Diabetic retinopathy screening with confocal fundus camera and artificial intelligence - assisted grading.

PURPOSE: Screening for diabetic retinopathy (DR) by ophthalmologists is costly and labour-intensive. Artificial Intelligence (AI) for automated DR detection could be a clinically and economically alternative. We assessed the performance of a confocal fundus imaging system (DRSplus, Centervue SpA), coupled with an AI algorithm (RetCAD, Thirona B.V.) in a real-world setting. METHODS: 45° non-mydriatic retinal images from 506 patients with diabetes were graded both by an ophthalmologist and by the AI algorithm, according to the International Clinical Diabetic Retinopathy severity scale. Less than moderate retinopathy (DR scores 0, 1) was defined as non-referable, while more severe stages were defined as referable retinopathy. The gradings were then compared both at eye-level and patient-level. Key metrics included sensitivity, specificity all measured with a 95% Confidence Interval. RESULTS: The percentage of ungradable eyes according to the AI was 2.58%. The performances of the AI algorithm for detecting referable DR were 97.18% sensitivity, 93.73% specificity at eye-level and 98.70% sensitivity and 91.06% specificity at patient-level. CONCLUSIONS: DRSplus paired with RetCAD represents a reliable DR screening solution in a real-world setting. The high sensitivity of the system ensures that almost all patients requiring medical attention for DR are referred to an ophthalmologist for further evaluation.

Feasibility and accuracy of the screening for diabetic retinopathy using a fundus camera and an artificial intelligence pre-evaluation application.

AIMS: Periodical screening for diabetic retinopathy (DR) by an ophthalmologist is expensive and demanding. Automated DR image evaluation with Artificial Intelligence tools may represent a clinical and cost-effective alternative for the detection of retinopathy. We aimed to evaluate the accuracy and reliability of a machine learning algorithm. METHODS: This was an observational diagnostic precision study that compared human grader classification with that of DAIRET®, an algorithm nested in an electronic medical record powered by Retmarker SA. Retinal images were taken from 637 consecutive patients attending a routine annual diabetic visit between June 2021 and February 2023. They were manually graded by an ophthalmologist following the International Clinical Diabetic Retinopathy Severity Scale and the results were compared with those of the AI responses. The main outcome measures were screening performance, such as sensitivity and specificity and diagnostic accuracy by 95% confidence intervals. RESULTS: The rate of cases classified as ungradable was 1.2%, a figure consistent with the literature. DAIRET® sensitivity in the detection of cases of referable DR (moderate and above, "sight-threatening" forms of retinopathy) was equal to 1 (100%). The specificity, that is the true negative rate of absence of DR, was 80 ± 0.04. CONCLUSIONS: DAIRET® achieved excellent sensitivity for referable retinopathy compared with that of human graders. This is undoubtedly the key finding of the study and translates into the certainty that no patient in need of the ophthalmologist is misdiagnosed as negative. It also had sufficient specificity to represent a cost-effective alternative to manual grade alone.

A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position.

The question whether antidiabetes drugs can cause acute pancreatitis dates back to the 1970s. Recently, old concerns have re-emerged following claims that use of incretins, a new class of drugs for type 2 diabetes, might increase the relative risk of acute pancreatitis up to 30-fold. Given that diabetes is per se a potent risk factor for acute pancreatitis and that drug-related acute pancreatitis is rare and difficult to diagnose, we searched the medical databases for information linking acute pancreatitis and type 2 diabetes drugs. Among the biguanides, both phenformin and metformin (the latter in patients with renal insufficiency) have been cited in case reports as a potential cause of acute pancreatitis. Sulphonylureas, as both entire class and single compound (glibenclamide), have also been found in cohort studies to increase its risk. No direct link was found between pancreatic damage and therapy with metaglinide, acarbose, pramlintide or SGLT-2 inhibitors. In animal models, thiazolinediones have demonstrated proprieties to attenuate pancreatic damage, opening perspectives for their use in treating acute pancreatitis in humans. Several case reports and the US Food and Drug Administration pharmacovigilance database indicate an association between acute pancreatitis and incretins, dipeptidyl peptidase-4 (DPP-4) inhibitors, and GLP-1 receptor agonists. To date, however, a clear-cut odds ratio for this association has been reported in only one of eight pharmacoepidemiological studies. Finally, none of the intervention trials investigating these compounds, including two large randomized controlled trials with cardiovascular endpoints, confirmed the purportedly increased risk of acute pancreatitis with incretin use.

