Characteristics of macular microvasculature before and after idiopathic macular hole surgery

AIM: To evaluate the macular microvasculature before and after surgery for idiopathic macular hole (MH) and the association of preoperative vascular parameters with postoperative recovery of visual acuity and configuration. METHODS: Twenty eyes from 20 patients with idiopathic MH were enrolled. Optical coherence tomography angiography (OCTA) images were obtained before, 2wk, 1, and 3mo after vitrectomy with internal limiting membrane peeling. Preoperative foveal avascular zone (FAZ) area and perimeter and regional vessel density (VD) in both layers were compared according to the 3-month best-corrected visual acuity (BCVA). RESULTS: The BCVA improved from 0.98±0.59 (logMAR, Snellen 20/200) preoperatively to 0.30±0.25 (Snellen 20/40) at 3mo postoperatively. The preoperative deep VD was smaller and the FAZ perimeter was larger in the 3-month BCVA<20/32 group (all P<0.05). A significant reduction was observed in FAZ parameters and all VDs 2wk postoperatively. Except for deep perifoveal VD, all VDs recovered only to their preoperative values. The postoperative FAZ parameters were lower during follow-up. Decreases in preoperative deep VDs were correlated with worse postoperative BCVA (Pearson's r=-0.667 and -0.619, respectively). A larger FAZ perimeter (Spearman's r=-0.524) and a lower deep perifoveal VD preoperatively (Pearson's r=0.486) were associated with lower healing stage. CONCLUSION: The status of the deep vasculature may be an indicator of visual acuity in patients with a closed MH. Except for the deep perifoveal region, VD recovers only to preoperative levels.

Pericoronary Fat Attenuation Index Is Associated With Vulnerable Plaque Components and Local Immune‐Inflammatory Activation in Patients With Non‐ST Elevation Acute Coronary Syndrome

Background The pericoronary fat attenuation index (FAI) is assessed using standard coronary computed tomography angiography, and it has emerged as a novel imaging biomarker of coronary inflammation. The present study assessed whether increased pericoronary FAI values on coronary computed tomography angiography were associated with vulnerable plaque components and their intracellular cytokine levels in patients with non‐ST elevation acute coronary syndrome. Methods and Results A total of 195 lesions in 130 patients with non‐ST elevation acute coronary syndrome were prospectively included. Lesion‐specific pericoronary FAI, plaque components and other plaque features were evaluated by coronary computed tomography angiography. Local T cell subsets and their intracellular cytokine levels were detected by flow cytometry. Lesions with pericoronary FAI values >−70.1 Hounsfield units exhibited spotty calcification (43.1% versus 25.0%, P =0.015) and low‐attenuation plaques (17.6% versus 4.2%, P =0.016) more frequently than lesions with lower pericoronary FAI values. Further quantitative plaque compositional analysis showed that increased necrotic core volume (Pearson’s r=0.324, P <0.001) and fibrofatty volume (Pearson’s r=0.270, P <0.001) were positively associated with the pericoronary FAI, and fibrous volume (Pearson’s r=−0.333, P <0.001) showed a negative association. An increasing proinflammatory intracellular cytokine profile was found in lesions with higher pericoronary FAI values. Conclusions The pericoronary FAI may be a reliable indicator of local immune‐inflammatory response activation, which is closely related to plaque vulnerability. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04792047.

Correlation Between β2-Microglobulin, Grobulin Levels & The Number of Plasmatic Cells in Patients with Multiple Myeloma

Introduction: Multiple myeloma is multifocal neoplasia of plasmatic cells that affects the bone marrow. It is associated with the production of a urinary or serum protein. It represents approximately 1 percent of cancer cases worldwide and between 10 to 15 percent of all cases of hematological malignancy. Furthermore, it has been proposed that the β2-microglobulin levels are correlated with other factors that can predict multiple myelomas such as the number of plasmatic cells and the creatine levels. Goals: To determine the correlation between β2-microglobulin, globulin levels, and the number of plasmatic cells in patients with multiple myeloma. Methods and techniques: We conducted an observational, retrospective, transversal, and analytical study in the Hospital of the Mexican Institute of Social Security at the Veracruz port. Our population analyzed comprehended 45 patients between the ages 30 and 80 with a confirmed diagnosis of multiple myeloma. We measured the β2-microglobulin levels and globulin levels, and the number of plasmatic cells during the diagnosis of patients. Furthermore, we conducted a statistical analysis using a Pearson correlation. Results: The average age was 61 years with a margin of error of 11.48 years. The myeloma of IgG type was the one of major prevalence and represent 82.2 percent. It was followed by the IgA type and the IgM type, which represented 15.5 and 2.2 percent respectively. The Pearson correlation coefficient (Pearson's r) between the β2-microglobulin levels and globulin levels was 0.92. The Pearson's r between the number of plasmatic cells and β2-microglobulin, excluding patients with high serum creatine levels (i.e. larger than 1.2 mg/dl), was 0.371. Conclusions: The predominant type of myeloma in the analyzed population was the IgG type. Furthermore, this myeloma affected mainly men in our study. The average age was 61 years with a margin of error of 11.48 years when compared to other populations in our study.

Improving ΔΔG predictions with a multi-task convolutional Siamese Network

The lead optimization phase of drug discovery refines an initial hit molecule for desired properties, especially potency. Synthesis and experimental testing of the small perturbations during this refinement can be quite costly and time consuming. Relative binding free energy (RBFE, also referred to as ∆∆G) methods allow the estimation of binding free energy changes after small changes to a ligand scaffold. Here we propose and evaluate a Convolutional Neural Network (CNN) Siamese network for the prediction of RBFE between two bound ligands. We show that our multi-task loss is able to improve on a previous state-of-the-art Siamese network for RBFE prediction via increased regularization of the latent space. The Siamese network architecture is well suited to the prediction of RBFE in comparison to a standard CNN trained on the same data (Pearson’s R of 0.553 and 0.5, respectively). When evaluated on a left-out protein family, our CNN Siamese network shows variability in its RBFE predictive performance depending on the protein family being evaluated (Pearson’s R ranging from-0.44 to 0.97). RBFE prediction performance can be improved during generalization by injecting only a few examples (few-shot learning) from the evaluation dataset during model training.

MACROECONOMIC STABILITY AND TRANSPORT COMPANIES’ SUSTAINABLE DEVELOPMENT IN THE EASTERN EUROPEAN UNION

The paper’s primary aim is to evaluate the influence of macroeconomic stability on transport companies’ sustainable development in the eastern EU from 2008 to 2019. The first part discusses the theoretical problems. The empirical part includes the methodology, results of the research and conclusions. To determine the relationship between variables, we use Pearson’s R and the Ordinary Least Square Method. The contribution to knowledge is using the pentagon of macroeconomic stability to evaluate macroeconomic stabilisation’s influence on transport companies’ sustainable development. The results indicate that macroeconomic stability is one of the essential determinants of the transport companies’ sustainable development. According to Pearson’s R, the highest level of dependence is in Slovenia (0.96), Bulgaria (0.9), and Slovenia (0.83). The lowest is in Latvia (0.69). The OLS regression results indicate that the highest significance is in Slovakia (α1 = 1.994), the lowest is in Lithuania (α1 = 0.691). The states’ economic policies should favour the freedom to conduct business, create appropriate legal regulations, and support ecological investments. It is necessary to act for a stable and fair tax system, ensure access to finance. The issue is contemporary and requires further analysis.

610 Fontan associated kidney and liver disease: can we predict organ involvement with echocardiographic assessment of systolic function and atrioventricular valve insufficiency?

