZO group, the sensitivity and specificity of the VZV DNA tests were 100% each. The median value (range) of number of VZV DNA copies for affected eyes was 5.3 × 105 copies/µL (under a lower detection limit of 5.6 × 10-2). CONCLUSION: In conclusion, quantitative PCR for HSV and VZV DNA in tears using a microfluidic real-time PCR system is useful for diagnosing and monitoring HSK and HZO.

A Comparison of the Corneal Thickness Following Descemet's Stripping Automated Endothelial Keratoplasty and Descemet's Membrane Endothelial Keratoplasty.

PURPOSE: To compare the central corneal thickness before and after Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK), and to evaluate the recipient corneal thickness following DSAEK. METHODS: The corneal thickness was compared between two groups of eyes following DMEK and DSAEK, performed by a single surgeon between 2015 and 2017. We evaluated the recipient corneal thickness and central corneal thickness pre- and postoperatively at 1, 3, and 6 months using anterior segment optical coherence tomography. Recipient corneal thickness was defined as the corneal thickness without graft thickness. RESULTS: We included DMEK and DSAEK eyes (n = 26 each), which were similar in terms of their etiologies. Preoperatively, there was no significant difference in the central corneal thickness between the groups (DSAEK, median [interquartile range]: 721 [606.5 to 847.8] µm; and DMEK: 690 [618 to 722.3] µm; p = 0.30). Despite the tendency of the central corneal thickness to be significantly greater (p < .01) at 6 months following DSAEK (619.5 [607.8 to 661.3] µm) compared with that following DMEK (497.5 [475.8 to 525.3] µm), there was no significant difference at 6 months between the recipient corneal thickness following DSAEK (488.5 [443.8 to 515] µm) and central corneal thickness following DMEK (p = 0.54). CONCLUSIONS: DSAEK eyes display a similar tendency of stromal thinning as DMEK eyes.

Two cases of dupilumab-associated conjunctivitis with high expression of IL-8 mRNA on the ocular surface: a case report.

BACKGROUND: Dupilumab-induced ocular surface disease (DIOSD) has been reported in patients with atopic dermatitis treated with dupilumab, and has been recognized as an adverse event of dupilumab. Our objective was to describe two cases of DIOSD with alterations in eotaxin-2 and interleukin (IL)-8 messenger ribonucleic acid (mRNA) expression on the ocular surface. CASE PRESENTATION: In the ocular surface test, specimens were collected from the patient's ocular surface, and eotaxin-2 and IL-8 mRNA levels in the specimens were measured using real-time polymerase chain reaction. The clinical score of ocular surface findings was quantified using a 5-5-5 exacerbation grading scale for allergic conjunctivitis. The first case was of a 27-year-old man who developed DIOSD 3 months after starting treatment with dupilumab injection for atopic dermatitis. After 5 weeks of topical instillation of tacrolimus ophthalmic suspension, the clinical score of ocular surface findings improved and IL-8 and eotaxin-2 mRNA expression levels gradually decreased. The second patient was a 55-year-old man who developed DIOSD 11 weeks after the start of treatment with dupilumab injection for atopic dermatitis. Four weeks after starting ophthalmological treatment with tacrolimus ophthalmic suspension, his clinical scores on ocular surface findings improved and IL-8 mRNA expression levels decreased. The ocular surface test in this case revealed increased expression levels of IL-8 mRNA on the ocular surface at the onset of DIOSD, which decreased with the improvement of objective findings. CONCLUSIONS: DIOSD, which has been successfully treated with tacrolimus ophthalmic suspension, may involve IL-8-related inflammation in addition to type 2 inflammation.

Executive summary: Japanese guidelines for allergic conjunctival diseases 2021.

Allergic conjunctival disease (ACD) is an inflammatory disease of the conjunctiva that is mainly caused by type I hypersensitivity response to allergens and accompanied by subjective symptoms and other findings induced by antigens. ACD is classified as allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. This article summarizes the third edition of the Japanese guidelines for allergic conjunctival diseases published in 2021 and outlines the diagnosis, pathogenesis, and treatment of ACD. Since the introduction of immunosuppressive eye drops, the treatment strategies for severe ACDs have significantly changed. To clarify the recommended standard treatment protocols for ACD, the advantages and disadvantages of these treatments were assessed using clinical questions, with a focus on the use of steroids and immunosuppressive drugs. This knowledge will assist healthcare providers and patients in taking an active role in medical decision making.

