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1. Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity [2021]

  • Koshy, Cherian, Wise, Emma, Cortes, Nick, Lynch, Jessica, Kidd, Stephen, Mori, Matilde, Fairley, Derek J., Curran, Tanya, McKenna, James P., Adams, Helen, Fraser, Christophe, Golubchik, Tanya, Bonsall, David, Moore, Catrin, Caddy, Sarah L., Khokhar, Fahad A., Wantoch, Michelle, Reynolds, Nicola, Warne, Ben, Maksimovic, Joshua, Spellman, Karla, McCluggage, Kathryn, John, Michaela, Beer, Robert, Afifi, Safiah, Morgan, Sian, Marchbank, Angela, Price, Anna, Kitchen, Christine, Gulliver, Huw, Merrick, Ian, Southgate, Joel, Guest, Martyn, Munn, Robert, Workman, Trudy, Connor, Thomas R., Fuller, William, Bresner, Catherine, Snell, Luke B., Charalampous, Themoula, Nebbia, Gaia, Batra, Rahul, Edgeworth, Jonathan, Robson, Samuel C., Beckett, Angela, Loveson, Katie F., Aanensen, David M., Underwood, Anthony P., Yeats, Corin A., Abudahab, Khalil, Taylor, Ben E.W., Menegazzo, Mirko, Clark, Gemma, Smith, Wendy, Khakh, Manjinder, Fleming, Vicki M., Lister, Michelle M., Howson-Wells, Hannah C., Berry, Louise, Boswell, Tim, Joseph, Amelia, Willingham, Iona, Bird, Paul, Helmer, Thomas, Fallon, Karlie, Holmes, Christopher, Tang, Julian, Raviprakash, Veena, Campbell, Sharon, Sheriff, Nicola, Loose, Matthew W., Holmes, Nadine, Moore, Christopher, Carlile, Matthew, Wright, Victoria, Sang, Fei, Debebe, Johnny, Coll, Francesc, Signell, Adrian W., Betancor, Gilberto, Wilson, Harry D., Feltwell, Theresa, Houldcroft, Charlotte J., Eldirdiri, Sahar, Kenyon, Anita, Davis, Thomas, Pybus, Oliver, du Plessis, Louis, Zarebski, Alex, Raghwani, Jayna, Kraemer, Moritz, Francois, Sarah, Attwood, Stephen, Vasylyeva, Tetyana, Torok, M. Estee, Hamilton, William L., Goodfellow, Ian G., Hall, Grant, Jahun, Aminu S., Chaudhry, Yasmin, Hosmillo, Myra, Pinckert, Malte L., Georgana, Iliana, Yakovleva, Anna, Meredith, Luke W., Moses, Samuel, Lowe, Hannah, Ryan, Felicity, Fisher, Chloe L., Awan, Ali R., Boyes, John, Breuer, Judith, Harris, Kathryn Ann, Brown, Julianne Rose, Shah, Divya, Atkinson, Laura, Lee, Jack C.D., Alcolea-Medina, Adela, Moore, Nathan, Cortes, Nicholas, Williams, Rebecca, Chapman, Michael R., Levett, Lisa J., Heaney, Judith, Smith, Darren L., Bashton, Matthew, Young, Gregory R., Allan, John, Loh, Joshua, Randell, Paul A., Cox, Alison, Madona, Pinglawathee, Holmes, Alison, Bolt, Frances, Price, James, Mookerjee, Siddharth, Rowan, Aileen, Taylor, Graham P., Ragonnet-Cronin, Manon, Nascimento, Fabricia F., Jorgensen, David, Siveroni, Igor, Johnson, Rob, Boyd, Olivia, Geidelberg, Lily, Volz, Erik M., Brunker, Kirstyn, Smollett, Katherine L., Loman, Nicholas J., Quick, Joshua, McMurray, Claire, Stockton, Joanne, Nicholls, Sam, Rowe, Will, Poplawski, Radoslaw, Martinez-Nunez, Rocio T., Mason, Jenifer, Robinson, Trevor I., O'Toole, Elaine, Watts, Joanne, Breen, Cassie, Cowell, Angela, Ludden, Catherine, Sluga, Graciela, Machin, Nicholas W., Ahmad, Shazaad S.Y., George, Ryan P., Halstead, Fenella, Sivaprakasam, Venkat, Thomson, Emma C., Shepherd, James G., Asamaphan, Patawee, Niebel, Marc O., Li, Kathy K., Shah, Rajiv N., Jesudason, Natasha G., Parr, Yasmin A., Tong, Lily, Broos, Alice, Mair, Daniel, Nichols, Jenna, Carmichael, Stephen N., Nomikou, Kyriaki, Aranday-Cortes, Elihu, Johnson, Natasha, Starinskij, Igor, da Silva Filipe, Ana, Robertson, David L., Orton, Richard J., Hughes, Joseph, Vattipally, Sreenu, Singer, Joshua B., Hale, Antony D., Macfarlane-Smith, Louissa R., Harper, Katherine L., Taha, Yusri, Payne, Brendan A.I., Burton-Fanning, Shirelle, Waugh, Sheila, Collins, Jennifer, Eltringham, Gary, Templeton, Kate E., McHugh, Martin P., Dewar, Rebecca, Wastenge, Elizabeth, Dervisevic, Samir, Stanley, Rachael, Prakash, Reenesh, Stuart, Claire, Elumogo, Ngozi, Sethi, Dheeraj K., Meader, Emma J., Coupland, Lindsay J., Potter, Will, Graham, Clive, Barton, Edward, Padgett, Debra, Scott, Garren, Swindells, Emma, Greenaway, Jane, Nelson, Andrew, Yew, Wen C., Resende Silva, Paola C., Andersson, Monique, Shaw, Robert, Peto, Timothy, Justice, Anita, Eyre, David, Crooke, Derrick, Hoosdally, Sarah, Sloan, Tim J., Duckworth, Nichola, Walsh, Sarah, Chauhan, Anoop J., Glaysher, Sharon, Bicknell, Kelly, Wyllie, Sarah, Butcher, Ethan, Elliott, Scott, Lloyd, Allyson, Impey, Robert, Levene, Nick, Monaghan, Lynn, Bradley, Declan T., Allara, Elias, Pearson, Clare, Muir, Peter, Vipond, Ian B., Hopes, Richard, Pymont, Hannah M., Hutchings, Stephanie, Curran, Martin D., Parmar, Surendra, Lackenby, Angie, Mbisa, Tamyo, Platt, Steven, Miah, Shahjahan, Bibby, David, Manso, Carmen, Hubb, Jonathan, Chand, Meera, Dabrera, Gavin, Ramsay, Mary, Bradshaw, Daniel, Thornton, Alicia, Myers, Richard, Schaefer, Ulf, Groves, Natalie, Gallagher, Eileen, Lee, David, Williams, David, Ellaby, Nicholas, Harrison, Ian, Hartman, Hassan, Manesis, Nikos, Patel, Vineet, Bishop, Chloe, Chalker, Vicki, Osman, Husam, Bosworth, Andrew, Robinson, Esther, Holden, Matthew T.G., Shaaban, Sharif, Birchley, Alec, Adams, Alexander, Davies, Alisha, Gaskin, Amy, Plimmer, Amy, Gatica-Wilcox, Bree, McKerr, Caoimhe, Moore, Catherine, Williams, Chris, Heyburn, David, De