Aims Fontan operation represents the surgical palliative option for congenital heart disease with single ventricle physiology. With the improvement of surgical and percutaneous technique, we are facing a growing population of patients with an unique pathophysiology and potential complications. Methods and results Patients that underwent Fontan palliation in our centre between 1993 and 2016 were included in this prospective study. We excluded patients with major congenital renal anomalies, those that underwent cardiac transplantation, and redo-Fontan patients. All the subjects underwent clinical evaluation, laboratory exams with complete renal and hepatic function, transient hepatic elastography, and complete cardiac evaluation. We used Schwartz equation for estimating glomerular filtration rate in patients younger than 18 years, and CDK-EPI equation for adult patients. We enrolled 35 patients, 46% female (N = 16), and 54% male (N = 19). Medium age was 17 years old, median age 15 years old (range: 10–31 years old). Medium time from Fontan completion was 160 months (range: 57–340 months). Regarding to cardiac anatomy, 10 patients had functional single left ventricle (FSLV, 28.5%) and 21 a functional single right ventricle (FSRV, 60%); 4 patients had undetermined single ventricle (11.5%). Total cavo-pulmonary connection (TCPC) with intracardiac lateral tunnel was performed in 7 patients (20%, N = 7), whereas 28 patients had TCPC with external conduit (80%). Data from echocardiographic evaluation showed a medium EF established with Simpson’s method of 60% in patients with FSLV; patients with a FSRV or undetermined single ventricle had a medium FAC of 41.1%, with 15.1% having a reduced FAC &lt; 35%. No FSLV patients had an EF &lt; 50%. When using creatinine-based formula, data about renal function in our population showed a stage 2 chronic kidney disease (eGFR: 60–89 ml/min 1.73 mq) in 11% of total population (N = 4), that became 26% when using cystatin C-based equation (N = 9), with one patient showing a moderate reduced loss of kidney function (eGFR: 40–59 ml/min 1.73 mq). Urinalysis showed 29% (N = 10) of patients having microalbuminuria (microalbumin/creatinine ratio between 30 and 300 mg/g). Statistical analysis demonstrated a negative correlation between systolic function (TAPSE for FSRV) and cystatin C blood levels (Pearson’s R −0.428, P = 0.053), and between systolic function (FAC and Simpson) and microalbuminuria (Pearson’s R −0.414 with P = 0.049 and Pearson’s R −0.754 with P = 0.019, respectively). Transient elastography reported 10 patients (29.4%) with abnormal hepatic stiffness for Fontan patients. That condition appeared to be more frequent in patients with higher grade of AV valve insufficiency (P &lt; 0.05). Conclusions Our population showed an higher prevalence of FSRV Fontan patients, with an expected lower systolic function compared with FSLV. 2D evaluation of systolic function showed a linear inverse correlation with renal function, suggesting that Fontan patients need a closer renal monitoring. Hepatic stiffness, which is a warning sign of potential hepatic cirrhosis need to be monitored in all Fontan patients, especially those with a worse AV valve insufficiency.

613 Fontan associated nephropathy: does diastolic function play a role?

Aims In Fontan patients, the pathophysiology of diastolic function and its relationship with systemic complications are still not well understood. Methods and results This is a prospective study including patients who underwent Fontan completion in our centre between 1993 and 2016. We excluded patients with major congenital renal anomalies, those who underwent cardiac transplantation and redo-Fontan patients. All the subjects underwent clinical evaluation, laboratory exams with complete renal and hepatic function, transient hepatic elastography, and complete cardiac evaluation. We used Schwartz equation for estimating glomerular filtration rate in patients younger than 18 years, and CDK-EPI equation for adult patients. We enrolled 35 patients, 46% female (N = 16), and 54% male (N = 19). Medium age was 17 years old (range: 10–31 years old). Medium time from Fontan completion was 160 months (range: 57–340 months). Ten patients had a functional single left ventricle (FSLV, 28.5%) and 21 a functional single right ventricle (FSRV, 60%); four patients had an undetermined single ventricle (11.5%). Data from renal function assessment showed a prevalence of stage 2 chronic kidney disease (eGFR: 60–89 ml/min 1.73 mq). Of those, 11% with creatinine-based equation and 26% (N = 9) when using cystatin C-based equation, with one patients showing a moderate reduced loss of kidney function (eGFR: 40–59 ml/min/1.73 mq). Most of the patients with reduced eGFR measured with cystatin C were FSRV (89%). None had laboratory markers of acute tubular damage, but four patients had signs of chronic tubular dysfunction with elevation of beta 2 microglobulin (13%). Echocardiographic evaluation of diastolic function showed two patients with baseline E/A &lt; 1 (6%, tot N = 33) and 11/33 (33%) pts with abnormal E/E′ (&gt;12). All of them were FSRV patients (100%). Interestingly, statistical correlation between diastolic parameters and renal function showed a significant association between tubular damage parameters, such as alfa1microglobulin and beta2microglobulin, and E/E′ (Pearson’s R 0.4 and 0.48, respectively, P &lt; 0.05), both for FSLV and FSRV patients. Diastolic function appeared to be associated also with glomerular filtration: we found a statistically significant direct correlation between diastolic pulmonary wave deceleration time (dt D wave) and creatinine value (Pearson’s R 0.49, P &lt; 0.05). Supporting the role of diastolic function in Fontan systemic complications is the linear correlation we found with hepatic tests: higher values of aspartate aminotransferase and of gamma-glutamyltransferase were associated with worse diastolic ventricular filling (longer dt D wave and E wave deceleration time, lower TDI early diastolic wave; Pearson’s R 0.45, 0.5, and −0.41, respectively, P &lt; 0.05). Conclusions Fontan-related nephropathy is associated with worsening diastolic function, which was more represented in FSRV patients. Diastolic function is also associated with liver disease in Fontan patients. Those data suggest renal and liver function should be closely monitored in patients with impaired diastolic function.

