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SEVERE VISUAL LOSS DURING ANTI-VEGF INTRAVITREAL INJECTIONS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: TIMING, PROGNOSIS, AND OPTICAL COHERENCE TOMOGRAPHY FINDINGS.
Grassi, MO, Monteleone, G, Pozharitskiy, N, Molfetta, T, Boscia, G, Alessio, G, Boscia, F
Retina (Philadelphia, Pa.). 2023;(7):1081-1087
Abstract
PURPOSE Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard of care for neovascular age-related macular degeneration (nAMD). However, a small subgroup of patients still experience severe visual impairment, which may be related to the number of IVI administered. METHODS This retrospective observational study analyzed data from patients with sudden severe visual decline (≥15 Early Treatment Diabetic Retinopathy Study [ETDRS] letters loss between two consecutive IVIs) during anti-VEGF treatment for nAMD. Best-corrected visual acuity examination, optical coherence tomography (OCT), and OCT angiography (OCTA) were performed before every IVI and central macular thickness (CMT) and drug injected were collected. RESULTS 1,019 eyes received anti-VEGF IVI for nAMD from December 2017 to March 2021. Severe VA loss occurred in 15.1% after a median of 6 (range 1-38) IVI. Ranibizumab was injected in 52.8% and aflibercept in 31.9% of cases. Functional recovery after 3 months was significant, without further improvement at 6 months. Visual prognosis relative to the percentage of CMT change showed better visual outcome in eyes with no substantial change in CMT compared with an increase of >20% or a decrease of >5%. CONCLUSION In this first real-life study exploring severe VA loss during anti-VEGF treatment in patients with nAMD, it was found that it was not unusual for a ≥15 ETDRS letters loss to occur between two consecutive IVIs, often within 9 months of diagnosis and 2 months after the last IVI. Close follow-up and a proactive regimen should be preferred, at least in the first year.
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Influence of Defatting and Pasteurization on Nutrients and Oxidative Stress Markers in Human Milk.
D'Alessandro, A, Pastore, A, Amadio, P, D'Agostini, M, Terreri, S, Carsetti, R, Argentieri, M, Bernaschi, P, Onetti Muda, A, Porzio, O, et al
Journal of human lactation : official journal of International Lactation Consultant Association. 2023;(2):278-287
Abstract
BACKGROUND It is well known that the best nutritional option for infants is human milk, and that when breastfeeding is not possible, human milk banks are a possible alternative. However, in the case of infants with fat transport disorder like chylothorax, defatting of human milk is mandatory. RESEARCH AIM The aim of the study was to reduce milk fat content without reducing other nutrients, increasing oxidative stress, or introducing harmful microorganisms. METHODS In this prospective, cross-sectional, observational study, we examined the influence of defatting and pasteurization of 50 donor samples on fat, macro- and micronutrients, as well as on oxidative stress markers. RESULTS Low-temperature centrifugation proved to be very efficient in defatting, reducing the concentration of triglycerides by 85% and cholesterol by 50%. The macronutrients (proteins, albumin, and Immunoglobulin A) did not undergo significant changes due to defatting and pasteurization procedures, while iron decreased by 36%. However, as the majority of iron is retained, this result does not remarkably change the milk composition. Furthermore, oxidative stress markers and antioxidant levels were unchanged, and the milk result was microbiologically safe. CONCLUSIONS Cold milk centrifugation proved to be an effective technique that allows the reduction of human milk lipids. The determination of triglycerides and cholesterol can be used as an indicator of skimming. This procedure is not accompanied by substantial modifications of other components present in the milk.
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The combined consumption of fresh/minimally processed food and ultra-processed food on food insecurity: COVID Inconfidentes, a population-based survey.