Lacy, Elen, Hilvers, Ember, Downing, Fatima, Shankar, Giri, Jones, Hannah, Asad, Hibo, Coombes, Jason, Watkins, Joanne, Evans, Johnathan M., Fina, Laia, Gifford, Laura, Gilbert, Lauren, Graham, Lee, Perry, Malorie, Morgan, Mari, Bull, Matthew, Cronin, Michelle, Pacchiarini, Nicole, Craine, Noel, Jones, Rachel, Howe, Robin, Corden, Sally, Rey, Sara, Kumziene-Summerhayes, Sara, Taylor, Sarah, Cottrell, Simon, Jones, Sophie, Edwards, Sue, O’Grady, Justin, Page, Andrew J., Wain, John, Webber, Mark A., Mather, Alison E., Baker, David J., Rudder, Steven, Yasir, Muhammad, Thomson, Nicholas M., Aydin, Alp, Tedim, Ana P., Kay, Gemma L., Trotter, Alexander J., Gilroy, Rachel A.J., Alikhan, Nabil-Fareed, de Oliveira Martins, Leonardo, Le-Viet, Thanh, Meadows, Lizzie, Kolyva, Anastasia, Diaz, Maria, Bell, Andrew, Gutierrez, Ana Victoria, Charles, Ian G., Adriaenssens, Evelien M., Kingsley, Robert A., Casey, Anna, Simpson, David A., Molnar, Zoltan, Thompson, Thomas, Acheson, Erwan, Masoli, Jane A.H., Knight, Bridget A., Hattersley, Andrew, Ellard, Sian, Auckland, Cressida, Mahungu, Tabitha W., Irish-Tavares, Dianne, Haque, Tanzina, Bourgeois, Yann, Scarlett, Garry P., Partridge, David G., Raza, Mohammad, Evans, Cariad, Johnson, Kate, Liggett, Steven, Baker, Paul, Essex, Sarah, Lyons, Ronan A., Caller, Laura G., Castellano, Sergi, Williams, Rachel J., Kristiansen, Mark, Roy, Sunando, Williams, Charlotte A., Dyal, Patricia L., Tutill, Helena J., Panchbhaya, Yasmin N., Forrest, Leysa M., Niola, Paola, Findlay, Jacqueline, Brooks, Tony T., Gavriil, Artemis, Mestek-Boukhibar, Lamia, Weeks, Sam, Pandey, Sarojini, Berry, Lisa, Jones, Katie, Richter, Alex, Beggs, Andrew, Smith, Colin P., Bucca, Giselda, Hesketh, Andrew R., Harrison, Ewan M., Peacock, Sharon J., Palmer, Sophie, Churcher, Carol M., Bellis, Katherine L., Girgis, Sophia T., Naydenova, Plamena, Blane, Beth, Sridhar, Sushmita, Ruis, Chris, Forrest, Sally, Cormie, Claire, Gill, Harmeet K., Dias, Joana, Higginson, Ellen E., Maes, Mailis, Young, Jamie, Kermack, Leanne M., Hadjirin, Nazreen F., Aggarwal, Dinesh, Griffith, Luke, Swingler, Tracey, Davidson, Rose K., Rambaut, Andrew, Williams, Thomas, Balcazar, Carlos E., Gallagher, Michael D., O'Toole, Áine, Rooke, Stefan, Jackson, Ben, Colquhoun, Rachel, Ashworth, Jordan, Hill, Verity, McCrone, J.T., Scher, Emily, Yu, Xiaoyu, Williamson, Kathleen A., Stanton, Thomas D., Michell, Stephen L., Bewshea, Claire M., Temperton, Ben, Michelsen, Michelle L., Warwick-Dugdale, Joanna, Manley, Robin, Farbos, Audrey, Harrison, James W., Sambles, Christine M., Studholme, David J., Jeffries, Aaron R., Darby, Alistair C., Hiscox, Julian A., Paterson, Steve, Iturriza-Gomara, Miren, Jackson, Kathryn A., Lucaci, Anita O., Vamos, Edith E., Hughes, Margaret, Rainbow, Lucille, Eccles, Richard, Nelson, Charlotte, Whitehead, Mark, Turtle, Lance, Haldenby, Sam T., Gregory, Richard, Gemmell, Matthew, Kwiatkowski, Dominic, de Silva, Thushan I., Smith, Nikki, Angyal, Adrienn, Lindsey, Benjamin B., Groves, Danielle C., Green, Luke R., Wang, Dennis, Freeman, Timothy M., Parker, Matthew D., Keeley, Alexander J., Parsons, Paul J., Tucker, Rachel M., Brown, Rebecca, Wyles, Matthew, Constantinidou, Chrystala, Unnikrishnan, Meera, Ott, Sascha, Cheng, Jeffrey K.J., Bridgewater, Hannah E., Frost, Lucy R., Taylor-Joyce, Grace, Stark, Richard, Baxter, Laura, Alam, Mohammad T., Brown, Paul E., McClure, Patrick C., Chappell, Joseph G., Tsoleridis, Theocharis, Ball, Jonathan, Gramatopoulos, Dimitris, Buck, David, Todd, John A., Green, Angie, Trebes, Amy, MacIntyre-Cockett, George, de Cesare, Mariateresa, Langford, Cordelia, Alderton, Alex, Amato, Roberto, Goncalves, Sonia, Jackson, David K., Johnston, Ian, Sillitoe, John, Palmer, Steve, Lawniczak, Mara, Berriman, Matt, Danesh, John, Livett, Rich, Shirley, Lesley, Farr, Ben, Quail, Mike, Thurston, Scott, Park, Naomi, Betteridge, Emma, Weldon, Danni, Goodwin, Scott, Nelson, Rachel, Beaver, Charlotte, Letchford, Laura, Jackson, David A., Foulser, Luke, McMinn, Liz, Prestwood, Liam, Kay, Sally, Kane, Leanne, Dorman, Matthew J., Martincorena, Inigo, Puethe, Christoph, Keatley, Jon-Paul, Tonkin-Hill, Gerry, Smith, Christen, Jamrozy, Dorota, Beale, Mathew A., Patel, Minal, Ariani, Cristina, Spencer-Chapman, Michael, Drury, Eleanor, Lo, Stephanie, Rajatileka, Shavanthi, Scott, Carol, James, Keith, Buddenborg, Sarah K., Berger, Duncan J., Patel, Gaurang, Garcia-Casado, Maria V., Dibling, Thomas, McGuigan, Samantha, Rogers, Hazel A., Hunter, Adam D., Souster, Emily, Neaverson, Alexandra S., Volz, Erik, Hill, Verity, McCrone, John T., Price, Anna, Jorgensen, David, O’Toole, Áine, Southgate, Joel, Johnson, Robert, Jackson, Ben, Nascimento, Fabricia F., Rey, Sara M., Nicholls, Samuel M., Colquhoun, Rachel M., da Silva Filipe, Ana, Shepherd, James, Pascall, David J., Shah, Rajiv, Jesudason, Natasha, Li, Kathy, Jarrett, Ruth, Pacchiarini, Nicole, Bull, Matthew, Geidelberg, Lily, Siveroni, Igor, Goodfellow, Ian, Loman, Nicholas J., Pybus, Oliver G., Robertson, David L., Thomson, Emma C., Rambaut, Andrew, and Connor, Thomas R.
  • In Cell 7 January 2021 184(1):64-75

