Advancements in metabolic-associated steatotic liver disease research: Diagnostics, small molecule developments, and future directions.

Metabolic (dysfunction)-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, is a growing global health concern with no approved pharmacological treatments. At the same time, there are no standard methods to definitively screen for the presence of MASLD because of its progressive nature and symptomatic commonality with other disorders. Recent advances in molecular understanding of MASLD pathophysiology have intensified research on development of new drug molecules, repurposing of existing drugs approved for other indications, and an educated use of dietary supplements for its treatment and prophylaxis. This review focused on depicting the latest advancements in MASLD research related to small molecule development for prophylaxis or treatment and diagnosis, with emphasis on mechanistic basis at the molecular level.

PARS PLANA VITRECTOMY WITH OR WITHOUT INTERNAL LIMITING MEMBRANE PEEL FOR MACULAR HOLE: A Systematic Review and Meta-Analysis.

PURPOSE: To compare the efficacy and safety of pars plana vitrectomy with and without internal limiting membrane (ILM) peeling for macular hole (MH). METHODS: A systematic literature search on Ovid MEDLINE, Embase, Cochrane Library, and Google Scholar was performed from January 2000 to 2023. The primary outcome was the final best-corrected visual acuity (BCVA). Secondary outcomes included MH closure rates and the need for repeat surgery. The authors performed a random-effects meta-analysis on Review Manager 5.4. RESULTS: Fourteen studies on 880 eyes were included. Pars plana vitrectomy with and without ILM peel achieved a similar final BCVA ( P = 0.66). However, pars plana vitrectomy without ILM peeling achieved a significantly better final BCVA in eyes with closed MHs (WMD = 0.05 logMAR, 95% CI, 0.01-0.10, P = 0.02). Pars plana vitrectomy with ILM peeling achieved a significantly higher primary MH closure rate (RR = 1.21, 95% CI, 1.04-1.42, P = 0.02) and lower incidence of MH reoperation (RR = 0.19, 95% CI, 0.11-0.33, P < 0.001). The final MH closure rate ( P = 0.12) and incidence of MH recurrence ( P = 0.25) were similar between groups. CONCLUSION: Pars plana vitrectomy with and without ILM peel achieved a similar final BCVA. However, pars plana vitrectomy without ILM peeling achieved a better final BCVA in eyes with closed MHs. ILM peeling achieved a greater primary MH closure rate and reduced need for reoperation.

THE ABILITY OF ARTIFICIAL INTELLIGENCE CHATBOTS ChatGPT AND GOOGLE BARD TO ACCURATELY CONVEY PREOPERATIVE INFORMATION FOR PATIENTS UNDERGOING OPHTHALMIC SURGERIES.

INTRODUCTION: To determine whether the two popular artificial intelligence chatbots, ChatGPT and Bard, can provide high-quality information concerning procedure description, risks, benefits, and alternatives of various ophthalmic surgeries. METHODS: ChatGPT and Bard were prompted with questions pertaining to the description, potential risks, benefits, alternatives, and implications of not proceeding with various surgeries in different subspecialties of ophthalmology. Six common ophthalmic procedures were included in the authors' analysis. Two comprehensive ophthalmologists and one subspecialist graded each response independently using a 5-point Likert scale. RESULTS: Likert grading for accuracy was significantly higher for ChatGPT in comparison with Bard (4.5 ± 0.6 vs. 3.8 ± 0.8, P < 0.0001). Generally, ChatGPT performed better than Bard even when questions were stratified by the type of ophthalmic surgery. There was no significant difference between ChatGPT and Bard for response length (2,104.7 ± 271.4 characters vs. 2,441.0 ± 633.9 characters, P = 0.12). ChatGPT responded significantly slower than Bard (46.0 ± 3.0 vs. 6.6 ± 1.2 seconds, P < 0.0001). CONCLUSION: Both ChatGPT and Bard may offer accessible and high-quality information relevant to the informed consent process for various ophthalmic procedures. Nonetheless, both artificial intelligence chatbots overlooked the probability of adverse events, hence limiting their potential and introducing patients to information that may be difficult to interpret.

Intravitreal Triamcinolone Acetonide for Diabetic Macular Edema and Macular Edema Secondary to Retinal Vein Occlusion: A Meta-Analysis.

BACKGROUND: The comparative safety and efficacy of different doses of intravitreal triamcinolone acetonide (IVTA) for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is unclear. OBJECTIVES: This meta-analysis aimed to compare the safety and efficacy of different doses of IVTA in this setting. METHODS: A systematic literature search for randomized clinical trials (RCTs) was conducted on Cochrane Library, Ovid MEDLINE, and EMBASE from January 2005 to May 2022. Studies that reported on patients with DME or ME secondary to RVO that received treatment with different doses of IVTA were included. A random-effects meta-analysis was performed. Cochrane's Risk of Bias Tool 2 was used to assess the risk of bias, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were used to assess certainty of evidence. RESULTS: Five RCTs reporting on 1,041 eyes at baseline were included in this meta-analysis. In eyes with ME secondary to RVO, high-dose (4 mg) IVTA achieved a significantly better change in best-corrected visual acuity (WMD = -4.75 ETDRS letters, 95% CI = [-7.73, -1.78], p = 0.002) and reduction in retinal thickness (WMD = -93.02 µm, 95% CI = [-153.23, -32.82], p = 0.002) at months 4-6 compared to low-dose (1-2 mg) IVTA. However, high-dose IVTA had a higher risk of intraocular pressure-related adverse events (RR = 2.99, 95% CI = [1.05, 8.50], p = 0.04) and cataract surgery (RR = 5.67, 95% CI = [3.09, 10.41], p < 0.00001) than low-dose IVTA in eyes with ME secondary to RVO. These efficacy and safety differences in high-dose and low-dose IVTA were not observed in DME eyes. CONCLUSIONS: The RCT evidence in this setting is limited. High-dose IVTA achieved greater improvements in visual acuity and reductions in retinal thickness than low-dose IVTA at months 4-6. However, high-dose IVTA had a less favorable safety profile than low-dose IVTA. The significance of these outcomes was based on patients with ME secondary to RVO, but not DME.

Pars Plana Vitrectomy with or without Internal Limiting Membrane Peel for Epiretinal Membrane: A Systematic Review and Meta-Analysis.

BACKGROUND: The safety and effectiveness of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling remains poorly understood for the treatment of epiretinal membrane (ERM). OBJECTIVES: Our study aims to compare the safety and effectiveness of PPV with and without ILM peeling for ERM. METHODS: A systematic literature search was conducted on Ovid MEDLINE, Embase, Cochrane Library, and Google Scholar from January 2000 to January 2023 for comparative studies reporting visual and anatomical outcomes for patients with ERM that received PPV with or without ILM peeling. Primary outcomes included best-corrected visual acuity (BCVA) at last study observation and change in BCVA from baseline. Secondary outcomes included retinal thickness (RT) at last study observation, change in RT from baseline, risk of ERM recurrence, and adverse events. A random-effects meta-analysis was performed. Risk of bias of randomized controlled trials was assessed using the Risk of Bias 2 tool of observational studies using the Risk of Bias in Non-randomized Studies of Interventions-I tool. The certainty of evidence of outcomes was evaluated using Grading of Recommendations, Assessment, Development and Evaluation criteria. RESULTS: Nineteen studies reporting on 1,291 eyes at baseline were included. PPV with and without ILM peel achieved a similar BCVA at last study observation (p = 0.68) and change in BCVA from baseline (p = 0.79). These findings remained consistent irrespective of whether simultaneous phacoemulsification was performed. PPV with ILM peel achieved a significantly lower incidence of ERM recurrence (risk ratio [RR] = 0.26, 95% CI = [0.13, 0.51], p < 0.0001) and additional surgery (RR = 0.17, 95% CI = [0.04, 0.74], p = 0.02) compared to PPV without ILM peel. CONCLUSION: PPV with and without ILM peel achieved a similar BCVA at last study observation in ERM patients. Patients treated with PPV and ILM peel also had a reduced risk of ERM recurrence and lower reoperation risk. These conclusions are associated with a moderate certainty of evidence and potential for bias from multiple non-randomized studies.

Artificial Intelligence Chatbots' Understanding of the Risks and Benefits of Computed Tomography and Magnetic Resonance Imaging Scenarios.

