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1.
Purpose of Review
Hyperglycemia occurs frequently in hospitalized patients with stroke and peripheral vascular disease (PVD). Guidelines for inpatient glycemic management are not well established for this patient population. We will review the clinical impact of hyperglycemia in this acute setting and review the evidence for glycemic control.Recent Findings
Hyperglycemia in acute stroke is associated with poor short and long-term outcomes, and perioperative hyperglycemia in those undergoing revascularization for PVD is linked to increased post-surgical complications. Studies evaluating tight glucose control do not demonstrate improvement in clinical outcomes, although the risk for hypoglycemia increases substantially. Additional studies are needed to evaluate tight glucose goals relative to our current standard of care and the role of permissive hyperglycemia.Summary
Given the limited data to guide glycemic management in these patient populations, it is recommended that general guidelines for inpatient glycemic control be followed. Special considerations should be made to address factors that may impact glucose management, including neurological deficits and clinical changes that occur in the postoperative state.2.
Stelios F. Assimakopoulos Christos Triantos Konstantinos Thomopoulos Fotini Fligou Ioannis Maroulis Markos Marangos Charalambos A. Gogos 《Infection》2018,46(6):751-760
Introduction
Gut permeability is increased in critically ill patients, and associated with the development of the systemic inflammatory response syndrome and multiple organ dysfunction syndrome (MODS). The pathogenetic link(s) and potential therapies are an area of intense research over the last decades.Methods
We thoroughly reviewed the literature on gut-origin sepsis and MODS in critically ill patients, with emphasis on the implicated pathophysiological mechanisms and therapeutic interventions.Findings
Intestinal barrier failure leading to systemic bacterial translocation associated with MODS was the predominant pathophysiological theory for several years. However, clinical studies with critically ill patients failed to provide the evidence of systemic spread of gut-derived bacteria and/or their products as a cause of MODS. Newer experimental data highlight the role of the mesenteric lymph as a carrier of gut-derived danger-associated molecular patterns (DAMPs) to the lung and the systemic circulation. These substances are recognized by pattern recognition receptor-bearing cells in diverse tissues and promote proinflammatory pathways and the development MODS. Therefore, the gut becomes a pivotal proinflammatory organ, driving the systemic inflammatory response through DAMPs release in mesenteric lymph, without the need for systemic bacterial translocation.Conclusions
There is an emerging need for application of sensitive non-invasive and easily measured biomarkers of early intestinal injury (e.g., citrulline, intestinal fatty acid protein, and zonulin) in our everyday clinical practice, guiding the early pharmacological intervention in critically ill patients to restore or prevent intestinal injury and improve their outcomes.3.
Purpose of Review
The oral glucose tolerance test (OGTT) is used both in clinical practice and research to assess glucose tolerance. In addition, the OGTT is utilized for surrogate measures of insulin sensitivity and the insulin response to enteral glucose and has been widely applied in the evaluation of β-cell dysfunction in obesity, prediabetes, and type 2 diabetes. Here we review the use of the OGTT and the OGTT-derived indices for measurement of risk markers for type 2 diabetes in youth.Recent Findings
Advantages of using the OGTT for measures of diabetes risk include its accessibility and the incorporation of physiological contributions of the gut-pancreas axis in the measures of insulin response to glucose. Mathematical modeling expands the potential gains from the OGTT in physiology and clinical research. Disadvantages include individual differences in the rate of glucose absorption that modify insulin responses, imperfect control of the glycemic stimulus, and poor intraindividual reproducibility.Summary
Available research suggests the OGTT provides valuable information about the development of impaired glycemic control and β-cell function in obese youth along the spectrum of glucose tolerance.4.
Anne M. Masich Mojdeh S. Heavner Jeffrey P. Gonzales Kimberly C. Claeys 《Current infectious disease reports》2018,20(5):9
Purpose of Review
Beta-lactam antibiotics are commonly prescribed in critically ill patients for a variety of infectious conditions. Our understanding of how critical illness alters beta-lactam pharmacokinetics/pharmacodynamics (PK/PD) is rapidly evolving.Recent Findings
There is a growing body of literature in adult patients demonstrating that physiological alterations occurring in critically ill patients may limit our ability to optimally dose beta-lactam antibiotics to reach these PK/PD targets. These alterations include changes in volume of distribution and renal clearance with multiple, often overlapping causative pathways, including hypoalbuminemia, renal replacement therapy, and extracorporeal membrane oxygenation. Strategies to overcome these PK alterations include extended infusions and therapeutic drug monitoring. Combined data has demonstrated a possible survival benefit associated with extending beta-lactam infusions in critically ill adult patients.Summary
This review highlights research on physiological derangements affecting beta-lactam concentrations and strategies to optimize beta-lactam PK/PD in critically ill adults.5.