2. Effects of COVID-19 pandemic on pediatric kidney transplant in the United States. [2021]

  • Charnaya O, Chiang TP, Wang R, Motter JD, Boyarsky BJ, King EA, Werbel WA, Durand CM, Avery RK, Segev DL, Massie AB, and Garonzik-Wang JM
  • Pediatric nephrology (Berlin, Germany) [Pediatr Nephrol] 2021 Jan; Vol. 36 (1), pp. 143-151. Date of Electronic Publication: 2020 Sep 26.
Subjects
Adolescent, Adult, COVID-19 epidemiology, Child, Child, Preschool, Female, Health Services Accessibility statistics numerical data, Humans, Infant, Infant, Newborn, Male, Middle Aged, Pandemics, Registries, SARS-CoV-2, United States epidemiology, Young Adult, Kidney Transplantation statistics numerical data, Living Donors statistics numerical data, and Waiting Lists mortality
Abstract
Background: In March 2020, COVID-19 infections began to rise exponentially in the USA, placing substantial burden on the healthcare system. As a result, there was a rapid change in transplant practices and policies, with cessation of most procedures. Our goal was to understand changes to pediatric kidney transplantation (KT) at the national level during the COVID-19 epidemic.
Methods: Using SRTR data, we examined changes in pediatric waitlist registration, waitlist removal or inactivation, and deceased donor and living donor (DDKT/LDKT) events during the start of the disease transmission in the USA compared with the same time the previous year.
Results: We saw an initial decrease in DDKT and LDKT by 47% and 82% compared with expected events and then a continual increase, with numbers reaching expected prepandemic levels by May 2020. In the early phase of the pandemic, waitlist inactivation and removals due to death or deteriorating condition rose above expected values by 152% and 189%, respectively. There was a statistically significant decrease in new waitlist additions (IRR 0.49 0.65 0.85 ) and LDKT (IRR 0.17 0.38 0.84 ) in states with high vs. low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar calculated panel-reactive antibody (cPRA) values, waitlist time, and cause of kidney failure as before the pandemic.
Conclusions: The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the USA but has not had a sustained effect.

3. Characterizing the landscape and impact of infections following kidney transplantation. [2021]

  • Jackson KR, Motter JD, Bae S, Kernodle A, Long JJ, Werbel W, Avery R, Durand C, Massie AB, Desai N, Garonzik-Wang J, and Segev DL
  • American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2021 Jan; Vol. 21 (1), pp. 198-207. Date of Electronic Publication: 2020 Jun 28.
Abstract
Infections remain a major threat to successful kidney transplantation (KT). To characterize the landscape and impact of post-KT infections in the modern era, we used United States Renal Data System (USRDS) data linked to the Scientific Registry of Transplant Recipients (SRTR) to study 141 661 Medicare-primary kidney transplant recipients from January 1, 1999 to December 31, 2014. Infection diagnoses were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. The cumulative incidence of a post-KT infection was 36.9% at 3 months, 53.7% at 1 year, and 78.0% at 5 years. The most common infections were urinary tract infection (UTI; 46.8%) and pneumonia (28.2%). Five-year mortality for kidney transplant recipients who developed an infection was 24.9% vs 7.9% for those who did not, and 5-year death-censored graft failure (DCGF) was 20.6% vs 10.1% (P < .001). This translated to a 2.22-fold higher mortality risk (adjusted hazard ratio [aHR]: 2.15 2.22 2.29 , P < .001) and 1.92-fold higher DCGF risk (aHR: 1.84 1.91 1.98 , P < .001) for kidney transplant recipients who developed an infection, although the magnitude of this higher risk varied across infection types (for example, 3.11-fold higher mortality risk for sepsis vs 1.62-fold for a UTI). Post-KT infections are common and substantially impact mortality and DCGF, even in the modern era. Kidney transplant recipients at high risk for infections might benefit from enhanced surveillance or follow-up to mitigate these risks.
(© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

4. Effects of COVID-19 pandemic on pediatric kidney transplant in the United States [2021]

  • Charnaya, Olga, Chiang, Teresa Po-Yu, Wang, Richard, Motter, Jennifer D., Boyarsky, Brian J., King, Elizabeth A., Werbel, William A., Durand, Christine M., Avery, Robin K., Segev, Dorry L., Massie, Allan B., and Garonzik-Wang, Jacqueline M.
  • Pediatric Nephrology: Journal of the International Pediatric Nephrology Association. 36(1):143-151

5. The Yin-Yang Military Ambidextrous Perspectives on Change in Military Organizations edited by Jacqueline Heeren-Bogers, René Moelker, Esmeralda Kleinreesink, Jan Van der Meulen, Joseph Soeters, Robert Beeres [2021]

  • Heeren-Bogers, Jacqueline, edt, HerausgeberIn, Moelker, René., edt, HerausgeberIn, Kleinreesink, Esmeralda, edt, HerausgeberIn, Van der Meulen, Jan, edt, HerausgeberIn, Soeters, Joseph, edt, HerausgeberIn, and Beeres, Robert, edt, HerausgeberIn
  • 2021

6. Sex cells: Why we need sex- and gender-based analyses in rehabilitation research now. [2020]

  • Quigley A, McArthur C, Parker R, and Gahagan J
  • Annals of physical and rehabilitation medicine [Ann Phys Rehabil Med] 2020 Dec 14, pp. 101472. Date of Electronic Publication: 2020 Dec 14.

7. Inpatient COVID-19 Outcomes in Solid Organ Transplant Recipients Compared to Non-Solid Organ Transplant Patients: A Retrospective Cohort. [2020]

  • Avery RK, Chiang TP, Marr KA, Brennan DC, Sait AS, Garibaldi BT, Shah P, Ostrander D, Mehta Steinke S, Permpalung N, Cochran W, Makary MA, Garonzik-Wang J, Segev DL, and Massie AB
  • American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2020 Dec 07. Date of Electronic Publication: 2020 Dec 07.
Abstract
Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (3/1/20-8/21/20), evaluating hospital length-of-stay and inpatient mortality using competing risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p < 0.001), hypertension (69% vs. 44%, p = 0.001), HIV (7% vs 1.4%, p = 0.024), and peripheral vascular disorders (19% vs. 8%, p = 0.018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p = 0.13), length-of-stay (sHR= 0.9 1.1 1.4 , p = 0.5), or mortality (sHR: 0.1 0.4 1.6 , p = 0.19), although the severity score on admission was slightly lower for SOT (median (IQR) 3 (3, 4)) than for non-SOT (median (IQR) 4 (3-4)), (p = 0.042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR= 0.76 0.81 0.86 , p < 0.001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.
(This article is protected by copyright. All rights reserved.)

