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    Serum phosphate and mortality in incident dialysis patients in Australia and New Zealand
    Tiong, MK ; Ullah, S ; McDonald, SP ; Tan, S-J ; Lioufas, NM ; Roberts, MA ; Toussaint, ND (WILEY, 2021-06-01)
    AIM: Hyperphosphataemia is associated with increased adverse outcomes, including mortality. Re-examining this association using up-to-date data reflecting current and real-world practices, across different global regions and in both haemodialysis and peritoneal dialysis patients, is important. METHODS: We describe the association between serum phosphate and all-cause and cardiovascular mortality in incident dialysis patients between 2008 and 2018 using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Time-dependent Cox proportionate hazards models were used. Models were adjusted for available covariates and fitted for the overall cohort, and also each dialysis modality. RESULTS: 31 989 patients were followed over 97 122 person-years at risk (mean age at first dialysis 61 years, 38% female, 67% haemodialysis). We observed a U-shaped association between serum phosphate and all-cause mortality. In the fully adjusted model, categories of serum phosphate above and below 1.25-1.99 mmol/L were associated with progressively higher risk, reaching a hazard ratio of 2.13 (95% CI 1.93-2.36, p < .001) for serum phosphate ≥2.75 mmol/L, and 1.56 (95% CI 1.44-1.69, p < .001) for serum phosphate <1.00 mmol/L. Low and high levels of serum phosphate were also associated with increased risk of cardiovascular mortality, however the association with high serum phosphate was more pronounced ("J-shaped relationship"). The associations were consistent across sub-analyses of patients receiving haemodialysis and peritoneal dialysis treatment. CONCLUSION: In this large contemporary dialysis cohort, both high and low levels of serum phosphate were independently associated with increased risk of mortality. Future studies are required to determine whether treatment of abnormal serum phosphate levels improves mortality.
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    Redundancy in meta-analyses publications-Time to pull the plug.
    Ofori-Asenso, R ; Liew, D (Wiley, 2021-06)
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    Evaluation of palliative treatments in unresectable pancreatic cancer
    Choi, CC-M ; Choi, J ; Houli, N ; Smith, M ; Usatoff, V ; Lipton, L ; Chan, S (WILEY, 2021-04-18)
    BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) presents as unresectable disease in 80% of patients. Limited Australian data exists regarding management and outcome of palliative management for PDAC. This study aims to: (i) identify patients with PDAC being managed with palliative intent; (ii) assess the type of palliative management being used. METHODS: A prospectively maintained pancreatic database at Western Health (2015-2017) was used to identify patient demographics; stage and multidisciplinary decision regarding resectability and operative interventions; palliative care; use of chemotherapy, radiotherapy and; management of exocrine and endocrine insufficiency. Data on chemotherapy use, number of hospital admissions, emergency department attendances and intensive care unit admissions 30 days prior to death were recorded. RESULTS: One-hundred and eleven patients had diagnosis of PDAC, 15% with locally advanced and 45% with metastatic PDAC. Among the locally advanced and metastatic PDAC, 48% received biliary stent insertions, 93% had palliative care referral, 45% received palliative chemotherapy and 10% received radiotherapy. Dietitian referral occurred in 79% and 36% were prescribed with a pancreatic enzyme replacement therapy. Diabetes mellitus was present in 52% of which 31% was new onset. Within 30 days prior to death, 11% patients received palliative chemotherapy, 32% were hospitalized and 11% visited an emergency department more than once. Sixty-five percent died in hospital. CONCLUSION: A high proportion of patients diagnosed with locally advanced and metastatic PDAC received palliative care referrals and appropriate level of end-of-life care. Further prospective studies are necessary, examining the management and impacts of pancreatic insufficiency in this group.
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    Cost-analysis of opportunistic influenza vaccination in general medical inpatients.