PURPOSE: Patients may seek online information to better understand medical imaging procedures. The purpose of this study was to assess the accuracy of information provided by 2 popular artificial intelligence (AI) chatbots pertaining to common imaging scenarios' risks, benefits, and alternatives. METHODS: Fourteen imaging-related scenarios pertaining to computed tomography (CT) or magnetic resonance imaging (MRI) were used. Factors including the use of intravenous contrast, the presence of renal disease, and whether the patient was pregnant were included in the analysis. For each scenario, 3 prompts for outlining the (1) risks, (2) benefits, and (3) alternative imaging choices or potential implications of not using contrast were inputted into ChatGPT and Bard. A grading rubric and a 5-point Likert scale was used by 2 independent reviewers to grade responses. Prompt variability and chatbot context dependency were also assessed. RESULTS: ChatGPT's performance was superior to Bard's in accurately responding to prompts per Likert grading (4.36 ± 0.63 vs 3.25 ± 1.03 seconds, P < .0001). There was substantial agreement between independent reviewer grading for ChatGPT (κ = 0.621) and Bard (κ = 0.684). Response text length was not statistically different between ChatGPT and Bard (2087 ± 256 characters vs 2162 ± 369 characters, P = .24). Response time was longer for ChatGPT (34 ± 2 vs 8 ± 1 seconds, P < .0001). CONCLUSIONS: ChatGPT performed superior to Bard at outlining risks, benefits, and alternatives to common imaging scenarios. Generally, context dependency and prompt variability did not change chatbot response content. Due to the lack of detailed scientific reasoning and inability to provide patient-specific information, both AI chatbots have limitations as a patient information resource.

Role of ERK1/2 Signaling in Cinnabarinic Acid-Driven Stanniocalcin 2-Mediated Protection against Alcohol-Induced Apoptosis.

We have previously shown that a bona fide aryl hydrocarbon receptor (AhR) agonist, cinnabarinic acid (CA), protects against alcohol-induced hepatocyte apoptosis via activation of a novel AhR target gene, stanniocalcin 2 (Stc2). Stc2 translates to a secreted disulfide-linked hormone, STC2, known to function in cell development, calcium and phosphate regulation, angiogenesis, and antiapoptosis-albeit the comprehensive mechanism by which the CA-AhR-STC2 axis confers antiapoptosis is yet to be characterized. In this study, using RNA interference library screening, downstream antiapoptotic molecular signaling components involved in CA-induced STC2-mediated protection against ethanol-induced apoptosis were investigated. RNA interference library screening of kinases and phosphatases in Hepa1 cells and subsequent pathway analysis identified mitogen-activated protein kinase (MAPK) signaling as a critical molecular pathway involved in CA-mediated protection. Specifically, phosphorylation of ERK1/2 was induced in response to CA treatment without alterations in p38 and JNK signaling pathways. Silencing Stc2 in Hepa1 cells and in vivo experiments performed in Stc2-/- (Stc2 knockout) mice, which failed to confer CA-mediated protection against ethanol-induced apoptosis, showed abrogation of ERK1/2 activation, underlining the significance of ERK1/2 signaling in CA-STC2-mediated protection. In conclusion, activation of ERK1/2 signaling in CA-driven AhR-dependent Stc2-mediated protection represents a novel mechanism of protection against acute alcohol-induced apoptosis. SIGNIFICANCE STATEMENT: Previous studies have shown the role of stanniocalcin 2 (Stc2) in cinnabarinic acid (CA)-mediated protection against alcohol-induced apoptosis. Here, using RNA interference library screening and subsequent in vivo studies, the functional significance of ERK1/2 activation in CA-induced Stc2-mediated protection against acute ethanol-induced apoptosis was identified. This study is thus significant as it illustrates a comprehensive downstream mechanism by which CA-induced Stc2 protects against alcoholic liver disease.

Anti-Vascular Endothelial Growth Factor Therapy Regimens for Polypoidal Choroidal Vasculopathy: A Systematic Review.

