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6. Cardiovascular Considerations and Implications for Treatment in Psoriasis: An Updated Review

Author

Mehta H, Narang T, Dogra S, Handa S, Hatwal J, and Batta A

Subjects
psoriasis, cardiovascular diseases, tnf inhibitors, methotrexate, cardiovascular risk, inflammation., Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Hitaishi Mehta,1 Tarun Narang,1 Sunil Dogra,1 Sanjeev Handa,1 Juniali Hatwal,2 Akash Batta3 1Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India; 2Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India; 3Department of Cardiology, Dayanand Medical College and Hospital (DMCH), Ludhiana, 141001, IndiaCorrespondence: Akash Batta, Department of Cardiology, Dayanand Medical College and Hospital, Civil Lines, Ludhiana, 141001, India, Tel +91 9815496786, Email akashbatta02@gmail.comAbstract: Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2– 3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.Plain Language Summary: Psoriasis is a skin condition that not only affects the skin but is also linked to issues in the body’s fat tissue, which can lead to inflammation and heart problems. The fat tissue in people with psoriasis contains various immune cells, contributing to obesity and insulin resistance. Research has found a strong connection between inflammation in fat tissues and cardiovascular problems in people with psoriasis. Specific substances released by fat tissue, like leptin, resistin, and adiponectin, can impact inflammation and cardiovascular health. Psoriasis patients often show increased levels of these substances.Treatment for psoriasis may influence cardiovascular health. Some studies suggest that certain medications, like methotrexate or TNF inhibitors, may lower the risk of heart events. However, there are also concerns about potential adverse effects, and further research is needed to fully understand how psoriasis treatments affect cardiovascular outcomes.To manage the cardiovascular risks associated with psoriasis, regular screening for heart-related issues is recommended. Lifestyle changes, such as a healthy diet, stress management, and smoking cessation, are also essential. Additionally, specific medications, like statins and metformin, may be beneficial in controlling cardiovascular risk factors in people with psoriasis.Despite advancements in understanding the relationship between psoriasis and cardiovascular health, there are still challenges. Research is ongoing to develop better screening guidelines and treatment strategies. Collaboration between dermatologists, rheumatologists, and cardiologists is crucial to address the complex nature of this condition and its impact on the heart.Keywords: psoriasis, cardiovascular diseases, TNF inhibitors, methotrexate, cardiovascular risk, inflammation

Published
2024

8. Effect Analysis of Heat Extraction on the Performance of the TAE

Author

Solanki, S. R., Desai, A. B., Mehta, H. B., Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Ivanov, Vitalii, Series Editor, Cavas-Martínez, Francisco, Editorial Board Member, di Mare, Francesca, Editorial Board Member, Haddar, Mohamed, Editorial Board Member, Kwon, Young W., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Mehta, Hemant B., editor, Rathod, Manish K., editor, Abiev, Rufat, editor, and Arıcı, Müslüm, editor

Published
2023
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13. Pore-scale supercritical CO2 dissolution and mass transfer under drainage conditions

Author

Chang, C, Zhou, Q, Oostrom, M, Kneafsey, TJ, and Mehta, H

Subjects
Geological carbon sequestration, Micromodel, Drainage, Dissolution, Mass transfer, Environmental Engineering, Applied Mathematics, Civil Engineering
Abstract

Recently, both core- and pore-scale imbibition experiments have shown non-equilibrium dissolution of supercritical CO2 (scCO2) and a prolonged depletion of residual scCO2. In this study, pore-scale scCO2 dissolution and mass transfer under drainage conditions were investigated using a two-dimensional heterogeneous micromodel and a novel fluorescent water dye with a sensitive pH range between 3.7 and 6.5. Drainage experiments were conducted at 9 MPa and 40 °C by injecting scCO2 into the sandstone-analogue pore network initially saturated by water without dissolved CO2 (dsCO2). During the experiments, time-lapse images of dye intensity, reflecting water pH, were obtained. These images show non-uniform pH in individual pores and pore clusters, with average pH levels gradually decreasing with time. Further analysis on selected pores and pore clusters shows that (1) rate-limited mass transfer prevails with slowly decreasing pH over time when the scCO2-water interface area is low with respect to the volume of water-filled pores and pore clusters, (2) fast scCO2 dissolution and phase equilibrium occurs when scCO2 bubbles invade into water-filled pores, significantly enhancing the area-to-volume ratio, and (3) a transition from rate-limited to diffusion-limited mass transfer occurs in a single pore when a medium area-to-volume ratio is prevalent. The analysis also shows that two fundamental processes – scCO2 dissolution at phase interfaces and diffusion of dsCO2 at the pore scale (10–100 µm) observed after scCO2 bubble invasion into water-filled pores without pore throat constraints – are relatively fast. The overall slow dissolution of scCO2 in the millimeter-scale micromodel can be attributed to the small area-to-volume ratios that represent pore-throat configurations and characteristics of phase interfaces. This finding is applicable for the behavior of dissolution at pore, core, and field scales when water-filled pores and pore clusters of varying size are surrounded by scCO2 at narrow pore throats.