Purpose of Review
The prevalence of combined obesity and diabetes has increased dramatically in the last few decades. Although medical and surgical weight management are variably effective in addressing this epidemic, it is essential to parallel these strategies with a hypocaloric diet comprising the appropriate macronutrient composition to induce weight loss, enhance glycemic control, and improve cardiovascular risk factors. This review reports the current evidence of the role of carbohydrates and fat-based diets for weight management in patients with combined type 2 diabetes (T2D) and obesity.Recent Findings
Low-carbohydrate diets were shown to decrease postprandial glucose levels whereas high-carbohydrate, low-fat diets are considered cardio-protective.Summary
A diet with an optimal macronutrient composition remains uncertain for patients with combined T2D and obesity. Further research is still needed to define the best dietary composition that achieves the maximum benefits on weight management, glycemic control, and cardiovascular risk factors.6.
Background
Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) have major roles in the evaluation of parenchymal lung diseases in immunocompromised patients. Given the limited evidence, lack of standardized practice, and variable perception of procedural safety, uncertainty still exists on what constitutes the best approach in critically ill patients with immunocompromised state who present with pulmonary infiltrates in the era of prophylactic antimicrobials and the presence of new diagnostic tests.Objective
To evaluate the diagnostic yield, safety and impact of FB and BAL on management decisions in immunocompromised critically ill patients admitted to the intensive care unit (ICU).Methods
A prospective, observational study of 106 non-HIV immunocompromised patients admitted to the intensive care unit with pulmonary infiltrates who underwent FB with BAL.Results
FB and BAL established the diagnosis in 38 (33%) of cases, and had a positive impact on management in 44 (38.3%) of cases. Escalation of ventilator support was not required in 94 (81.7%) of cases, while 18 (15.7%) required invasive and 3 (2.6%) required non-invasive positive pressure ventilation after the procedure. Three patients (2.6%) died within 24 h of bronchoscopy, and 46 patients (40%) died in ICU. Significant hypoxemia developed in 5% of cases.Conclusion
FB can be safely performed in immunocompromised critically ill patients in the ICU. The yield can be improved when FB is done prior to initiation of empiric antimicrobials, within 24 h of admission to the ICU, and in patients with focal disease.7.
8.
Purpose of Review
New treatment strategies are needed for patients with type 1 diabetes (T1D). Closed loop insulin delivery and beta-cell replacement therapy are promising new strategies. This review aims to give an insight in the most relevant literature on this topic and to compare the two radically different treatment modalities.Recent Findings
Multiple clinical studies have been performed with closed loop insulin delivery devices and have shown an improvement in overall glycemic control and time spent in hypoglycemia. Beta-cell transplantation has been shown to normalize or greatly improve glycemic control in T1D, but the donor organ shortage and the necessity to use immunosuppressive agents are major drawbacks. Donor organ shortage may be solved by the utilization of stem cell-derived beta cells, which has shown great promise in animal models and are now tested in clinical studies. Immunosuppression may be avoided by encapsulation.Summary
Closed loop insulin delivery devices are promising treatment strategies and are likely to be used in clinical practice in the short term. But this approach will always suffer from delays in glucose measurement and insulin action preventing it from normalizing glycemic control. In the long term, stem cell-derived beta cell transplantation may be able to achieve this, but wide implementation in clinical practice is still far away.9.