INTRODUCTION: There are no guidelines on the optimal anti-vascular endothelial growth factor (anti-VEGF) monotherapy regimen for patients with polypoidal choroidal vasculopathy (PCV). In this study, we aimed to assess the comparative safety and efficacy of different treatment regimens of anti-VEGF monotherapy for PCV. METHODS: We conducted a systematic literature search on Ovid MEDLINE, Embase, and Cochrane Library from January 2000 to May 2023 for comparative articles reporting on different treatment regimens of anti-VEGF agents in PCV. Our primary outcomes were the final best-corrected visual acuity (BCVA) and the change in BCVA from baseline. Secondary outcomes were the final retinal thickness (RT), the change in RT from baseline, the rate of polyp closure, and the incidence of adverse events. RESULTS: A total of 10,440 studies were screened, and seven studies reporting on 636 eyes with PCV at baseline were included in this systematic review. One RCT of 53 eyes found a similar final BCVA, change in BCVA from baseline, final RT, and complete polyp closure rate between a treat-and-extend (T&E) regimen and a bimonthly fixed-dosing regimen of aflibercept. This trial also found superiority of T&E for change in RT from baseline. One observational study of 33 eyes found a similar BCVA at last study observation between a pro re nata (PRN) regimen and bimonthly fixed-dosing regimen of aflibercept. One observational study of 42 eyes found a similar change in BCVA from baseline and complete polyp closure rate between a PRN regimen and bimonthly fixed-dosing regimen of aflibercept. One RCT of 249 eyes found a similar change in BCVA and RT from baseline, as well as polyp closure, between a T&E regimen and fixed 12-week dosing regimen of conbercept. One observational study of 30 eyes found a superiority of T&E aflibercept for change in BCVA and risk of polyp recurrence, compared to a PRN regimen. CONCLUSION: Overall, there is a paucity of evidence comparing various treatment regimens of anti-VEGF therapy in patients with PCV. This limited evidence suggests that current treatment regimens are similarly efficacious, though T&E aflibercept achieved superior outcomes when compared to bimonthly dosing or PRN in some individual studies. Further trials are needed to confirm or refute these findings.

Understanding the diagnosis of superior mesenteric artery syndrome: analysis of the location of duodenal impression on upper gastrointestinal studies.

BACKGROUND: Upper gastrointestinal (GI) contrast studies are frequently requested to aid superior mesenteric artery syndrome diagnosis, a rare entity. Compression of the third duodenal part is expected to be mid-to-left of the midline where the superior mesenteric artery arises from the aorta; however, a duodenal impression to the right of the midline due to normal anatomic impression by the inferior vena cava (IVC) is often encountered and frequently misdiagnosed. OBJECTIVE: The purpose of this study was to determine the frequencies of (1) normal right-of-midline duodenal impressions and (2) mid-to-left of midline compressions in upper GI studies in a tertiary pediatric referral center. MATERIALS AND METHODS: All upper GI studies performed at our institution over 2 years were retrospectively evaluated to determine whether the duodenum had vertical duodenal impression to the right of the vertebral midline, mid-to-left of the vertebral midline, or no identifiable duodenal impression at all. RESULTS: In total, 538 upper GI studies were included in this analysis. A total of 275 male and 247 female patients between 0 and 17 years of age (median: 6 years, range: 1 month-17 years) were included. Of 538 total upper GI studies, there were 240 studies (44.6%) with a right-of-midline impression. There were only 10 studies (1.9%) with a mid-to-left of midline compression, and 9/10 also showed a concurrent right-sided impression sign. CONCLUSION: Right-of-midline duodenal impression is a normal anatomic finding caused by the IVC and should not be confused with superior mesenteric artery syndrome. In the presence of an appropriate clinical context, proximal duodenal dilation, "to-and-fro" motion of contrast, and duodenal impression at mid-to-left of midline, a diagnosis of superior mesenteric artery syndrome should be considered.

Study of Thyroid Profile in Patients of Type II Diabetes Mellitus.

INTRODUCTION: Thyroid hormones play an indispensable role in various metabolic process in our body. Excess or deficiency of either insulin or thyroid hormones can result in functional abnormalities of one another. Though it has been since long recognised that diabetes and thyroid disorder share a complex interplay of factors, the present study is planned to study the thyroid profile in patients of type 2 diabetes mellitus. MATERIALS: To study the Thyroid profile in patients of Type 2 Diabetes. Observational, single centre, case control study. All patients of either gender, aged 30 to 60 years, with Type 2 diabetes mellitus were included in the study. RESULT: it was found that only 61% of the patients with Diabetes were euthyroid. Amongst the patients with thyroid disorder, hypothyroidism was more prevalent than hyperthyroidism 31% and 10% respectively. On further assessment with respect to primary and subclinical thyroid disorder, it was found that subclinical hypothyroidism (21%) was more common as compared to Primary hypothyroidism (10%) and subclinical hyperthyroidism (5%) was more common than hyperthyroidism (3%) in the patients with diabetes. CONCLUSION: The study concluded that screening for thyroid dysfunction among patients with diabetes mellitus should be routinely performed, to recognize these dysfunctions early. This will ensure timely therapeutic intervention and in turn will improve the management of both diseases leading to better quality of life and decreasing the burden of complications. References American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care 2018;41(Suppl 1):S13-S27. Akbar DH, Ahmed MM, Al-Mughales J. Thyroid dysfunction and thyroid autoimmunity in Saudi type 2 diabetics. Acta Diabetol 2006;43(1):14-18.

Comparative Performance of ChatGPT and Bard in a Text-Based Radiology Knowledge Assessment.

PURPOSE: Bard by Google, a direct competitor to ChatGPT, was recently released. Understanding the relative performance of these different chatbots can provide important insight into their strengths and weaknesses as well as which roles they are most suited to fill. In this project, we aimed to compare the most recent version of ChatGPT, ChatGPT-4, and Bard by Google, in their ability to accurately respond to radiology board examination practice questions. METHODS: Text-based questions were collected from the 2017-2021 American College of Radiology's Diagnostic Radiology In-Training (DXIT) examinations. ChatGPT-4 and Bard were queried, and their comparative accuracies, response lengths, and response times were documented. Subspecialty-specific performance was analyzed as well. RESULTS: 318 questions were included in our analysis. ChatGPT answered significantly more accurately than Bard (87.11% vs 70.44%, P < .0001). ChatGPT's response length was significantly shorter than Bard's (935.28 ± 440.88 characters vs 1437.52 ± 415.91 characters, P < .0001). ChatGPT's response time was significantly longer than Bard's (26.79 ± 3.27 seconds vs 7.55 ± 1.88 seconds, P < .0001). ChatGPT performed superiorly to Bard in neuroradiology, (100.00% vs 86.21%, P = .03), general & physics (85.39% vs 68.54%, P < .001), nuclear medicine (80.00% vs 56.67%, P < .01), pediatric radiology (93.75% vs 68.75%, P = .03), and ultrasound (100.00% vs 63.64%, P < .001). In the remaining subspecialties, there were no significant differences between ChatGPT and Bard's performance. CONCLUSION: ChatGPT displayed superior radiology knowledge compared to Bard. While both chatbots display reasonable radiology knowledge, they should be used with conscious knowledge of their limitations and fallibility. Both chatbots provided incorrect or illogical answer explanations and did not always address the educational content of the question.

Chemotherapy-Induced Toxicities: An Imaging Primer[Formula: see text].

The Coronavirus Disease of 2019 (COVID-19) pandemic has caused significant delays in the delivery of cancer treatments in Canada. As cancer treatment and imaging volumes return to normal, radiologists will encounter more cases of chemotherapy-induced toxicities. These toxicities have varied appearances on imaging, and can affect multiple organ systems. The purpose of this review is to offer a unified resource for general radiologists regarding the imaging appearances of chemotherapy-induced toxicities.

Decoding Cinnabarinic Acid-Specific Stanniocalcin 2 Induction by Aryl Hydrocarbon Receptor.

Aryl hydrocarbon receptor (AhR) is a ligand-mediated transcription factor known for regulating response to xenobiotics, including prototypical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the activation of CYP1A1 expression. Upon ligand-binding, AhR translocates to the nucleus, interacts with the AhR nuclear translocator, and binds to xenobiotic response elements (XREs; GCGTG) present in the promoter region of AhR-regulated genes. Recently, we identified a novel tryptophan catabolite, cinnabarinic acid (CA), as an endogenous AhR agonist capable of activating expression of AhR target gene stanniocalcin 2 (stc2). The CA-driven stc2 induction bestowed cytoprotection against hepatotoxicity in an AhR-dependent manner. Interestingly, only CA but not TCDD was able to induce stc2 expression in liver, and CA was unable to upregulate the TCDD responsive cyp1a1 gene. In this report, we identified CA-specific histone H4 lysine 5 acetylation and H3 lysine 79 methylation at the AhR-bound stc2 promoter. Moreover, histone H4 lysine 5 acetylation writer, activating transcription factor 2 (Atf2), and H3 lysine 79 methylation writer, disruptor of telomeric silencing 1-like histone lysine methyltransferase (Dot1l), were interacting with the AhR complex at the stc2 promoter exclusively in response to CA treatment concurrent with the histone epigenetic marks. Suppressing Atf2 and Dot1l expression using RNA interference confirmed their role in stc2 expression. CRISPR/Cas9-assisted replacement of cyp1a1 promoter-encompassing XREs with stc2 promoter XREs resulted in CA-dependent induction of cyp1a1, underlining a fundamental role of quaternary structure of XRE sequence in agonist-specific gene regulation. In conclusion, CA-driven recruitment of specific chromatin regulators to the AhR complex and resulting histone epigenetic modifications may serve as a molecular basis for agonist-specific stc2 regulation by AhR. SIGNIFICANCE STATEMENT: Results reported here provide a mechanistic explanation for the agonist-specific differential gene regulation by identifying interaction of aryl hydrogen receptor with specific chromatin regulators concomitant with unique histone epigenetic marks. This study also demonstrated that the agonist-specific target-gene expression can be transferred with the gene-specific promoter xenobiotic response element-sequence in the context of chromatin architecture.

