Coexisting Cardiac and Hematologic Disorders.

Patients with concomitant cardiac and hematologic disorders presenting for noncardiac surgery are challenging. Anemic patients with cardiac disease should be approached in a methodical fashion. Transfusion triggers and target should be based on underlying symptomatology. The approach to anticoagulation management in patients with artificial heart valves, cardiac devices, or severe heart failure in the operative setting must encompass a complete understanding of the rationale of a patient\u27s therapy as well as calculate the risk of changing this regimen. This article focuses common disorders and discusses strategies to optimize care in patients with coexisting cardiac and hematologic disease

Type 2 diabetes mellitus and the cardiometabolic syndrome: impact of incretin-based therapies

The rates of type 2 diabetes mellitus, obesity, and cardiovascular disease (CVD) continue to increase at epidemic proportions. It has become clear that these disease states are not independent but are frequently interrelated. By addressing conditions such as obesity, insulin resistance, stress hyperglycemia, impaired glucose tolerance, and diabetes mellitus, with its micro- and macrovascular complications, a specific treatment strategy can be developed. These conditions can be addressed by early identification of patients at high risk for type 2 diabetes, prompt and aggressive treatment of their hyperglycemia, recognition of the pleiotropic and synergistic benefits of certain antidiabetes agents on CVD, and thus, avoiding potential complications including hypoglycemia and weight gain. Incretin-based therapies, which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-IV (DPP-IV) inhibitors, have the potential to alter the course of type 2 diabetes and associated CVD complications. Advantages of these therapies include glucose-dependent enhancement of insulin secretion, infrequent instances of hypoglycemia, weight loss with GLP-1 receptor agonists, weight maintenance with DPP-IV inhibitors, decreased blood pressure, improvements in dyslipidemia, and potential beneficial effects on CV function

Evaluation and Enhancement of an Intraoperative Insulin Infusion Protocol via In-Silico Simulation

Intraoperative glycemic control, particularly in cardiac surgical patients, remains challenging. Patients with impaired insulin sensitivity and/or secretion (i.e., type 1 diabetes mellitus) often manifest extremely labile blood glucose measurements during periods of stress and inflammation. Most current insulin infusion protocols are developed based on clinical experiences and consensus among a local group of physicians. Recent advances in human glucose metabolism modeling have established a computer model that invokes algorithms representing many of the pathways involved in glucose dysregulation for patients with diabetes. In this study, we used an FDA approved glucose metabolism model to evaluate an existing institutional intraoperative insulin infusion protocol via closedloop simulation on the virtual diabetic population that comes with the computer model. A comparison of simulated responses to actual retrospective clinical data from 57 type 1 diabetic patients undergoing cardiac surgery managed by the institutional protocol was performed. We then designed a proportional-derivative controller that overcomes the weaknesses exhibited by our old protocol while preserving its strengths. In-silico evaluation results show that our proportional-derivative controller more effectively manages intraoperative hyperglycemia while simultaneously reducing hypoglycemia and glycemic variability. By performing insilico simulation on intraoperative glucose and insulin responses, robust and seemingly efficacious algorithms can be generated that warrant prospective evaluation in human subjects

Telemedicine coverage for post-operative ICU patients.