Evaluation of Clinical Efficacy and Safety of Prolonged Treatment of Vernal and Atopic Keratoconjunctivitis Using Topical Tacrolimus.

PURPOSE: To evaluate the clinical improvement and safety of prolonged treatment of vernal (VKC) and atopic keratoconjunctivitis (AKC) using topical tacrolimus. METHODS: We included 36 eyes of 36 patients who had VKC and AKC and were treated with topical tacrolimus ophthalmic suspension (0.1%) for 24 months. The demographic data of the enrolled patients were collected from their medical files. Clinical scores, remission rates, number of relapses, concomitant use of steroids, and refractory indices were assessed. Clinical outcomes were determined using papillae-limbus-cornea (PLC) scores and 5-5-5 exacerbation grading scale scores. Clinical characteristics associated with the need for concomitant steroid eye drops administration were determined using logistic regression analysis. All patients were classified into 3 subgroups using cluster analysis. RESULTS: PLC scores recorded in the sixth month were significantly improved compared with those recorded at baseline. PLC scores recorded in the 18th, 21st, and 24th months were significantly improved compared with those recorded in the sixth month. The remission rates increased diachronically and significantly, reaching 92% in the 24th month. Logistic regression analysis showed that, for every 10-year increase in patient age, the risk for requiring concomitant administration of steroid eye drops was reduced by half (odds ratio, 0.53; 95% confidence interval, 0.29-0.96). Using cluster analysis, the patients were divided into 3 clusters: adolescent type, pediatric type, and adult type. CONCLUSIONS: Two years of treatment with topical tacrolimus ophthalmic suspension is an effective method for inducing and maintaining the stable stages of VKC and AKC.

Dysbiosis of Ocular Surface Microbiota in Patients With Refractive Allergic Conjunctival Diseases.

PURPOSE: We investigated ocular surface microbiota dysbiosis in patients with refractory allergic conjunctival diseases (ACDs; stratified into mild and severe groups) treated with topical tacrolimus. METHODS: Patients (n = 21) with refractory ACDs (including vernal and atopic keratoconjunctivitis) actively treated with topical tacrolimus and 6 healthy controls were evaluated. Based on clinical scores and expression of specific cytokines on the ocular surface, patients with ACDs were divided into mild and severe groups using cluster analysis. The microbial composition of tear specimens collected from patients with mild and severe ACD and control subjects using the Schirmer test paper was determined through next-generation 16S rRNA sequencing analysis. RESULTS: Compared with healthy controls, patients with ACDs exhibited significantly decreased ocular surface microbiota α-diversity. Ocular surface microbiota mainly comprised members of the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria in all groups. The relative abundance of ocular surface microbiota in patients with ACDs was increased for phylum Firmicutes and decreased for phylum Proteobacteria (compared with control subjects). The genera Blautia (vs. mild ACD group) and Morganella (vs. control group) exhibited significantly increased abundance only in the severe ACD group. CONCLUSIONS: The ocular surface microbiota in patients with severe ACD exhibited decreased diversity and exacerbation of dysbiosis compared with that in patients with mild ACD and control subjects. Patients with mild refractory ACD also exhibited decreased diversity of these microbiota. These alterations in microbiota indicated a change in the ocular surface of patients with refractory ACD (be it because of disease pathogenesis or topical immunomodulatory treatment).

Alterations in Mucin-Associated Gene Expression on the Ocular Surface in Active and Stable Stages of Atopic and Vernal Keratoconjunctivitis.