Cinnabarinic Acid Provides Hepatoprotection Against Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition in which excess lipids accumulate in the liver and can lead to a range of progressive liver disorders including non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. While lifestyle and diet modifications have proven to be effective as NAFLD treatments, they are not sustainable in the long-term, and currently no pharmacological therapies are approved to treat NAFLD. Our previous studies demonstrated that cinnabarinic acid (CA), a novel endogenous Aryl hydrocarbon Receptor (AhR) agonist, activates the AhR target gene, Stanniocalcin 2, and confers cytoprotection against a plethora of ER/oxidative stressors. In this study, the hepatoprotective and anti-steatotic properties of CA were examined against free fatty-acid-induced in vitro and high-fat-diet fed in vivo NAFLD models. The results demonstrated that CA treatment significantly lowered weight gain and attenuated hepatic lipotoxicity both before and after the established fatty liver, thereby protecting against steatosis, inflammation, and liver injury. CA mitigated intracellular free fatty acid uptake concomitant with the downregulation of CD36/fatty acid translocase. Genes involved in fatty acid and triglyceride synthesis were also downregulated in response to CA treatment. Additionally, suppressing AhR and Stc2 expression using RNA interference in vitro verified that the hepatoprotective effects of CA were absolutely dependent on both AhR and its target, Stc2. Collectively, our results demonstrate that the endogenous AhR agonist, CA, confers hepatoprotection against NAFLD by regulating hepatic fatty acid uptake and lipogenesis. SIGNIFICANCE STATEMENT: In this study using in vitro and in vivo models, we demonstrate that cinnabarinic acid (CA), an endogenous AhR agonist, provides protection against non-alcoholic fatty liver disease. CA bestows cytoprotection against steatosis and liver injury by controlling expression of several key genes associated with lipid metabolism pathways, limiting the hepatic lipid uptake, and controlling liver inflammation. Moreover, CA-induced hepatoprotection is absolutely dependent on AhR and Stc2 expression.

RISK OF INTRAOCULAR INFLAMMATION AFTER INJECTION OF ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS: A Meta-analysis.

PURPOSE: This meta-analysis investigates the incidence of intraocular inflammation (IOI) after intravitreal antivascular endothelial growth factor injections in neovascular age-related macular degeneration. METHODS: A systematic search was performed on Ovid MEDLINE, Embase, and Cochrane Central from January 2005 to April 2021. Randomized controlled trials comparing IOI after intravitreal bevacizumab, ranibizumab, brolucizumab, or aflibercept in neovascular age-related macular degeneration were included. Primary outcomes were sight-threatening IOI, final best-corrected visual acuity, and change in best-corrected visual acuity from baseline. Secondary outcomes included the incidence of other IOI events. Meta-analysis was performed using a random-effects model. RESULTS: Overall, 11,460 unique studies were screened, of which 14 randomized controlled trials and 6,759 eyes at baseline were included. There was no difference between agents for the risk of endophthalmitis and retinal vascular occlusion. Compared with aflibercept, brolucizumab had a higher incidence of generalized IOI (risk ratio = 6.24, 95% confidence interval = [1.40-27.90]) and vitreous haze/floaters (risk ratio = 1.64, 95% confidence interval = [1.00-2.67]). There were no significant differences between comparators for other secondary end points. CONCLUSION: There was no difference in the risk of severe sight-threatening IOI outcomes between intravitreal antivascular endothelial growth factor agents. There was a significantly higher risk of generalized IOI after brolucizumab relative to aflibercept. Our results alongside other recent safety findings suggest the need for further investigation in the risk-benefit profile of brolucizumab for the treatment of neovascular age-related macular degeneration.

