Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

A comparison of keratoconus progression following collagen cross-linkage using standard or personalised keratometry thresholds.

OBJECTIVE: To define how estimates of keratoconus progression following collagen cross-linking (CXL) vary according to the parameter selected to measure corneal shape. MATERIALS AND METHODS: We estimated progression following CXL in 1677 eyes. We compared standard definitions of keratoconus progression based on published thresholds for Kmax, front K2, or back K2, or progression of any two of these three parameters, with the option of an increased threshold for Kmax values ≥ 55D. As corneal thickness reduces unpredictably after CXL, it was excluded from the principal analysis. We then repeated the analysis using novel adaptive estimates of progression for Kmax, front K2, or back K2, developed separately using 6463 paired readings from keratoconus eyes, with a variation of the Bland-Altman method to determine the 95% regression-based limits of agreement (LoA). We created Kaplan-Meier survival plots for both standard and adaptive thresholds. The primary outcome was progression five years after a baseline visit 9-15 months following CXL. RESULTS: Progression rates were 8% with a standard (≥ 1.5D) threshold for K2 or 6% with the static multi-parameter definition. With a ≥ 1D threshold for Kmax, the progression was significantly higher at 29%. With adaptive Kmax or K2, the progression rates were similar (20%) but less than with the adaptive multi-parameter method (22%). CONCLUSIONS: Estimates of keratoconus progression following CXL vary widely according to the reference criteria. Using adaptive thresholds (LoA) to define the repeatability of keratometry gives estimates for progression that are markedly higher than with the standard multi-parameter method.

Arabidopsis protein S-acyl transferases positively mediate BR signaling through S-acylation of BSK1.

Protein S-acyl transferases (PATs) catalyze S-acylation, a reversible post-translational modification critical for membrane association, trafficking, and stability of substrate proteins. Many plant proteins are potentially S-acylated but few have corresponding PATs identified. By using genomic editing, confocal imaging, pharmacological, genetic, and biochemical assays, we demonstrate that three Arabidopsis class C PATs positively regulate BR signaling through S-acylation of BRASSINOSTEROID-SIGNALING KINASE1 (BSK1). PAT19, PAT20, and PAT22 associate with the plasma membrane (PM) and the trans-Golgi network/early endosome (TGN/EE). Functional loss of all three genes results in a plethora of defects, indicative of reduced BR signaling and rescued by enhanced BR signaling. PAT19, PAT20, and PAT22 interact with BSK1 and are critical for the S-acylation of BSK1, and for BR signaling. The PM abundance of BSK1 was reduced by functional loss of PAT19, PAT20, and PAT22 whereas abolished by its S-acylation-deficient point mutations, suggesting a key role of S-acylation in its PM targeting. Finally, an active BR analog induces vacuolar trafficking and degradation of PAT19, PAT20, or PAT22, suggesting that the S-acylation of BSK1 by the three PATs serves as a negative feedback module in BR signaling.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Corneal astigmatic outcomes after femtosecond laser-assisted cataract surgery combined with surface penetrating arcuate keratotomies.

AIM: To evaluate corneal astigmatic outcomes of femtosecond laser-assisted arcuate keratotomies (FAKs) combined with femtosecond-laser assisted cataract surgery (FLACS) over 12mo follow-up. METHODS: Totally 145 patients with bilateral cataracts and no ocular co-morbidities were recruited to a single-centre, single-masked, prospective randomized controlled trial (RCT) comparing two monofocal hydrophobic acrylic intraocular lenses. Eyes with corneal astigmatism (CA) of >0.8 dioptres (D) received unpaired, unopened, surface penetrating FAKs at the time of FLACS. Visual acuity, subjective refraction and Scheimpflug tomography were recorded at 1, 6, and 12mo. Alpins vectoral analyses were performed. RESULTS: Fifty-one patients (61 eyes), mean age 68.2±9.6y [standard deviation (SD)], received FAKs. Sixty eyes were available for analysis, except at 12mo when 59 attended. There were no complications due to FAKs. Mean pre-operative CA was 1.13±0.20 D. There was a reduction of astigmatism at all post-operative visits (residual CA 1mo: 0.85±0.42 D, P=0.0001; 6mo: 0.86±0.35 D, P=0001; and 12mo: 0.90±0.39, P=0.0001). Alpins indices remained stable over 12mo. Overall, the cohort was under-corrected at all time points. At 12mo, 61% of eyes were within ±15 degrees of pre-operative astigmatic meridian. CONCLUSION: Unpaired unopened penetrating FAKs combined with on-axis phacoemulsification are safe but minimally effective. CA is largely under-corrected in this cohort using an existing unmodified nomogram. The effect of arcuate keratotomies on CA remained stable over 12mo.

