Comment on "Keratoprosthesis in dry eye disease"

We have identified a few inaccuracies that we would like to clarify to enhance the quality of the work in dry eye disease

OCT biomarkers as predictors of visual improvement in diabetic macular edema eyes receiving dexamethasone implants

Background: Several optical coherence tomography (OCT) biomarkers have been proposed as predictors for functional and anatomical outcomes in Diabetic Macular Edema (DME). This study aims to examine the impact of these OCT features on the visual acuity improvement of patients with DME after long-acting Dexamethasone intravitreal implants (DEX-I) injection. Furthermore, the safety and impact of DEX-I on clinical parameters, including intraocular pressure (IOP) were assessed. Methods: In this retrospective observational study, we reviewed the medical records of naïve and non-naïve eyes with DME who received at least one DEX-I. The primary endpoint was visual acuity improvement of ≥ 5 ETDRS letters at 1 month and 4 months after treatment. Secondary outcomes were the changes in OCT biomarkers and the impact of DEX-I on IOP at 1 and 4 months of follow-up. Linear panel regression analysis was used to test for differences in central subfield thickness (CST) over time and it was stratified according to biomarkers at baseline. Finally, a logistic regression analysis was used to identify factors predicting visual improvement at 1 and 4 months. Results: We included 33 eyes of which 63.6% were at an advanced stage of DME. Overall, CST, cube average thickness (CAT), cube volume (CV), and intraretinal cystoid spaces > 200 μm (ICS) decreased following DEX-I injection (p < 0.001). Additionally, a thicker CST at baseline was observed in eyes with better visual improvement at one month (p = 0.048). After logistic regression analysis, CST was retained as the only predictor for visual improvement at one month (p = 0.044). Furthermore, panel regression analysis identified a relation between subfoveal neuroretinal detachment (SND) at baseline and CST increase at four months. Lastly, only 15.2% of the eyes necessitated topical medication for IOP reduction, with no differences observed when stratifying between naïve and non-naïve eyes. Conclusion: Our analyses suggest that a ticker baseline CST may serve as a positive predictor of early visual improvement and SND presence at baseline may be a negative prognostic factor for CST increase 4 months after DEX-I injection. Other well-known biomarkers, such as disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HF), did not demonstrate prognostic value on visual outcomes, at least within the first four months following the injection

Eye health screening in migrant population: primary care experience in Lazio (Italy) from the PROTECT project

Italy is a natural corridor for entry into Europe, receiving thousands of refugees and migrants needing socio-economic and health assistance yearly. Impaired vision due to eye disease is estimated to affect at least 2.2 billion people worldwide, especially in this underprivileged population. To overcome this deep disparity, new intervention strategies, such as the PROTECT project, were planned with the aim of assessing, in the context of the head–neck area, the eye health in vulnerable applicants and holders of international protection. A total of 3023 migrants were involved in the project. Demographic factors and eye history were collected using a questionnaire. Using portable diagnostic instruments, an eye screening including monocular visual acuity, intraocular pressure, anterior segment, and ocular fundus was performed. The mean age was 31.6 ± 13.1 years and more than 50% underwent the first eye evaluation. Vision impairment was claimed by 16.6% of subjects and the most frequent diseases diagnosed were: refractive errors (11%), strabismus (6%), red eye (6%), cataract (5.3%), and ocular hypertension (1%). Retinal alterations were observed in 5% of migrants. The PROTECT project allows us to increase the accessibility of head–neck disease prevention care. Moreover, our results confirm the utility of an eye screening assessment for early identification of the most relevant and preventable ocular diseases, especially in disadvantaged populations

Digital Twins for Health: Opportunities, Barriers and a Path Forward

The concept of precision medicine involves tailoring medical interventions to each patient’s specific needs, considering factors such as their genetic makeup, lifestyle, environment and response to therapies. The emergence of digital twin (DT) technology is anticipated to enable such customization. The healthcare field is, thus, increasingly exploring the use of digital twins (DTs), benefiting from successful proof of concept demonstrated in various industries. If their full potential is realized, DTs have the capability to revolutionize connected care and reshape the management of lifestyle, health, wellness and chronic diseases in the future. However, the realization of DTs’ full potential in healthcare is currently impeded by technical, regulatory and ethical challenges. In this chapter, we map the current applications of DTs in healthcare, with a primary focus on precision medicine. We also explore their potential applications in clinical trial design and hospital operations. We identify the key enablers of DTs in healthcare and discuss the opportunities and barriers that foster or hinder their larger and faster diffusion. By providing a comprehensive view of the current landscape, opportunities and challenges, we aim to contribute to DTs’ ongoing development and help policymakers facilitate the growth of DTs’ application in healthcare

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

PRK transepiteliale a guida topografica per la correzione di astigmatismi irregolari dopo cheratoplastica perforante

Scopo del lavoro: Descrivere l'efficacia e la sicurezza della cheratectomia fotorifrattiva (PRK) transepiteliale a guida topografica per la correzione di astigmatismi altamente irregolari dopo la cheratoplastica perforante (PK). Materiali e metodi: Studio prospettico su 12 occhi di 12 pazienti affetti da astigmatismo altamente irregolare dopo PK per cheratocono. Ogni paziente è stato sottoposto a un'ablazione transepiteliale a guida topografica (software CIPTA®2, iVis Technologies). Sono stati raccolti i dati della tomografia corneale, l'acuità visiva corretta (CDVA) e non corretta (UDVA) e l'equivalente sferico (SEQ) prima dell'intervento (T0) e poi a 1 mese (T1), 3 mesi (T2) e 12 mesi (T3) dopo l'intervento laser. Risultati: L’UDVA e la CDVA medie sono migliorate significativamente, rispettivamente, da 1.22±0.17 e 0.18±0.03 logMAR al T0, arrivando a 0.63±0.17 (CI 95%, P <0.001) e 0.04±0.03 logMAR al T3 (CI 95%, p<0.001). Lo SEQ medio è diminuito significativamente da -3.75±1.32 a -1.60±1.32 D (CI 95%, p<0,02). L'astigmatismo rifrattivo soggettivo medio (SRAST) e l'astigmatismo alla cheratometria simulata (SimK) sono diminuiti significativamente, rispettivamente, da 7.83±0.98 e 8.10±1.48 D a 2.83±0.98 e 5.29±1.48 D (CI 95%, p<0,001). L'indice di irregolarità morfologica corneale (CMI) è diminuito significativamente da 62.76±7.26 µm a 23.24±7.26 µm (CI 95%, p<0.001). A parte un singolo episodio di rigetto dell'innesto 5 giorni dopo l'ablazione, ripristinato con successo con steroidi topici, non sono state notate altre complicazioni. Un lieve haze corneale è stato osservato in due occhi (16.7%) a 3 mesi dopo la PRK. Discussione e conclusioni: Il nostro studio dimostra la sicurezza e l'efficacia a lungo termine di un'ablazione transepiteliale a guida topografica nel trattamento dell'astigmatismo altamente irregolare dopo PK