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Louis Antoine Bonnet, R Max Conway, Li-Anne Lim University of Sydney, Sydney, New South Wales, AustraliaCorrespondence: Louis Antoine Bonnet, 83 Western Line, RD1, Whanganui, 4571, New Zealand, Tel +64 0273947946, Email labonnet101@gmail.comPurpose: Familial adenomatous polyposis (FAP) has an almost 100% colorectal cancer risk warranting early detection in gene carriers. This study presents congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a highly specific phenotypical marker for FAP that can be used in screening at-risk individuals. Screening recommendations including morphological subclassification were formulated with supporting literature.Methods: A systematic literature review with a comprehensive search strategy was conducted using online databases. Manual searches of bibliographies and reference lists were also performed. Studies meeting inclusion criteria were graded with respect to their hierarchy of evidence and strength of recommendations according to the National Health and Medical Research Council (NHMRC) guidelines of Australia.Results: Almost 4500 participants were analysed across 28 included studies. The mean specificity of CHRPE as a phenotypical screening marker of FAP was 89% (standard deviation (SD); 14) with a mean sensitivity of 79% (SD; 8). The mean prevalence of CHRPE amongst FAP participants; at-risk participants were found to be 76% (SD; 24) and 37% (SD; 21) respectively. Bilateralism and multiple lesion number ≥ 3 are features highly specific for FAP.Conclusion: CHRPE was found to be a non-invasive, rapid, early phenotypical screening marker of FAP. Clinical recognition further allows increased gene analysis efficiency. The absence of CHRPE alone cannot exclude FAP. Our screening recommendations provide guidance to clinicians on evidence based CHRPE assessment. We would advocate inclusion of ocular examinations as part of a three-pronged approach, along with endoscopy and genetic testing, for efficient, timely FAP assessment in at-risk individuals.Keywords: genetic disease, congenital anomalies, retinal examination, screening

Li-Anne Lim,1 Michele C Madigan,1,2 R Max Conway1 1Save Sight Institute, Clinical Ophthalmology, The University of Sydney, Sydney, New South Wales, Australia; 2School of Optometry and Vision Science, The University of New South Wales, Sydney, New South Wales, Australia Abstract: The aim of this study was to review the available literature and identify recent advances in the classification and management of conjunctival melanoma (CM) for clinicians working in this field. English-based articles were identified using the MEDLINE® database, and additional cited works not detected in the initial search were also obtained. Articles were assessed according to the Australian National Health and Medical Research Council levels of evidence criteria. Review of the literature indicated that the current classification and management of CM is predominantly based upon primarily nonrandomized, single-institution, retrospective case series. While these studies provide the basis for the recent seventh edition of the tumor node metastasis staging classification, this classification more accurately reflects the current knowledge of prognostic factors for CM. Application of this revised classification system together with prospective trials will provide the opportunity for future consistent and comparable data collection across centers, and it will improve the quality of evidence upon which current classification and management of CM is based. Furthermore, the high risk of local recurrence with current standard management suggests that adjuvant therapy, particularly mitomycin C and/or brachytherapy, may improve outcomes regardless of clinical staging. Finally, the use of sentinel lymph node biopsy may have significant benefit for a select group of CM patients. Keywords: adjuvant therapy, melanoma in situ, mitomycin C, metastases

We are reporting a case of post-traumatic chronic osteomyelitis of the tibia with an open wound exposing an intra medullar nail implant for 13 years. The patient presented with fresh ipsilateral tibia plateau fracture. He was treated by removal of the implant, debridement and local placement of Gentamicin-impregnated PMMA beads according to guidelines of the two-stage Belfast technique . After five months of wound treatment, the exposed bone was covered by healthy granulation tissue and the patient was able to fully bear weight.

Printed electronics specifically printed strain sensor is emerging as a way forward for wearable application because of its flexibility and sustainability. Many efforts have been made to ensure the eco-friendliness of synthesized carbon-based ink to reduce the electronic waste. Carbon based fillers such as carbon nanotube have been widely used because of high electrical conductivity and excellent mechanical properties. However, the production of carbon-based fillers towards the environment still needs to be attended due to the involvement of hazardous fossil-based precursors that may harm the environment. Besides, the involvement of binders such as polyvinyl chloride (PVC), synthetic solvents and additives in the synthesis of the carbon-based conductive ink can impact serious health and environmental issues. Hence, the usage of natural precursors for green synthesis of carbon and the incorporation of biopolymer binder which are environmentally friendly and renewable need to be considered as an alternative to produce eco-friendly conductive ink. This review article presents the progress in green synthesis of the carbon-based filler, recyclability of the ink and material selection for the ink composition from biopolymer binder, solvent and additives that are eco-friendly. The performances of the carbon-based conductive ink are discussed in terms of the percolation theory and tunneling effect that form the conductive pathway in microscopic level in stretching and relaxing phenomena for printed strain sensor applications. The rheological properties of the printed ink such as viscosity, surface tension and adhesion properties to the chosen substrate also plays crucial role depending on the chosen printing technique of the printed strain sensor. The highlight of this paper is it also correlates the performance of the printed strain sensor in terms of its sensitivity using different eco-friendly carbon-based conductive ink with different printing techniques.