Early detection of visual impairment in young children using a smartphone-based deep learning system.

Early detection of visual impairment is crucial but is frequently missed in young children, who are capable of only limited cooperation with standard vision tests. Although certain features of visually impaired children, such as facial appearance and ocular movements, can assist ophthalmic practice, applying these features to real-world screening remains challenging. Here, we present a mobile health (mHealth) system, the smartphone-based Apollo Infant Sight (AIS), which identifies visually impaired children with any of 16 ophthalmic disorders by recording and analyzing their gazing behaviors and facial features under visual stimuli. Videos from 3,652 children (≤48 months in age; 54.5% boys) were prospectively collected to develop and validate this system. For detecting visual impairment, AIS achieved an area under the receiver operating curve (AUC) of 0.940 in an internal validation set and an AUC of 0.843 in an external validation set collected in multiple ophthalmology clinics across China. In a further test of AIS for at-home implementation by untrained parents or caregivers using their smartphones, the system was able to adapt to different testing conditions and achieved an AUC of 0.859. This mHealth system has the potential to be used by healthcare professionals, parents and caregivers for identifying young children with visual impairment across a wide range of ophthalmic disorders.

Robotic Gastrectomy Versus Laparoscopic Gastrectomy for Gastric Cancer: A Multicenter Cohort Study of 5402 Patients in China.

OBJECTIVE: A large-scale multicenter retrospective cohort study was conducted to compare the short- and long-term outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. SUMMARY OF BACKGROUND DATA: RG is being increasingly used worldwide, but data from large-scale multicenter studies on the short- and long-term oncologic outcomes of RG versus LG are limited. The potential benefits of RG compared with LG for gastric cancer remain controversial. METHODS: Data from eligible patients who underwent RG or LG for gastric cancer of 11 experienced surgeons from 7 centers in China between March 2010 and October 2019 were collected. The RG group was matched 1:1 with the LG group by using propensity score matching. The primary outcome was postoperative complications. RESULTS: After propensity score matching, a well-balanced cohort of 3552 patients was included for further analysis. The occurrence of overall complications (12.6% vs 15.2%, P = 0.023) was lower in the RG group than in the LG group. RG was associated with less blood loss (126.8 vs 142.5 mL, P < 0.001) and more retrieved lymph nodes in total (32.5 vs 30.7, P < 0.001) and in suprapancreatic areas (13.3 vs 11.6, P < 0.001).The long-term oncological outcomes were comparable between the two groups. CONCLUSIONS: The results of this multicenter study demonstrate that RG is a safe and effective treatment for gastric cancer when performed by experienced surgeons, although longer operation time and higher costs are still concerns about RG. This study provides evidence suggesting that RG may represent an alternative surgical treatment to LG.

Chemical Constituents from Mushroom Suillus luteus (Agaricomycetes) and Their Bioactivities.

Wild edible mushrooms are a huge source to discover bioactive natural products. In this work, one new polyprenylphenol derivative, termed 2-geranylgeranyl-1,4-benzenediol 1-O-acetate (1), together with eight known compounds (2-9) were isolated from wild edible mushroom Suillus luteus. The structure of new compound was elucidated by high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance data. The structures of known compounds were elucidated by comparison of their nuclear magnetic resonance data with literature data. Compounds 1-7 exhibited significant 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity with IC50 values ranging from 1.55 ± 0.29 to 19.89 ± 2.28 µM. In addition, compounds 1-7 also showed tyrosinase inhibitory activity with IC50 values ranging from 21.97 ± 3.74 to 66.26 ± 6.85 µM.

Changes in axial length after vitrectomy for rhegmatogenous retinal detachment combined with choroidal detachment.

AIM: To report the postoperative axial length (AL) changes in rhegmatogenous retinal detachment combined with choroidal detachment (RRD-CD) patients. METHODS: The medical records of 97 consecutive patients from January 2015 to December 2018 were reviewed. Patients included were divided into RRD-CD and RRD only groups. All patients had received AL measurements before pars plana vitrectomy (PPV) and before silicone oil removal (SOR). The changes in AL of the two groups were compared. In addition, the potential factors related to AL changes were analyzed. RESULTS: AL elongation after PPV was 1.01 mm [interquartile range (IQR): 0.37, 1.79; P=0.02] in the RRD-CD group, which was greater than in RRD only group (0.15 mm, IQR: 0.04, 0.41; P<0.001). AL increased 0.06 mm per 1 mm Hg intraocular pressure changes in the RRD-CD group (R 2=0.11, P=0.03). RRD-CD patient was 11.42 times (3.54-46.80) more likely to experience post-PPV AL elongation of more than 1 mm [P<0.001, Akaike information criterion (AIC)=92.33, area under the curve (AUC)=0.839]. CONCLUSION: RRD-CD patients are very likely to have a postoperative elongation of AL. The primary intraoclular lens implantation using presurgery AL data may cause a significant refractive error in RRD-CD patients who underwent PPV.

Intelligent cataract surgery supervision and evaluation via deep learning.

PURPOSE: To assess the performance of a deep learning (DL) algorithm for evaluating and supervising cataract extraction using phacoemulsification with intraocular lens (IOL) implantation based on cataract surgery (CS) videos. MATERIALS AND METHODS: DeepSurgery was trained using 186 standard CS videos to recognize 12 CS steps and was validated in two datasets that contained 50 and 21 CS videos, respectively. A supervision test including 50 CS videos was used to assess the DeepSurgery guidance and alert function. In addition, a real-time test containing 54 CSs was used to compare the DeepSurgery grading performance to an expert panel and residents. RESULTS: DeepSurgery achieved stable performance for all 12 recognition steps, including the duration between two pairs of adjacent steps in internal validation with an ACC of 95.06% and external validations with ACCs of 88.77% and 88.34%. DeepSurgery also recognized the chronology of surgical steps and alerted surgeons to order of incorrect steps. Six main steps are automatically and simultaneously quantified during the evaluation process (centesimal system). In a real-time comparative test, the DeepSurgery step recognition performance was robust (ACC of 90.30%). In addition, DeepSurgery and an expert panel achieved comparable performance when assessing the surgical steps (kappa ranged from 0.58 to 0.77). CONCLUSIONS: DeepSurgery represents a potential approach to provide a real-time supervision and an objective surgical evaluation system for routine CS and to improve surgical outcomes.

Morpho-Molecular Evidence Reveals Four Novel Species of Gymnopus (Agaricales, Omphalotaceae) from China.

Nine collections of gymnopoid fungi were studied based on morpho-molecular characteristics. The macromorphology was made according to the photograph of fresh basidiomata and field notes, while the micromorphology was examined via an optical microscope. Simultaneously, the phylogenetic analyses were performed by maximum likelihood and Bayesian inference methods based on a combined dataset of nrITS1-nr5.8S-nrITS2-nrLSU sequences. Integrated analysis of these results was therefore, G. efibulatus belonging to sect. Androsacei, G. iodes and G. sinopolyphyllus belonging to sect. Impudicae and G. strigosipes belonging to sect. Levipedes are proposed as new to science. The detailed descriptions, colour photos of basidiomata and line-drawings of microscopic structures are provided. The comparisons with closely related species and a key to known species of Gymnopus s. str. reported with morpho-molecular evidence in China is also given.

Personalized Model to Predict Keratoconus Progression From Demographic, Topographic, and Genetic Data.

PURPOSE: To generate a prognostic model to predict keratoconus progression to corneal crosslinking (CXL). DESIGN: Retrospective cohort study. METHODS: We recruited 5025 patients (9341 eyes) with early keratoconus between January 2011 and November 2020. Genetic data from 926 patients were available. We investigated both keratometry or CXL as end points for progression and used the Royston-Parmar method on the proportional hazards scale to generate a prognostic model. We calculated hazard ratios (HRs) for each significant covariate, with explained variation and discrimination, and performed internal-external cross validation by geographic regions. RESULTS: After exclusions, model fitting comprised 8701 eyes, of which 3232 underwent CXL. For early keratoconus, CXL provided a more robust prognostic model than keratometric progression. The final model explained 33% of the variation in time to event: age HR (95% CI) 0.9 (0.90-0.91), maximum anterior keratometry 1.08 (1.07-1.09), and minimum corneal thickness 0.95 (0.93-0.96) as significant covariates. Single-nucleotide polymorphisms (SNPs) associated with keratoconus (n=28) did not significantly contribute to the model. The predicted time-to-event curves closely followed the observed curves during internal-external validation. Differences in discrimination between geographic regions was low, suggesting the model maintained its predictive ability. CONCLUSIONS: A prognostic model to predict keratoconus progression could aid patient empowerment, triage, and service provision. Age at presentation is the most significant predictor of progression risk. Candidate SNPs associated with keratoconus do not contribute to progression risk.

Emending Gymnopus sect. Gymnopus (Agaricales, Omphalotaceae) by including two new species from southern China.

Based on phylogenetic analyses, some newly studied Chinese mushroom specimens were found to represent two distinct species within the genus Gymnopus. Along with G.fusipes (sect. Gymnopus) they form a distinct clade with high support, although their macromorphological characters seem to be closer to members of Gymnopus sect. Levipedes or sect. Vestipedes (Collybiopsis). When examined in detail, their micromorphological characters, especially the type of pileipellis, support them as new members of G. sect. Gymnopus. Therefore, two new species, G.omphalinoides and G.schizophyllus, and the emended circumscription of sect. Gymnopus are proposed in this paper. Detailed morphological descriptions, colour photos, illustrations of the two new species, morphological comparisons with similar taxa and the molecular-phylogenetic analyses of the combined nrITS and nrLSU data are presented. A key to the known species of G. sect. Gymnopus is also presented.

Morphological and Phylogenetic Evidence Reveal Five New Telamonioid Species of Cortinarius (Agaricales) from East Asia.

Five new Cortinarius species, C. neobalaustinus, C. pseudocamphoratus, C. subnymphatus, C. wuliangshanensis and C. yanjiensis spp. nov., are proposed based on a combination of morphological and molecular evidence. Cortinarius neobalaustinus is characterized by a very weakly hygrophanous and yellowish-brown to brown pileus and small and weakly verrucose basidiospores. Cortinarius pseudocamphoratus can be characterized by a viscid pileus, a strongly unpleasant smell, amygdaloid to somewhat ellipsoid basidiospores and lageniform to subfusiform cheilocystidia. Cortinarius subnymphatus is identified by a strongly hygrophanous pileus that is reddish-brown with a black-brown umbo, a yellowish universal veil and ellipsoid to subamygdaloid basidiospores. Cortinarius wuliangshanensis is characterized by a moderately to strongly hygrophanous, translucently striated and yellowish to reddish-brown pileus and rather weakly and moderately verrucose basidiospores. Cortinarius yanjiensis is distinguished by a weakly to moderately hygrophanous and yellowish to brown pileus and moderately to rather strongly verrucose basidiospores. The phylogenetic analyses were performed with maximum likelihood and Bayesian inference methods based on the data set of nuc rDNA ITS1-5.8S-ITS2 (ITS), D1-D2 domains of nuc 28S rDNA (28S) and RNA polymerase II second largest subunit (rpb2), and the results show that C. neobalaustinus, C. wulianghsanensis and C. yanjiensis cluster in sect. Illumini, C. pseudocamporatus belongs to sect. Camphorati and C. subnymphatus belongs to sect. Laeti. In addition, a study of basidiospores under field emission scanning electron microscopy (FESEM) was conducted. An identification key for the five new species and related species from China is also provided.

Ubiquitination/de-ubiquitination: A promising therapeutic target for PTEN reactivation in cancer.

Tumor suppressor activation or reactivation has long been a sought-after, yet elusive, therapeutic strategy for human cancer. Phosphatase and tensin homolog (PTEN) is one of the most frequently mutated tumor suppressor genes that regulate many biological processes, including proliferation, survival, cellular architecture, motility, energy metabolism, and genomic stability. As a dose-dependent tumor suppressor, subtle reductions in PTEN protein levels and activity will alter the gene-expression profiles involved in tumor progression, laying the foundation for PTEN reactivation in cancer treatment. However, treatment strategies that manipulate and/or replace PTEN activity to successfully block and reverse the destructive progression of cancer are not yet available. Ubiquitination/de-ubiquitination is one of the major regulatory mechanisms of PTEN by influencing its stability, subcellular localization, and activity. Recent discoveries, including new ubiquitination sites, E3 ubiquitin ligases, de-ubiquitinases of PTEN, and participation of accessory and adaptor proteins, have revealed new modes of PTEN ubiquitination regulation. Furthermore, either pharmaceutical or gene-targeted inhibition of E3 ligase-mediated ubiquitination of PTEN potently releases PTEN's anticancer activity and suppresses tumorigenesis. These findings shed light on therapeutic strategies for reactivating PTEN in cancer that target ubiquitination/de-ubiquitination. Therefore, a comprehensive understanding of the ubiquitination/de-ubiquitination regulation of PTEN could help improve clinical conceptualization and treatment of cancer. This review aimed to summarize and discuss recent discoveries on PTEN ubiquitination and de-ubiquitination, with the goal of providing a systematic summary in the field and promoting clinical transformation of targeting ubiquitination for PTEN reactivation in the treatment of cancer.

Fungal diversity notes 1512-1610: taxonomic and phylogenetic contributions on genera and species of fungal taxa.

This article is the 14th in the Fungal Diversity Notes series, wherein we report 98 taxa distributed in two phyla, seven classes, 26 orders and 50 families which are described and illustrated. Taxa in this study were collected from Australia, Brazil, Burkina Faso, Chile, China, Cyprus, Egypt, France, French Guiana, India, Indonesia, Italy, Laos, Mexico, Russia, Sri Lanka, Thailand, and Vietnam. There are 59 new taxa, 39 new hosts and new geographical distributions with one new combination. The 59 new species comprise Angustimassarina kunmingense, Asterina lopi, Asterina brigadeirensis, Bartalinia bidenticola, Bartalinia caryotae, Buellia pruinocalcarea, Coltricia insularis, Colletotrichum flexuosum, Colletotrichum thasutense, Coniochaeta caraganae, Coniothyrium yuccicola, Dematipyriforma aquatic, Dematipyriforma globispora, Dematipyriforma nilotica, Distoseptispora bambusicola, Fulvifomes jawadhuvensis, Fulvifomes malaiyanurensis, Fulvifomes thiruvannamalaiensis, Fusarium purpurea, Gerronema atrovirens, Gerronema flavum, Gerronema keralense, Gerronema kuruvense, Grammothele taiwanensis, Hongkongmyces changchunensis, Hypoxylon inaequale, Kirschsteiniothelia acutisporum, Kirschsteiniothelia crustaceum, Kirschsteiniothelia extensum, Kirschsteiniothelia septemseptatum, Kirschsteiniothelia spatiosum, Lecanora immersocalcarea, Lepiota subthailandica, Lindgomyces guizhouensis, Marthe asmius pallidoaurantiacus, Marasmius tangerinus, Neovaginatispora mangiferae, Pararamichloridium aquisubtropicum, Pestalotiopsis piraubensis, Phacidium chinaum, Phaeoisaria goiasensis, Phaeoseptum thailandicum, Pleurothecium aquisubtropicum, Pseudocercospora vernoniae, Pyrenophora verruculosa, Rhachomyces cruralis, Rhachomyces hyperommae, Rhachomyces magrinii, Rhachomyces platyprosophi, Rhizomarasmius cunninghamietorum, Skeletocutis cangshanensis, Skeletocutis subchrysella, Sporisorium anadelphiae-leptocomae, Tetraploa dashaoensis, Tomentella exiguelata, Tomentella fuscoaraneosa, Tricholomopsis lechatii, Vaginatispora flavispora and Wetmoreana blastidiocalcarea. The new combination is Torula sundara. The 39 new records on hosts and geographical distribution comprise Apiospora guiyangensis, Aplosporella artocarpi, Ascochyta medicaginicola, Astrocystis bambusicola, Athelia rolfsii, Bambusicola bambusae, Bipolaris luttrellii, Botryosphaeria dothidea, Chlorophyllum squamulosum, Colletotrichum aeschynomenes, Colletotrichum pandanicola, Coprinopsis cinerea, Corylicola italica, Curvularia alcornii, Curvularia senegalensis, Diaporthe foeniculina, Diaporthe longicolla, Diaporthe phaseolorum, Diatrypella quercina, Fusarium brachygibbosum, Helicoma aquaticum, Lepiota metulispora, Lepiota pongduadensis, Lepiota subvenenata, Melanconiella meridionalis, Monotosporella erecta, Nodulosphaeria digitalis, Palmiascoma gregariascomum, Periconia byssoides, Periconia cortaderiae, Pleopunctum ellipsoideum, Psilocybe keralensis, Scedosporium apiospermum, Scedosporium dehoogii, Scedosporium marina, Spegazzinia deightonii, Torula fici, Wiesneriomyces laurinus and Xylaria venosula. All these taxa are supported by morphological and multigene phylogenetic analyses. This article allows the researchers to publish fungal collections which are important for future studies. An updated, accurate and timely report of fungus-host and fungus-geography is important. We also provide an updated list of fungal taxa published in the previous fungal diversity notes. In this list, erroneous taxa and synonyms are marked and corrected accordingly.

Bacterial keratitis: identifying the areas of clinical uncertainty.

Bacterial keratitis is a common corneal infection that is treated with topical antimicrobials. By the time of presentation there may already be severe visual loss from corneal ulceration and opacity, which may persist despite treatment. There are significant differences in the associated risk factors and the bacterial isolates between high income and low- or middle-income countries, so that general management guidelines may not be appropriate. Although the diagnosis of bacterial keratitis may seem intuitive there are multiple uncertainties about the criteria that are used, which impacts the interpretation of investigations and recruitment to clinical studies. Importantly, the concept that bacterial keratitis can only be confirmed by culture ignores the approximately 50% of cases clinically consistent with bacterial keratitis in which investigations are negative. The aetiology of these culture-negative cases is unknown. Currently, the estimation of bacterial susceptibility to antimicrobials is based on data from systemic administration and achievable serum or tissue concentrations, rather than relevant corneal concentrations and biological activity in the cornea. The provision to the clinician of minimum inhibitory concentrations of the antimicrobials for the isolated bacteria would be an important step forward. An increase in the prevalence of antimicrobial resistance is a concern, but the effect this has on disease outcomes is yet unclear. Virulence factors are not routinely assessed although they may affect the pathogenicity of bacteria within species and affect outcomes. New technologies have been developed to detect and kill bacteria, and their application to bacterial keratitis is discussed. In this review we present the multiple areas of clinical uncertainty that hamper research and the clinical management of bacterial keratitis, and we address some of the assumptions and dogma that have become established in the literature.

Multimodal Machine Learning Using Visual Fields and Peripapillary Circular OCT Scans in Detection of Glaucomatous Optic Neuropathy.

PURPOSE: To develop and validate a multimodal artificial intelligence algorithm, FusionNet, using the pattern deviation probability plots from visual field (VF) reports and circular peripapillary OCT scans to detect glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. SUBJECTS: Two thousand four hundred sixty-three pairs of VF and OCT images from 1083 patients. METHODS: FusionNet based on bimodal input of VF and OCT paired data was developed to detect GON. Visual field data were collected using the Humphrey Field Analyzer (HFA). OCT images were collected from 3 types of devices (DRI-OCT, Cirrus OCT, and Spectralis). Two thousand four hundred sixty-three pairs of VF and OCT images were divided into 4 datasets: 1567 for training (HFA and DRI-OCT), 441 for primary validation (HFA and DRI-OCT), 255 for the internal test (HFA and Cirrus OCT), and 200 for the external test set (HFA and Spectralis). GON was defined as retinal nerve fiber layer thinning with corresponding VF defects. MAIN OUTCOME MEASURES: Diagnostic performance of FusionNet compared with that of VFNet (with VF data as input) and OCTNet (with OCT data as input). RESULTS: FusionNet achieved an area under the receiver operating characteristic curve (AUC) of 0.950 (0.931-0.968) and outperformed VFNet (AUC, 0.868 [95% confidence interval (CI), 0.834-0.902]), OCTNet (AUC, 0.809 [95% CI, 0.768-0.850]), and 2 glaucoma specialists (glaucoma specialist 1: AUC, 0.882 [95% CI, 0.847-0.917]; glaucoma specialist 2: AUC, 0.883 [95% CI, 0.849-0.918]) in the primary validation set. In the internal and external test sets, the performances of FusionNet were also superior to VFNet and OCTNet (FusionNet vs VFNet vs OCTNet: internal test set 0.917 vs 0.854 vs 0.811; external test set 0.873 vs 0.772 vs 0.785). No significant difference was found between the 2 glaucoma specialists and FusionNet in the internal and external test sets, except for glaucoma specialist 2 (AUC, 0.858 [95% CI, 0.805-0.912]) in the internal test set. CONCLUSIONS: FusionNet, developed using paired VF and OCT data, demonstrated superior performance to both VFNet and OCTNet in detecting GON, suggesting that multimodal machine learning models are valuable in detecting GON.