8. Lobar distribution of white matter abnormalities in Alzheimer's, vascular and mixed dementias: Neuroimaging / differential diagnosis. [2020]

  • Lee, Hyunwoo, Wiggermann, Vanessa, Rauscher, Alexander, Beg, Mirza Faisal, Popuri, Karteek, Tam, Roger, Lam, Kevin, Jacova, Claudia, Sossi, Vesna, Pettersen, Jacqueline, Benavente, Oscar R., and Hsiung, Ging‐Yuek Robin
  • Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2020 Supplement S11, Vol. 16 Issue 11, p1-2, 2p
Abstract
Background: Vascular dementia (VaD) is often difficult to distinguish from Alzheimer's disease (AD).[O'Brien_2015] Areas of cognitive/clinical decline due to cerebrovascular diseases depend on the frequency and location of the lesions, and may overlap with those found in AD.[Suri_2014] Moreover, AD and cerebrovascular diseases frequently occur simultaneously, leading to heterogeneous 'mixed dementia (MixD)'.[Wang_2012][Langa_2004] It is unclear whether the presence of both neurodegenerative and cerebrovascular pathologies further aggravates dementia‐related imaging abnormalities. We investigated whether the lobar distribution of white matter hyperintensities (WMHs) on MRI differed among AD, VaD and MixD. Method: N=17 participants (cross‐sectional; subtypes:7 MixD/5 Subcortical VaD/5 AD; Sex: 11M/6F; Age: 75±8yrs) were scanned on a 3T Philips Achieva. T1‐weighted MP‐RAGE images were processed with Freesurfer 6.0. Areas of WMHs were segmented on Fluid Attenuated Inversion Recovery (3D‐FLAIR) images using a combination of intensity thresholding and manual correction. Left and right frontal, temporal, occipital and parietal lobes plus basal ganglia volumes were constructed using the Freesurfer segmentation outputs. Individual WMH masks were transformed to their respective T1‐weighted spaces, and the ratios of WMH volumes to different lobar volumes were calculated. Result: Average WMH volumes were (mean±SD) AD: 5191±4693mm3, MixD: 34680±17059mm3 (sig. greater than AD), SVaD: 20896±14920mm3 (n.s. from MixD or AD). We used a linear model to predict the ratios of WMH to lobar volumes from the diagnosis subtypes, adjusting for age and sex. A significant diagnosis‐subtype effect was found in both the left and right frontal lobes. (p=0.012 and 0.045, respectively). In the left frontal lobe, the proportion of WMHs was significantly greater in the MixD subgroup compared to the AD (p=0.0045) or the VaD (p=0.026) subtypes. In the right frontal lobe, the proportion was greater in the MixD subtype compared to the AD (p=0.018) but not compared to VaD (p=0.074) subtype. AD vs. VaD were not significantly different in either sides (p=0.5). Conclusion: The MixD subtype of our pilot study cohort was characterized by a significantly greater presence of WMHs in the frontal lobar areas. Future studies are warranted to investigate the characteristics of underlying tissue abnormalities that could be specific to the diagnosis subtypes. [ABSTRACT FROM AUTHOR]

9. Pilot study of MRI white matter tissue properties in Alzheimer's, vascular and mixed dementias: Neuroimaging / differential diagnosis. [2020]

  • Lee, Hyunwoo, Wiggermann, Vanessa, Rauscher, Alexander, Beg, Mirza Faisal, Popuri, Karteek, Tam, Roger, Lam, Kevin, Jacova, Claudia, Sossi, Vesna, Pettersen, Jacqueline, Benavente, Oscar R., and Hsiung, Ging‐Yuek Robin
  • Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2020 Supplement S11, Vol. 16 Issue 11, p1-2, 2p
Abstract
Background: Alzheimer's disease (AD) with cerebrovascular disease is known as 'mixed' dementia (MixD).[Wang_2012][Langa_2004] MixD can have heterogeneous clinical/imaging presentations. This makes it difficult to distinguish MixD from AD or vascular dementia (VaD) using structural markers such as atrophy or white matter hyperintensity (WMH) volumes. [Suri_2014] We explored whether WM tissue properties on MRI, represented by R2* and diffusion‐tensor (DTI) images, could distinguish MixD from AD or VaD. Method: N=17 participants (cross‐sectional; 7 MixD/5 Subcortical VaD/5 AD; Sex: 11M/6F; Age: 75±8yrs) were scanned on a 3T Philips Achieva. WMHs were segmented on 3D‐Fluid Attenuated Inversion Recovery images. T1‐weighted MP‐RAGE images were segmented into the grey/white‐matters using SPM12. These outputs were combined to construct WMH and normal‐appearing WM (NAWM) masks. DTI images were processed using FSL. R2* images were computed using in‐house software. For each participant, the average R2*, fractional anisotropy (FA) and mean diffusivity (MDf) values were calculated within the WMH and NAWM masks. Result: Average WMH volumes were (mean±SD) AD: 5191±4693mm3, MD: 34680±17059mm3 (p<.05 compared to AD), SVaD: 20896±14920mm3 (p>.05 compared to MixD or AD). A linear model was used to predict the measured R2*, FA or MDf values from the diagnosis subtypes, adjusting for age and sex. R2* results: Pairwise t‐tests revealed significantly lower R2* values within the WMHs compared to NAWM (all subtypes p<0.0005). MixD had significantly lower WMH R2* values compared to AD (p=0.01) or VaD (p=0.02) subgroups. DTI results: Pairwise t‐tests revealed significantly higher MDf values within the WMHs compared to NAWM (all subtypes p<0.009). FA values were significantly lower within the WMHs compared to NAWM for the MixD (p=0.0002) and VaD (p=0.03) but not the AD (p=0.09) subtype. Conclusion: Our MixD cohort was characterized by potentially disrupted fiber integrity (represented by decreased FA) and increased water content (represented by lower R2*) within the WMH areas. These abnormalities likely represent etiologies caused by both neurodegenerative and cerebrovascular factors. Future studies that incorporate measures of neurodegeneration or neuroinflammation, such as biofluid markers, may help to further characterize WM tissue abnormalities in MixD compared to those found in 'pure' AD or VaD. [ABSTRACT FROM AUTHOR]

10. Associations between white matter hyperintensities and cognitive dysfunction in Alzheimer's, vascular and mixed dementias: Neuroimaging / Optimal neuroimaging measures for early detection. [2020]