Ensuring the quality and functionality of printed circuit boards (PCBs) during manufacturing requires precise, automated visual inspection. Detecting integrated circuits (ICs) on PCBs poses a significant challenge due to diverse component sizes, types, and intricate board markings that complicate accurate object detection. This study addresses this challenge by proposing an enhanced EfficientNet-YOLOv4 algorithm tailored explicitly for the IC detection of PCBs. Numerous modifications are integrated into YOLOv4, with the replacement of its original backbone by a robust feature extraction network, EfficientNetv2-L, and meticulous hyperparameter tuning, including variations in loss functions, anchor size configurations, and other training techniques. The methodology further incorporates diverse data augmentation techniques to enrich the training dataset and enhance the model’s generalization ability. Extensive experiments conducted in this study showed the efficacy and robustness of the algorithm in handling complex PCB layouts and varying lighting conditions, outperforming existing PCB inspection models. The proposed method, EfficientNetv2-L-YOLOv4, achieved an impressive F1-score of 99.22 with an inference speed of 0.14 s per image. The proposed method also performed well compared to EfficientNet-B7-FasterRCNN and the original YOLOv4; it attains an F1-score of 98.96 and an inference speed of 0.10 s per image (with a batch size of 4). These results highlight the significance of effective feature extraction networks for object detection. Beyond addressing IC detection challenges, this algorithm advances the fields of computer vision and object detection. The implementation of EfficientNetv2-L-YOLOv4 in real manufacturing scenarios holds promise for automating component inspections and potentially eliminating the need for human intervention.

Intestinal Behçet disease (BD), associated with myelodysplastic syndrome (MDS), is often refractory to treatment. An 80-year-old man with trisomy 8 MDS (refractory anemia) developed intermittent fever. Despite investigations to exclude infectious disease, autoimmune disease, and malignancy as the cause of the fever, the etiology could not be determined. A colonoscopy revealed several shallow round ulcers in the ileocecal region and ascending colon, and the biopsy specimens showed nonspecific inflammation. Thereafter, the patient experienced abdominal pain and diarrhea. Other than an oral aphthous ulcer, the patient did not show symptoms to meet the diagnostic criteria for BD. The patient was diagnosed with intestinal ulcers (intestinal BD-like disease) with MDS and trisomy 8. After treatment failure with 5-aminosalicylic acid, steroid, colchicine, and azacitidine, cerebral infarction occurred. Eating was difficult because of the patient’s impaired consciousness; hence, total parenteral nutrition (TPN) was commenced. The fever and abdominal symptoms improved with bowel rest over approximately 1 month. Small amounts of food were orally administered to the patient following recovery from the after-effects of the cerebral infarction, but diarrhea and fever repeatedly flared up. Therefore, TPN was continued at home. The patient has not experienced any further intestinal BD symptoms for approximately 1 year with bowel rest. Nutritional therapy, including bowel rest, may be an effective treatment option for intestinal BD with MDS, and might be used as an induction therapy of remission or a supportive therapy for other treatments.

There is increased usage of flexible electronics recently in various applications such as wearable devices, flexible displays and sensors. Studies on the durability of conductive metal traces under cyclic mechanical loading is crucial since these conductors will be subjected to repeated bending. In this work, the mechanical and electrical behavior of silver printed conductors was tested using cyclic three-point bend test. The samples were flexible polymer thick film (PTF) silver (Ag) ink printed on a flexible polyethylene terephthalate (PET) substrate. The durability of this PTF Ag ink, which has a hyper-elastic binder and Ag flakes, was studied by performing cyclic bending tests. Four-point resistivity measurements and imaging of the sample both before and after bending were performed. A custom tester machine was used to apply strain to the circuit and measure the resistivity of the silver trace. The results of the bending test show that the silver trace does not undergo significant deformation and the change in resistance is less than 0.6% under both tensile and compressive tests. Fatigue tests were also performed by cyclic bending tests for three trials in which batches of 10,000 cycles were completed. The printed silver wire withstood 30,000 cycles of bend tests and produced only 2.64% change in resistance. This indicates that the printed wires are very durable even after 30,000 cycles of outer bending. Imaging was also conducted on these samples to study the effect of repeated bending on the morphology of the silver conductive trace. Although there was an increase in surface roughness before and after cyclic bending, there was no obvious deformation or delamination observed in the samples.

Objective Many tertiary students access social networking sites on a daily basis. With the increased usage of smartphones, accessing social networking sites while commuting, in schools, waiting for friends, television commercial breaks has become prevalent among tertiary students. What started as a lifestyle choice has now become a daily necessity. Such behavior among tertiary students raises an important question for educators: how does social media usage affect tertiary students’ sleep patterns and daytime sleepiness, their attention difficulties, especially in school? Thus, the aim of this study was to examine the relationships between tertiary students' self-reports of social media usage and daytime sleepiness. Design The design was a cross-sectional, quantitative research study. Methods We used a survey that contained questions concerning demographic data, daytime sleepiness, total sleep time and social media usage and a version of the Cleveland Adolescent Sleepiness Questionnaire, modified for use in tertiary students, were used for data collection ( n = 969). Results The most preferred tool for accessing social networking sites was smartphones and WhatsApp was the most accessed site. Results indicated that nocturnal technology use has a weak, negative impact on tertiary students’ quantity of sleep that may lead to daytime sleepiness. Local Singapore students spent significantly more time on social networking sites at night compared to foreign students. As a result, local students experienced more daytime sleepiness compared to foreign students. Conclusions Prolonged social media usage, especially in bed, has a negative impact on tertiary students’ daytime sleepiness. Since the technology is such an integral part of most tertiary students’ lives, it is important to understand the impact it has on their sleep and daytime sleepiness.