Coletro, HN, Menezes-Júnior, LAA, Mendonça, RD, Meireles, AL, Machado-Coelho, GLL, Menezes, MC
Public health nutrition. 2023;(7):1414-1423
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OBJECTIVE To investigate whether the combined consumption of fresh/minimally processed and ultra-processed food is associated with food insecurity (FI) during the COVID-19 pandemic. DESIGN Cross-sectional observational study was derived from a survey using a population-based search of a complex sample. FI was assessed using the validated Brazilian Food Insecurity Scale. Food consumption was assessed using a qualitative FFQ and the NOVA classification for fresh/minimally processed food and ultra-processed food. A scoring system was used to evaluate combined food consumption according to the extent and purpose of processing, considering the weekly consumption of the two groups (according to the NOVA classification). Higher punctuation reflects worse diet quality (higher consumption of ultra-processed foods and lower consumption of fresh/minimally processed foods). A theoretical causality model was constructed using a directed acyclic graph, and multivariate analysis was performed using Poisson regression to test the association between FI and food consumption. SETTING Ouro Preto and Mariana, Brazil, between October and December 2020. PARTICIPANTS An epidemiological household survey was conducted with 1753 individuals selected through a stratified and clustered sampling design in three stages. RESULTS Those with food consumption scores in the fourth quartile had a 60 % higher prevalence ratio (PR) for FI (PR: 1·60 and 95 % CI: 1·06 - 2·40). Also, the increased consumption of fresh/minimally processed foods and low consumption of ultra-processed foods presented a 45 % lower prevalence ratio of FI (PR: 0·55 and 95 % CI: 0·40 - 0·80). CONCLUSION These results indicate an inverse association between FI and diet quality.
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Changes in Coagulation and Fibrinolytic Factors in Patients With Cirrhotic Refractory Ascites Undergoing Cell-free and Concentrated Ascites Reinfusion Therapy: A Retrospective Observational Study in Japan.
Yorioka, N, Namisaki, T, Shibamoto, A, Suzuki, J, Kubo, T, Iwai, S, Tomooka, F, Tanaka, M, Takeda, S, Fujimoto, Y, et al
In vivo (Athens, Greece). 2023;(3):1226-1235
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BACKGROUND/AIM: The management of refractory ascites is critical for the treatment of patients with decompensated cirrhosis. This study aimed to evaluate the feasibility and safety of cell-free and concentrated ascites reinfusion therapy (CART) in patients with cirrhosis and refractory ascites, with a focus on changes in coagulation and fibrinolytic factors in ascitic fluid following CART. PATIENTS AND METHODS This was a retrospective cohort study including 23 patients with refractory ascites undergoing CART. Serum endotoxin activity (EA) before and after CART and the levels of coagulation and fibrinolytic factors and proinflammatory cytokines in original and processed ascitic fluid were measured. The Ascites Symptom Inventory-7 (ASI-7) scale was used for subjective symptom assessment before and after CART. RESULTS Body weight and waist circumference significantly decreased after CART, whereas serum EA did not significantly change after CART. Similar to the previous reports, ascitic fluid concentrations of total protein, albumin, high-density lipoprotein cholesterol, γ-globulin, and immunoglobulin G levels were significantly increased after CART; mild elevations in body temperature and interleukin 6 and tumor necrosis factor-alpha levels in ascitic fluid were also observed. Importantly, the levels of antithrombin-III, factor VII, and X, which are useful for patients with decompensated cirrhosis, were markedly increased in the reinfused fluid during CART. Finally, the total ASI-7 score was significantly lower following CART, compared with the pre-CART score. CONCLUSION CART is an effective and safe approach for the treatment of refractory ascites that allows the intravenous reinfusion of coagulation and fibrinolytic factors in the filtered and concentrated ascites.
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Weight-loss Independent Clinical and Metabolic Biomarkers Associated with Type 2 Diabetes Remission Post-bariatric/metabolic Surgery.
