XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

https://biblio.ugent.be/publication/8555786/file/8555788.pdf

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Toll-like receptors (TLRs) play crucial roles in the innate immune system by recognizing pathogen-associated molecular patterns derived from various microbes. TLRs signal through the recruitment of specific adaptor molecules, leading to activation of the transcription factors NF-κB and IRFs, which dictate the outcome of innate immune responses. During the past decade, the precise mechanisms underlying TLR signaling have been clarified by various approaches involving genetic, biochemical, structural, cell biological and bioinformatics studies. TLR signaling appears to be divergent and to play important roles in many aspects of the innate immune responses to given pathogens. In this review, we describe recent progress in our understanding of TLR signaling regulation and its contributions to host defense.

/pdf/toll-like-receptor-signaling-pathways-9g5tlgz2h3.pdf

Toll-like receptor signaling pathways.

Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression suggesting diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A unique phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling. These data suggest that type-I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.

https://science.sciencemag.org/content/sci/early/2020/07/10/science.abc6027.full.pdf

Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients.

Innate immunity is the most ancient form of response to pathogens and it relies on evolutionary conserved signaling pathways, i.e. those involving the NF-κB pathway. Nevertheless, increasing evidence suggests that factors that have appeared more recently in evolution, such as the nuclear factor of activated T-cell transcription factor family (NFATc), also contribute to innate immune-response regulation in vertebrates. Exposure to inflammatory stimuli induces the activation of NFATc factors in innate immune cells, including conventional dendritic cells (DCs), granulocytes, mast cells and under pathological circumstances, also macrophages. While the evolutionary conserved functions of innate immunity, such as direct microbial killing and interferon production, are expected to be NFATc independent, other aspects of innate immunity, including collaboration with adaptive immunity and mechanisms to limit the tissue damage generated by the inflammatory process, are presumably controlled by NFATc members in collaboration with other transcription factors. In this article, we discuss the recent advances regarding the role of the NFATc signaling pathway in regulating DC, neutrophil and macrophage responses to specific inflammatory stimuli, including lipopolysaccharide and β-glucan-bearing microorganisms. We also discuss how NFATc signaling influences the interactions of myeloid cells with lymphocytes.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.201242580

Regulation and dysregulation of innate immunity by NFAT signaling downstream of pattern recognition receptors (PRRs)

Dendritic cells (DCs) sense the presence of pathogens through germline-encoded pattern recognition receptors (PRRs), which recognize molecular patterns expressed by various microorganisms and endogenous stimuli. Toll-like receptors (TLRs) are the best characterized PRRs. TLR activation has a profound effect on a number of DC activities, including endocytosis, cytoskeleton rearrangement, migration, antigen processing and presentation, survival, and death. The goal of TLR-induced DC reprogramming is to promote the appropriate activation and differentiation of lymphocytes bearing clonally distributed antigen-specific receptors. In this review, we will focus on the functional consequences of TLR engagement for conventional DCs.

Ivan Zanoni

Papers

Regulation and dysregulation of innate immunity by NFAT signaling downstream of pattern recognition receptors (PRRs)

Regulation of antigen uptake, migration, and lifespan of dendritic cell by Toll-like receptors.

Lambda interferons come to light: dual function cytokines mediating antiviral immunity and damage control

Drug nanocarriers to treat autoimmunity and chronic inflammatory diseases

A novel bioactive peptide: assessing its activity over murine neural stem cells and its potential for neural tissue engineering