Abstract omitted due to copyright. [ABSTRACT FROM AUTHOR]

Although the fecal immunochemical test for hemoglobin (FIT) is a widely used screening test for colorectal cancer, it is not sensitive enough to detect advanced colorectal adenoma. To address this issue, we performed this study to investigate whether combining the FIT and fecal DNA testing of methylated somatostatin (SST) could improve diagnostic performance for advanced colorectal adenoma. We collected feces from 79 healthy subjects with negative results on colonoscopy, 43 patients with non-advanced colorectal adenoma, 117 patients with advanced colorectal adenoma, and 126 patients with colorectal cancer. After fecal DNA was incubated with methylation-sensitive restriction enzymes, SST methylation levels were measured by droplet digital PCR. Using logistic multivariate analysis, we established a prediction formula for detecting colorectal neoplasia and named it the FAMS (FIT, age, methylated SST) index. The diagnostic performance of a single use of FIT for advanced colorectal adenoma showed a sensitivity of 29.1% (34/117) and specificity of 89.3% (109/122). In contrast, the FAMS index showed a sensitivity of 56.4% (66/117) at a similar specificity point of 91.0% (111/122). Furthermore, even at the higher specificity point of 94.3% (115/122), the sensitivity was still higher than that of FIT, reaching 42.7% (50/117). As the FAMS index showed better diagnostic performance for advanced colorectal adenoma than a single use of FIT, the FAMS index could be a promising tool for detecting advanced colorectal adenoma., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: To describe the development of a web-based data collection tool to track the management and outcomes of uveal melanoma patients., Design: Description of a clinical registry., Participants: Patients with uveal melanoma., Methods: A panel of expert ocular oncologists, with input from other relevant specialties and individuals with expertise in registry development, collaborated to formulate a minimum data set to be collected to track patient centred, real-world outcomes in uveal melanoma. This data set was used to create the Fight Tumour Blindness! (FTB!) registry within Save Sight Registries., Results: The data set to be collected includes patient demographics and medical history, baseline visit, follow-up visit including tumour treatment, metastatic staging and surveillance, pathology, and patient-reported questionnaires. The inbuilt mechanisms to ensure efficient and complete data collection are described., Conclusions: The FTB! registry can be used to monitor outcomes for patients with uveal melanoma. It allows benchmarking of outcomes and comparisons between different clinics and countries., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Uveal melanoma (UM) is the principal type of intraocular malignancy in adults. Up to 50% of UM patients develop metastatic disease with very poor survival. There are few drugs available to treat the primary or metastatic UM. This study was undertaken to evaluate the anti-cancer effect of lapatinib and corroborate the potential of HER2 inhibition in the treatment of UM. The anti-UM activity of lapatinib was assessed using cell viability, cell death and cell cycle analysis, and its anti-metastatic actions were evaluated using would healing, invasion and colony formation assays. Immunoblotting was used to substantiate the actions of lapatinib on apoptotic and HER2 signaling. The anti-UM activity of lapatinib was further evaluated in a UM xenograft mouse model. Lapatinib decreased the viability of four UM cell lines (IC 50 : 3.67-6.53 µM). The antiproliferative activity of lapatinib was corroborated in three primary cell lines isolated from UM patient tumors. In UM cell lines, lapatinib promoted apoptosis and cell cycle arrest, and strongly inhibited cell migration, invasion and reproductive cell growth. Lapatinib dysregulated HER2-AKT/ERK/PI3K signalling leading to the altered expression of apoptotic factors and cell cycle mediators in UM cell lines. Importantly, lapatinib suppressed tumourigenesis in mice carrying UM cell xenografts. Together the present findings are consistent with the assertion that HER2 is a viable therapeutic target in UM. Lapatinib is active in primary and metastatic UM as a clinically approved HER2 inhibitor. The activity of lapatinib in UM patients could be evaluated in future clinical trials., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Although faecal DNA testing of Fusobacterium nucleatum ( Fn ) is expected to be useful for colorectal neoplasia detection, there is no standardized quantification method of Fn . We performed this study to establish a possible standardized method., Methods: In this study, 322 participants including 71 subjects without colorectal neoplasia (control group), 31 patients with non-advanced colorectal adenoma, 93 patients with advanced colorectal adenoma, and 127 patients with colorectal cancer were enrolled. Faecal Fn were quantified by droplet digital PCR (ddPCR) using two PCR primer-probe sets reported previously that are tentatively named Fn1 and Fn2. Fn1 has been used in ddPCR by us and Fn2 has been widely used in quantitative real-time PCR., Results: The Fn copy number using Fn1 was five times higher than that using Fn2, with a linear relationship shown between them. Receiver operating characteristic curve analysis showed the area under the curve (AUC) to be almost the same between Fn1 and Fn2 in discriminating between the control group and the colorectal cancer group (AUC = 0.81 and 0.81, respectively), and between the control/non-advanced colorectal adenoma group and the advanced colorectal adenoma/colorectal cancer group (AUC = 0.74 and 0.74, respectively)., Conclusions: As the diagnostic performance was quite similar between Fn1 and Fn2, ddPCR-based Fn testing using Fn1 and Fn2 could be a possible standardized method for a colorectal neoplasia screening test, considering that Fn levels quantified by Fn1 are about five times higher than those by Fn2.