PURPOSE: To evaluate the presence of ocular surface mucin in patients with atopic and vernal keratoconjunctivitis (AKC/VKC), we investigated the mRNA expression levels of SAM-pointed domain-containing ETS-like factor (SPDEF) and mucin-related genes on the ocular surface. METHODS: Nineteen patients with AKC or VKC were divided into two groups based on the severity of the disease as determined by their clinical scores for AKC/VKC: the stable group and the active group. Impression cytology was performed in all patients using filter paper, and the expression levels of SPDEF, MUC1, MUC4, MUC5AC, MUC16, and eotaxin-2 mRNA were determined by real-time reverse-transcription polymerase chain reaction. RESULTS: The results showed that the expression levels of SPDEF and MUC5AC mRNA in the active group were significantly decreased compared with those in the stable group. Furthermore, clinical scores were significantly negatively correlated with the expression levels of SPDEF mRNA and significantly positively correlated with the expression levels of eotaxin-2, which is a biomarker for eosinophilic inflammation on the ocular surface. Cluster analysis classified the patients with AKC/VKC into three clusters, and the stable group was divided into two clusters according to the condition of ocular surface mucin. CONCLUSIONS: Ocular surface mucin in patients with AKC/VKC is altered in accordance with the clinical severity of the disease.

Importance of experienced thermal history: Effect of acclimation temperatures on the high-temperature tolerance and growth performance of juvenile marbled flounder.

Experienced thermal history often affects the temperature tolerance of fish; however, the effect of thermal history on growth performance is unclear. To contribute to effective stocking (release of hatchery-reared juveniles in the field), we conducted four laboratory experiments using juvenile marbled flounder (Pseudopleuronectes yokohamae, around 30 mm standard length and 0.3 g body wet weight) acclimated at 12 °C and 24 °C for approximately 2 weeks to investigate the effects of acclimation temperature on high-temperature tolerance, food consumption, and growth performance. The acclimation to 24 °C increased tolerance to high temperatures, as shown in a 24-h exposure experiment and in a temperature elevation experiment. The 50% lethal temperature (upper incipient lethal temperature) was estimated to be 25.9 °C and 29.0 °C for the 12 °C and 24 °C acclimation groups, respectively. In subsequent experiments, we tested the effects of high and low temperature acclimation on the food consumption and growth performance of two size groups of juveniles (28.7 ± 2.0 and 34.5 ± 2.9 mm, mean ± SD), that were reared at temperatures ranging from 14 °C to 23 °C. The optimal temperature for growth was 20 °C and did not differ between the acclimation temperatures or between the size groups. However, food consumption and growth performance were suppressed by acute temperature changes. Specifically, feeding and growth were lower in the 24 °C-acclimated group than in the 12 °C-acclimated group when exposed to 14 °C, which is close to the natural water temperature at release in the field. These results suggest that experienced thermal history does not affect the optimal temperature but can affect the growth performance of juveniles. To maximize the post-release growth of hatchery-reared juveniles, the influence of thermal history should be taken into consideration and acute thermal changes before release should be avoided.

IL-1α antibody inhibits dose-dependent exacerbation of eosinophilic inflammation by crude house-dust-mite antigen in the conjunctiva of an atopic keratoconjunctivitis mouse model.

PURPOSE: To investigate whether crude house-dust-mite antigen exacerbates eosinophilic inflammation in the conjunctival tissues of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. MATERIALS AND METHODS: An atopic keratoconjunctivitis mouse model was established by percutaneous sensitization and crude house-dust-mite antigen application in NC/Nga mice. To assess the dose-dependent response, conjunctival specimens from groups that were administered high- (High-HDM) or low-dose house-dust-mite antigen (Low-HDM) following percutaneous sensitization and the control without house-dust-mite antigen administration (control group) were evaluated. Histological examination and immunofluorescence staining were performed to determine eosinophil density and the number of IL-13-positive cells. Polymerase chain reaction array was used to obtain adaptive and innate immunity-related factor profile, and quantitative polymerase chain reaction was used to determine Il13, Il17a, Ccl11, and Ccl24 expression. Atopic keratoconjunctivitis model mice injected with anti-IL-1α antibody (IL-1α group) or vehicle (vehicle group) to the upper and lower eyelids before atopic keratoconjunctivitis development were evaluated. RESULTS: Eosinophil density in the conjunctiva increased with house-dust-mite antigen application in a dose-dependent manner. CD4, CXCL10, CCR6, C3, and IL-13 mRNA levels increased more than 5-fold in the conjunctiva of the High-HDM group animals compared to those in control animals. mRNA expression of Il13 and Ccl11 in the conjunctiva of the High-HDM group animals significantly increased compared with that in the Low-HDM and control group animals. Conversely, the eosinophil density and Il13 mRNA expression significantly decreased in the IL-1α group compared with those in the vehicle group. CONCLUSIONS: The house-dust-mite antigen increased eosinophilic infiltration and Il13 mRNA expression in the conjunctiva of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. These inflammatory alterations were partially alleviated by eyelid injection of anti-IL-1α antibody. These findings indicate that IL-1α-induced IL-13 production constitutes a major exacerbating factor for house-dust-mite antigen-induced atopic keratoconjunctivitis.