Jody C. Olson 《Current Treatment Options in Gastroenterology》2018,16(2):241-252
Purpose of review
Cirrhosis is a major worldwide health problem which results in a high level of morbidity and mortality. Patients with cirrhosis who require intensive care support have high mortality rates of near 50%. The goal of this review is to address the management of common complications of cirrhosis in the ICU.Recent findings
Recent epidemiological studies have shown an increase in hospitalizations due to advanced liver disease with an associated increase in intensive care utilization. Given an increasing burden on the healthcare system, it is imperative that we strive to improve our management cirrhotic patients in the intensive care unit.Summary
Large studies evaluating the management of patients in the intensive care setting are lacking. To date, most recommendations are based on extrapolation of data from studies in cirrhosis outside of the ICU or by applying general critical care principles which may or may not be appropriate for the critically ill cirrhotic patient. Future research is required to answer important management questions.10.
Katia M. Perez Emily R. Hamburger Morgan Lyttle Rodayne Williams Erin Bergner Sachini Kahanda Erin Cobry Sarah S. Jaser 《Current diabetes reports》2018,18(2):5
Purpose of Review
To highlight recent findings from studies of sleep in type 1 diabetes (T1D), with a focus on the role of sleep in self-management, the cognitive and psychosocial outcomes related to sleep disturbances, and factors associated with sleep disturbances specific to T1D.Recent Findings
People with T1D experience higher rates of sleep disturbances than people without diabetes, and these disturbances have negative implications for glycemic control and diabetes management, as well as psychosocial and cognitive outcomes. Inconsistent sleep timing (bedtime and wake time) has emerged as a potential target for interventions, as variability in sleep timing has been linked with poorer glycemic control and adherence to treatment. Sleep-promoting interventions and new diabetes technology have the potential to improve sleep in people with T1D.Summary
Sleep is increasingly considered a critical factor in diabetes management, but more multi-method and longitudinal research is needed. We emphasize the importance of sufficient and consistent sleep for people with T1D, and the need for providers to routinely assess sleep among patients with T1D.11.
Mojdeh S. Heavner Kimberly C. Claeys Anne M. Masich Jeffrey P. Gonzales 《Current infectious disease reports》2018,20(5):10
Purpose of Review
We provide an overview of antimicrobials that are considered last resort for the treatment of resistant gram-negative infections in adult critically ill patients. The role in therapy, pharmacodynamic (PD) goals, and pharmacokinetic (PK) changes in critical illness for aminoglycosides, polymyxins, tigecycline, fosfomycin, and fluoroquinolones are summarized.Recent Findings
Altered PK in septic patients in the intensive care unit (ICU) is observed with many of our agents of last resort. Based on the available literature, dosage adjustments may be required to optimize PK parameters and meet PD targets for most effective bacterial killing. Data is limited, studies are conducted in heterogeneous patient populations, and conclusions are frequently conflicting. Strategic dosing regimens such as high-dose extended interval dosing of aminoglycosides or loading doses with colistin and polymyxin B are examples of ways to optimize antibiotic PK in critically ill patients. Benefits of these strategies must be balanced with risks of increased toxicity.Summary
Patients with resistant gram-negative infections may present with septic shock in the ICU. Sepsis can significantly alter the PK of antibiotics and require dosage adjustments to attain optimal drug levels. An understanding of PK and PD properties of these agents of last resort will help to maximize therapeutic efficacy while minimizing toxic effects.12.
13.
Antonio Sircana Luciana Framarin Nicola Leone Mara Berrutti Francesca Castellino Renato Parente Franco De Michieli Elena Paschetta Giovanni Musso 《Current diabetes reports》2018,18(10):98
Purpose of Review
In the last decade many studies have suggested an association between the altered gut microbiota and multiple systemic diseases including diabetes. In this review, we will discuss potential pathophysiological mechanisms, the latest findings regarding the mechanisms linking gut dysbiosis and type 2 diabetes (T2D), and the results obtained with experimental modulation of microbiota.Recent Findings
In T2D, gut dysbiosis contributes to onset and maintenance of insulin resistance. Different strategies that reduce dysbiosis can improve glycemic control.Summary
Evidence in animals and humans reveals differences between the gut microbial composition in healthy individuals and those with T2D. Changes in the intestinal ecosystem could cause inflammation, alter intestinal permeability, and modulate metabolism of bile acids, short-chain fatty acids and metabolites that act synergistically on metabolic regulation systems contributing to insulin resistance. Interventions that restore equilibrium in the gut appear to have beneficial effects and improve glycemic control. Future research should examine in detail and in larger studies other possible pathophysiological mechanisms to identify specific pathways modulated by microbiota modulation and identify new potential therapeutic targets.14.