Published
2017

17. Trends in Real-World Neovascular AMD Treatment Outcomes in the UK

Author

Mehta H, Kim LN, Mathis T, Zalmay P, Ghanchi F, Amoaku WM, and Kodjikian L

Subjects
anti-vascular endothelial growth factor (anti-vegf), macular degeneration, treatment, systematic review, aflibercept, ranibizumab, intravitreal therapy, united kingdom, national health service., Ophthalmology, RE1-994
Abstract

Hemal Mehta,1,2 Leah N Kim,2 Thibaud Mathis,3,4 Pardis Zalmay,1 Faruque Ghanchi,5 Winfried M Amoaku,6 Laurent Kodjikian3,4 1Ophthalmology, Royal Free London NHS Foundation Trust, London, UK; 2Macular Research Group, Save Sight Institute, Sydney University, Sydney, Australia; 3Service d’ophtalmologie, Hospices Civils de Lyon, Groupement Hospitalier Nord, Hôpital de la Croix-Rousse, Lyon, France; 4Laboratoire UMR-CNRS 5510 Matéis, Université Lyon 1, Villeurbanne, Lyon, France; 5Ophthalmology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK; 6Academic Ophthalmology and Vision Sciences, Division of Clinical Neurosciences, Eye and ENT Centre, Queen’s Medical Centre, University of Nottingham, Nottingham, UKCorrespondence: Hemal MehtaRoyal Free London NHS Foundation Trust, Pond Street, Hampstead, London, UKEmail HM@cantab.netPurpose: To report trends in real-world outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) over the last decade.Design: Systematic review.Methods: Medline, PubMed, and Embase databases were searched from 9 April 2010 to 8 April 2020 for publications that met the inclusion criteria: treatment-naïve eyes, UK-only data and ≥ 1 year of follow-up. ICHOM (International Consortium for Health Outcome Measures) outcomes and study quality were assessed. Visual acuity (VA) trends were assessed in studies with ≥ 100 eyes at baseline.Results: Twenty-six studies (n=25,761 eyes) were included, meeting 14– 17 out of 20 Institute of Health Economics Quality Appraisal of Case Series checklist domains. Only ranibizumab and aflibercept outcome data were available. The mean injection number in the first year of treatment was 5.9 in publications from 2010 to 2015 and 7.1 from 2015 to 2020. Average baseline VA and mean one-year, two-year and three-year VA gains gradually improved over the last decade. Longer-term studies reported that the visual gains achieved in the first year of treatment were rarely maintained, with under-treatment a likely contributing factor.Conclusion: UK real-world outcomes have improved over the last decade with improved service delivery and the adoption of more proactive treatment regimens but are still not always as impressive as registration clinical trial results. Access to longer-acting anti-VEGF therapies would reduce the treatment burden for patients, carers, and the healthcare system, potentially making replication of clinical trial results possible in the NHS.Keywords: anti-vascular endothelial growth factor, anti-VEGF, macular degeneration, treatment, systematic review, aflibercept, ranibizumab, intravitreal therapy

Published
2020

21. Initiation and maintenance of a Treat-and-Extend regimen for ranibizumab therapy in wet age-related macular degeneration: recommendations from the UK Retinal Outcomes Group

Author

Amoaku W, Balaskas K, Cudrnak T, Downey L, Groppe M, Mahmood S, Mehta H, Mohamed Q, Mushtaq B, Severn P, Vardarinos A, Yang Y, and Younis S

Subjects
ranibizumab, age-related macular degeneration, nAMD, treat and extend, anti-VEGF treatment., Ophthalmology, RE1-994
Abstract