Immunohistochemical detection of citrullinated histone H3-positive neutrophils is useful for identifying active glomerular and interstitial lesions in antineutrophil cytoplasmic antibody-associated vasculitis.

AIMS: Activated neutrophils release neutrophil extracellular traps (NETs), resulting in a form of cell death called NETosis. NET formation is reportedly involved in the onset of systemic lupus erythematosus and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Citrullination of histones is a key step in NET formation, and the presence of citrullinated histones in neutrophils may be associated with disease induction and activity. The aim of this study was to investigate the relationship between infiltrating citrullinated histone H3 (H3Cit)-positive neutrophils and disease specificity and activity in various glomerulonephritides. METHODS AND RESULTS: We selected 32 kidney biopsies with glomerulonephritides, including AAV, lupus nephritis (LN), Henoch-Schönlein purpura nephritis (HSPN), and poststreptococcal acute glomerulonephritis (PSAGN). We examined the presence of H3Cit in infiltrating neutrophils and their association with necrotising, crescentic lesions and tubulointerstitial lesions. In PSAGN and HSPN, we found many myeloperoxidase (MPO)+ neutrophils in glomeruli; however, only a few were H3Cit+. In LN, MPO+ neutrophils mainly existed in the margins of glomerular tufts forming wire-loop lesions, and some of these were noted to be H3Cit+ neutrophils. In contrast, we found a significantly higher frequency of H3Cit+ neutrophils, despite the small number of MPO+ neutrophils, in microscopic polyangiitis in AAV. In particular, H3Cit+ neutrophils were prominent in necrotising lesions along the glomerular capillaries. Moreover, we also found H3Cit+ neutrophils in the interstitium, with marked peritubular capillaritis in AAV. CONCLUSIONS: H3Cit immunostaining is a useful tool for identifying activated neutrophils. The frequency of H3Cit+ neutrophils is not only a disease-specific marker but also a potential marker for disease activity in AAV.

Update on Recurrent Focal Segmental Glomerulosclerosis in Kidney Transplantation.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome characterized by nephrotic-range proteinuria with high incidence of progression to end-stage renal disease (ESRD). In primary FSGS, 40-60% of patients develop ESRD within 10-20 years. SUMMARY: Recurrence of FSGS after kidney transplantation is frequent and is associated with poor allograft survival. The risk factors for recurrent FSGS include onset of FSGS during childhood, rapid progression of primary FSGS to ESRD, history of recurrent FSGS in previous allograft, and diffuse mesangial hypercellularity or collapsing variant of FSGS in the native kidney. The early histological findings of recurrent FSGS consist of unremarkable glomerular changes on light microscopy but significant podocyte effacement on electron microscopy; the loss of foot processes with eventual dropout of podocytes leads to the development of segmental lesions in the glomerulus. Experimental and clinical data suggest the existence of circulating permeability factors, such as soluble urokinase-type plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor-1 (CLCF-1), CD40 axis, and apolipoprotein A-Ib (ApoA-Ib), in the pathogenesis of recurrent FSGS. These biomarkers including circulating permeability factors may facilitate earlier diagnosis of FSGS posttransplant and may guide in the development of novel therapies that may be more effective and improve long-term outcomes in kidney transplantation. Key Messages: Several studies have suggested the possible circulating permeability factors, such as suPAR, CLCF-1, CD40 axis, and ApoA-Ib, in the pathogenesis and disease progression of FSGS and recurrent FSGS. Further studies should be performed to elucidate the true essential biomarker(s) associated with the onset and progression of FSGS as well as recurrent FSGS.

Japanese guidelines for allergic conjunctival diseases 2020.

The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease 2019. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs.

Microincision vitrectomy surgery: experimental visualization and quantification of vitreous contamination.