443. Pre-vaccination Antibody Titers Against Seasonal Coronaviruses And Antibody Responses to the Pfizer-BioNTech BNT162b2 COVID-19 mRNA Vaccine in Healthcare Workers

Background The Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study is following over 200 healthcare workers who have received the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine. A major aim of the study is to determine whether baseline antibody titers against the seasonal human coronaviruses are associated with altered levels of vaccine-induced antibody responses to SARS-CoV-2. Methods Serial serum samples obtained pre-vaccination and 1 month after the second dose were tested for IgG antibodies against the full pre-fusion spike protein and the receptor binding domain (RBD) of SARS-CoV-2, as well as the full pre-fusion spike proteins of OC43, HKU1, 229E, and NL63. Antibodies were measured using highly sensitive and specific multiplex assays based on Luminex-xMAP technology. Results Preliminary analyses of the first 103 subjects in whom we have 1 month post-vaccination serum demonstrate development of high IgG geometric mean titers (GMT) to both the full spike protein (GMT: 13,685, 12,014-15,589, 95% CI) and the RBD (GMT: 19,448, 17,264-21,908, 95% CI) of SARS-CoV-2 after the 2nd vaccine dose. Preliminary analysis demonstrates no association between baseline antibody titers against spike protein of OC43 and antibody titers against SARS-CoV-2 spike protein (Pearson’s r-value= 0.13, P-value= 0.21) or RBD (Pearson’s r-value= 0.09, P-value= 0.36) one month after vaccination. Future analyses will evaluate whether there is an association with baseline seasonal coronavirus antibody titers and either SARS-CoV-2 neutralization titers or anti-SARS-CoV-2 spike protein titers at 6 months after vaccination. Conclusion These preliminary results suggest that baseline antibody responses to seasonal coronaviruses neither boost nor impede SARS-CoV-2 vaccine-induced antibody responses. Longitudinal sampling will enable assessment of vaccine durability and determination of whether baseline seasonal coronavirus antibody levels are associated with altered duration of detectable COVID-19 vaccine-induced antibody responses. Disclosures Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work)) David Tribble, M.D., DrPH, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work))

Validation of the Korean Quick Dementia Rating System (K-QDRS)

Background: The Quick Dementia Rating System (QDRS) is a brief and rapid dementia staging tool that does not require a trained rater. Objective: The purpose of this study is to demonstrate the validity, reliability, and diagnostic usefulness of the Korean version of the QDRS (K-QDRS). Methods: We collected a total of 411 subject-informant dyads including cognitively unimpaired (CU, n = 22), mild cognitive impairment (MCI, n = 198), and dementia (n = 191). The Clinical Dementia Rating (CDR) scale, Korean version of the Mini-Mental State Examination (K-MMSE), Korean version of instrumental activity of daily living (K-IADL), Short Form of the Geriatric Depression Scale, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI), and detailed neuropsychological tests were administered as gold standards of dementia staging, cognition, function, mood, and behavior. Results: Internal consistency of the K-QDRS was excellent with Cronbach’s alpha of 0.933. Concurrent validity was also satisfactory, with the K-QDRS correlating highly with the CDR Sum of Boxes (Pearson’s r = 0.791), K-MMSE (Pearson’s r = –0.518), K-IADL (Pearson’s r = 0.727), and CGA-NPI (Pearson’s r = 0.700). The K-QDRS was highly correlated with the global CDR, K-IADL, and CGA-NPI. We suggested two types of comparisons (for initial diagnosis and for follow-up evaluation). The cutoff scores for follow-up were 1.0 for MCI, 3.5 for very mild dementia, 6.5 for mild dementia, and 11.0 for moderate dementia. Conclusion: The K-QDRS is a valid and reliable dementia rating questionnaire and can be used, briefly and rapidly, in various settings like clinical practices, longitudinal cohort studies, and community primary care.