Winfried Amoaku,1 Konstantinos Balaskas,2,3 Tomas Cudrnak,4 Louise Downey,5 Markus Groppe,6 Sajjad Mahmood,7 Hemal Mehta,8 Quresh Mohamed,9 Bushra Mushtaq,10 Philip Severn,11 Athanasios Vardarinos,12 Yit Yang,13 Saad Younis14 1Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK; 2NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and University College of London Institute of Ophthalmology, London, UK; 3University of Manchester, Manchester, UK; 4Royal Eye Infirmary, University Hospitals Plymouth NHS Trust, Plymouth, UK; 5Hull and East Yorkshire Eye Hospital, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK; 6Ophthalmology, Stoke Mandeville, Buckinghamshire Healthcare NHS Trust, Aylesbury, UK; 7Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 8Royal Free London NHS Foundation Trust, London, UK; 9Gloucestershire Eye Unit, Cheltenham General Hospital, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK; 10Birmingham and Midland Eye Centre, Sandwell and West Birmingham NHS Trust, Birmingham, UK; 11South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK; 12Eye Treatment Centre, West Suffolk Hospital, West Suffolk NHS Foundation Trust, Bury St Edmunds, UK; 13Wolverhampton Eye Infirmary, The Royal Wolverhampton NHS Trust, Wolverhampton, UK; 14Ophthalmology, Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK Abstract: The treatment of neovascular (wet) age-related macular degeneration (AMD) with ranibizumab is now very well established in terms of efficacy and safety. Recent clinical trials and real-world studies have demonstrated the advantages of a Treat-and-Extend (T&E) regimen, and many hospital departments are now in the process of adopting this new regimen in favor of the pro re nata regimen for initiating and continuing ranibizumab therapy for patients with wet AMD. The comprehensive spectrum of issues related to implementation of the regimen is covered qualitatively in ten didactic topics provided by a group of clinicians with direct experience of this regimen in their department. The topics include definition, new and previously treated eyes, management of high-frequency injections, maximum extensions, discontinuing T&E, bilateral cases, clerical, audit, and patient counseling. This article aims to provide a useful resource for the implementation of the T&E regimen. A quantitative summary of the visual outcomes in key publications is also provided in this article. This article should be a valuable resource for staff training. Keywords: ranibizumab, age-related macular degeneration, nAMD, Treat and Extend, anti-VEGF treatment

Published
2018

23. CHROMATIC NUMBER OF 2-STRONG PRODUCT GRAPH.

Author

Mehta, H. S. and George, J.

Subjects
NEW product development, NUMBER theory, INTERSECTION graph theory
Abstract

Cartesian product, tensor product, and strong product are well-known product graphs, which have been studied in detail. Some of these products are generalized by defining 2-Cartesian product, 2-tensor product, and distance product. Additionally, certain basic graph parameters of these products have been studied. Recently, a new graph product, 2-strong product graph has been defined, and the connectedness of this graph has been discussed. In this paper, we studied chromatic number and clique number of 2-strong product graph. [ABSTRACT FROM AUTHOR]

Published
2024

24. Five-year outcomes of eyes initially enrolled in the 2-year BEVORDEX trial of bevacizumab or dexamethasone implants for diabetic macular oedema

Author

Cornish, EE, Teo, KYC, Gillies, MC, Lim, LL, Nguyen, V, Wickremasinghe, S, Mehta, H, McAllister, IL, Fraser-Bell, S, Cornish, EE, Teo, KYC, Gillies, MC, Lim, LL, Nguyen, V, Wickremasinghe, S, Mehta, H, McAllister, IL, and Fraser-Bell, S

