Immunotherapy using T cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.

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Chimeric antigen receptor T-cell therapy — assessment and management of toxicities

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Health care-associated infections (HCAIs) are infections that occur while receiving health care, developed in a hospital or other health care facility that first appear 48 hours or more after hospital admission, or within 30 days after having received health care. Multiple studies indicate that the common types of adverse events affecting hospitalized patients are adverse drug events, HCAIs, and surgical complications. The US Center for Disease Control and Prevention identifies that nearly 1.7 million hospitalized patients annually acquire HCAIs while being treated for other health issues and that more than 98,000 patients (one in 17) die due to these. Several studies suggest that simple infection-control procedures such as cleaning hands with an alcohol-based hand rub can help prevent HCAIs and save lives, reduce morbidity, and minimize health care costs. Routine educational interventions for health care professionals can help change their hand-washing practices to prevent the spread of infection. In support of this, the WHO has produced guidelines to promote hand-washing practices among member countries.

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Health care-associated infections – an overview

Diabetes is fast gaining the status of a potential epidemic in India with more than 62 million diabetic individuals currently diagnosed with the disease. 1,2 In 2000, India (31.7 million) topped the world with the highest number of people with diabetes mellitus followed by China (20.8 million) with the United States (17.7 million) in second and third place respectively. According to Wild et al. 3 the prevalence of diabetes is predicted to double globally from 171 million in 2000 to 366 million in 2030 with a maximum increase in India. It is predicted that by 2030 diabetes mellitus may afflict up to 79.4 million individuals in India, while China (42.3 million) and the United States (30.3 million) will also see significant increases in those affected by the disease. 3,4 India currently faces an uncertain future in relation to the potential burden that diabetes may impose upon the country. Many influences affect the prevalence of disease throughout a country, and identification of those factors is necessary to facilitate change when facing health challenges. So what are the factors currently affecting diabetes in India that are making this problem so extreme?

The current state of diabetes mellitus in India

Context The frequency of remission of type 2 diabetes achievable with lifestyle intervention is unclear. Objective To examine the association of a long-term intensive weight-loss intervention with the frequency of remission from type 2 diabetes to prediabetes or normoglycemia. Design, Setting, and Participants Ancillary observational analysis of a 4-year randomized controlled trial (baseline visit, August 2001–April 2004; last follow-up, April 2008) comparing an intensive lifestyle intervention (ILI) with a diabetes support and education control condition (DSE) among 4503 US adults with body mass index of 25 or higher and type 2 diabetes. Interventions Participants were randomly assigned to receive the ILI, which included weekly group and individual counseling in the first 6 months followed by 3 sessions per month for the second 6 months and twice-monthly contact and regular refresher group series and campaigns in years 2 to 4 (n=2241) or the DSE, which was an offer of 3 group sessions per year on diet, physical activity, and social support (n=2262). Main Outcome Measures Partial or complete remission of diabetes, defined as transition from meeting diabetes criteria to a prediabetes or nondiabetic level of glycemia (fasting plasma glucose 1c Results Intensive lifestyle intervention participants lost significantly more weight than DSE participants at year 1 (net difference, −7.9%; 95% CI, −8.3% to −7.6%) and at year 4 (−3.9%; 95% CI, −4.4% to −3.5%) and had greater fitness increases at year 1 (net difference, 15.4%; 95% CI, 13.7%-17.0%) and at year 4 (6.4%; 95% CI, 4.7%-8.1%) (P  Conclusions In these exploratory analyses of overweight adults, an intensive lifestyle intervention was associated with a greater likelihood of partial remission of type 2 diabetes compared with diabetes support and education. However, the absolute remission rates were modest. Trial Registration clinicaltrials.gov Identifier: NCT00017953

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Association of an intensive lifestyle intervention with remission of type 2 diabetes.

Vision for Transformation Strengths: The SHSIP describes a holistic transformation plan and ensures connections between various plan components. The State’s Plan seeks to reward health care providers for better care, smarter spending, and healthier people through higher quality, instead of quantity of services by utilizing valuebased purchasing across public and private payers. The SHSIP provides a well-detailed description of the proposed value-based models of care through the Patient-Centered Medical Home (PCMH) model, resulting in the statewide implementation of Accountable Health Communities (AHCs). The SHSIP outlines a long-term vision of building and expanding the PCMH model into a Community Centered Health Homes (CCHHs) model, which will focus on prevention and collaboration with other communitybased organizations. Another strength identified is the amount of existing PCMHs operating within the State. The SHSIP provides a course of action to assist non-PCMH practices to become nationally certified, as well as, goals for a single, statewide PCMH model to be used by all providers and payers within the state. The implementation of the AHCs will be key in addressing social determinants of health within various communities and seems to align well with the PCMH goals. This focus on population and community health will enable the State to make a broader impact and support the long-term goal of moving towards a CCHH model. The focus on the improvement of clinical, behavioral, and oral health care within the urban, rural, and frontier communities is well aligned and consistent with the SIM goals and the overall Triple Aim initiative. Figure 18: Driver Diagram clearly shows how the State plans to achieve the Triple Aim by 2020.

Anne Schuchat

Papers

Department of health & human services

Centers for Control and Prevention