Background: People living with HIV (PLWH) face greater risks of developing non-AIDS-defining cancers (NADCs) than the general population; however, the underlying mechanisms remain elusive. The tumor microenvironment plays a significant role in the carcinogenesis of colorectal cancer (CRC), an NADC. We studied this carcinogenesis in PLWH by determining inflammatory phenotypes and assessing PD-1/PD-L1 expression in premalignant CRC stages of colon adenomas in HIV-positive and HIV-negative patients., Methods: We obtained polyp specimens from 22 HIV-positive and 61 HIV-negative participants treated with colonoscopy and polyp excision. We analyzed adenomas from 33 HIV-positive and 99 HIV-negative patients by immunohistochemistry using anti-CD4, anti-CD8, anti-FoxP3, and anti-CD163 antibodies. Additionally, we analyzed the expression levels of immune checkpoint proteins. We also evaluated the correlation between cell infiltration and blood cell counts., Results: HIV-positive participants had fewer infiltrating CD4 + T cells than HIV-negative participants (p = 0.0016). However, no statistical differences were observed in infiltrating CD8 + and FoxP3 + T cells and CD163 + macrophages. Moreover, epithelial cells did not express PD-1 or PD-L1. Notably, CD4 + T cell infiltration correlated with nadir blood CD4 + T cell counts (p <  0.05) but not with current blood CD4 + T cell counts., Conclusion: Immune surveillance dysfunction owing to decreased CD4 + T cell infiltration in colon adenomas might be involved in colon carcinogenesis in HIV-positive individuals. Collectively, since the nadir blood CD4 + T cell count is strongly correlated with CD4 + T cell infiltration, it could facilitate efficient follow-up and enable treatment strategies for HIV-positive patients with colon adenomas., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: Uveal melanoma (UM) is the most common primary intraocular tumour in adults. UM has a poor overall prognosis and ~50% of patients progress to metastatic disease that has a median survival of 5.2 months. There are currently no proven pharmacological treatments for primary or metastatic UM. Research efforts continue to seek new agents. Many natural compounds have shown promising anti-UM activity in in-vitro and/or in-vivo studies. This review summarises the current findings for natural compounds that may be potentially useful in treating UM., Key Findings: Literature suggests that natural compounds, such as pristimerin, picropodophyllin, oridonin, zeaxanthin, withaferin and FR-900359, may be promising candidate compounds to treat UM. Most of these compounds have demonstrated satisfactory efficacy in inhibiting in-vitro UM cell growth., Summary: The evidence regarding the anti-UM effects of natural compounds is mainly limited to in-vitro studies; to date, only a small number of these agents have been evaluated in vivo. The molecular mechanisms underpinning the anti-UM properties of these compounds remain largely undefined. Further studies are required to evaluate the in-vivo anticancer activity, appropriate dosage regimen and safety of natural compounds that could be developed for use in UM., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Background: Prognostic cytological and molecular features of uveal melanoma have been well researched and are essential in management. Samples can be obtained in vivo through fine needle aspirate biopsy, vitrector cutter, forceps or post-enucleation for off-site testing. This study aims to examine cytological and chromosome microarray yields of these samples., Methods: A retrospective cohort analysis of 119 uveal melanoma biopsies submitted to our laboratory. Samples included those taken in vivo (n = 57) and post-enucleation (n = 62). Patient and tumour features were collected including age, sex, primary tumour location, basal diameter and tumour height. Prognostic outcomes measured include cell morphology, chromosomal status and immunohistochemistry., Results: Post-enucleation biopsies accounted for just over half of our samples (52%). Post-enucleation samples had a more successful genetic yield than in vivo biopsies (77% vs. 50%, p = 0.04) though there was no difference for cytological yields. There was no difference in cytological or microarray yields between instruments. The vitrector biopsy group had the smallest tumour thickness (5 mm vs. 10 mm [fine-needle aspirate biopsy], p = 0.003). There was a strong correlation between monosomy 3, BAP1 aberrancy and epithelioid cell type in post-enucleation samples (T b  = 0.742, p = 0.005). However, epithelioid morphology was not associated with either monosomy 3 (p = 0.07) or BAP1 aberrancy (p = 0.24) for in vivo biopsies., Conclusions: All three biopsy instruments provide similar cytological yields as post-enucleation sampling, although post-enucleation samples had a more successful chromosome microarray yield. Epithelioid cytomorphology alone is insufficient for prognostication in in vivo biopsies, immunohistochemistry would be a useful surrogate test., (© 2021 Royal Australian and New Zealand College of Ophthalmologists.)

