Project description:PurposeTo determine the association of gut microbiome diversity and sight-threatening diabetic retinopathy (STDR) amongst patients with pre-existing diabetes.MethodsA cross-sectional study was performed, wherein 54 participants selected in total were placed into cases cohort if diagnosed with STDR and those without STDR but had a diagnosis of diabetes mellitus of at least 10-year duration were taken as controls. Statistical analysis comparing the gut microbial alpha diversity between cases and control groups as well as patients differentiated based on previously hypothesized Bacteroidetes/Firmicutes(B/F) ratio with an optimal cut-off 1.05 to identify patients with STDR were performed.ResultsComparing gut microbial alpha diversity did not show any difference between cases and control groups. However, statistically significant difference was noted amongst patients with B/F ratio ≥1.05 when compared to B/F ratio < 1.05; ACE index [Cut-off < 1.05:773.83 ± 362.73; Cut-off > 1.05:728.03 ± 227.37; p-0.016]; Chao1index [Cut-off < 1.05:773.63 ± 361.88; Cut-off > 1.05:728.13 ± 227.58; p-0.016]; Simpson index [Cut-off < 1.05:0.998 ± 0.001; Cut-off > 1.05:0.997 ± 0.001; p-0.006]; Shannon index [Cut-off < 1.05:6.37 ± 0.49; Cut-off > 1.05:6.10 ± 0.43; p-0.003]. Sub-group analysis showed that cases with B/F ratio ≥ 1.05, divided into proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME), showed decreased diversity compared to controls (B/F ratio < 1.05). For PDR, all four diversity indices significantly decreased (p < 0.05). However, for CSME, only Shannon and Simpson indices showed significant decrease in diversity (p < 0.05).ConclusionsBased on clinical diagnosis, decreasing gut microbial diversity was observed among patients with STDR, although not statistically significant. When utilizing B/F ratio, the decreasing gut microbial diversity in STDR patients seems to be associated due to species richness and evenness in PDR when compared to decreasing species richness in CSME.

Project description:ImportanceIt is a global challenge to provide regular retinal screening for all people with diabetes to detect sight-threatening diabetic retinopathy (STDR).ObjectiveTo determine if circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect STDR.Design, setting, and participantsThis cross-sectional study collected data from October 22, 2018, to December 31, 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort, and provided with the database containing the clinical data. This was a multicenter study conducted in parallel in 3 outpatient ophthalmology clinics in the UK and 2 centers in India. Adults 40 years and older were categorized into 4 groups: (1) no history of diabetes, (2) type 2 diabetes of at least 5 years' duration with no evidence of DR, (3) nonproliferative DR with diabetic macular edema (DME), or (4) proliferative DR. STDR comprised groups 3 and 4.ExposuresThirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assay.Main outcomes and measuresSeverity of DR and presence of DME were diagnosed using fundus photographs and optical coherence tomography. Weighted logistic regression and receiver operating characteristic curve analysis (ROC) were performed to identify biomarkers that discriminate STDR from no DR beyond the standard clinical parameters of age, disease duration, ethnicity (in the UK) and hemoglobin A1c.ResultsA total of 538 participants (mean [SD] age, 60.8 [9.8] years; 319 men [59.3%]) were recruited into the study. A total of 264 participants (49.1%) were from India (group 1, 54 [20.5%]; group 2, 53 [20.1%]; group 3, 52 [19.7%]; group 4, 105 [39.8%]), and 274 participants (50.9%) were from the UK (group 1, 50 [18.2%]; group 2, 70 [25.5%]; group 3, 55 [20.1%]; group 4, 99 [36.1%]). ROC analysis (no DR vs STDR) showed that in addition to age, disease duration, ethnicity (in the UK) and hemoglobin A1c, inclusion of cystatin C had near-acceptable discrimination power in both countries (area under the receiver operating characteristic curve [AUC], 0.779; 95% CI, 0.700-0.857 in 215 patients in the UK with complete data; AUC, 0.696; 95% CI, 0.602-0.791 in 208 patients in India with complete data).Conclusions and relevanceResults of this cross-sectional study suggest that serum cystatin C had good discrimination power in the UK and India. Circulating cystatin-C levels may be considered as a test to identify those who require prioritization for retinal screening for STDR.

Project description:ImportanceTo prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness.ObjectivesTo create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment.Design, setting, and participantsIn this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models.Main outcomes and measuresThe study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).ResultsAmong 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data.Conclusions and relevanceThis study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.