  • Lee, Hyunwoo, Wiggermann, Vanessa, Rauscher, Alexander, Beg, Mirza Faisal, Popuri, Karteek, Tam, Roger, Lam, Kevin, Liu‐Ambrose, Teresa, Dao, Elizabeth, Keridy, Walid Ahmed Al, Jacova, Claudia, Sossi, Vesna, Pettersen, Jacqueline, Benavente, Oscar R., and Hsiung, Ging‐Yuek Robin
  • Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2020 Supplement S11, Vol. 16 Issue 11, p1-2, 2p
Abstract
Background: Increased burden of white‐matter hyperintensities (WMHs) on MRI is common among different types of dementia. WMHs can be caused by various underlying etiologies and are non‐specific markers of tissue abnormality. Therefore, global measures such as WMH burdens may not distinguish between degrees of cognitive impairment. We explored the associations between lobar‐specific WMH volumes and cognitive dysfunction across different dementia subtypes. Method: N=57 participants (7 Alzheimer's disease [AD]/5 subcortical vascular dementia [SVaD]/7 mixed dementia [MixD]/38 vascular cognitive impairment [VCI]; Sex:34M/23F; Age:73±8yrs; pooled from three independent studies) were scanned on 3T MRI. WMHs were segmented on 3D‐FLAIR (MixD/AD/SVaD) or dual‐echo PD/T2‐weighted (VCI) images. T1‐weighted images were processed with Freesurfer 6.0. Left and right frontal, temporal, occipital and parietal lobes plus basal ganglia volumes were constructed using the Freesurfer segmentation outputs. We calculated the proportion of WMH burden within each lobe, i.e. the ratio of lobar WMH volume over the lobar volume. The Montreal Cognitive Assessment (MoCA) was used as a measure of cognitive function. We used a general linear model to determine the association between the WMH/lobar volume ratios and the MoCA scores. Covariates included age, sex, and presence of AD‐related (yes for MixD/AD, no for rest) and vascular‐related conditions (yes for SVaD/VCI/MixD, no for AD). Additionally, we assessed the relationship between the MoCA scores and the ratio of total WMH burden over the whole‐brain parenchymal volume. Result: The model yielded a significant association between the MoCA scores and WMH/lobar ratios within the left (p=0.031) and the right (p=0.035) frontal lobes, with higher ratios predicting lower MoCA scores. The effect was not significant within the temporal, occipital, parietal lobes and the basal ganglia. The effect was insignificant at the whole‐brain level (p=0.08). Conclusion: We found a significant association between the frontal lobe WMH burden and the MoCA scores, especially sensitive to frontal executive functions. This suggests that region‐specific assessments of WMHs may provide improved imaging‐cognitive correlations over the global WMH burden. Future studies with more consistent imaging protocols and broader cognitive/clinical assessments are warranted to further characterize the relationship between WMHs and cognitive impairment. [ABSTRACT FROM AUTHOR]

11. Evolving Impact of COVID-19 on Transplant Center Practices and Policies in the United States. [2020]

  • Boyarsky BJ, Ruck JM, Chiang TP, Werbel WA, Strauss AT, Getsin SN, Jackson KR, Kernodle AB, Van Pilsum Rasmussen SE, Baker TB, Al Ammary F, Durand CM, Avery RK, Massie AB, Segev DL, and Garonzik-Wang JM
  • Clinical transplantation [Clin Transplant] 2020 Dec; Vol. 34 (12), pp. e14086. Date of Electronic Publication: 2020 Sep 28.
Subjects
Adult, COVID-19 diagnosis, COVID-19 epidemiology, COVID-19 etiology, COVID-19 Testing, Clinical Decision-Making, Follow-Up Studies, Health Care Surveys, Health Services Accessibility organization administration, Humans, Incidence, Infection Control methods, Infection Control trends, Organ Transplantation methods, Postoperative Complications epidemiology, Postoperative Complications prevention control, Postoperative Complications virology, Tissue and Organ Procurement organization administration, United States epidemiology, COVID-19 prevention control, Health Services Accessibility trends, Organ Transplantation trends, Organizational Policy, Practice Patterns, Physicians' trends, Telemedicine trends, and Tissue and Organ Procurement trends
Abstract
In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID-19 on transplant recipients and center-level practices. We therefore conducted a six-week follow-up survey May 7-15, 2020, and linked responses to the COVID-19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID-19-positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS-CoV-2. Our findings demonstrate persistent heterogeneity in center-level response to COVID-19 even as transplant activity resumes, making ongoing national data collection and real-time analysis critical to inform best practices.
(© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

12. Circulating Tumor Cell Subtypes and T-cell Populations as Prognostic Biomarkers to Combination Immunotherapy in Patients with Metastatic Genitourinary Cancer. [2020]

  • Chalfin HJ, Pramparo T, Mortazavi A, Niglio SA, Schonhoft JD, Jendrisak A, Chu YL, Richardson R, Krupa R, Anderson AKL, Wang Y, Dittamore R, Pal SK, Lara PN, Stein MN, Quinn DI, Steinberg SM, Cordes LM, Ley L, Mallek M, Sierra Ortiz O, Costello R, Cadena J, Diaz C, Gulley JL, Dahut WL, Streicher H, Wright JJ, Trepel JB, Bottaro DP, and Apolo AB
  • Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Dec 01. Date of Electronic Publication: 2020 Dec 01.
Abstract
Purpose: Circulating tumor cells (CTC) are under investigation as a minimally invasive liquid biopsy that may improve risk stratification and treatment selection. CTCs uniquely allow for digital pathology of individual malignant cell morphology and marker expression. We compared CTC features and T-cell counts with survival endpoints in a cohort of patients with metastatic genitourinary cancer treated with combination immunotherapy.
Experimental Design: Markers evaluated included pan-CK/CD45/PD-L1/DAPI for CTCs and CD4/CD8/Ki-67/DAPI for T cells. ANOVA was used to compare CTC burden and T-cell populations across timepoints. Differences in survival and disease progression were evaluated using the maximum log-rank test.
Results: From December 2016 to January 2019, 183 samples from 81 patients were tested. CTCs were found in 75% of patients at baseline. CTC burden was associated with shorter overall survival (OS) at baseline ( P = 0.022), but not on-therapy. Five morphologic subtypes were detected, and the presence of two specific subtypes with unique cellular features at baseline and on-therapy was associated with worse OS (0.9-2.3 vs. 28.2 months; P < 0.0001-0.013). Increasing CTC heterogeneity on-therapy had a trend toward worse OS ( P = 0.045). PD-L1 + CTCs on-therapy were associated with worse OS ( P < 0.01, cycle 2). Low baseline and on-therapy CD4/CD8 counts were also associated with poor OS and response category.
Conclusions: Shorter survival may be associated with high CTC counts at baseline, presence of specific CTC morphologic subtypes, PD-L1 + CTCs, and low %CD4/8 T cells in patients with metastatic genitourinary cancer. A future study is warranted to validate the prognostic utility of CTC heterogeneity and detection of specific CTC morphologies.
(©2020 American Association for Cancer Research.)

13. Circulating sex hormone binding globulin levels are modified with intensive lifestyle intervention, but their changes did not independently predict diabetes risk in the Diabetes Prevention Program [2020]