Comparison of direct costs of type 2 diabetes care: different care models with different outcomes.

BACKGROUNDS AND AIMS: To compare direct costs of four different care models and health outcomes in adults with type 2 diabetes. METHODS AND RESULTS: We used multiple independent data sources to identify 25,570 adults with type 2 diabetes residing in Turin, Italy, as of 1 July 2003. Data extracted from administrative data databases were used to create four care models ranging in organization from highly structured care (integrated primary and specialist care) to progressively less structured care (unstructured care). Regression analyses, adjusted for main confounders, were applied to examine the differences between the models in direct costs, mortality, and diabetes-related hospitalizations rates over a 4-year period. In patients managed according to the unstructured care model (i.e., usual care by a primary care provider and without strict guidelines adherence), excess of all-cause mortality was 84% and 4-year direct cost was 8% higher than in those managed according to the highly structured care model. Cost ratio analysis revealed that the major cost driver in the unstructured care model was hospital admissions, which were 31% higher than the rate calculated for the more structured care models. In contrast, spending on prescription medications and specialist consultations was higher in the highly structured care model. CONCLUSION: A diabetes care model that integrates primary and specialty care, together with practices that adhere to guideline recommendations, was associated with a reduction in all-cause mortality and hospitalizations, as compared with less structured models, without increasing direct health costs.

Propafenone-induced liver injury: report of a case and review of the literature.

A case of an acute cholestatic syndrome associated with use of the antiarrhythmic drug propafenone is reported here. The close time relationship between the administration of the drug and the acute onset of the liver damage, the histological findings, and the reappearance of biochemical signs of liver dysfunction upon rechallenge with the same medication strongly suggest that propafenone was involved in the pathogenesis of this syndrome. Although rare, hepatotoxicity from this widely used antiarrhythmic medication should be kept in mind in the differential diagnosis of sudden cholestatic syndrome of obscure origin.

[Verapamil inhibits the in vitro synthesis of DNA. I. Study of human lymphocyte cultures]. / Il Verapamil inibisce la sintesi del DNA "in vitro". I. Studio su colture di linfociti umani.

Verapamil in vitro reduced 3H-TdR incorporation into lymphocytes. High doses of Verapamil were lethal for cells; low doses inhibit DNA synthesis, but cell viability by the Trypan blue exclusion method is preserved. Increasing the concentration of Ca++ in the medium partially improved lymphocyte viability and 3H-TdR incorporation. Modification of the Na+ and K+ content in the medium did not interfere with Verapamil action. The inhibitory action was not completely reversible even when the cells were exposed to the drug for a short time (15'). Our results confirm the dependency of lymphocyte blast transformation on Ca++ during the first 20 h. Nifedipine did not inhibit cell replication, which suggests a different mechanism of action. Our investigation suggests that there is more than one model for calcium-antagonism and that the action of Verapamil can not be explained only by its influence on transmembrane Ca++ flux. We believe that Verapamil has a negative action on cell metabolism directly through an interaction on transmembrane Ca++ flux and on intracellular Ca++.

[Parameters of cellular immunity in subjects with bronchial squamous cell tumors]. / Alcuni parametri dell'immunità cellulare in soggetti con neoplasia bronchiale a cellule squamouse.

We studied some cell mediated immunologic assay in a normal population and in patients with squamous cell carcinoma of the bronchus. In cancer patients lymphocyte mitogen stimulation with PHA and PWM did not show any significant difference from normal population; PPD antigenic stimulation was lower in eight patients of ten. E-total rosette forming cells count was reduced, there was no difference in E-active rosette forming cells. Electrophoretic mobility of lymphocytes showed that a part of lymphocytes have a lower electrophoretic cell migration. Lymphocytes subpopulations isolated by E rosetting technique are different in cancer patients from subpopulations separated by electrophoresis; in controls similar subpopulations were obtained by the two methods. In cancer patients cell mediated immunity shows altered functions which is though not uniformly modified. We think that serum factors and cells with blocking action cause these effects rather than intrinsic changes of lymphocytes.

[In vitro lymphocyte immunoreactivity in sarcoidosis patients. Stimulation with Kveim antigens]. / Immunoreattività linfocitaria "in vitro" in pazienti affetti da sarcoidosi. Stimolazione con antigene di Kveim.