BACKGROUND: To visualize and quantify vitreous contamination following microincision vitrectomy surgery (MIVS) using an experimental vitreous contamination model (EVCM). METHODS: Enucleated porcine eyes with fluoresbrite carboxylate microspheres applied to the conjunctival surface were used as a type 1 EVCM. Twenty-five- or 27-gauge (G) trocar cannulas were inserted through the conjunctiva and sclera, followed by the placing and opening of an infusion cannula. These procedures were monitored by an intraocular fiber catheter. Secondly, condensed microspheres were applied to an excised sheet of porcine sclera to serve as type 2 EVCM. Twenty-five- or 27-G trocar cannulas were inserted perpendicularly through the top of the sclera where the condensed microspheres were applied, an infusion cannula was inserted, 0.1 mL of saline solution injected through the infusion cannula, and samples collected. The fluorescence strength of samples was then measured using fluorophotometry. RESULTS: We visually detected fluorescent microspheres in 10/10 eyes with 25-G and 10/10 with 27-G MIVS. In the experimental quantification study, each MIVS gauge value was significantly higher than the control (P < 0.01). However, there was no significant difference between 25-G and 27-G MIVS. CONCLUSIONS: MIVS carries the risk of introducing contamination directly into the eyes when the trocar cannula is inserted and infusion cannula is opened, even when a 27-G MIVS is used. Our study has shown it is essential that the surgeon be aware of the possibility of introducing contamination from the conjunctiva at all times during MIVS.

Molecular Insights in Transmission of Cancer From an Organ Donor to Four Transplant Recipients.

Organ donors are systematically screened for infection, whereas screening for malignancy is less rigorous. The true incidence of donor-transmitted malignancies is unknown due to a lack of universal tumor testing in the posttransplant setting. Donor-transmitted malignancy may occur even when not suspected based on donor or recipient factors, including age and time to cancer diagnosis. We describe the detection of a gastrointestinal adenocarcinoma transmitted from a young donor to 4 transplant recipients. Multidimensional histopathologic and genomic profiling showed a CDH1 mutation and MET amplification, consistent with gastric origin. At the time of writing, one patient in this series remains alive and without evidence of cancer after prompt organ explant after cancer was reported in other recipients. Because identification of a donor-derived malignancy changes management, our recommendation is to routinely perform short tandem repeat testing (or a comparable assay) immediately upon diagnosis of cancer in any organ transplant recipient. Routine testing for a donor-origin cancer and centralized reporting of outcomes are necessary to establish a robust evidence base for the future development of clinical practice guidelines.

Assessment of mucin-related gene alterations following treatment with rebamipide ophthalmic suspension in Sjögren's syndrome-associated dry eyes.

Ocular surface mucins are thought to play vital roles in maintaining the homeostasis of the pre-ocular surface tear film. We performed ocular surface tests with impression cytology to assess the expression levels of mucin-related genes on the ocular surface in healthy eyes. In addition, we investigated alterations in mucin-related gene expression secondary to treatment with rebamipide ophthalmic suspension in patients with Sjögren's syndrome-associated dry eyes (SS-DE). Thirty-three healthy individuals (control group) and 13 patients from our hospital with SS-DE were enrolled. Impression cytology was performed using Schirmer's test paper for RNA sampling. The mRNA levels of SAM-pointed domain-containing ETS-like factor (SPDEF), mucin 5AC (MUC5AC), and mucin 16 (MUC16) were determined using a real-time reverse transcription-polymerase chain reaction. The ocular surface test was performed once for the control group, and at baseline as well as 2, 4, 8, and 12 weeks after treatment in the Sjögren's syndrome-associated dry eyes group. mRNA levels of SPDEF, MUC5AC, and MUC16 were not significantly different between the control and SS-DE groups before rebamipide ophthalmic suspension treatment. SPDEF mRNA levels in control subjects were significantly correlated with levels of MUC5AC. Among SS-DE patients, SPDEF mRNA levels were significantly increased at 2, 4, and 8 weeks after treatment compared with baseline levels. MUC16 mRNA levels were significantly decreased from baseline levels at 4 and 8 weeks post-treatment. Ocular surface test using impression cytology is a clinically useful tool for assessing mucous conditions on the ocular surface and can be used to determine the effects of instillation treatment with eye drops that affect mucin production at the ocular surface.