  • Mike Reidy, Christine Lee, Michael Brändle, Sherita Hill Golden, Samuel Dagogo-Jack, David Kessler, Elizabeth Barrett-Connor, Steve Jones, Ling Chen, Judith Wylie-Rosett, Ping Zhang, Paula Williamson, Carlos Lorenzo, Leigh Perreault, Dana Dabelea, Santica Marcovina, Rachel Williams, Marie Smith, Carmen Pal, Patricia Katz, William H. Herman, Sharon L Edelstein, Yong Ma, Vanita R Aroda, Costas A Christophi, Catherine Kim, Sherita H Golden, Edward Horton, Kieren J Mather, George A. Bray, Kishore Gadde, Iris W. Culbert, Jennifer Arceneaux, Annie Chatellier, Amber Dragg, Catherine M. Champagne, Crystal Duncan, Barbara Eberhardt, Frank Greenway, Fonda G. Guillory, April A. Herbert, Michael L. Jeffirs, Betty M. Kennedy, Erma Levy, Monica Lockett, Jennifer C. Lovejoy, Laura H. Morris, Lee E. Melancon, Donna H. Ryan, Deborah A. Sanford, Kenneth G. Smith, Lisa L. Smith, Julia A. St, Richard T. Tulley Amant, Paula C. Vicknair, Donald Williamson, Jeffery J. Zachwieja, Kenneth S. Polonsky, Janet Tobian, David A. Ehrmann, Margaret J. Matulik, Bart Clark, Kirsten Czech, Catherine DeSandre, Ruthanne Hilbrich, Wylie McNabb, Ann R. Semenske, Jose F. Caro, Kevin Furlong, Barry J. Goldstein, Pamela G. Watson, Kellie A. Smith, Jewel Mendoza, Wendi Wildman, Renee Liberoni, John Spandorfer, Constance Pepe, Richard P. Donahue, Ronald B. Goldberg, Ronald Prineas, Jeanette Calles, Juliet Ojito, Patricia Rowe, Paul Cassanova-Romero, Sumaya Castillo-Florez, Hermes J. Florez, Anna Giannella, Lascelles Kirby, Carmen Larreal, Olga Lara, Valerie McLymont, Jadell Mendez, Arlette Perry, Patrice Saab, Beth Veciana, Steven M. Haffner, Helen P. Hazuda, Maria G. Montez, Kathy Hattaway, Arlene Martinez, Tatiana Walker, Richard F. Hamman, Patricia V. Nash, Sheila C. Steinke, Lisa Testaverde, Denise R. Anderson, Larry B. Ballonoff, Alexis Bouffard, Brian Bucca, B. Ned Calonge, Lynne Delve, Martha Farago, James O. Hill, Shelley R. Hoyer, Tonya Jenkins, Bonnie T. Jortberg, Dione Lenz, Marsha Miller, David W. Price, Judith G. Regensteiner, Helen Seagle, Carissa M. Smith, Brent VanDorsten, Edward S. Horton, Kathleen E. Lawton, Catherine S. Poirier, Kati Swift, Ronald A. Arky, Marybeth Bryant, Jacqueline P. Burke, Enrique Caballero, Karen M. Callaphan, Barbara Fargnoli, Therese Franklin, Om P. Ganda, Ashley Guidi, Mathew Guido, Sharon D. Jackson, Alan M. Jacobsen, Lori Lambert, Sarah Ledbury, Margaret Kocal, Lyn M. Kula, Maureen A. Malloy, Maryanne Nicosia, Cathryn F. Oldmixon, Jocelyn Pan, Marizel Quitingon, Stacy Rubtchinsky, Jessica Sansoucy, Dana Schweizer, Ellen W. Seely, Donald Simonson, Fannie Smith, Caren G. Solomon, Jeanne Spellman, James Warram, Steven E. Kahn, Brenda K. Montgomery, Wilfred Fujimoto, Robert H. Knopp, Edward W. Lipkin, Michelle Marr, Ivy Morgan-Taggart, Anne Murillo, Dace Trence, Lonnese Taylor, April Thomas, Elaine C. Tsai, Abbas E. Kitabchi, Mary E. Murphy, Laura Taylor, Jennifer Dolgoff, William B. Applegate, Michael Bryer-Ash, Debra Clark, Sandra L. Frieson, Uzoma Ibebuogu, Raed Imseis, Helen Lambeth, Lynne C. Lichtermann, Hooman Oktaei, Harriet Ricks, Lily M.K. Rutledge, Amy R. Sherman, Clara M. Smith, Judith E. Soberman, Beverly Williams-Cleaves, Boyd E. Metzger, Mark E. Molitch, Mariana K. Johnson, Daphne T. Adelman, Catherine Behrends, Michelle Cook, Marian Fitzgibbon, Mimi M. Giles, Deloris Heard, Cheryl K.H. Johnson, Diane Larsen, Anne Lowe, Megan Lyman, David McPherson, Samsam C. Penn, Thomas Pitts, Renee Reinhart, Susan Roston, Pamela A. Schinleber, David M. Nathan, Charles McKitrick, Heather Turgeon, Mary Larkin, Kathy Abbott, Ellen Anderson, Laurie Bissett, Kristy Bondi, Enrico Cagliero, Jose C. Florez, Kali D’Anna, Linda Delahanty, Valerie Goldman, Peter Lou, Alexandra Poulos, Elyse Raymond, Christine Stevens, Beverly Tseng, Jerrold M. Olefsky, Mary Lou Carrion-Petersen, Madeline Beltran, Lauren N. Claravall, Jonalle M. Dowden, Steven V. Edelman, Robert R. Henry, Javiva Horne, Marycie Lamkin, Simona Szerdi Janesch, Diana Leos, Sunder Mudaliar, William Polonsky, Jean Smith, Jennifer Torio-Hurley, Karen Vejvoda, F. Xavier Pi-Sunyer, Jane E. Lee, David B. Allison, Nnenna Agharanya, Nancy J. Aronoff, Maria Baldo, Jill P. Crandall, Sandra T. Foo, Susan Hagamen, Jose A. Luchsinger, Kathy Parkes, Mary Beth Pena, Ellen S. Rooney, Gretchen E.H. Van Wye, Kristine A. Viscovich, David G. Marrero, Kieren J. Mather, Melvin J. Prince, Susie M. Kelly, Marcia A. Jackson, Gina McAtee, Paula Putenney, Ronald T. Ackermann, Carolyn M. Cantrell, Yolanda F. Dotson, Edwin S. Fineberg, Megan Fultz, John C. Guare, Angela Hadden, James M. Ignaut, Marion S. Kirkman, Erin O’Kelly Phillips, Beverly D. Porter, Paris J. Roach, Nancy D. Rowland, Madelyn L. Wheeler, Vanita Aroda, Robert E. Ratner, Gretchen Youssef, Sue Shapiro, Catherine Bavido-Arrage, Geraldine Boggs, Marjorie Bronsord, Ernestine Brown, Wayman W. Cheatham, Susan Cola, Cindy Evans, Peggy Gibbs, Tracy Kellum, Renee Wiggins, Milvia Lagarda, Lilia Leon, Claresa Levatan, Milajurine Lindsay, Asha K. Nair, Maureen Passaro, Angela Silverman, Gabriel Uwaifo, Debra Wells-Thayer, Mohammed F. Saad, Karol Watson, Maria Budget, Sujata Jinagouda, Medhat Botrous, Khan Akbar, Claudia