12 patients suffering from sarcoidosis have been studied in addition to clinical and bioptic investigations, they were submitted to intradermal reaction with PPD, Candida Albicans and Kveim's antigen. Lymphocytes from the 12 patients were placed in culture and stimulated with phytohaemagglutinin (PHA), pokeweed mitogen (PWM), concanavalin A (CON-A), PPD, Candidin and Kveim's antigen. Six patients proved positive to Kveim's antigen in vivo, and four of them (66%) in vitro also. No patient was immunodepressed. Of the 6 patients negative to Kveim's antigen both in vivo and in vitro, 4 were clearly immunodepressed, as shown by the reduced mitogen response, the negative response to antigen stimulation, and to the intradermal reaction. The results are discussed in the light of recent findings regarding the role of the immunocompetent system in sarcoidosis.

[Lymphocyte immunoreactivity in subjects vaccinated with Calmette-Guerin bacillus (BCG)]. / Immunoreattività linfocitaria in soggetti vaccinati con bacillo di Calmette e Guerin (BCG).

PHA, Pokeweed and PPD lymphocytes transformation in vitro was studied in four groups of people. One group was negative to PPD skin testing; one was positive for a "naturally" acquired infection; the third group were people vaccinated with BCG in the last year; fourth group people vaccinated with BCG within one and five years. Last two groups had generally low or negative reaction to PPD skin test. PPD was used at different concentration, from 0.025 to 35 microgram/ml; maximum stimulation was at 1 microgram/ml. Stimulation index was lower in vaccinated people than in "natural" positive. Lymphocytes of people vaccinated from more than one year showed no difference from PPD negative people. Highly significant difference was observed between these two groups and people "naturally" positive and within one year of vaccination. We discuss our data and interpret the findings as showing that there are less PPD sensitive lymphocytes in patients vaccinated with BCG than in people with a "natural" infection and that this circulating population of lymphocytes disappears or decreases in the years following vaccination.

[The action of insulin on human lymphocytes stimulated with mitogens "in vitro". I. Study on normal subjects]. / L'azione dell'insulina sui linfociti umani stimolati con mitogeni "in vitro". I--Studio su soggetti normali.

Insulin at 25, 50, 250, 500 and 1000 mcU/ml concentration added to lymphocyte cultures under PHA stimulation increases [3H] Thymidine incorporation. Maximum effect is obtained at 50 mcg/ml of PHA and 250 mcU/ml of insulin after 96 hours of incubation. Insulin stimulates cultures when it is added between the 12th and the 24th hour. Cultures stimulated wih high dose (250 mcg/ml) of PHA do not show any increase in mitosis. Ours and other Authors results seem to show that the mechanism of action of insulin works through specific receptors on lymphocytes. These receptors appear some hours after mitogen stimulation; our results showing maximum effect when insulin is added after 12-24 hours support this hypothesis.

[Behavior of serum alpha 1-antitrypsin in chronic hepatopathies and its diagnostic significance]. / Comportamento dell' alfa 1 antitripsina sierica in corso di epatopatie croniche e suo significato diagnostico.

The behaviour of alpha 1 antitrypsin in 76 subjects with cirrhosis of the liver, 14 subjects with chronic persistent hepatitis, 14 subjects with chronic active hepatitis, 8 subjects with toxic hepatitis, 5 subjects with obstructive jaundice, 5 subjects with liver carcinoma. 4 of these groups (cirrhosis, chronic active hepatitis, obstructive jaundice, hepatoma) showed alpha 1 antitrypsin blood levels significantly higher than the control group (82 healthy subjects). Very high alpha 1 antitrypsin blood levels, significantly greater than in cirrhosis, were found in the patients with hepatoma. All these subjects also showed blood levels of alpha fetoprotein higher than 100 ng/ml. The diagnostic meaning of these finding was considered.

[Active E rosette test in the study of PPD hypersensitivity]. / Il test delle rosette E attive nello studio della ipersensibilità alla PPF.

In our study we show that pre-incubation of lymphocytes with PPD "in vitro", produces a significant increase in the number of E active rosettes. This increase is only for subjects with cutaneous hypersensitivity to tuberculin. We think this is a specific test and we studied the confidence interval for our results. We discuss the possibility to evaluate the immune-status of a subject, testing his lymphocytes with a panel of antigens. The active E rosette test is simpler, cheaper and easier to perform than other tests to evaluate the cellular immune-status of patients.