Abstract

BACKGROUND: The BEVORDEX trial compared outcomes of eyes with diabetic macular oedema (DMO) randomised to receive either intravitreal dexamethasone (DEX-) implant or bevacizumab over 2 years. We assessed long-term efficacy and safety outcomes 5 years from enrolment. METHODS: Patients received standard clinical care after they finished the study. Their files were reviewed for visual and anatomical outcomes, post-trial treatments and complications. RESULTS: Three-year and five-year data were available for 82% and 59% of eyes enrolled in the BEVORDEX study, respectively. Visual acuity gains at end of trial were generally lost by both treatment groups at 5 years but the macular thickness did not change from end of trial to 5 years. A similar proportion of eyes from each treatment group gained ≥10 letters at 5 years from enrolment in the BEVORDEX trial.Eyes that were initially randomised to the DEX-implant group had significantly fewer treatments but were more likely to develop proliferative diabetic retinopathy (PDR) over the 5-year period compared with eyes initially randomised to bevacizumab. The proportion of eyes that had cataract surgery by 5 years was similar between initial treatment groups. CONCLUSIONS: Eyes in the BEVORDEX trial had similar 5-year rates of cataract surgery, however, more eyes converted to PDR in the group initially treated with DEX-implant. Eyes that were initially treated for 2 years with either intravitreal DEX-implant of bevacizumab followed by standard of care had similar visual and anatomical outcomes at 5 years.

Published
2023

26. Adrenal function recovery after durable oral corticosteroid sparing with benralizumab in the PONENTE study

Author

Menzies-Gow, A., Gurnell, M., Heaney, L. G., Corren, J., Bel, E. H., Maspero, J., Harrison, T., Jackson, D. J., Price, D., Lugogo, N., Kreindler, J., Burden, A., de Giorgio-Miller, A., Faison, S., Padilla, K., Martin, U. J., Gil, E. G., Ardusso, L., Bazerque, R. F., Doreski, P. A. C., Elias, P. C., Gattolin, G., Medina, A. C., Ruiz, X. B., Salvado, A., Del Olmo Sansone, R. A., Wehbe, L., Verra, F. J. B., Brusselle, G., Pilette, C., Martinot, J. -B., Antila, M. A., Blanco, D. C., Cerci, A., Cunha, T. M., Fiss, E., Franza, L., Machado, A. S., De Mattos, W. L. L. D., Grava, S., Minamoto, S. E. T., De Oliveira, C. A., Cheema, A. S., Dorscheid, D., Fera, T. A. E., Gagnon, R., Philteos, G., Sussman, G., Yang, W. H. -C., Aguilar, C. D., Jaller, R., Jazime, M. L., Serrano, F. O., Vanegas, A. C., Vargas, L. K., Villegas, M. F., Hilberg, O., Nielsen, H. B., Nielsen, J., Weinreich, U. M., Ulrik, C. S., Adam, S. M., Deslee, G., Pegliasco, H., Pradelli, J., Roux, P. -M., Russier, M., Deckelmann, R., Eich, A., Forster, A., Herth, F., Kirschner, J., Kirsten, A. -M., Schuhmann, M., Schultz, T. K., Ludwig-Sengpiel, A., Teber, I., Zimmermann, G. S., Almerigogna, F., Celi, A., Paggiaro, P., D'Amato, M., Palange, P., Pirina, P., Spanevello, A., Colin, D. D. H., Hernandez, A. R., Garcia, E. A. R., Gonzalez, E. M., Terrones, R. A. R., Javier, R. C., Suarez, J. F. R., Cheimihska, M., Cudzik, K., Olech-Cudzik, A., Filipek, K., Golinski, L., Kwasniewski, A., Madra-Rogacka, D., Mroz, R., Nittner-Marszalska, M., Pawlukiewicz, M., Lekarska, P. P., Pioszczuk, A., Springer, E., Swiderska, A., Zurowska-Gebala, M., Emelyanov, A. V., Kurbacheva, O., Odegova, A., Peskov, A., Petrov, D. V., Rubanik, T. V., Vasilev, M., Vershinina, M., Barcala, F. J. G., Blanco, V. R., Fernandez, A. M. P., Fernandez, C. G., Garcia, J. M. I., Munoz, A. V. A., Ramos, C. C., Sanz, C. C., Bjermer, L., Chen, C. -Y., Fang, W. -F., Hang, L. -W., Hsu, J. -Y., Kuo, H. -P., Lee, K. -Y., Shen, S. -Y., Sheu, C. -C., Gore, R., Saralaya, D., Alpizar, S. A., Bansal, S., Ismail, H., Kaelin, T. D., Koura, F., Lee, M. D., Maddipati, V., Malur, A., Mcevoy, C. E., Mehta, H., Mohan, A., Moore, W. C., Krings, J., Pippins, A., Deaton, I., Hmieleski, B., Field, P., Reibman, J., Siri, D. D., Sumino, K., Swenson, C., Tilley, S. L., Villareal, M., Pulmonology, and Pulmonary medicine