Anti-Vascular Endothelial Growth Factor Treatment Compared with Steroid Treatment for Retinal Vein Occlusion: A Meta-Analysis.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) and steroid treatment are both used for macular edema (ME) secondary to retinal vein occlusion (RVO), however a continual reevaluation of their comparative efficacy is required. OBJECTIVES: This meta-analysis aimed to compare the efficacy and safety of intravitreal anti-VEGF agents and intravitreal steroids for the treatment of ME secondary to RVO. METHODS: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials for studies published between January 2005 and November 2021. Randomized controlled trials (RCTs) reporting on patients with ME secondary to RVO who were treated with intravitreal steroids or anti-VEGF agents were included. A random effects meta-analysis was performed. RESULTS: 879 eyes from 11 RCTs were included. At the last study observation, intravitreal anti-VEGF agents were associated with a significantly better best corrected visual acuity (WMD = -0.14 logMAR, 95% CI = [-0.19, -0.09], p < 0.00001) and lower retinal thickness (WMD = -38.01 µm, 95% CI = [-56.17, -19.85], p < 0.0001) relative to intravitreal steroids. Similar findings were found at 3-12 month time points. Intravitreal anti-VEGF agents were associated with a significantly lower incidence of IOP-related adverse events (RR = 0.28, 95% CI = [0.15, 0.51], p < 0.0001), cataract development/progression (RR = 0.22, 95% CI = [0.09, 0.49], p = 0.0003), and conjunctival hemorrhage (RR = 0.52, 95% CI = [0.32, 0.86], p = 0.01). CONCLUSIONS: Our meta-analysis found superiority of intravitreal anti-VEGF agents relative to intravitreal steroids for the treatment of ME secondary to RVO with regards to visual acuity, anatomic outcomes, and safety endpoints.

Validation of New Interactive Nutrition Assistant - Diet in India Study of Health (NINA-DISH) FFQ with multiple 24-h dietary recalls among pregnant women in Pune, India.

Adequate dietary intake is critical to prevent adverse pregnancy outcomes. India has a high burden of maternal and child morbidity and mortality, but there is a lack of adequate tools to assess dietary intake. We validate an FFQ, New Interactive Nutrition Assistant - Diet in India Study of Health (NINA-DISH), among pregnant women living with and without HIV in Pune, India. Women were selected from a cohort study investigating immune responses to HIV and latent tuberculosis during pregnancy. The FFQ was administered during the third trimester and validated against multiple 24-h dietary recalls (24-HDR) collected in second and third trimesters. Data for analysis were available from fifty-eight women out of seventy enrolled into this sub-study, after excluding those with incomplete data or implausible energy intake. The median (Q1, Q3) age of study participants was 23 (20, 25) years. Median (Q1, Q3) daily energy intakes were 10 552 (8000, 11 958) and 10 673 (8510, 13 962) kJ by 24-HDR and FFQ, respectively, with FFQ overestimating nutrient intake. Pearson correlations between log-transformed estimates from FFQ and 24-HDR for energy, protein, carbohydrate, fat, Fe and Zn were 0·47, 0·48, 0·45, 0·33, 0·4 and 0·54, respectively. Energy-adjusted and de-attenuated correlations ranged from 0·41 (saturated fat) to 0·73 (Na). The highest misclassification into extreme tertiles was observed for fat (22 %), saturated fat (21 %) and Na (21 %). Bias existed at higher intake levels as observed by Bland-Altman plots. In conclusion, NINA-DISH is a valid and feasible tool for estimating dietary intakes among urban pregnant women in Western India.

Needleless electrospun phytochemicals encapsulated nanofibre based 3-ply biodegradable mask for combating COVID-19 pandemic.

The emergence of COVID-19 pandemic has severely affected human health and world economies. According to WHO guidelines, continuous use of face mask is mandatory for personal protection for restricting the spread of bacteria and virus. Here, we report a 3-ply cotton-PLA-cotton layered biodegradable face-mask containing encapsulated phytochemicals in the inner-filtration layer. The nano-fibrous PLA filtration layer was fabricated using needleless electrospinning of PLA & phytochemical-based herbal-extracts. This 3-layred face mask exhibits enhanced air permeability with a differential pressure of 35.78 Pa/cm2 and superior bacterial filtration efficiency of 97.9% compared to conventional face masks. Close-packed mesh structure of the nano-fibrous mat results in effective adsorption of particulate matter, aerosol particles, and bacterial targets deep inside the filtration layer. The outer hydrophobic layer of mask exhibited effective blood splash resistance up to a distance of 30 cm, ensuring its utilization for medical practices. Computational analysis of constituent phytochemicals using the LibDock algorithm predicted inhibitory activity of chemicals against the protein structured bacterial sites. The computational analysis projected superior performance of phytochemicals considering the presence of stearic acid, oleic acid, linoleic acid, and Arachidic acid exhibiting structural complementarity to inhibit targeted bacterial interface. Natural cotton fibers and PLA bio-polymer demonstrated promising biodegradable characteristics in the presence of in-house cow-dung based biodegradation slurry. Addition of jaggery to the slurry elevated the biodegradation performance, resulting in increment of change of weight from 07% to 12%. The improved performance was attributed to the increased sucrose content in biodegradation slurry, elevating the bacterial growth in the slurry. An innovative face mask has shown promising results for utilization in day-to-day life and medical frontline workers, considering the post-pandemic environmental impacts.