Mohamed Abo El-Asrar Nancy Samir Elbarbary Eman Abdel Rahman Ismail AlShaimaa Abo Bakr 《Angiogenesis》2016,19(3):421-431
Background
Angiopoietin-2 is a growth factor involved in the pathophysiology of vascular and inflammatory diseases such as arteriosclerosis. Carotid or aortic scans provide noninvasive screening tools for assessment of preclinical atherosclerosis in high-risk children.Aim
We assessed serum angiopoietin-2 in children and adolescents with type 1 diabetes mellitus as a potential marker for vascular complications in relation to glycemic control, inflammation and vascular structure.Methods
Sixty patients with type 1 diabetes were divided into 2 groups according to the presence of micro-vascular complications and compared with 30 healthy controls. High-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), urinary albumin/creatinine ratio, serum angiopoietin-2, carotid and aortic intima-media thickness (CIMT and AIMT) were measured.Results
CIMT, AIMT and serum angiopoietin-2 levels were significantly increased in patients with and without micro-vascular complications compared with controls, and the highest levels were in patients with complications (p < 0.001). Angiopoietin-2 was higher in patients with microalbuminuria than normoalbuminuric group (p < 0.001). Fasting blood glucose, HbA1c, hs-CRP, CIMT and AIMT were independently related to angiopoietin-2 in multiple regression analysis. Disease duration, hyperglycemia, poor glycemic control, hypercholesterolemia, inflammation and angiopoietin-2 were independent factors contributing to atherosclerosis risk.Conclusion
The relation between angiopoietin-2 and assessed parameters of vascular structure in type 1 diabetes reflects a state of endothelial injury and highlights the role of disturbed angiogenesis and vascular inflammation in the occurrence of diabetic complications.15.
Marissa A. Feldman Lindsay M. Anderson Jenna B. Shapiro Aneta M. Jedraszko Meredyth Evans Lindsey E. G. Weil Kimberly P. Garza Jill Weissberg-Benchell 《Current diabetes reports》2018,18(3):15
Purpose of Review
A systematic review was conducted of family-based interventions to improve glycemic control, adherence, and psychosocial outcomes in children and adolescents with type 1 diabetes (T1D). Electronic databases were searched for randomized controlled trials (RCTs) published since the seminal Diabetes Control and Compliance Trial (DCCT). Interventions are summarized and findings reviewed to help guide clinical practice and future research.Recent Findings
Twenty-five RCTs are reviewed. The majority of studies (n?=?15) focused on interventions targeting both children and adolescents and their caregivers and were delivered in diabetes clinics, outpatient settings, mental health clinics, or participants’ homes.Summary
Family-based interventions for youth with T1D appear effective at improving diabetes and family-centered outcomes. Additional research is needed to examine the pathways to improvement in glycemic control, as outcomes were mixed. Future research should also involve measures beyond HbA1c given new markers for sustained health improvement and outcomes are being explored.16.
Thorsten Feige 《Der Diabetologe》2018,14(7):465-469
Background
Most type 1 diabetes mellitus patients are not capable of achieving close to normal glucose levels and thus face a constant risk of severe hypoglycemia and diabetic ketoacidosis.Objectives
Patients develop their own personal non-approved medical devices to compensate for gaps in the existing medical technology.Materials and methods
Current studies are assessed and basic work and challenges are discussed.Results
The authorization of such systems from patients themselves results in the development of medical devices suitable for use but approved only based on freely available algorithms. Legal framework conditions, lack of standards on the interoperability of medical devices and uncertainties about future technology trends are giving rise to ongoing controversies.Conclusions
There is a need to validate these new approaches, agree upon success criteria and provide solid evidence of their effectiveness.17.