Subjects
Pulmonary and Respiratory Medicine, Adrenal Cortex Hormones, Humans, Anti-Asthmatic Agents, Recovery of Function, Asthma, Adrenal Insufficiency
Abstract

BackgroundOral corticosteroid (OCS) dependence among patients with severe eosinophilic asthma can cause adverse outcomes, including adrenal insufficiency. PONENTE's OCS reduction phase showed that, following benralizumab initiation, 91.5% of patients eliminated corticosteroids or achieved a final dosage ≤5 mg·day−1(median (range) 0.0 (0.0–40.0) mg).MethodsThe maintenance phase assessed the durability of corticosteroid reduction and further adrenal function recovery. For ∼6 months, patients continued benralizumab 30 mg every 8 weeks without corticosteroids or with the final dosage achieved during the reduction phase. Investigators could prescribe corticosteroids for asthma exacerbations or increase daily dosages for asthma control deteriorations. Outcomes included changes in daily OCS dosage, Asthma Control Questionnaire (ACQ)-6 and St George's Respiratory Questionnaire (SGRQ), as well as adrenal status, asthma exacerbations and adverse events.Results598 patients entered PONENTE; 563 (94.1%) completed the reduction phase and entered the maintenance phase. From the end of reduction to the end of maintenance, the median (range) OCS dosage was unchanged (0.0 (0.0–40.0) mg), 3.2% (n=18/563) of patients experienced daily dosage increases, the mean ACQ-6 score decreased from 1.26 to 1.18 and 84.5% (n=476/563) of patients were exacerbation free. The mean SGRQ improvement (–19.65 points) from baseline to the end of maintenance indicated substantial quality-of-life improvements. Of patients entering the maintenance phase with adrenal insufficiency, 32.4% (n=104/321) demonstrated an improvement in adrenal function. Adverse events were consistent with previous reports.ConclusionsMost patients successfully maintained maximal OCS reduction while achieving improved asthma control with few exacerbations and maintaining or recovering adrenal function.

Published
2022

27. Incidence, Risk Factors, and Outcomes of Rhegmatogenous Retinal Detachment after Intravitreal Injections of Anti-VEGF for Retinal Diseases