Chaiyasoot, K, Sakai, NS, Zakeri, R, Makaronidis, J, Crisóstomo, L, Alves, MG, Gan, W, Firman, C, Jassil, FC, Hall-Craggs, MA, et al
Obesity surgery. 2023;(12):3988-3998
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PURPOSE Remission of type 2 diabetes (T2D) can be achieved by many, but not all, people following bariatric/metabolic surgery. The mechanisms underlying T2D remission remain incompletely understood. This observational study aimed to identify novel weight-loss independent clinical, metabolic and genetic factors that associate with T2D remission using comprehensive phenotyping. MATERIALS AND METHODS Ten patients without T2D remission (non-remitters) were matched to 10 patients with T2D remission (remitters) for age, sex, type of surgery, body weight, BMI, post-operative weight loss, duration from surgery and duration of T2D. Detailed body composition assessed using magnetic resonance imaging, gut hormones, serum metabolomics, insulin sensitivity, and genetic risk scores for T2D and anthropometric traits were assessed. RESULTS Remitters had significantly greater β-cell function and circulating acyl ghrelin levels, but lower visceral adipose tissue (VAT): subcutaneous adipose tissue (SAT) ratio than non-remitters. Branched-chain amino acids (BCAAs) and VLDL particle size were the most discriminant metabolites between groups. A significant positive correlation between, VAT area, VAT:SAT ratio and circulating levels of BCAAs was observed, whereas a significant negative correlation between BCAAs and β-cell function was revealed. CONCLUSION We highlight a potentially novel relationship between VAT and BCAAs, which may play a role in glucoregulatory control. Improvement in β-cell function, and the role ghrelin plays in its recovery, is likely another key factor influencing T2D remission post-surgery. These findings suggest that adjunctive approaches that target VAT loss and restoration of BCAA metabolism might achieve higher rates of long-term T2D remission post-surgery.
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Dynamic Thiol-Disulfide Homeostasis in Lung Transplant Recipients.
Beyoglu, MA, Sahin, MF, Turkkan, S, Yazicioglu, A, Akbulut, ED, Neselioglu, S, Erel, O, Yekeler, E
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2023;(10):841-847
Abstract
OBJECTIVES In this study, we investigated dynamic thiol-disulfide homeostasis as a new indicator of oxidative stress in lung transplant recipients. In addition, we compared dynamic thiol-disulfide homeostasis parameters according to transplant indication and time after transplant. MATERIALS AND METHODS This study had a single-center, observational, randomized design. In terms of transplant indications, lung transplant recipients were grouped as chronic obstructive pulmonary disease, interstitial lung disease, bronchiectasis, and other indications. To make comparisons based on time after transplant, lung transplant recipients were categorized into the following groups: >6 and ≤24 months, >24 and ≤48 months, >48 and ≤72 months, and >72 months. A fully automated spectrophotometric technique was used to measure dynamic thiol-disulfide homeostasis in fasting blood samples. RESULTS Our study included 34 lung transplant recipients and 36 healthy volunteers. Native thiol (P = .005) and total thiol levels (P = .06) were lower in lung transplant recipients. Disulfide levels were similar. Disulfide-to-native thiol (P = .027) and disulfide-to-total thiol ratios (P = .027) were significantly higher in lung transplant recipients. Native thiol-to-total thiol ratios were lower in lung transplant recipients (P = .027). When we examined patients according to transplant indication, no statistically significant differences were found in dynamic thiol-disulfide homeostasis parameters, except for total thiol and disulfide levels. We also found no significant differences when we examined dynamic thiol-disulfide homeostasis parameters according to time after transplant. CONCLUSIONS Thiol-related antioxidant activity is significantly reduced after lung transplant, regardless of indication and transplant time. Ensuring oxidative balance in lung transplant recipients with an antioxidant supplement regimen can prevent damage from oxidative stress.
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Variables related to bronchopulmonary dysplasia severity: a Six-Year retrospective study.
Yan, B, Li, Y, Sun, M, Meng, Y, Li, X
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2023;(2):2248335
Abstract
OBJECTIVES This was a retrospective observational study conducted in a tertiary neonatal intensive care unit, in order to investigate factors which influenced the severity of bronchopulmonary dysplasia under NICHD new classification. METHODS Six years of clinical data with different grades of bronchopulmonary dysplasia patients were collected and analyzed, bivariate ordinal logistic regression model and multivariable ordinal logistic regression model were used with sensitivity analyses. RESULTS We identified seven variables were associated with the severity of BPD via a bivariate ordinal logistic regression model, including the level of referral hospital (OR 0.273;95% CI 0.117, 0.636), method of caffeine administration (OR 00.418;95% CI 0.177, 0.991), more than two occurrences of reintubation (OR 4.925;95% CI 1.878, 12.915), CPAP reapplication (OR 2.255;95% CI 1.059, 4.802), presence of positive sputum cultures (OR 2.574;95% CI 1.200, 5.519), the cumulative duration of invasive ventilation (OR 1.047;95% CI 1.017, 1.078), and postmenstrual age at the discontinuation of oxygen supplementation (OR 1.190;95% CI 1.027, 1.38). These seven variables were further analyzed via all multivariable ordinal logistic regression models, and we found that tertiary hospital birth and early administration of caffeine could reduce the severity of BPD by approximately 70% (OR 0.263;95% CI 0.090, 0.770) and 60% (OR 0.371;95% CI 0.138, 0.995), respectively. In contrast, multiple reintubations were related to higher BPD severity with an OR of 3.358 (95% CI 1.002, 11.252). CONCLUSION Improving perinatal care in level II hospitals, standardized caffeine administration, and optimized extubation strategy could potentially decrease the severity of BPD.
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Associations between neighborhood socioeconomic deprivation, IFNγ, and high-density lipoprotein particle size: Data from the Washington, D.C. cardiovascular health and needs assessment.
Ortiz-Whittingham, LR, Baumer, Y, Pang, APS, Sampson, M, Baez, AS, Rose, RR, Noonan, SH, Mendez-Silva, J, Collins, BS, Mitchell, VM, et al
Psychoneuroendocrinology. 2023;:106346
Abstract
INTRODUCTION Neighborhood socioeconomic deprivation is associated with increased cardiovascular risk factors, including inflammation. Inflammation plays an important role in modifying the cardioprotective function of high-density lipoprotein (HDL). Moreover, recent studies suggest that very high HDL is associated with adverse cardiovascular disease (CVD) outcomes. Thus, we sought to explore the relationships between neighborhood socioeconomic deprivation as a marker of chronic stress, inflammation, proprotein convertase subtilisin/kexin type 9 (PCSK9) (a core component of the HDL proteome), HDL characterisitcs, and biological aging as a predictor of CVD and all-cause mortality. METHODS Sixty African American subjects were recruited to the NIH Clinical Center as part of a community-based participatory research-designed observational study. Neighborhood deprivation index (NDI), a marker of neighborhood socioeconomic deprivation, was measured using US Census data. HDL characteristics (cholesterol, particle number, size, subspecies) were determined from NMR lipoprotein profiling, and plasma cytokines (IL-1β, IL-6, IL-8, TNFα, IFNγ) were measured using an ELISA-based multiplex technique. Epigenetic clock biomarkers of aging were measured using DNA methylation data obtained from participants' buffy coat samples. We used linear regression modeling adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index (BMI), and lipid-lowering medication use to investigate relationships of interest. RESULTS NDI directly associated with large HDL particle count (H7P) and IFNγ and trended toward significance with HDL-C and PCSK9. IFNγ and PCSK9 then directly associated with H7P. H7P also directly associated with higher DNA methylation phenotypic age (PhenoAge). CONCLUSION We highlight associations between neighborhood socioeconomic deprivation, IFNγ, PCSK9, HDL subspecies, and epigenetic biomarkers of aging. Taken together, our findings suggest indirect pathways linking neighborhood deprivation-related stress and inflammation to HDL and immune epigenetic changes. Moreover, these results add to recent work showing the pathogenicity of high HDL levels and underscore the need to understand how chronic stress-related inflammation and lipoprotein subspecies relate to CVD risk across diverse populations.
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Choriocapillaris Flow Deficit as a Biomarker for Diabetic Retinopathy and Diabetic Macular Edema: 3-Year Longitudinal Cohort.