Background
Malnutrition is associated with poor outcomes in surgical patients and corrective enteral feeding may not be possible. This is a particular problem in the acute setting where malnutrition is prevalent. The aim of this systematic review was to evaluate the use of parenteral nutrition (PN) in critically ill surgical patients.Methods
This review was registered with PROSPERO (CRD42017079567). Searches of the CENTRAL, EMBASE, and MEDLINE databases were performed using a predefined strategy. Randomised trials published in English since 1995, reporting a comparison of PN vs any comparator in a critically ill surgical population were included. The primary outcome was mortality. Risk of bias was assessed using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation assessment. Meta-analysis was performed using a random effects model to assess variation in mortality and length of stay.Results
Fourteen RCTs were identified; standard PN was compared vs other forms of PN in ten studies, to PN with variable dose amino acids in one, and to enteral nutrition (EN) in three. In trials comparing glutamine-supplemented PN (PN-GLN) to PN, a non-significant reduction in mortality was noted (risk difference ??0.08. 95% CI ??0.17, 0.01, p = 0.08). A trend for a reduction in length of stay was seen in PN-GLN to PN comparator (mean reduction ??2.4, 95% CI ??7.19 to 2.32 days, I2 = 92%). Impact on other outcome measures varied in direction of effect.Conclusions
PN may offer benefit in critically ill surgical patients. The size and quality of studies lead to uncertainty around the estimates of clinical effect, meaning a robust trial is required.18.
Conditional islet hypovascularisation does not preclude beta cell expansion during pregnancy in mice
Willem Staels Yves Heremans Gunter Leuckx Naomi Van Gassen Ciro Salinno Sofie De Groef Martine Cools Eli Keshet Yuval Dor Harry Heimberg Nico De Leu 《Diabetologia》2017,60(6):1051-1056
Aims/hypothesis
Endothelial–endocrine cell interactions and vascular endothelial growth factor (VEGF)-A signalling are deemed essential for maternal islet vascularisation, glucose control and beta cell expansion during mouse pregnancy. The aim of this study was to assess whether pregnancy-associated beta cell expansion was affected under conditions of islet hypovascularisation.Methods
Soluble fms-like tyrosine kinase 1 (sFLT1), a VEGF-A decoy receptor, was conditionally overexpressed in maternal mouse beta cells from 1.5 to 14.5 days post coitum. Islet vascularisation, glycaemic control, beta cell proliferation, individual beta cell size and total beta cell volume were assessed in both pregnant mice and non-pregnant littermates.Results
Conditional overexpression of sFLT1 in beta cells resulted in islet hypovascularisation and glucose intolerance in both pregnant and non-pregnant mice. In contrast to non-pregnant littermates, glucose intolerance in pregnant mice was transient. sFLT1 overexpression did not affect pregnancy-associated changes in beta cell proliferation, individual beta cell size or total beta cell volume.Conclusions/interpretation
Reduced intra-islet VEGF-A signalling results in maternal islet hypovascularisation and impaired glycaemic control but does not preclude beta cell expansion during mouse pregnancy.19.
Charlotte C. Heuvelings Sabine Bélard Saskia Janssen Claudia Wallrauch Martin P. Grobusch Enrico Brunetti Maria Teresa Giordani Tom Heller 《Infection》2016,44(1):1-10
Introduction
Pulmonary disease is common in HIV-infected patients. Diagnostic means, however, are often scarce in areas where most HIV patients are living. Chest ultrasonography has recently evolved as a highly sensitive and specific imaging tool for diagnosing chest conditions such as pneumothorax, pneumonia and pulmonary edema in critically ill patients. This article addresses the issue of imaging and differentiating common pulmonary conditions in HIV-infected patients by chest ultrasonography.Methods
We report chest ultrasound features of five different common pulmonary diseases in HIV-infected patients (bacterial pneumonia, Pneumocystis jirovecii pneumonia, tuberculosis, cytomegalovirus pneumonia and non-Hodgkin lymphoma) and review the respective literature.Conclusions
We observed characteristic ultrasound patterns especially in Pneumocystis jirovecii pneumonia and pulmonary lymphoma. Further exploration of chest ultrasonography in HIV-infected patients appears promising and may translate into new diagnostic approaches for pulmonary conditions in patients living with HIV.20.
J. Daryl Thornton Catherine Sullivan Jeffrey M. Albert Maria Cedeño Bridget Patrick Julie Pencak Kristine A. Wong Margaret D. Allen Linda Kimble Heather Mekesa Gordon Bowen Ashwini R. Sehgal 《Journal of general internal medicine》2016,31(8):832-839