Author

Gabrielle, Pierre-Henry, primary, Nguyen, Vuong, additional, Arnould, Louis, additional, Viola, Francesco, additional, Zarranz-Ventura, Javier, additional, Barthelmes, Daniel, additional, Creuzot-Garcher, Catherine, additional, Gillies, Mark, additional, Squirrell, D., additional, Gilhotra, J., additional, Brooijmans, C., additional, Tigchelaar-Besling, O., additional, Cohn, A., additional, Chen, F., additional, McGeorge, A., additional, Welch, S., additional, Jaross, N., additional, Peters, P., additional, Barry, R., additional, McLean, I., additional, Guillaumie, T., additional, Miri, A., additional, Korobelnik, J., additional, Gabrielle, P., additional, Weber, M., additional, Walid, B., additional, Tick, S., additional, Valen, S., additional, Field, A., additional, Wickremasinghe, S., additional, Dayajeewa, C., additional, Wells, J., additional, Essex, R., additional, Dunlop, A., additional, Michalova, K., additional, Ng, C., additional, Young, S., additional, MIMOUN, G., additional, Generic, C., additional, Guymer, R., additional, Carnota, P., additional, Torres Borrego, C., additional, Dolz Marco, R., additional, Gallego-Pinazo, R., additional, Pareja Esteban, J., additional, García Layana, A., additional, Saenz-de-Viteri, M., additional, Uzzan, J., additional, Ferrier, R., additional, Ah-Chan, J., additional, Chow, L., additional, Steiner, H., additional, Amini, A., additional, Clark, G., additional, Wittles, N., additional, Windle, P., additional, Vingerling, J., additional, Clement, C., additional, Gillies, M., additional, Hunt, A., additional, Beaumont, P., additional, Cottee, L., additional, Lee, K., additional, Mack, H., additional, Louw, Z., additional, Lusthaus, J., additional, Chen, J., additional, Landers, J., additional, Billing, K., additional, Saha, N., additional, Lake, S., additional, Qatarneh, D., additional, Phillips, R., additional, Perks, M., additional, Banon, K., additional, Guarro, M., additional, Londoño, G., additional, Rethati, C., additional, Sararols, L., additional, Suarez, J., additional, Viola, F., additional, Lan Oei, S., additional, Fraser-Bell, S., additional, Montejano Milner, R., additional, Arruabarrena, C., additional, Chong, E., additional, Lal, S., additional, Higueras, A., additional, Ascaso, F., additional, Boned Murillo, A., additional, Díaz, M., additional, Perez Rivases, G., additional, Alforja Castiella, S., additional, Bernal-Morales, C., additional, Casaroli-Marano, R., additional, Figueras-Roca, M., additional, Izquierdo-Serra, J., additional, Moll Udina, A., additional, Parrado-Carrillo, A., additional, Zarranz-Ventura, J., additional, escobar, j., additional, Lavid, F., additional, Alvarez Gil, M., additional, Catalán Muñoz, P., additional, Tena Sempere, M., additional, Cerri, L., additional, RICCI, F., additional, Broc Iturralde, L., additional, Campos Figueroa, P., additional, Gómez Sánchez, S., additional, Valldeperas, X., additional, Vilaplana, F., additional, Carreño, E., additional, Munoz Sanz, N., additional, Ventura Abreu, N., additional, Asencio Duran, M., additional, Calvo, P., additional, Sanchez, J., additional, Almazan Alonso, E., additional, Flores-Moreno, I., additional, Garcia Zamora, M., additional, Ciancas, E., additional, Gonzalez-Lopez, J., additional, de la Fuente, M., additional, Rodriguez Maqueda, M., additional, Cobos, E., additional, Lorenzo, D., additional, Cordoves, L., additional, Acebes, m., additional, Aparicio-Sanchis, S., additional, Fernández Hortelano, A., additional, Zarallo-Gallardo, J., additional, Azrak, C., additional, Piñero Sánchez, A., additional, Almuina-Varela, P., additional, García García, L., additional, Salinas Martínez, E., additional, Castilla Marti, M., additional, Campo Gesto, A., additional, Rodriguez Núñez, M., additional, Furness, G., additional, Ponsioen, T., additional, Wilson, G., additional, Manning, L., additional, McAllister, I., additional, Isaacs, Tim, additional, Invernizzi, A., additional, Castelnovo, L., additional, Michel, G., additional, Wolff, B., additional, Arnold, J., additional, Cass, H., additional, Chan, D., additional, Tan, T., additional, OToole, L., additional, Tang, K., additional, Chung, C., additional, Beylerian, H., additional, DAIEN, V., additional, Banerjee, G., additional, Morgan, M., additional, Reddie, I., additional, Ongkosuwito, J., additional, Verbraak, F., additional, Schlingemann, R., additional, piermarocchi, s., additional, Thompson, A., additional, Game, J., additional, Thompson, C., additional, Chalasani, R., additional, Chilov, M., additional, Fung, A., additional, Nothling, S., additional, Chong, R., additional, Hunyor, A., additional, Younan, C., additional, Barnes, R., additional, Sharp, D., additional, Vincent, A., additional, Murray, N., additional, Ah-Moye, S., additional, Hennings, C., additional, Mehta, H., additional, Monaco, P., additional, Cheung, G., additional, Karia, N., additional, Louis, D., additional, Every, S., additional, Lockie, P., additional, van Hecke, M., additional, van Lith-Verhoeven, J., additional, Wong, J., additional, Grigg, J., additional, Hinchcliffe, P., additional, Barthelmes, D., additional, Diaz De Durana Santa Coloma, E., additional, Garay-Aramburu, G., additional, Vujosevic, S., additional, Brosa Morros, H., additional, Daniell, M., additional, Harper, A., additional, Lim, L., additional, ODay, J., additional, Velazquez Villoria, D., additional, Hooper, C., additional, Klaassen-Broekema, N., additional, and Smit, R., additional

Published
2022
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33. Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study

Author

Hong, S., Kahkoska, A., Evans, M.D., N3C core authors, Alamgir, J., Johnson, S.G., Harper, J., Yang, K., Garcia, V., Bramante, C.T., Buse, J.B., Stürmer, T., Wilkins, K.J., Alexander, C., Abrahamsen, T., Huling, J.D., Hartman, K., Tronieri, J., Koraishy, F., and Mehta, H.