    Darmaputra, DC ; Zaman, FY ; Khu, YL ; Nagalingam, V ; Liew, D ; Aung, AK (Wiley, 2021-04)
    Influenza vaccination is an important preventative health measure in the elderly and those with medical comorbidities. It has been shown to reduce hospitalisations, cardiovascular and respiratory complications. A significant proportion of patients admitted to general medicine are eligible for opportunistic inpatient influenza vaccination. This study explores the cost-effectiveness of such a strategy in reducing subsequent healthcare utilisation costs.
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    Caustic ingestions over 10 years in Victoria, Australia: high rates in migrants and women.
    Rouse, S ; Buckle, A ; Hebbard, G ; Metz, A ; Sood, S (Wiley, 2022-07)
    BACKGROUND: Caustic ingestion is relatively common in developing countries and can result in life-threatening sequelae. There is limited understanding of the epidemiology and incidence in Australia. AIMS: This statewide 10-year audit aims to document the rate of caustic injury in a defined Australian pouplation. METHODS: A retrospective review was conducted over 10 years (2007-2016), including all admissions to hospitals in Victoria. This includes a population of 5.9 million people and 22 hospitals. RESULTS: Three hundred and eighty-four cases of caustic ingestion were admitted to hospital between January 2007 and December 2016. The overall incidence was 7 cases/million/year. This cohort included 217 (56.5%) females, 193 (50.2%) overseas born patients and 196 (51%) people with a history of mental illness. The countries of birth with the highest incidence of caustic ingestion were Ethiopia (11 patients; 227 cases/million/year; relative risk (RR) 31.7; P < 0.0001), Sudan (11 patients; 161 cases/million/year; RR 22.6; P < 0.0001) and India (38 patients; 27 cases/million/year; RR 3.9; P < 0.0001). All had a significantly higher incidence than the Australian-born population of only 6.5 cases/million/year (RR 0.4; P < 0.0001). Of those born in India, Sudan and Ethiopia, rates of females (72%) were considerably higher than males. The overall mortality rate in this cohort was 2.3%. CONCLUSIONS: Caustic ingestion remains a significant cause of morbidity and health expenditure in Victoria, particularly among vulnerable groups such as recent female migrants from areas in Africa and India. The high frequency of events seen in migrant populations highlights the significant need for awareness of risks in these groups for the development of possible prevention strategies that are required.
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    Reliability of the breathing pattern assessment tool for in-person or remote assessment in people with asthma.
    Bondarenko, J ; Hew, M ; Button, B ; Webb, E ; Jackson, V ; Clark, R ; Holland, AE (Wiley, 2021-09)
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    Severe asthma assessment, management and the organisation of care in Australia and New Zealand: expert forum roundtable meetings
    Maltby, S ; McDonald, VM ; Upham, JW ; Bowler, SD ; Chung, LP ; Denton, EJ ; Fingleton, J ; Garrett, J ; Grainge, CL ; Hew, M ; James, AL ; Jenkins, C ; Katsoulotos, G ; King, GG ; Langton, D ; Marks, GB ; Menzies-Gow, A ; Niven, RM ; Peters, M ; Reddel, HK ; Thien, F ; Thomas, PS ; Wark, PAB ; Yap, E ; Gibson, PG (WILEY, 2021-02-01)
    Severe asthma imposes a significant burden on individuals, families and the healthcare system. Treatment is complex, due to disease heterogeneity, comorbidities and complexity in care pathways. New approaches and treatments improve health outcomes for people with severe asthma. However, emerging multidimensional and targeted treatment strategies require a reorganisation of asthma care. Consensus is required on how reorganisation should occur and what areas require further research. The Centre of Excellence in Severe Asthma convened three forums between 2015 and 2018, hosting experts from Australia, New Zealand and the UK. The forums were complemented by a survey of clinicians involved in the management of people with severe asthma. We sought to: (i) identify areas of consensus among experts; (ii) define activities and resources required for the implementation of findings into practice; and (iii) identify specific priority areas for future research. Discussions identified areas of unmet need including assessment and diagnosis of severe asthma, models of care and treatment pathways, add-on treatment approaches and patient perspectives. We recommend development of education and training activities, clinical resources and standards of care documents, increased stakeholder engagement and public awareness campaigns and improved access to infrastructure and funding. Further, we propose specific future research to inform clinical decision-making and develop novel therapies. A concerted effort is required from all stakeholders (including patients, healthcare professionals and organisations and government) to integrate new evidence-based practices into clinical care and to advance research to resolve questions relevant to improving outcomes for people with severe asthma.