Conzues, Perpetua Magpuri, Kathy Ngo, Amer Rassam, Debra Waters, Kathy Xapthalamous, Julio V. Santiago, Neil H. White, Angela L. Brown, Samia Das, Prajakta Khare-Ranade, Tamara Stich, Ana Santiago, Edwin Fisher, Emma Hurt, Tracy Jones, Michelle Kerr, Lucy Ryder, Cormarie Wernimont, Christopher D. Saudek, Vanessa Bradley, Emily Sullivan, Tracy Whittington, Caroline Abbas, Adrienne Allen, Frederick L. Brancati, Sharon Cappelli, Jeanne M. Clark, Jeanne B. Charleston, Janice Freel, Katherine Horak, Alicia Greene, Dawn Jiggetts, Deloris Johnson, Hope Joseph, Kimberly Loman, Henry Mosley, John Reusing, Richard R. Rubin, Alafia Samuels, Thomas Shields, Shawne Stephens, Kerry J. Stewart, LeeLana Thomas, Evonne Utsey, David S. Schade, Karwyn S. Adams, Janene L. Canady, Carolyn Johannes, Claire Hemphill, Penny Hyde, Leslie F. Atler, Patrick J. Boyle, Mark R. Burge, Lisa Chai, Kathleen Colleran, Ysela Gonzales, Doris A. Hernandez-McGinnis, Carolyn King, Sofya Rubinchik, Willette Senter, Jill Crandall, Harry Shamoon, Janet O. Brown, Gilda Trandafirescu, Elsie Adorno, Liane Cox, Helena Duffy, Samuel Engel, Allison Friedler, Angela Goldstein, Crystal J. Howard-Century, Jennifer Lukin, Stacey Kloiber, Nadege Longchamp, Helen Martinez, Dorothy Pompi, Jonathan Scheindlin, Elissa Violino, Elizabeth A. Walker, Elise Zimmerman, Joel Zonszein, Trevor Orchard, Rena R. Wing, Susan Jeffries, Gaye Koenning, M. Kaye Kramer, Susan Barr, Catherine Benchoff, Miriam Boraz, Lisa Clifford, Rebecca Culyba, Marlene Frazier, Ryan Gilligan, Stephanie Guimond, Susan Harrier, Louann Harris, Andrea Kriska, Bonny Rockette-Wagner, Qurashia Manjoo, Monica Mullen, Alicia Noel, Amy Otto, Jessica Pettigrew, Debra Rubinstein, Linda Semler, Cheryl F. Smith, Elizabeth Venditti, Valarie Weinzierl, Katherine V. Williams, Tara Wilson, Richard F. Arakaki, Renee W. Latimer, Narleen K. Baker-Ladao, Mae K. Isonaga, Ralph Beddow, Nina E. Bermudez, Lorna Dias, Jillian Inouye, Marjorie K. Mau, John S. Melish, Kathy Mikami, Pharis Mohideen, Sharon K. Odom, Raynette U. Perry, Robin E. Yamamoto, William C. Knowler, Norman Cooeyate, Mary A. Hoskin, Carol A. Percy, Alvera Enote, Camille Natewa, Kelly J. Acton, Vickie L. Andre, Rosalyn Barber, Shandiin Begay, Peter H. Bennett, Mary Beth Benson, Evelyn C. Bird, Brenda A. Broussard, Brian C. Bucca, Marcella Chavez, Sherron Cook, Jeff Curtis, Tara Dacawyma, Matthew S. Doughty, Roberta Duncan, Charlotte Dodge, Cyndy Edgerton, Jacqueline M. Ghahate, Justin Glass, Martia Glass, Dorothy Gohdes, Wendy Grant, Robert L. Hanson, Ellie Horse, Louise E. Ingraham, Merry Jackson, Priscilla Jay, Roylen S. Kaskalla, Kathleen M. Kobus, Jonathan Krakoff, Jason Kurland, Catherine Manus, Cherie McCabe, Sara Michaels, Tina Morgan, Yolanda Nashboo, Julie A. Nelson, Steven Poirier, Evette Polczynski, Christopher Piromalli, Jeanine Roumain, Debra Rowse, Robert J. Roy, Sandra Sangster, Janet Sewenemewa, Miranda Smart, Darryl Tonemah, Charlton Wilson, Michelle Yazzie, Raymond Bain, Sarah Fowler, Marinella Temprosa, Michael D. Larsen, Tina Brenneman, Sharon L. Edelstein, Solome Abebe, Julie Bamdad, Melanie Barkalow, Joel Bethepu, Tsedenia Bezabeh, Nicole Butler, Jackie Callaghan, Caitlin E. Carter, Costas Christophi, Gregory M. Dwyer, Mary Foulkes, Yuping Gao, Robert Gooding, Adrienne Gottlieb, Kristina L. Grimes, Nisha Grover-Fairchild, Lori Haffner, Heather Hoffman, Kathleen Jablonski, Tara L. Jones, Richard Katz, Preethy Kolinjivadi, John M. Lachin, Pamela Mucik, Robert Orlosky, Qing Pan, Susan Reamer, James Rochon, Alla Sapozhnikova, Hanna Sherif, Charlotte Stimpson, Ashley Hogan Tjaden, Fredricka Walker-Murray, Elizabeth M. Venditti, Andrea M. Kriska, Valerie Weinzierl, Jessica Harting, F. Alan Aldrich, John Albers, Greg Strylewicz, R. Eastman, Judith Fradkin, Sanford Garfield, Edward Gregg, Morton B. Brown, David Altshuler, Liana K. Billings, Maegan Harden, Toni I. Pollin, Alan R. Shuldiner, Paul W. Franks, and Marie-France Hivert
  • BMJ Open Diabetes Research & Care, Vol 8, Iss 2 (2020)
Subjects
Diseases of the endocrine glands. Clinical endocrinology and RC648-665
Abstract
Introduction Sex hormone binding globulin (SHBG) levels are reported to be inversely associated with diabetes risk. It is unknown whether diabetes prevention interventions increase SHBG and whether resultant changes in SHBG affect diabetes risk. The purpose of this analysis was to determine whether intensive lifestyle intervention (ILS) or metformin changed circulating SHBG and if resultant changes influenced diabetes risk in the Diabetes Prevention Program (DPP).Research design and methods This is a secondary analysis from the DPP (1996–2001), a randomized trial of ILS or metformin versus placebo on diabetes risk over a mean follow-up of 3.2 years. The DPP was conducted across 27 academic study centers in the USA. Men, premenopausal and postmenopausal women without hormone use in the DPP were evaluated. The DPP included overweight/obese persons with elevated fasting glucose and impaired glucose tolerance. Main outcomes measures were changes in SHBG levels at 1 year and risk of diabetes over 3 years.Results ILS resulted in significantly higher increases (postmenopausal women: p