Introduction There is an increased demand for intensive care unit (ICU) beds. We sought to determine if we could create a safe surge capacity model to increase ICU capacity by treating ICU patients in the post-anaesthesia care unit (PACU) utilizing a collaborative model between an ICU service and a telemedicine service during peak ICU bed demand. Methods We evaluated patients managed by the surgical critical care service in the surgical intensive care unit (SICU) compared to patients managed in the virtual intensive care unit (VICU) located within the PACU. A retrospective review of all patients seen by the surgical critical care service from January 1st 2008 to July 31st 2011 was conducted at an urban, academic, tertiary centre and level 1 trauma centre. Results Compared to the SICU group ( n = 6652), patients in the VICU group ( n = 1037) were slightly older (median age 60 (IQR 47-69) versus 58 (IQR 44-70) years, p = 0.002) and had lower acute physiology and chronic health evaluation (APACHE) II scores (median 10 (IQR 7-14) versus 15 (IQR 11-21), p \u3c 0.001). The average amount of time patients spent in the VICU was 13.7 + /-9.6 hours. In the VICU group, 750 (72%) of patients were able to be transferred directly to the floor; 287 (28%) required subsequent admission to the surgical intensive care unit. All patients in the VICU group were alive upon transfer out of the PACU while mortality in the surgical intensive unit cohort was 5.5%. Discussion A collaborative care model between a surgical critical care service and a telemedicine ICU service may safely provide surge capacity during peak periods of ICU bed demand. The specific patient populations for which this approach is most appropriate merits further investigation

Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV. Cell cultures were infected pre- or post-myelination for various intervals, then stained with cell-type and ZIKV-specific antibodies. In bypassing systemic immunity using ex vivo culture, and the type I interferon response in Ifnar1 deficient cells, we were able to evaluate the intrinsic infectivity of neural cells. Through systematic quantification of ZIKV infected cells in myelinating cultures, we found that ZIKV infection is enhanced in the absence of the type I interferon responses and that CNS cells are considerably more susceptible to infection than PNS cells. In particular, we demonstrate that CNS axons and myelinating oligodendrocytes are especially vulnerable to injury. These results have implications for understanding the pathobiology of neurological symptoms associated with ZIKV infection. Furthermore, we provide a quantifiable ex vivo infection model that can be used for fundamental and therapeutic studies on viral neuroinvasion and its consequences

The Effects of Electric Power Lines on the Breeding Ecology of Greater Sage-Grouse

Anthropogenic infrastructure can negatively affect wildlife through direct mortality and/or displacement behaviors. Some tetranoids (grouse spp.) species are particularly vulnerable to tall anthropogenic structures because they evolved in ecosystems void of vertical structures. In western North America, electric power transmission and distribution lines (power lines) occur in sagebrush (Artemisia spp.) landscapes within the range of the greater sage-grouse (Centrocercus urophasianus; sage-grouse). The U.S. Fish and Wildlife Service recommended using buffer zones near leks to mitigate the potential impacts of power lines on sage-grouse. However, recommended buffer distances are inconsistent across state and federal agencies because data are lacking. To address this, we evaluated the effects of power lines on sage-grouse breeding ecology within Utah, portions of southeastern Idaho, and southwestern Wyoming from 1998–2013. Overall, power lines negatively affected lek trends up to a distance of 2.7 and 2.8 km, respectively. Power lines died not affect lek persistence. Female sage-grouse avoided transmission lines during the nesting and brooding seasons at distances up to 1.1 and 0.8 km, respectively. Nest and brood success were negatively affected by transmission lines up to distances of 2.6 and 1.1 km, respectively. Distribution lines did not appear to affect sage-grouse habitat selection or reproductive fitness. Our analyses demonstrated the value of sagebrush cover in mitigating potential power line impacts. Managers can minimize the effects of new transmission power lines by placing them in existing anthropogenic corridors and/or incorporating buffers at least 2.8 km from active leks. Given the uncertainty we observed in our analyses regarding sage-grouse response to distribution lines coupled with their role in providing electric power service directly to individual consumers, we recommend that buffers for these power lines be considered on a case-by-case basis. Micrositing to avoid important habitats and habitat reclamation may reduce the potential impacts of new power line construction

Assessment of iron oxide nanoparticle ecotoxicity on regeneration and homeostasis in the replacement model system Schmidtea mediterranea

