Time-restricted versus standard-duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON-96 trial.

Cyclosporine A combined with mycophenolate mofetil (CsA/MMF) has become an established regimen for the prevention of graft-versus-host disease (GVHD) following non-myeloablative (NMA) allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the optimal duration of immunosuppression (IS) has not yet been defined and overtreatment is of concern. We hypothesized that time-restricted IS with CsA/MMF would increase the proportion of patients with non-severe GVHD compared to standard-duration IS, thereby resulting in reduction of the relapse rate and improvement of progression-free survival (PFS) and overall survival (OS).

The Minnesota Critical Care Working Group 1: Monitoring and Coordinating Statewide Critical Care Surge Response in the COVID-19 Pandemic, March 2020 Through July 1, 2021.

Background: In response to the COVID-19 pandemic and as part of the statewide health care coalition response, the Minnesota Critical Care Working Group (CCWG), composed of interprofessional leaders from the state's nine largest health systems, was established and entrusted to plan and coordinate critical care support for Minnesota from March 2020 through July 1, 2021.

Research Question: Can a statewide CCWG develop contingency and crisis-level surge strategies and indicators in response to the COVID-19 pandemic while evolving into a highly collaborative team?

Study Design And Methods: CCWG members (intensivists, ethicists, nurses, Minnesota Department of Health and Minnesota Hospital Association leaders) met by audio video conferencing as often as daily assessing COVID-19 and non-COVID-19 hospitalization data, developed surge indicators reflecting contingency vs crisis conditions, and planned responses collaboratively. A foundation of collaboration and teamwork developed which facilitated an effective statewide response.

The Minnesota Critical Care Working Group 2: Crisis Conditions During the COVID-19 Pandemic, July 2021 through March 2022.

Background: The Minnesota Statewide Healthcare Coordination Center requested that the Minnesota Critical Care Working Group (CCWG) and Ethics Working Group (EWG), comprising interprofessional leaders from Minnesota's 9 largest health systems, plan and coordinate critical care operations during the COVID-19 pandemic, including the fall 2021 surge.

Research Question: Can a statewide working group collaboratively analyze real-time evidence to identify crisis conditions and to engage state leadership to implement care processes?

Study Design And Methods: The CCWG and EWG met via videoconferencing during the severe surge of fall 2021 to analyze evidence and plan for potential crisis care conditions. Five sources of evidence informed their actions: group consensus on operating conditions, federal teletracking data, the Medical Operations Coordination Center (MOCC) patient placement data, and 2 surveys created and distributed to hospitals and health care professionals.

De novo missense variants in the PP2A regulatory subunit PPP2R2B in a neurodevelopmental syndrome: potential links to mitochondrial dynamics and spinocerebellar ataxias.

The heterotrimeric protein phosphatase 2A (PP2A) complex catalyzes about half of Ser/Thr dephosphorylations in eukaryotic cells. A CAG repeat expansion in the neuron-specific protein PP2A regulatory subunit PPP2R2B gene causes spinocerebellar ataxia type 12 (SCA12). We established five monoallelic missense variants in PPP2R2B (four confirmed as de novo) as a cause of intellectual disability with developmental delay (R149P, T246K, N310K, E37K, I427T).