Abstract

Background While vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size. Methods Conducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome. Results 6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32–1.44), and mortality (RR 0.82, 0.41–1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28–0.98, p = 0.044) and mortality (RR 0.56, 95% CI 0.33–0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control. Conclusions There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.

Published
2022
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39. Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

Author

Skelly, DT, Harding, AC, Gilbert-Jaramillo, J, Knight, ML, Longet, S, Brown, A, Adele, S, Adland, E, Brown, H, Chinnakannan, S, Donnison, T, Ali, M, Rongkard, P, Pace, M, Zacharopoulou, P, Robinson, N, Csala, A, De Lara, C, Hutchings, CL, Mehta, H, Lee, LN, Edmans, M, Hackstein, C-P, Phalora, P, Li, W, Phillips, E, Malone, T, Ogbe, A, Jay, C, Tipoe, T, Tipton, T, Stafford, L, Mentzer, AJ, Johnson, SA, Amini, A, Marjot, T, Dimitriadis, S, Simmons, B, Deeks, A, Kerneis, S, Abuelgasim, H, Wilson, R, Thomas, SR, Watson, A, Alhussni, A, Cutteridge, J, Weeks, E, Denly, L, Lillie, K, Holmes, J, Matthews, PC, O’Donnell, D, Tan, TK, Schimanski, L, Huang, K-YA, Rijal, P, Turtle, L, de Silva, T, Richter, A, Duncan, CJA, Payne, RP, Moore, SC, Knight, JC, Cassar, MP, Raman, B, Neubauer, S, Fries, A, Talbot, NP, Petousi, N, Ho, L-P, Peng, Y, Dong, T, Camara, S, Marinou, S, Linder, A, Adlou, S, Kasanyinga, M, Bridges-Webb, A, Hill, J, Silva-Reyes, L, Blackwell, L, Frater, J, Goulder, P, Conlon, CP, Jeffery, K, Dold, C, Pollard, AJ, Sigal, A, de Oliveira, T, Townsend, AR, Klenerman, P, Dunachie, SJ, Barnes, E, Carroll, MW, and James, WS

Abstract

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.

Published
2021

46. MAIT cells in the liver environment

Author

Mehta, H, Willberg, C, and Klenerman, P

Subjects
Immunology
Abstract

MAIT cells are an important innate T cell population capable of recognising riboflavin-derived ligands presented by the evolutionary conserved MR1 molecule. The ability to activate MAIT cells either through their TCR or cytokines alone enables them to respond to both bacterial and viral infections. The liver is a common site of bacterial and viral infection, due partly to its anatomical setting and partly its tolerogenic environment. MAIT cell enrichment and function in the liver and their impairment in liver and non-liver diseases is not fully defined/understood. In this project I looked closely at the individual, liver resident, cell-specific influence on MAIT cells and their possible role in liver protection or pathogenesis. Using liver cell lines and primary MAIT cell co-cultures and flow cytometry I investigated the ability of liver resident cells to influence primary MAIT cells derived from healthy donors. I have identified that MAIT cells could be activated by LECs using both MR1 and cytokine pathway in response to bacterial stimuli which was not seen with hepatocytes or hepatic stellate cells. MAIT cells were suppressed indirectly in a contact-independent manner, by a small, soluble, COX-dependent, hepatocyte specific mediator/s. Strong suppression of MAIT IFN- by prostaglandins and a partial recovery with COX inhibitor treatment of hepatocytes strongly indicate the role of prostaglandins as well as other factors in controlling MAIT cell activation and function. Prostaglandins can be produced by several liver cell types, are primary involved in liver homeostasis and regeneration but can also impact MAIT cell function by potently suppressing their pro-inflammatory and cytotoxic capacity. The role of MAIT cells in liver disease was analysed by high dimensional, multiparametric spectral flow cytometry. MAIT cell numbers declined significantly in cirrhosis and LT, displayed an exhausted phenotype and were highly dysfunctional. Unsupervised analysis of the same cohort reveals exhaustion and loss of several MAIT cell-related populations which had reduced cytotoxic and inflammatory potential. Overall our data identifies the potential for MAIT cell activation by liver resident cells which can be altered by paracrine signals from neighbouring cells. Furthermore, the loss and functional defects in MAIT cells results in reduced liver protection.