Iron oxide nanoparticles (IONs) are used in a number of applications, from food to cosmetics, from medical applications to magnetic storage. In spite of the 550 tons produced each year in Europe alone, no effective dose limit recommendations are established and the overall risks connected to IONs are still debated. The incorporation of IONs in daily life raises a concern about their effects on the environment, on living organisms, and on human health. In this study, we used freshwater planarians to assess the nanoecotoxicity of IONs. Planarians are free-living invertebrates known for their astonishing regenerative ability. Because of their sensitivity to toxicants, they are often used to determine the effects of toxic, genotoxic and carcinogenic environmental compounds with an approach in line with the 3Rs (Reduce, Refine, Replace) principle. Planarians were exposed to IONs at concentrations up to 1 mg/mL and their effects were evaluated at the behavioral, morphofunctional and molecular levels, with a special emphasis on the regeneration process. Our results indicate that IONs did not affect the stem cell population dynamics, nor did they induce substantial changes in either homeostatic or regenerating planarians. As positive controls, gold nanoparticles coated with the pro-apoptotic anti-cancer drug hexadecylmethylammonium bromide, silver nanoparticles and highly concentrated polystyrene nanoparticles were used. These all elicited toxic effects. Therefore, we conclude that IONs at environmental concentrations are safe for planarians, and that the planarian is a powerful model system that can replace vertebrate animal models in nanoecotoxicology research and for nanoecotoxicology studies

Full genome sequence and sfRNA interferon antagonist activity of Zika virus from Recife, Brazil

Background: The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into a major public health concern. Little is currently known about the evolution and biology of ZIKV and the factors that contribute to the associated pathogenesis. Determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative processes and virus-host interactions. Methodology/Principal findings: We obtained a ZIKV isolate from a patient who presented with classical ZIKV-associated symptoms, and used high throughput sequencing and other molecular biology approaches to determine its full genome sequence, including non-coding regions. Genome regions were characterized and compared to the sequences of other isolates where available. Furthermore, we identified a subgenomic flavivirus RNA (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced type I interferon induction, with a lesser effect on MDA-5 mediated action. Conclusions/Significance: The full-length genome sequence including non-coding regions of a South American ZIKV isolate from a patient with classical symptoms will support efforts to develop genetic tools for this virus. Detection of sfRNA that counteracts interferon responses is likely to be important for further understanding of pathogenesis and virus-host interactions

Declining Intensive Care Unit Mortality of COVID-19: A Multi-Center Study

Background: Coronavirus disease 2019 (COVID-19) mortality has waned significantly over time; however, factors contributing towards this reduction largely remain unidentified. The purpose of this study was to evaluate the trend in mortality at our large tertiary academic health system and factors contributing to this trend. Methods: This is a retrospective cohort study of intensive care unit (ICU) patients diagnosed with COVID-19 between March and August 2020 admitted across 14 hospitals in the Philadelphia area. Collected data included demographics, comorbidities, admission risk of mortality score, laboratory values, medical interventions, survival outcomes, hospital and ICU length of stay (LOS) and discharge disposition. Chi-square (χ2) test, Fisher exact test, Cochran-Mantel-Haenszel method, multinomial logistic regression models, independent sample t-test, Mann-Whitney U test and one-way analysis of variance (ANOVA) were used. Results: A total of 1,204 patients were included. Overall mortality was 39%. Mortality declined significantly from 46% in March to 14% in August 2020 (P \u3c 0.05). The most common underlying comorbidities were hypertension (60.2%), diabetes mellitus (44.7%), dyslipidemia (31.6%) and congestive heart failure (14.7%). Hydroxychloroquine (HCQ) use was more commonly associated with the patients who died, while the use of remdesivir, tocilizumab, steroids and duration of these medications were not significantly different. Peak values of ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and D-dimer levels were significantly higher in patients who died (P \u3c 0.05). The mean hospital LOS was significantly longer in the patients who survived compared to the patients who died (18 vs. 12, P \u3c 0.05). Conclusions: The mortality of patients admitted to our ICU system significantly decreased over time. Factors that may have contributed to this may be the result of a better understanding of COVID-19 pathophysiology and treatments. Further research is needed to elucidate the factors contributing to a reduction in the mortality rate for this patient population