Project description:BACKGROUND:Internationally, systematic screening for sight-threatening diabetic retinopathy (STDR) usually includes annual recall. Researchers and policy-makers support extending screening intervals, citing evidence from observational studies with low incidence rates. However, there is little research around the acceptability to people with diabetes (PWD) and health care professionals (HCP) about changing eye screening intervals. METHODS:We conducted a qualitative study to explore issues surrounding acceptability and the barriers and enablers for changing from annual screening, using in-depth, semistructured interviews analysed using the constant comparative method. PWD were recruited from general practices and HCP from eye screening networks and related specialties in North West England using purposive sampling. Interviews were conducted prior to the commencement of and during a randomised controlled trial (RCT) comparing fixed annual with variable (6, 12 or 24?month) interval risk-based screening. RESULTS:Thirty PWD and 21 HCP participants were interviewed prior to and 30 PWD during the parallel RCT. The data suggests that a move to variable screening intervals was generally acceptable in principle, though highlighted significant concerns and challenges to successful implementation. The current annual interval was recognised as unsustainable against a backdrop of increasing diabetes prevalence. There were important caveats attached to acceptability and a need for clear safeguards around: the safety and reliability of calculating screening intervals, capturing all PWD, referral into screening of PWD with diabetic changes regardless of planned interval. For PWD the 6-month interval was perceived positively as medical reassurance, and the 12-month seen as usual treatment. Concerns were expressed by many HCP and PWD that a 2-year interval was too lengthy and was risky for detecting STDR. There were also concerns about a negative effect upon PWD care and increasing non-attendance rates. Amongst PWD, there was considerable conflation and misunderstanding about different eye-related appointments within the health care system. CONCLUSIONS:Implementing variable-interval screening into clinical practice is generally acceptable to PWD and HCP with important caveats, and misconceptions must be addressed. Clear safeguards against increasing non-attendance, loss of diabetes control and alternative referral pathways are required. For risk calculation systems to be safe, reliable monitoring and clear communication is required.

Project description:Immune-mediated endocrinopathies are among the most frequent immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICIs) targeting programmed death-ligand 1 (PD-L1)/PD-1. However, the development of auto-immune diabetes is an uncommon event during PD(L)-1 blockade, either as monotherapy or in combination therapy. Here we report a case of a 75-year-old male with a mediastinal recurrence from a stage IA squamous cell carcinoma of the lung previously treated with stereotactic body radiotherapy (SBRT) who early developed a severe diabetic ketoacidosis (DKA) caused by new-onset auto-immune diabetes, with positive glutamic acid decarboxylase (GAD65) autoantibodies, during durvalumab consolidation therapy after concurrent chemoradiation. The patient had no personal or family history of diabetes or auto-immune diseases and was admitted after the second cycle of durvalumab to the intensive care unit (ICU) with severe DKA. During his hospitalization, insulin and fluid therapy were started and the patient had a favorable clinical course. Durvalumab treatment was interrupted and thyroiditis was verified during follow-up, without anti-thyroid antibodies, that progressed to subsequent hypothyroidism with need of thyroid hormone replacement therapy. This case highlights the rare irAE of autoimmune type 1 diabetes during anti-PD(L)-1 therapy, which can be life-threatening and requires adequate patient education and prompt medical treatment within a multidisciplinary team, including endocrinology and emergency medicine. Besides its low incidence, this case show how irAE must be taken in account about decision of ICI treatment, especially in curative setting, as they can be potentially fatal and impair overall survival. Furthermore, as reported in the present case, multiple endocrine irAEs can occur in the same patient either simultaneously or sequentially, suggesting that active surveillance is needed in those who develop endocrinopathies as a result of ICI treatment. Immune-mediated endocrinopathies are generally irreversible and cause life-long morbidity, which must be taken into consideration when deciding on further lines of treatment.

Project description:BackgroundAccumulating evidence has suggested a link between adipokines and diabetic retinopathy (DR). This study is aimed at investigating the risk factors for sight-threatening DR (STDR) and establishing a prognostic model for predicting STDR among a high-risk population of patients with type 2 diabetes mellitus (T2DM).MethodsPlasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. In the case-control set, principal component analysis (PCA) was performed to select optimal predictive cytokines for STDR, involving severe nonproliferative DR (NPDR) and proliferative DR. Support vector machine (SVM) was used to examine the possible combination of baseline plasma adipokines to discriminate the patients with mild NPDR who will later develop STDR. An individual prospective cohort with a follow-up period of 3 years was used for the external validation.ResultsIn both training and testing sets, involving 306 patients with T2DM, median levels of plasma adiponectin (APN), leptin, and fatty acid-binding protein 4 (FABP4) were significantly higher in the STDR group than those in mild NPDR. Except for adipsin, the other three adipokines, FABP4, APN, and leptin, were selected by PCA and integrated into SVM. The accuracy of the multivariate SVM classification model was acceptable in both the training set (AUC = 0.81, sensitivity = 71%, and specificity = 91%) and the testing set (AUC = 0.77, sensitivity = 61%, and specificity = 92%). 110 T2DM patients with mild NPDR, the high-risk population of STDR, were enrolled for external validation. Based on the SVM, the risk of each patient was calculated. More STDR occurred in the high-risk group than in the low-risk group, which were grouped by the median value of APN, FABP4, and leptin, respectively. The model was validated in an individual cohort using SVM with the AUC, sensitivity, and specificity reaching 0.77, 64%, and 91%, respectively.ConclusionsAdiponectin, leptin, and FABP4 were demonstrated to be associated with the severity of DR and maybe good predictors for STDR, suggesting that adipokines may play an important role in the pathophysiology of DR development.

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Sight-Threatening Immune Retinopathy Developing Secondary to Durvalumab Treatment of Small-Cell Lung Cancer: A Case Report

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