Published
2021

47. Impact of a Yogic Breathing Technique on the Well-Being of Healthcare Professionals During the COVID-19 Pandemic

Author

Kanchibhotla Divya, Saisudha Bharathi, Mehta H Darshan, and Ramrakhyani Somya

Subjects
Sudarshan Kriya Yoga, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), education, 03 medical and health sciences, 0302 clinical medicine, Nursing, well-being, Health care, Pandemic, Medicine, 030212 general & internal medicine, Resilience (network), resilience, lcsh:R5-920, Health professionals, business.industry, lcsh:Public aspects of medicine, pandemic, lcsh:RA1-1270, General Medicine, Ayurvedic Medicine’s Role in Global Health, healthcare providers, Well-being, Original Article, business, lcsh:Medicine (General), Healthcare providers, 030217 neurology & neurosurgery
Abstract

Background The COVID-19 pandemic has created unprecedented challenges for healthcare globally, the brunt of which has been borne by the health care providers (HCPs). These challenges are felt more keenly in India, as they stretch an insufficiently resourced healthcare system. The long hours, cross over of responsibilities, lack of resources to adequately care for patients, and concerns around safety of self and loves ones, have led to a spike in anxiety, depression, insomnia and other stress – related disorders in healthcare providers. Sudarshan Kriya Yoga (SKY) is a mind-body intervention that has been studied in multiple clinical populations. Prior to this study, there has been no exploration of the impact of SKY on healthcare providers, specifically the impact of a mind-body intervention like SKY on HCPs during a pandemic. Objective This study aims to investigate the impact of SKY on the well-being of HCPs during the COVID-19 pandemic. Methods We conducted a pilot feasibility study with a single arm pre-post design. SKY was taught to participants in a 4-day online breath and meditation workshop. We measured outcomes related to depression, anxiety, resilience, life satisfaction, and quality of sleep. Results Ninety-two subjects completed the study survey before and after the intervention. A significant reduction was observed in the levels of stress, anxiety and depression immediately after the program. In addition, the participants reported sig1nificant improvement in life satisfaction, resilience, and the quality of their sleep. Conclusion The results indicate that SKY breathing technique had a positive impact on the well-being of healthcare professionals during the pandemic. Participants experienced improved quality of sleep, enhanced satisfaction with life, and increased resilience after SKY. This pilot study provides important data for future multi-site randomized controlled trials to study the impact of yogic techniques on well-being of the HCPs.

Published
2021

48. MOTS-c reduces myostatin and muscle atrophy signaling

Author

Kumagai, Hiroshi, Coelho, Ana Raquel, Wan, Junxiang, Mehta H , Hemal, Yen, Kelvin, Huang, Amy, Zempo, Hirofumi, Fuku, Noriyuki, Maeda, Seiji, Oliveira J , Paulo, Cohen, Pinchas, and Kim, Su-Jeong

Published
2022

50. Performance of two aromatic grasses grown in association with mulberry trees on degraded land in the north-western Himalayan foothills

Author

Tomar, J.M.S., Kumar, Pawan, Gupta, A.K., Kaushal, R., and Mehta, H.

Abstract

ABSTRACTThe study investigated the potential of aromatic-grass-based agroforestry systems to rehabilitate degraded land in the north-western Himalayas. Five treatments; sole lemon grass (Cymbopogon flexuosus) (LG), sole java grass sole (Cymbopogon winterianus) (JG), lemon grass + Morus alba(LG + M), java grass + M. alba(JG + M) and sole M. alba(M) were planted in a randomised block design and the systems were evaluated in terms of plant and tree growth and yields over three years and effects on soil quality characteristics. Considering the 3-year averages, the highest survival rate of the grass (95%) was recorded in sole lemon grass, while the highest plant height (117 cm), number of tillers clump−1(67), clump diameter (104 cm), fresh biomass (179 Mg ha−1), dry biomass (60 Mg ha−1) and oil yield (89 kg ha−1) of the grass were recorded for the lemon grass + M. albatreatment. The highest total fresh root weight (128.7 g clump−1) and number of total roots (511.7 clump−1) were recorded under sole lemon grass and for lateral root spread (78.8 cm) was recorded under sole java grass. The highest soil organic carbon and potassium concentrations were recorded in sole M. alba. The treatment with sole M. albawas recorded to have the highest values for the soil biological properties followed by the treatments with lemon grass.

Published
2023
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