Background/purpose: To report the largest case series to date of uveitis occurring in association with immunomodulatory therapy for malignant melanoma., Methods: A retrospective multicenter case review. Twenty-two patients with uveitis occurring in association with either immunotherapy or targeted immune therapy for malignant melanoma were identified., Results: Of 22 patients, 11 had anterior uveitis in isolation. The remainder showed a variety of clinical features including panuveitis, ocular hypotony, papillitis, cystoid macular edema, and melanoma-associated retinopathy. Most patients responded well to treatment., Conclusion: We report the largest case series to date of patients with uveitis secondary to drug treatment for malignant melanoma. These cases are likely to increase in number in the future as newer immunomodulatory therapies for cancers are developed and the indications for these drugs increase. A dilemma arises when patients respond well to these drugs but develop vision-threatening side effects., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Hepatitis A virus (HAV) causes transient acute infection, and little is known of viral shedding via the duodenum and into the intestinal environment, including the gut microbiome, from the period of infection until after the recovery of symptoms. Therefore, in this study, we aimed to comprehensively observe the amount of virus excreted into the intestinal tract, the changes in the intestinal microbiome, and the level of inflammation during the healing process. We used blood and stool specimens from patients with human immunodeficiency virus who were infected with HAV during the HAV outbreak in Japan in 2018. Moreover, we observed changes in fecal HAV RNA and quantified the plasma cytokine level and gut microbiome by 16S rRNA analysis from clinical onset to at least 6 months after healing. HAV was detected from clinical onset up to a period of more than 150 days. Immediately after infection, many pro-inflammatory cytokines were elicited, and some cytokines showed different behaviors. The intestinal microbiome changed significantly after infection (dysbiosis), and the dysbiosis continued for a long time after healing. These observations suggest that the immunocompromised state is associated with prolonged viral shedding into the intestinal tract and delayed recovery of the intestinal environment.

Background: USA300 produces Panton-Valentin leucocidin (PVL) and is known as a predominant community-associated methicillin-resistant Staphylococcus aureus (MRSA) strain in the United States, but it was extremely rare in Japan. We report here an outbreak of USA300 in people with HIV (PWH) in Tokyo, Japan., Methods: We analyzed the cases of PVL-MRSA infection between 2010 and 2020 and screened for nasal colonization of PVL-MRSA in PWH who visited an HIV/AIDS referral hospital from December 2019 to March 2020. Whole-genome sequencing-based single nucleotide polymorphism (SNP) analysis was performed on these isolates., Results: During the study period, a total of 21 PVL-MRSA infections in 14 patients were identified after 2014. The carriage prevalence was 4.3% (12/277) and PVL-MRSA carriers were more likely to have sexually transmitted infections (STIs) within a year compared with patients who had neither a history of PVL-MRSA infection nor colonization (33.3% [4/12] vs 10.1% [26/258]; P = .03). SNP analysis showed that all 26 isolates were ST8-SCCmecIVa-USA300. Twenty-four isolates were closely related (≤100 SNP differences) and had the nonsynonymous SNPs associated with carbohydrate metabolism and antimicrobial tolerance., Conclusions: An outbreak of USA300 has been occurring among PWH in Tokyo and a history of STI was a risk of colonization., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Aim: Liver dysfunction is sometimes observed in patients with coronavirus disease 2019 (COVID-19), but most studies are from China, and the frequency in other countries is unclear. In addition, previous studies suggested several mechanisms of liver damage, but precise or additional mechanisms are not clearly elucidated. Therefore, we examined COVID-19 patients to explore the proportion of patients with liver dysfunction and also the factors associated with liver dysfunction., Methods: We retrospectively examined 60 COVID-19 patients hospitalized at the Hospital affiliated with The Institute of Medical Science, The University of Tokyo (Tokyo, Japan). Patients who presented ≥40 U/L alanine aminotransferase (ALT) levels at least once during their hospitalization were defined as high-ALT patients, and the others as normal-ALT patients. The worst values of physical and laboratory findings during hospitalization for each patient were extracted for the analyses. Univariable and multivariable logistic regression models with bootstrap (for 1000 times) were carried out., Results: Among 60 patients, there were 31 (52%) high-ALT patients. The high-ALT patients were obese, and had significantly higher levels of D-dimer and fibrin/fibrinogen degradation products, as well as white blood cell count, and levels of C-reactive protein, ferritin, and fibrinogen. Multivariable analysis showed D-dimer and white blood cells as independent factors., Conclusions: Considering that higher D-dimer level and white blood cell count were independently associated with ALT elevation, liver dysfunction in COVID-19 patients might be induced by microvascular thrombosis in addition to systemic inflammation., (© 2020 The Japan Society of Hepatology.)

Purpose: To examine the safety and economic effect of using fibrin glue to reduce suturing of a donor patch graft and in conjunctival closure during aqueous shunt implantation., Study Design: Retrospective interventional case series of 150 patients from a single institution including historical controls from before the introduction of the change in technique. The surgery was performed by multiple glaucoma surgeons., Results: One hundred and fifty eyes of 150 patients were identified. The mean age was 54.3 ± 21.1 years. Previous surgery included: cataract extraction (34.7%), trabeculectomy (36%) and retinal surgery (15.3%). All operations were carried out by either a consultant (57%) or fellow (43%). A Baerveldt Glaucoma Implant (Advanced Medical Optics, Santa Ana, California, USA) was used in 149 eyes. Conventional surgery (CS) was performed for 91 eyes and fibrin glue (FG) was used for 59 eyes. Compared with conventional surgery (CS) in which the donor patch graft and conjunctiva were sutured, use of fibrin glue (FG) reduced the overall mean operating time by 11.2 min ± 6.4 min (P = 0.031), though much less for consultants (8.5 min ± 6.2 min) (P = 0.16) than fellows (32.9 min ± 7.2 min) (P < 0.0001). There were four cases of conjunctival dehiscence-three in the FG group and one in the CS group (P = 0.30). Only one patient required re-suturing in the FG group., Conclusions: The use of fibrin glue is safe and effective during aqueous shunt implantation. We have shown that the mean operating time can be reduced significantly with the use of fibrin glue which has significant implications for resource utilisation.