Chen, Y, Zhu, Z, Cheng, W, Bulloch, G, Chen, Y, Liao, H, Li, Y, Liang, X, Huang, W, He, M, et al
American journal of ophthalmology. 2023;:76-86
Abstract
PURPOSE To investigate the relationship between choriocapillaris flow deficit percentage (CC FD%) by swept-source optical coherence tomography angiography (SS-OCTA) and 3-year risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development. DESIGN Prospective, observational cohort study. METHODS A total of 903 participants with type 2 diabetes mellitus (T2DM) without DR or with mild nonproliferative DR (NPDR) free of DME at baseline were followed up annually for 3 years. All participants underwent standard 7-field fundus photography and spectral-domain OCT. SS-OCTA was used for retinal and choriocapillaris imaging and 3 × 3-mm2 macular CC FD% was quantified. Univariate and multivariate logistic models were used to evaluate the association between CC FD% and 2 or more steps of DR progression and DME development. The additional predictive value of CC FD% for outcome events was assessed using C statistic, net reclassification index (NRI), and integrated discrimination improvement index (IDI). RESULTS Over 3 years, 295 of 1805 eyes (16.34%) developed DR progression, and 118 eyes (6.54%) developed DME. A higher average CC FD% was correlated with DR progression (odds ratio [OR], 3.41 per SD increase, 95% CI: 2.65-4.39, P < .001) and DME development (OR, 1.37 per SD increase, 95% CI: 1.06-1.77, P = .016) after adjusting for confounders. In the ETDRS regions, increased CC FD% in all fields was associated with DR progression; however, increased CC FD% in the inferior field was associated with DME development. Compared with the models based on established risk factors, the addition of average CC FD% significantly improved the C statistics for DR progression (0.712 to 0.777, P < .001) and DME occurrence (0.743 to 0.773, P = .044). The estimated NRIs and IDIs (all >0) indicated that the addition of CC FD% led to a significant improvement in the discriminative performance for end points. CONCLUSION CC FD% is independently associated with DR progression and DME development in the Chinese T2DM population and provides incremental predictive value beyond traditional risk factors and retinal microvascular parameters. Further inclusion of CC FD% in DR prediction models helps guide population-based screening and personalized management.
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Risk of Bleeding Associated With Outpatient Use of Rivaroxaban in VTE Management at a National Referral Hospital in Western Kenya.
Njuguna, D, Nwaneri, F, Prichard, AC, Manji, I, Kigen, G, Busakhala, N, Nyanje, S, O'Neil, E, Pastakia, SD
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2023;:10760296231184216
Abstract
There is limited data on the bleeding safety profile of direct oral anticoagulants, such as rivaroxaban, in low- and middle-income country settings like Kenya. In this prospective observational study, patients newly started on rivaroxaban or switching to rivaroxaban from warfarin for the management of venous thromboembolism (VTE) within the national referral hospital in western Kenya were assessed to determine the frequency of bleeding during treatment. Bleeding events were assessed at the 1- and 3-month visits, as well as at the end of follow-up. The International Society of Thrombosis and Hemostasis (ISTH) and the Bleeding Academic Research Consortium (BARC) criteria were used to categorize the bleeding events, and descriptive statistics were used to summarize categorical variables. Univariate and multivariate logistic regression model was used to calculate unadjusted and adjusted associations between patient characteristics and bleeding. The frequency of any type of bleeding was 14.4% (95% CI: 9.3%-20.8%) for an incidence rate of 30.9 bleeding events (95% CI: 20.1-45.6) per 100 patient-years of follow-up. The frequency of major bleeding was 1.9% while that of clinically relevant non-major bleeding was 13.8%. In the multivariate logistic regression model, being a beneficiary of the national insurance plan was associated with a lower risk of bleeding, while being unemployed was associated with a higher bleeding risk. The use of rivaroxaban in the management of VTE was associated with a higher frequency of bleeding. These findings warrant confirmation in larger and more targeted investigations in a similar population.