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    Impact of COVID-19 Pandemic on Cardiovascular Testing in Asia
    Kudo, T ; Lahey, R ; Hirschfeld, CB ; Williams, MC ; Lu, B ; Alasnag, M ; Bhatia, M ; Henry Bom, H-S ; Dautov, T ; Fazel, R ; Karthikeyan, G ; Keng, FYJ ; Rubinshtein, R ; Better, N ; Cerci, RJ ; Dorbala, S ; Raggi, P ; Shaw, LJ ; Villines, TC ; Vitola, JV ; Choi, AD ; Malkovskiy, E ; Goebel, B ; Cohen, YA ; Randazzo, M ; Pascual, TNB ; Pynda, Y ; Dondi, M ; Paez, D ; Einstein, AJ ; Einstein, AJ ; Paez, D ; Dondi, M ; Better, N ; Cerci, R ; Dorbala, S ; Pascual, TNB ; Raggi, P ; Shaw, LJ ; Villines, TC ; Vitola, JV ; Williams, MC ; Pynda, Y ; Hinterleitner, G ; Lu, Y ; Morozova, O ; Xu, Z ; Hirschfeld, CB ; Cohen, Y ; Goebel, B ; Malkovskiy, E ; Randazzo, M ; Choi, A ; Lopez-Mattei, J ; Parwani, P ; Nasery, MN ; Goda, A ; Shirka, E ; Benlabgaa, R ; Bouyoucef, S ; Medjahedi, A ; Nailli, Q ; Agolti, M ; Aguero, RN ; Alak, MDC ; Alberguina, LG ; Arroñada, G ; Astesiano, A ; Astesiano, A ; Norton, CB ; Benteo, P ; Blanco, J ; Bonelli, JM ; Bustos, JJ ; Cabrejas, R ; Cachero, J ; Campisi, R ; Canderoli, A ; Carames, S ; Carrascosa, P ; Castro, R ; Cendoya, O ; Cognigni, LM ; Collaud, C ; Collaud, C ; Cortes, C ; Courtis, J ; Cragnolino, D ; Daicz, M ; De La Vega, A ; De Maria, ST ; Del Riego, H ; Dettori, F ; Deviggiano, A ; Dragonetti, L ; Embon, M ; Enriquez, RE ; Ensinas, J ; Faccio, F ; Facello, A ; Garofalo, D ; Geronazzo, R ; Gonza, N ; Gutierrez, L ; Guzzo, MA ; Guzzo, MA ; Hasbani, V ; Huerin, M ; Jäger, V ; Lewkowicz, JM ; López De Munaín, MNA ; Lotti, JM ; Marquez, A ; Masoli, O ; Masoli, OH ; Mastrovito, E ; Mayoraz, M ; Melado, GE ; Mele, A ; Merani, MF ; Meretta, AH ; Molteni, S ; Montecinos, M ; Noguera, E ; Novoa, C ; Sueldo, CP ; Ascani, SP ; Pollono, P ; Pujol, MP ; Radzinschi, A ; Raimondi, G ; Redruello, M ; Rodríguez, M ; Rodríguez, M ; Romero, RL ; Acuña, AR ; Rovaletti, F ; San Miguel, L ; Solari, L ; Strada, B ; Traverso, S ; Traverzo, SS ; Espeche, MDHV ; Weihmuller, JS ; Wolcan, J ; Zeffiro, S ; Sakanyan, M ; Beuzeville, S ; Boktor, R ; Butler, P ; Calcott, J ; Carr, L ; Chan, V ; Chao, C ; Chong, W ; Dobson, M ; Downie, D ; Dwivedi, G ; Elison, B ; Engela, J ; Francis, R ; Gaikwad, A ; Basavaraj, AG ; Goodwin, B ; Greenough, R ; Hamilton-Craig, C ; Hsieh, V ; Joshi, S ; Lederer, K ; Lee, K ; Lee, J ; Magnussen, J ; Mai, N ; Mander, G ; Murton, F ; Nandurkar, D ; Neill, J ; O'Rourke, E ; O'Sullivan, P ; Pandos, G ; Pathmaraj, K ; Pitman, A ; Poulter, R ; Premaratne, M ; Prior, D ; Ridley, L ; Rutherford, N ; Salehi, H ; Saunders, C ; Scarlett, L ; Seneviratne, S ; Shetty, D ; Shrestha, G ; Shulman, J ; Solanki, V ; Stanton, T ; Stuart, M ; Stubbs, M ; Swainson, I ; Taubman, K ; Taylor, A ; Thomas, P ; Unger, S ; Upton, A ; Vamadevan, S ; Van Gaal, W ; Verjans, J ; Voutnis, D ; Wayne, V ; Wilson, P ; Wong, D ; Wong, K ; Younger, J ; Feuchtner, G ; Mirzaei, S ; Weiss, K ; Maroz-Vadalazhskaya, N ; Gheysens, O ; Homans, F ; Moreno-Reyes, R ; Pasquet, A ; Roelants, V ; Van De Heyning, CM ; Ríos, RA ; Soldat-Stankovic, V ; Stankovic, S ; Albernaz Siqueira, MH ; Almeida, A ; Alves Togni, PH ; Andrade, JH ; Andrade, L ; Anselmi, C ; Araújo, R ; Azevedo, G ; Bezerra, S ; Biancardi, R ; Grossman, GB ; Brandão, S ; Pianta, DB ; Carreira, L ; Castro, B ; Chang, T ; Cunali, F ; Cury, R ; Dantas, R ; de Amorim Fernandes, F ; De Lorenzo, A ; De Macedo Filho, R ; Erthal, F ; Fernandes, F ; Fernandes, J ; Fernandes, F ; De Souza, TF ; Alves, WF ; Ghini, B ; Goncalves, L ; Gottlieb, I ; Hadlich, M ; Kameoka, V ; Lima, R ; Lima, A ; Lopes, RW ; Machado e Silva, R ; Magalhães, T ; Silva, FM ; Mastrocola, LE ; Medeiros, F ; Meneghetti, JC ; Naue, V ; Naves, D ; Nolasco, R ; Nomura, C ; Oliveira, JB ; Paixao, E ; De Carvalho, FP ; Pinto, I ; Possetti, P ; Quinta, M ; Nogueira Ramos, RR ; Rocha, R ; Rodrigues, A ; Rodrigues, C ; Romantini, L ; Sanches, A ; Santana, S ; Sara da Silva, L ; Schvartzman, P ; Matushita, CS ; Senra, T ; Shiozaki, A ; Menezes de Siqueira, ME ; Siqueira, C ; Smanio, P ; Soares, CE ; Junior, JS ; Bittencourt, MS ; Spiro, B ; Mesquita, CT ; Torreao, J ; Torres, R ; Uellendahl, M ; Monte, GU ; Veríssimo, O ; Cabeda, EV ; Pedras, FV ; Waltrick, R ; Zapparoli, M ; Naseer, H ; Garcheva-Tsacheva, M ; Kostadinova, I ; Theng, Y ; Abikhzer, G ; Barette, R ; Chow, B ; Dabreo, D ; Friedrich, M ; Garg, R ; Hafez, MN ; Johnson, C ; Kiess, M ; Leipsic, J ; Leung, E ; Miller, R ; Oikonomou, A ; Probst, S ; Roifman, I ; Small, G ; Tandon, V ; Trivedi, A ; White, J ; Zukotynski, K ; Canessa, J ; Muñoz, GC ; Concha, C ; Hidalgo, P ; Lovera, C ; Massardo, T ; Vargas, LS ; Abad, P ; Arturo, H ; Ayala, S ; Benitez, L ; Cadena, A ; Caicedo, C ; Moncayo, AC ; Moncayo, AC ; Gomez, S ; Gutierrez Villamil, CT ; Jaimes, C ; Londoño, J ; Londoño Blair, JL ; Pabon, L ; Pineda, M ; Rojas, JC ; Ruiz, D ; Escobar, MV ; Vasquez, A ; Vergel, D ; Zuluaga, A ; Gamboa, IB ; Castro, G ; González, U ; Baric, A ; Batinic, T ; Franceschi, M ; Paar, MH ; Jukic, M ; Medakovic, P ; Persic, V ; Prpic, M ; Punda, A ; Batista, JF ; Gómez Lauchy, JM ; Gutierrez, YM ; Gutierrez, YM ; Menéndez, R ; Peix, A ; Rochela, L ; Panagidis, C ; Petrou, I ; Engelmann, V ; Kaminek, M ; Kincl, V ; Lang, O ; Simanek, M ; Abdulla, J ; Bøttcher, M ; Christensen, M ; Gormsen, LC ; Hasbak, P ; Hess, S ; Holdgaard, P ; Johansen, A ; Kyhl, K ; Norgaard, BL ; Øvrehus, KA ; Rønnow Sand, NP ; Steffensen, R ; Thomassen, A ; Zerahn, B ; Perez, A ; Escorza Velez, GA ; Velez, MS ; Abdel Aziz, IS ; Abougabal, M ; Ahmed, T ; Allam, A ; Asfour, A ; Hassan, M ; Hassan, A ; Ibrahim, A ; Kaffas, S ; Kandeel, A ; Ali, MM ; Mansy, A ; Maurice, H ; Nabil, S ; Shaaban, M ; Flores, AC ; Poksi, A ; Knuuti, J ; Kokkonen, V ; Larikka, M ; Uusitalo, V ; Bailly, M ; Burg, S ; Deux, J-F ; Habouzit, V ; Hyafil, F ; Lairez, O ; Proffit, F ; Regaieg, H ; Sarda-Mantel, L ; Tacher, V ; Schneider, RP ; Ayetey, H ; Angelidis, G ; Archontaki, A ; Chatziioannou, S ; Datseris, I ; Fragkaki, C ; Georgoulias, P ; Koukouraki, S ; Koutelou, M ; Kyrozi, E ; Repasos, E ; Stavrou, P ; Valsamaki, P ; Gonzalez, C ; Gutierrez, G ; Maldonado, A ; Buga, K ; Garai, I ; Maurovich-Horvat, P ; Schmidt, E ; Szilveszter, B ; Várady, E ; Banthia, N ; Bhagat, JK ; Bhargava, R ; Bhat, V ; Bhatia, M ; Choudhury, P ; Chowdekar, VS ; Irodi, A ; Jain, S ; Joseph, E ; Kumar, S ; Girijanandan Mahapatra, PD ; Mitra, D ; Mittal, BR ; Ozair, A ; Patel, C ; Patel, T ; Patel, R ; Patel, S ; Saxena, S ; Sengupta, S ; Singh, S ; Singh, B ; Sood, A ; Verma, A ; Affandi, E ; Alam, PS ; Edison, E ; Gunawan, G ; Hapkido, H ; Hidayat, B ; Huda, A ; Mukti, AP ; Prawiro, D ; Soeriadi, EA ; Syawaluddin, H ; Albadr, A ; Assadi, M ; Emami, F ; Houshmand, G ; Maleki, M ; Rostami, MT ; Zakavi, SR ; Zaid, EA ; Agranovich, S ; Arnson, Y ; Bar-Shalom, R ; Frenkel, A ; Knafo, G ; Lugassi, R ; Maor Moalem, IS ; Mor, M ; Muskal, N ; Ranser, S ; Shalev, A ; Albano, D ; Alongi, P ; Arnone, G ; Bagatin, E ; Baldari, S ; Bauckneht, M ; Bertelli, P ; Bianco, F ; Bonfiglioli, R ; Boni, R ; Bruno, A ; Bruno, I ; Busnardo, E ; Califaretti, E ; Camoni, L ; Carnevale, A ; Casoni, R ; Cavallo, AU ; Cavenaghi, G ; Chierichetti, F ; Chiocchi, M ; Cittanti, C ; Colletta, M ; Conti, U ; Cossu, A ; Cuocolo, A ; Cuzzocrea, M ; De Rimini, ML ; De Vincentis, G ; Del Giudice, E ; Del Torto, A ; Della Tommasina, V ; Durmo, R ; Erba, PA ; Evangelista, L ; Faletti, R ; Faragasso, E ; Farsad, M ; Ferro, P ; Florimonte, L ; Frantellizzi, V ; Fringuelli, FM ; Gatti, M ; Gaudiano, A ; Gimelli, A ; Giubbini, R ; Giuffrida, F ; Ialuna, S ; Laudicella, R ; Leccisotti, L ; Leva, L ; Liga, R ; Liguori, C ; Longo, G ; Maffione, M ; Mancini, ME ; Marcassa, C ; Milan, E ; Nardi, B ; Pacella, S ; Pepe, G ; Pontone, G ; Pulizzi, S ; Quartuccio, N ; Rampin, L ; Ricci, F ; Rossini, P ; Rubini, G ; Russo, V ; Sacchetti, GM ; Sambuceti, G ; Scarano, M ; Sciagrà, R ; Sperandio, M ; Stefanelli, A ; Ventroni, G ; Zoboli, S ; Baugh, D ; Chambers, D ; Madu, E ; Nunura, F ; Asano, H ; Chimura, CM ; Fujimoto, S ; Fujisue, K ; Fukunaga, T ; Fukushima, Y ; Fukuyama, K ; Hashimoto, J ; Ichikawa, Y ; Iguchi, N ; Imai, M ; Inaki, A ; Ishimura, H ; Isobe, S ; Kadokami, T ; Kato, T ; Kudo, T ; Kumita, S ; Maruno, H ; Mataki, H ; Miyagawa, M ; Morimoto, R ; Moroi, M ; Nagamachi, S ; Nakajima, K ; Nakata, T ; Nakazato, R ; Nanasato, M ; Naya, M ; Norikane, T ; Ohta, Y ; Okayama, S ; Okizaki, A ; Otomi, Y ; Otsuka, H ; Saito, M ; Sakata, SY ; Sarai, M ; Sato, D ; Shiraishi, S ; Suwa, Y ; Takanami, K ; Takehana, K ; Taki, J ; Tamaki, N ; Taniguchi, Y ; Teragawa, H ; Tomizawa, N ; Tsujita, K ; Umeji, K ; Wakabayashi, Y ; Yamada, S ; Yamazaki, S ; Yoneyama, T ; Rawashdeh, M ; Batyrkhanov, D ; Dautov, T ; Makhdomi, K ; Ombati, K ; Alkandari, F ; Garashi, M ; Coie, TL ; Rajvong, S ; Kalinin, A ; Kalnina, M ; Haidar, M ; Komiagiene, R ; Kviecinskiene, G ; Mataciunas, M ; Vajauskas, D ; Picard, C ; Karim, NKA ; Reichmuth, L ; Samuel, A ; Allarakha, MA ; Naojee, AS ; Alexanderson-Rosas, E ; Barragan, E ; González-Montecinos, AB ; Cabada, M ; Rodriguez, DC ; Carvajal-Juarez, I ; Cortés, V ; Cortés, F ; De La Peña, E ; Gama-Moreno, M ; González, L ; Ramírez, NG ; Jiménez-Santos, M ; Matos, L ; Monroy, E ; Morelos, M ; Ornelas, M ; Ortga