Background: Langerhans cell histiocytosis (LCH) is a rare disease primarily occurring in children, and commonly involves the bone and skin; gastrointestinal tract involvement is notably rare. The incidence and significance of gastrointestinal lesions in adult LCH are unclear; thus, we aimed to investigate adult Japanese cases of LCH and clarify the features of gastrointestinal involvement., Methods: We gathered clinical information on 43 Japanese cases of adult LCH and analyzed patient backgrounds, affected organs, features of the gastrointestinal lesions, and the clinical courses., Results: Thirteen patients underwent endoscopic examinations: an upper gastrointestinal endoscopy alone in 5, lower gastrointestinal endoscopy alone in 3, and both in 5 patients. A gastric lesion (one case), colonic lesion (one case), and both gastric and rectal lesions (one case) were detected. The three cases of gastrointestinal involvement also exhibited nongastrointestinal multisystem LCH lesions and showed no gastrointestinal symptoms or increased uptake on positron emission tomography. Endoscopy revealed small erosions without specific features; histological examinations were required for diagnosis. These three cases were treated with chemotherapy, comprising vinblastine/prednisolone, methotrexate, and daily 6-mercaptopurine, for 36 weeks; in two cases, the clinical condition remained stable for several years post-treatment. One case showed recurrence 1 year 7 months after treatment, and chemotherapy was re-administered. No case with single-system disease exhibited gastrointestinal involvement., Conclusions: Although gastrointestinal LCH lesions are rare, they were more common than expected in our cases of multisystem LCH. However, these lesions were relatively small and did not affect the patients' clinical courses.

Background: Hepatitis A virus (HAV) can be sexually transmitted. However, the level of HAV immunity among patients living with human immunodeficiency virus (HIV) in Japan is unknown. Determining the epidemiology of HAV infections among men who have sex with men (MSM) and who are living with HIV is essential for an HAV vaccination program. This study examined HAV immunity in patients living with HIV and applied the decision-tree analysis to explore the factors of immunoglobulin G (IgG)-hepatitis A (HA) antibodies in MSM living with HIV., Methods: We examined the presence of IgG-HA antibodies among patients living with HIV from January to December 2017 in The Hospital of The Institute of Medical Science, The University of Tokyo. We recorded each patient's age, sex, mode of HIV transmission, year of HIV diagnosis, HAV vaccine status, history of HAV infection, and history of other infectious diseases. A decision-tree algorithm was used to reveal the factors and profiles most relevant to the anti-HAV prevalence., Results: Overall, 378 MSM patients living with HIV were examined for IgG-HA antibodies. After excluding 24 patients who had received a HAV vaccine, the data of 354 MSM were analyzed (median age 45 years, interquartile range 39-51 years). Of the 354 patients, 60 (16.9%) were positive for IgG-HA antibodies. The HA positivity rate increased with patients' age, and age (> 63.5 years) was extracted as the most important variable by classification of the decision-tree algorithm., Conclusions: Our study, conducted just before the HAV outbreak among MSM in Tokyo, showed that age was the most relevant factor in anti-HAV prevalences. An extensive HAV vaccination program for MSM patients living with HIV is urgently needed, particularly for younger people., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Owing to similar routes of transmission, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection commonly occurs. Compared with patients infected with only HBV, coinfected patients develop persistent HBV infection followed by advanced liver diseases. However, the characteristics of HIV-infected patients who can achieve the clearance of HBV surface antigen (HBsAg) have not been clarified. In this study, we retrospectively examined patients coinfected with HBV and HIV and determined the host factors associated with HBsAg clearance.Among HIV-infected patients who visited our hospital between 1994 and 2017, we examined medical records of those who were seropositive for HBsAg at least once. Among them, patients who cleared HBsAg afterward were regarded as "cured," while those who remained HBsAg-seropositive until 2017 were "chronic."HBsAg seropositivity was found in 57 patients, and among them, 27 male patients were cured whereas 18 were chronic. The cured patients were significantly younger and had higher CD4 cell and platelet counts than the chronic patients. In addition, the cured patients had higher levels of transaminases after the detection of HBsAg. Multivariate analysis revealed age as an independent factor. Analyses of the patients infected with genotype A also showed that the cured patients had significantly higher CD4 cell counts.Considering that the CD4 cell and platelet counts were higher in the cured patients, immunological and liver functions were closely associated with HBsAg clearance. Higher levels of transaminases in the cured patients may also reflect the immunological function leading to HBsAg clearance.

Introduction: We have reported previously that fecal DNA testing of TWIST1 methylation in combination with the fecal immunochemical test for hemoglobin (FIT) (combination test) is useful for colorectal neoplasia screening. In this study, using larger sample sizes, we studied the clinical performance of the combination test for the detection of colorectal neoplasia and, especially, advanced colorectal adenoma., Methods: We performed a prospective study in which FIT, fecal DNA testing of TWIST1 methylation, and colonoscopy were performed on 372 patients with colorectal neoplasia and 71 subjects without colorectal neoplasia. We assessed the individual clinical performance of each of FIT and fecal DNA testing of TWIST1 methylation and of the combination test for the detection of colorectal neoplasia including advanced adenoma based on morphologic subtypes., Results: The FIT alone had a sensitivity of 7.5% (3/40) for nonadvanced adenoma, 32.3% (41/127) for advanced adenoma, and 93.7% (192/205) for colorectal cancer and a specificity of 87.3% (62/71). The combination test had a sensitivity of 35.0% (14/40) for nonadvanced adenoma, 68.5% (87/127) for advanced adenoma, and 95.6% (196/205) for colorectal cancer and a specificity of 80.3% (57/71). For morphological subtypes of advanced adenoma, the sensitivity of FIT was only 28.2% (20/71) for polypoid type and 16.1% (5/31) for nonpolypoid type, whereas the combination test increased the sensitivities to 64.8% (46/71) and 71.0% (22/31), respectively., Discussion: The combination of the fecal DNA test with FIT seemed to be useful to detect colorectal neoplasia and, especially, advanced adenoma of the nonpolypoid type.

Nivolumab, an antibody against human programmed cell death 1 (PD-1), enhances pre-existing immune responses and has antitumor activity. However, it may also cause undesirable immune-related adverse events (irAEs), such as anti-PD-1-related colitis. In addition, Nivolumab can worsen pre-existing autoimmune diseases. Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Its exact cause is unknown, but it may involve the dysregulation of the mucosal immune response. Thus, it is of great interest whether nivolumab can affect UC activity. This is the first report of a patient with epipharyngeal carcinoma and ulcerative colitis who was confirmed to have been safely treated with nivolumab based on autopsy findings.

Since 2017, hepatitis A virus (HAV) infection has been an epidemic among men who have sex with men (MSM) in Japan. We have come across 11 MSM patients with hepatitis A who were also infected with HIV. In 1999-2000, we came across 5 HIV-infected patients with hepatitis A. Since the conditions of current HIV-infected patients have changed owing to the recent progress in anti-HIV therapies, we compared clinical features of hepatitis A between patients in 2017-2018 and those in 1999-2000. By comparing the background characteristics of the patients, we found that the CD4/CD8 ratio was significantly higher in the 2017-2018 group. After the onset of hepatitis, peak levels of hepatic transaminases were found to be higher in the 2017-2018 group, suggesting severe hepatocellular damage. In contrast, neither the peak level of total bilirubin nor the nadir of prothrombin time was significantly different among the 2 groups. We also analyzed the HAV genome derived from some of the recently infected patients, and found that the HAV strains were almost the same among these patients; slight differences were observed from the previously identified strain. Thus, we concluded that the recovery of immunity by recent anti-HIV therapies may result in more severe hepatocellular damages and differences in clinical features.

Hepatitis C virus (HCV) coinfection is a strong risk factor for death of HIV-infected patients. Immune dysfunction affects the clinical course of acute hepatitis C (AHC). CD4/CD8 ratio is a biomarker of both persistent inflammation and immunosenescence in HIV-infected adults on effective antiretroviral therapy. A low CD4/CD8 ratio predicts immunosenescence and is associated with increased morbidity and mortality in both HIV-infected adults and elderly HIV-uninfected adults. Additionally, immunosenescence is associated with unresponsiveness to vaccine and could affect the immune reaction to pathogens during their primary infection. We retrospectively evaluated 12 AHC patients to assess the association between CD4/CD8 ratio and liver damage in AHC. We used the Spearman rank correlation test to assess the correlation. We found that CD4/CD8 ratio and peak alanine aminotransferase level (peak ALT) were positively correlated (r = 0.8322, p = 0.0013). The CD4 counts did not correlate with peak ALT (r = 0.5245, p = 0.0839). CD8 + T cells expansion for AHC did not affect these results, because the CD4/CD8 ratio before the onset of AHC and peak ALT positively correlate (n = 11; r = 0.7909, p = 0.0055) and there was no significant difference between CD4/CD8 ratios before and after the onset of AHC (n = 11; p = 0.9766). Immunosenescence may be negatively associated with the cellular immune response to acute HCV infection. We suggest that clinicians consider using CD4/CD8 ratio as a marker of immunosenescence in their management of patients with HIV infection and other complications., (Copyright © 2019. Published by Elsevier Ltd.)

We herein describe a case of Sweet's syndrome (SS) in a patient being treated for pulmonary toxoplasmosis complicated with myelodysplastic syndrome (MDS). The patient's SS developed after the pulmonary toxoplasmosis improved following treatment. We searched his cytokine profiles comprehensively using a bead-based immunoassay. The results showed no elevation of interleukin (IL)-2, interferon (IFN)-γ or IL-17A, and IL-6 was only observed to have increased at the onset of SS, suggesting that the pulmonary toxoplasmosis had been well controlled and that chronic inflammation may have been the cause of SS. Pulmonary toxoplasmosis is an extremely rare occurrence. The cytokine profile can help to clarify the pathological condition of SS and MDS complicated with severely invasive infectious diseases.

Objectives: To describe the 12-month outcomes of the Xen45 glaucoma stent., Methods: Non-comparative retrospective study of all cases who underwent Xen glaucoma surgery in April 2017 or earlier and completed 12 months of follow-up. The primary outcome measures were intraocular pressure (IOP) reduction and number of glaucoma medications at 12 months postoperatively. The secondary outcome measures were surgical complications and the success rate of surgery at 1 year. Success rate was defined according to the multiple IOP thresholds of 15 mmHg, 18 mmHg, and 21 mmHg with all requiring a drop of 20% and no additional glaucoma surgery. Revision or needling of the Xen conjunctival bleb was not considered to constitute a surgical failure., Results: Sixty-eight eyes were included in the study. Mean IOP dropped from 22.1 mmHg preoperatively to 14.8 mmHg at 12 months, a 33% drop (p < 0.0001). Mean number of glaucoma medications reduced from 2.9 preoperatively to 1.1 at 12 months (p < 0.0001). In total, 54.4% of cases were back on glaucoma medications by 12 months. Success rate varied from 32.4% when defined as IOP ≤ 15 mmHg and ≥ 6 mmHg and ≥ 20% reduction without medications to 70.6% when defined as IOP ≤ 21 mmHg and ≥ 6 mmHg and ≥ 20% reduction with or without medications. Thirty cases (44.1%) required bleb needling or surgical revision., Conclusions: The Xen45 is effective at reducing IOP and glaucoma medication use at 12 months postoperatively. Patients considering this procedure should be warned that by 12 months postoperatively there is a significant chance of requiring postoperative bleb intervention and glaucoma drops.

Racemose hemangioma is a rare, benign vascular malformation. In the episclera, it appears as dilated, tortuous blood vessels that pass from the fornix over the globe surface to the limbal area, without capillary architecture, and then loop backward into the fornix. Fluorescein angiogram reveals the vascular malformation with rapid flow and confirms the episcleral vessels to be large in caliber and with a curvilinear, twisted configuration. We report the case of a 22-year-old man with nonhemorrhagic, coincidental racemose hemangioma of the episclera., (Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

In our previous study on hepatocellular carcinoma (HCC) susceptibility genes in chronic hepatitis patients, we identified the MHC class I polypeptide-related sequence A (MICA). Natural killer cells eliminate various cancer cells, including HCC, by suppressing MICA shedding. Therefore, we investigated MICA sheddases and inhibitors for HCC immunotherapy. In this study, HepG2, PLC/PRF/5, and Hep3B were treated with the siRNA of a disintegrin and metalloproteases (ADAMs) and matrix metalloproteases to measure the concentration of soluble MICA (sMICA) by ELISA to detect the therapeutic target. Furthermore, an FDA-approved drug library was tested for the enzymatic inhibition of the targeted enzyme in an in vitro drug screening assay system. ADAM17 knockdown reduced sMICA levels and increased membrane-bound MICA (mMICA) expression in HCC cells. In an in vitro drug screen using an FDA-approved drug library, lomofungin, an antifungal drug, was found to strongly decrease ADAM17 activity. In HCC cells, mMICA expression was induced and sMICA production was inhibited in a dose-dependent manner. These effects were cancelled upon ADAM17 knockdown, suggesting that lomofungin targeted ADAM17. Analysis of lomofungin analogs revealed the responsible functional groups. In summary, we suggest lomofungin to be an attractive agent for the immunological control of HCC, via the suppression of ADAM17., (© 2018 UICC.)

Purpose: To describe the 3-year outcomes of combined cataract surgery and 360-degree endocyclophotocoagulation (ECP) in eyes with uncontrolled glaucoma and no previous glaucoma drainage surgery., Setting: University Hospital Eye Department, Exeter, United Kingdom., Design: Retrospective case series., Methods: The study included patients who had combined cataract surgery and 360-degree ECP. The primary outcome measure was intraocular pressure (IOP) reduction at 3 years postoperatively. Secondary outcome measures were the cumulative probability of failure of the surgical procedure at 3 years and the complications of surgery. Failure was defined by 1 of 2 criteria: (1) IOP higher than 21 mm Hg or lower than 6 mm Hg or not reduced by 20% from baseline at the 1-, 2-, or 3-year timepoint and (2) further laser or other surgery to reduce IOP at any timepoint., Results: The study comprised 84 patients (84 eyes). The mean IOP dropped from 18.7 mm Hg preoperatively to 13.3 mm Hg, 13.8 mm Hg, and 14.0 mm Hg at 1, 2, and 3 years postoperatively, respectively. By the 3-year timepoint, 58.3% had met the criteria for failure. The mean number of glaucoma medications was similar at 2.5 at 3 years postoperatively compared with 2.6 preoperatively. Nine patients (10.7%) had a significant complication, but all resolved without long-term sequelae., Conclusions: At 3 years postoperatively, combined cataract surgery and 360-degree ECP achieved a modest but significant drop in IOP in phakic patients with uncontrolled glaucoma and no previous drainage surgery. There was a low incidence of serious side effects but nearly 60% were classified as failures by 3 years., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)