14. An evaluation of an interprofessional simulation training session on end-of-life-care conversations in the intensive care unit [2020]

  • Nogi, Masayuki, Wong, Lorrie C., Yamanaka, Ashley B., Richardson, Karol, Ng-Osorio, Jacqueline, Arndt, Robin G., Petrov, Sergei, and Ganitano, Jr. Emilio
  • In Journal of Interprofessional Education & Practice December 2020 21

15. Evaluating risk to people with epilepsy during the COVID-19 pandemic: Preliminary findings from the COV-E study. [2020]

  • Thorpe J, Ashby S, Hallab A, Ding D, Andraus M, Dugan P, Perucca P, Costello D, French JA, O'Brien TJ, Depondt C, Andrade DM, Sengupta R, Delanty N, Jette N, Newton CR, Brodie MJ, Devinsky O, Helen Cross J, Sander JW, Hanna J, and Sen A
  • Epilepsy & behavior : E&B [Epilepsy Behav] 2020 Nov 28, pp. 107658. Date of Electronic Publication: 2020 Nov 28.
Abstract
The COVID-19 pandemic has caused global anguish unparalleled in recent times. As cases rise, increased pressure on health services, combined with severe disruption to people's everyday lives, can adversely affect individuals living with chronic illnesses, including people with epilepsy. Stressors related to disruption to healthcare, finances, mental well-being, relationships, schooling, physical activity, and increased isolation could increase seizures and impair epilepsy self-management. We aim to understand the impact that COVID-19 has had on the health and well-being of people with epilepsy focusing on exposure to increased risk of seizures, associated comorbidity, and mortality. We designed two online surveys with one addressing people with epilepsy directly and the second for caregivers to report on behalf of a person with epilepsy. The survey is ongoing and has yielded 463 UK-based responses by the end of September 2020. Forty percent of respondents reported health changes during the pandemic (n = 185). Respondents cited a change in seizures (19%, n = 88), mental health difficulties (34%, n = 161), and sleep disruption (26%, n = 121) as the main reasons. Thirteen percent found it difficult to take medication on time. A third had difficulty accessing medical services (n = 154), with 8% having had an appointment canceled (n = 39). Only a small proportion reported having had discussions about epilepsy-related risks, such as safety precautions (16%, n = 74); mental health (29%, n = 134); sleep (30%, n = 140); and Sudden Unexpected Death in Epilepsy (SUDEP; 15%, n = 69) in the previous 12 months. These findings suggest that people with epilepsy are currently experiencing health changes, coupled with inadequate access to services. Also, there seems to be a history of poor risk communication in the months preceding the pandemic. As the UK witnesses a second COVID-19 wave, those involved in healthcare delivery must ensure optimal care is provided for people with chronic conditions, such as epilepsy, to ensure that avoidable morbidity and mortality is prevented during the pandemic, and beyond.
(Copyright © 2020 Elsevier Inc. All rights reserved.)

16. Regulatory challenges with biosimilars: an update from 20 countries. [2020]

  • Kang HN, Thorpe R, Knezevic I, Casas Levano M, Chilufya MB, Chirachanakul P, Chua HM, Dalili D, Foo F, Gao K, Habahbeh S, Hamel H, Kim GH, Perez Rodriguez V, Putri DE, Rodgers J, Savkina M, Semeniuk O, Srivastava S, Tavares Neto J, Wadhwa M, and Yamaguchi T
  • Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2020 Nov 21. Date of Electronic Publication: 2020 Nov 21.
Abstract
The World Health Organization (WHO) issued guidelines for the regulatory evaluation of biosimilars in 2009 and has provided considerable effort toward helping member states implement the evaluation principles in the guidelines into their regulatory practices. Despite this effort, a recent WHO survey (conducted in 2019-2020) has revealed four main remaining challenges: unavailable/insufficient reference products in the country; lack of resources; problems with the quality of some biosimilars (and even more with noninnovator products); and difficulties with the practice of interchangeability and naming of biosimilars. The following have been identified as opportunities/solutions for regulatory authorities to deal with the existing challenges: (1) exchange of information on products with other regulatory authorities and accepting foreign licensed and sourced reference products, hence avoiding conducting unnecessary (duplicate) bridging studies; (2) use of a "reliance" concept and/or joint review for the assessment and approval of biosimilars; (3) review and reassessment of the products already approved before the establishment of a regulatory framework for biosimilar approval; and (4) setting appropriate regulatory oversight for good pharmacovigilance, which is essential for the identification of problems with products and establishing the safety and efficacy of interchangeability of biosimilars.
(© 2020 The Authors. Annals of the New York Academy of Sciences. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

17. Abstract 14370: Rapidly Improving Adherence to Guideline-Directed Medical Therapies in Metropolitan Heart Failure Systems of Care [2020]

  • Tomei, Jacqueline, Kiser, Robin Y, Mallas-Serdynski, Lynn, Scharnott, Michelle, Bolles, Michele M, Chahoud, Georges, and Saltzberg, Mitchell
  • Circulation. Nov 17, 2020, Vol. 142 Issue S_3 Suppl 3, A14370, 1 p.

18. Abstract 14370: Rapidly Improving Adherence to Guideline-Directed Medical Therapies in Metropolitan Heart Failure Systems of Care [2020]

  • Jacqueline, Tomei, Robin Y, Kiser, Lynn, Mallas-Serdynski, Michelle, Scharnott, Michele M, Bolles, Georges, Chahoud, Mitchell, Saltzberg, and Clyde, Yancy
  • Circulation. Nov 17, 2020 142(Suppl_3 Suppl 3):A14370-A14370

19. Discovery of Roblitinib (FGF401) as a Reversible-Covalent Inhibitor of the Kinase Activity of Fibroblast Growth Factor Receptor 4. [2020]

  • Fairhurst RA, Knoepfel T, Buschmann N, Leblanc C, Mah R, Todorov M, Nimsgern P, Ripoche S, Niklaus M, Warin N, Luu VH, Madoerin M, Wirth J, Graus-Porta D, Weiss A, Kiffe M, Wartmann M, Kinyamu-Akunda J, Sterker D, Stamm C, Adler F, Buhles A, Schadt H, Couttet P, Blank J, Galuba I, Trappe J, Voshol J, Ostermann N, Zou C, Berghausen J, Del Rio Espinola A, Jahnke W, and Furet P
  • Journal of medicinal chemistry [J Med Chem] 2020 Nov 12; Vol. 63 (21), pp. 12542-12573. Date of Electronic Publication: 2020 Oct 01.
Subjects
Amino Acid Sequence, Animals, Binding Sites, Cell Line, Tumor, Cell Proliferation drug effects, Cysteine chemistry, Dogs, Drug Design, Half-Life, Hepatocytes cytology, Hepatocytes drug effects, Hepatocytes metabolism, Liver Neoplasms drug therapy, Mice, Microsomes, Liver metabolism, Molecular Dynamics Simulation, Piperazines metabolism, Piperazines pharmacology, Piperazines therapeutic use, Protein Kinase Inhibitors metabolism, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Pyridines metabolism, Pyridines pharmacology, Pyridines therapeutic use, Rats, Receptor, Fibroblast Growth Factor, Type 4 metabolism, Structure-Activity Relationship, Xenograft Model Antitumor Assays, Piperazines chemistry, Protein Kinase Inhibitors chemistry, Pyridines chemistry, and Receptor, Fibroblast Growth Factor, Type 4 antagonists inhibitors
Abstract
FGF19 signaling through the FGFR4/β-klotho receptor complex has been shown to be a key driver of growth and survival in a subset of hepatocellular carcinomas, making selective FGFR4 inhibition an attractive treatment opportunity. A kinome-wide sequence alignment highlighted a poorly conserved cysteine residue within the FGFR4 ATP-binding site at position 552, two positions beyond the gate-keeper residue. Several strategies for targeting this cysteine to identify FGFR4 selective inhibitor starting points are summarized which made use of both rational and unbiased screening approaches. The optimization of a 2-formylquinoline amide hit series is described in which the aldehyde makes a hemithioacetal reversible-covalent interaction with cysteine 552. Key challenges addressed during the optimization are improving the FGFR4 potency, metabolic stability, and solubility leading ultimately to the highly selective first-in-class clinical candidate roblitinib.

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