Chemical-free transfer of patterned reduced graphene oxide thin films for large area flexible electronics and nanoelectromechanical systems.

In this paper, a wet-dry hybrid technique to transfer patterned reduced graphene oxide (rGO) thin film to arbitrary substrates at predetermined locations without using any chemicals is reported. The transfer process involves water-assisted delamination of rGO, followed by dry transfer to an acceptor substrate using viscoelastic stamp. Patterned reduced graphene oxide films are transferred to silicon dioxide (SiO2/Si) substrate to begin with. Subsequently, the method is deployed to transfer rGO to different polymer substrates such as poly(methyl methacrylate) (PMMA), and crosslinked poly(4-vinylphenol) (c-PVP), which are commonly used as gate dielectric in flexible electronic applications. The credibility of the transfer process with precise spatial positioning on the target substrate leads to fabrication of freely suspended reduced graphene oxide membrane towards nanoelectromechanical systems (NEMS) based devices such as nanomechanical drum resonators.

An Indian Experience of Endoscopic Treatment of Obesity by Using a Novel Technique of Endoscopic Sleeve Gastroplasty (Accordion Procedure).

INTRODUCTION: Endoscopic Sleeve gastroplasty (ESG) is a novel minimally invasive endoscopic restrictive bariatric procedure. We studied the safety, effectiveness, 6-month weight loss outcomes of ESG. METHODS: We prospectively collected data for patients undergoing ESG at a tertiary care referral center. Laboratory investigations were performed preoperatively, and at 6 months post-operatively. Anthropometric measurements were noted pre and post-operatively at a frequency of 3 months for a 6-month follow-up. Patients with BMI ≥28 kg/m2 who were ready for multidisciplinary follow up for at least 6 months were part of the study. Weight was evaluated at 1, 3 and 6 months' post procedure, and percent of total weight loss (%TWL) and percent of extra weight loss (% EWL) was calculated. Adverse events and new-onset symptoms were recorded. RESULTS: This prospective study included 58 patients, [55(94.8%)females] who underwent ESG (Jun 2018 - July 2019) using the Over Stitch device (Apollo Endosurgery, Inc., Austin, Texas, US). Mean age was 42.1 years (range 23-53) and mean BMI (kg/m2) was 37.88 (range 28.4-42.9). A median of 5 plications (range 4-6) were used to provide a tubular restriction to the gastric cavity. Mean procedural time (min) was 55 (Range 45 - 86). The mean (±SD) weight reduced significantly from baseline of 98.3±20.4 to 81.8±19.1 at 6 months (p<0.001). The mean BMI reduced significantly from baseline of 37.88±5.76 to 31.37±5.23 at 6months (p<0.001). The mean % of TWL was 8.8 (5.6-16.1), 12.6(10.4-19.1) and 17.1 (11.2-24.1) at 1, 3 and 6 months respectively. The % of EWL was 21.3(12.3-34.3), 30.5(17.7-45.6) and 42.8 (24.5-61.9) at 1, 3 and 6 months respectively. No major complications developed, and patients were discharged on postoperative day 2 (+4 days). Nausea 29 (50%) and moderate to severe abdominal pain 14 (24.1%) were the most common adverse events, treated conservatively. Stitch loosening was noted in 1(1.7%) patient at third month who underwent resuturing. CONCLUSIONS: ESG appears safe and effective in treating obesity at our center. Mindfulness to reduction in %TWL, %EWL and BMI are critical in evaluating the initial success of ESG. Long term follow-up is required to assess for its sustained effect. Further research into dietary and behavioral modifications with ESG is warranted.