Ramirez, JA ; Preciado-Anaya, A ; Preciado-Gutiérrez, ÓU ; Barragan, AP ; Rosales Uvera, SG ; Sandoval, S ; Tomas, MS ; Sierra-Galan, LM ; Sierra-Galan, LM ; Siu, S ; Vallejo, E ; Valles, M ; Faraggi, M ; Sereegotov, E ; Ilic, S ; Ben-Rais, N ; Alaoui, NI ; Taleb, S ; Pa Myo, KP ; Thu, PS ; Ghimire, RK ; Rajbanshi, B ; Barneveld, P ; Glaudemans, A ; Habets, J ; Koopmans, KP ; Manders, J ; Pool, S ; Scholte, A ; Scholtens, A ; Slart, R ; Thimister, P ; Van Asperen, E-J ; Veltman, N ; Verschure, D ; Wagenaar, N ; Edmond, J ; Ellis, C ; Johnson, K ; Keenan, R ; Kueh, SHA ; Occleshaw, C ; Sasse, A ; To, A ; Van Pelt, N ; Young, C ; Cuadra, T ; Roque Vanegas, HB ; Soli, IA ; Issoufou, DM ; Ayodele, T ; Madu, C ; Onimode, Y ; Efros-Monsen, E ; Forsdahl, SH ; Hildre Dimmen, J-M ; Jørgensen, A ; Krohn, I ; Løvhaugen, P ; Bråten, AT ; Al Dhuhli, H ; Al Kindi, F ; Al-Bulushi, N ; Jawa, Z ; Tag, N ; Afzal, MS ; Fatima, S ; Younis, MN ; Riaz, M ; Saadullah, M ; Herrera, Y ; Lenturut-Katal, D ; Vázquez, MC ; Ortellado, J ; Akhter, A ; Cao, D ; Cheung, S ; Dai, X ; Gong, L ; Han, D ; Hou, Y ; Li, C ; Li, T ; Li, D ; Li, S ; Liu, J ; Liu, H ; Lu, B ; Ng, MY ; Sun, K ; Tang, G ; Wang, J ; Wang, X ; Wang, Z-Q ; Wang, Y ; Wang, Y ; Wu, J ; Wu, Z ; Xia, L ; Xiao, J ; Xu, L ; Yang, Y ; Yin, W ; Yu, J ; Yuan, L ; Zhang, T ; Zhang, L ; Zhang, Y-G ; Zhang, X ; Zhu, L ; Alfaro, A ; Abrihan, P ; Barroso, A ; Cruz, E ; Gomez, MR ; Magboo, VP ; Medina, JM ; Obaldo, J ; Pastrana, D ; Pawhay, CM ; Quinon, A ; Tang, JM ; Tecson, B ; Uson, KJ ; Uy, M ; Kostkiewicz, M ; Kunikowska, J ; Bettencourt, N ; Cantinho, G ; Ferreira, A ; Syed, G ; Arnous, S ; Atyani, S ; Byrne, A ; Gleeson, T ; Kerins, D ; Meehan, C ; Murphy, D ; Murphy, M ; Murray, J ; O'Brien, J ; Bang, J-I ; Bom, H ; Cho, S-G ; Hong, CM ; Jang, SJ ; Jeong, YH ; Kang, WJ ; Kim, J-Y ; Lee, J ; Namgung, CK ; So, Y ; Won, KS ; Majstorov, V ; Vavlukis, M ; Salobir, BG ; Štalc, M ; Benedek, T ; Benedek, I ; Mititelu, R ; Stan, CA ; Ansheles, A ; Dariy, O ; Drozdova, O ; Gagarina, N ; Gulyaev, VM ; Itskovich, I ; Karalkin, A ; Kokov, A ; Migunova, E ; Pospelov, V ; Ryzhkova, D ; Saifullina, G ; Sazonova, S ; Sergienko, V ; Shurupova, I ; Trifonova, T ; Ussov, WY ; Vakhromeeva, M ; Valiullina, N ; Zavadovsky, K ; Zhuravlev, K ; Alasnag, M ; Okarvi, S ; Saranovic, DS ; Keng, F ; Jason See, JH ; Sekar, R ; Yew, MS ; Vondrak, A ; Bejai, S ; Bennie, G ; Bester, R ; Engelbrecht, G ; Evbuomwan, O ; Gongxeka, H ; Vuuren, MJ ; Kaplan, M ; Khushica, P ; Lakhi, H ; Louw, L ; Malan, N ; Milos, K ; Modiselle, M ; More, S ; Naidoo, M ; Scholtz, L ; Vangu, M ; Aguadé-Bruix, S ; Blanco, I ; Cabrera, A ; Camarero, A ; Casáns-Tormo, I ; Cuellar-Calabria, H ; Flotats, A ; Fuentes Cañamero, ME ; García, ME ; Jimenez-Heffernan, A ; Leta, R ; Diaz, JL ; Lumbreras, L ; Marquez-Cabeza, JJ ; Martin, F ; Martinez de Alegria, A ; Medina, F ; Canal, MP ; Peiro, V ; Pubul-Nuñez, V ; Rayo Madrid, JI ; Rey, CR ; Perez, RR ; Ruiz, J ; Hernández, GS ; Sevilla, A ; Zeidán, N ; Nanayakkara, D ; Udugama, C ; Simonsson, M ; Alkadhi, H ; Buechel, RR ; Burger, P ; Ceriani, L ; De Boeck, B ; Gräni, C ; Juillet de Saint Lager Lucas, A ; Kamani, CH ; Kawel-Boehm, N ; Manka, R ; Prior, JO ; Rominger, A ; Vallée, J-P ; Khiewvan, B ; Premprabha, T ; Thientunyakit, T ; Sellem, A ; Kir, KM ; Sayman, H ; Sebikali, MJ ; Muyinda, Z ; Kmetyuk, Y ; Korol, P ; Mykhalchenko, O ; Pliatsek, V ; Satyr, M ; Albalooshi, B ; Ahmed Hassan, MI ; Anderson, J ; Bedi, P ; Biggans, T ; Bularga, A ; Bull, R ; Burgul, R ; Carpenter, J-P ; Coles, D ; Cusack, D ; Deshpande, A ; Dougan, J ; Fairbairn, T ; Farrugia, A ; Gopalan, D ; Gummow, A ; Ramkumar, PG ; Hamilton, M ; Harbinson, M ; Hartley, T ; Hudson, B ; Joshi, N ; Kay, M ; Kelion, A ; Khokhar, A ; Kitt, J ; Lee, K ; Low, C ; Mak, SM ; Marousa, N ; Martin, J ; Mcalindon, E ; 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    Longitudinal analysis reveals that delayed bystander CD8(+) T cell activation and early immune pathology distinguish severe COVID-19 from mild disease
    Bergamaschi, L ; Mescia, F ; Turner, L ; Hanson, AL ; Kotagiri, P ; Dunmore, BJ ; Ruffieux, H ; De Sa, A ; Huhn, O ; Morgan, MD ; Gerber, PP ; Wills, MR ; Baker, S ; Calero-Nieto, FJ ; Doffinger, R ; Dougan, G ; Elmer, A ; Goodfellow, IG ; Gupta, RK ; Hosmillo, M ; Hunter, K ; Kingston, N ; Lehner, PJ ; Matheson, NJ ; Nicholson, JK ; Petrunkina, AM ; Richardson, S ; Saunders, C ; Thaventhiran, JED ; Toonen, EJM ; Weekes, MP ; Gottgens, B ; Toshner, M ; Hess, C ; Bradley, JR ; Lyons, PA ; Smith, KGC (CELL PRESS, 2021-06-08)
    The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications.