Point-of-Care Serum Proenkephalin as an Early Predictor of Mortality in Patients Presenting to the Emergency Department with Septic Shock.

BACKGROUND: The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients presenting to the emergency department (ED) with septic shock. METHODS: Bedside PENK was measured in consecutive patients presenting to the ED with septic shock according to the Sepsis-3 clinical criteria. The association of PENK with inflammatory and routine biomarkers, and its role as a predictor of in-hospital mortality, was examined. RESULTS: Sixty-one patients with septic shock [53% females, median age 83 years (IQR 71-88)] were evaluated. Median (IQR) values of creatinine, plasma lactate, soluble urokinase plasminogen activator receptor (SuPAR), procalcitonin and PENK were 1.7 (1.0-2.9) mg/dL, 3.6 (2.1-6.8) mmol/L, 13.1 (10.0-21.4) ng/mL, 2.06 (0.84-3.49) ng/mL, and 205 (129-425) pmol/L, respectively. LogPENK significantly correlated with LogLactate (rho = 0.369, p = 0.004), LogCreatinine (rho = 0.537, p < 0.001), LogProcalcitonin (rho = 0.557, p < 0.001), and LogSuPAR (rho = 0.327, p = 0.011). During hospitalization, 39/61 (64%) patients died. In a multivariable logistic regression model, logPENK was an independent predictor of in-hospital mortality (OR 11.9, 95% CI: 1.7-84.6, p = 0.013). CONCLUSION: POC PENK levels measured upon presentation to the ED strongly correlated with metabolic, renal and inflammatory biomarkers, and may serve as a predictor of in-hospital mortality in patients with septic shock.

Point-of-Care Ultrasound: A Multimodal Tool for the Management of Sepsis in the Emergency Department.

Sepsis and septic shock are life-threatening emergencies associated with increased morbidity and mortality. Hence, early diagnosis and management of both conditions is of paramount importance. Point-of-care ultrasound (POCUS) is a cost-effective and safe imaging modality performed at the bedside, which has rapidly emerged as an excellent multimodal tool and has been gradually incorporated as an adjunct to physical examination in order to facilitate evaluation, diagnosis and management. In sepsis, POCUS can assist in the evaluation of undifferentiated sepsis, while, in cases of shock, it can contribute to the differential diagnosis of other types of shock, thus facilitating the decision-making process. Other potential benefits of POCUS include prompt identification and control of the source of infection, as well as close haemodynamic and treatment monitoring. The aim of this review is to determine and highlight the role of POCUS in the evaluation, diagnosis, treatment and monitoring of the septic patient. Future research should focus on developing and implementing a well-defined algorithmic approach for the POCUS-guided management of sepsis in the emergency department setting given its unequivocal utility as a multimodal tool for the overall evaluation and management of the septic patient.

Gut Failure: A Review of the Pathophysiology and Therapeutic Potentials in the Gut-Heart Axis.

Despite considerable advances in the field, heart failure (HF) still poses a significant disease burden among affected individuals since it continues to cause high morbidity and mortality rates. Inflammation is considered to play a key role in disease progression, but the exact underlying pathophysiological mechanisms involved have not yet been fully elucidated. The gut, as a potential source of inflammation, could feasibly explain the state of low-grade inflammation seen in patients with chronic HF. Several derangements in the composition of the microbiota population, coupled with an imbalance between favorable and harmful metabolites and followed by gut barrier disruption and eventually bacterial translocation, could contribute to cardiac dysfunction and aggravate HF. On the other hand, HF-associated congestion and hypoperfusion alters intestinal function, thereby creating a vicious cycle. Based on this evidence, novel pharmaceutical agents have been developed and their potential therapeutic use has been tested in both animal and human subjects. The ultimate goal in these efforts is to reverse the aforementioned intestinal derangements and block the inflammation cascade. This review summarizes the gut-related causative pathways implicated in HF pathophysiology, as well as the associated therapeutic interventions described in the literature.

Point of Care Ultrasonography for the Septic Patient in the Emergency Department: A Literature Review.

The point-of-care ultrasound (POCUS) has been effectively used in intensive care units for the management of septic patients. Since it is a time- and cost-effective non-invasive imaging modality, its use in the emergency department (ED) has been advocated for by medical experts. This review summarizes the existing literature regarding the breadth of POCUS as a supplementary tool to the holistic approach of septic patients in the ED setting. A literature search was conducted via PubMed (MEDLINE), Cochrane Library, and Scopus databases, analyzing studies which examined the use of POCUS in the ED for non-traumatic, septic, and/or undifferentiated hypotensive patients, resulting in 26 studies. The first cluster of studies investigates the efficiency of POCUS protocols in the differential diagnosis and its reliability for distributive/septic shock and sepsis management. In the second cluster, POCUS use results in faster sepsis cause identification and improves therapeutic management. The third cluster confirms that POCUS aids in the accurate diagnosis and management, even in rare and complicated cases. The results of the present review support the well-documented utility of POCUS and highlight the importance of POCUS incorporation in the comprehensive management of the septic patient in the ED setting.

Serum fetuin-A levels are associated with serum triglycerides before and 6 months after bariatric surgery.

OBJECTIVE: The elucidation of the changes of fetuin-A in the context of bariatric surgery. DESIGN: Twenty obese patients (8 males, 12 females; body mass index = 42.5±3.4 kg/m2) were studied at baseline and 6 months after bariatric surgery. RESULTS: Serum fetuin-A levels did not differ with regard to the presence of each individual component of the Metabolic Syndrome (MetS) at baseline, except for hypertriglyceridaemia [increased serum fetuin-A levels (p=0.011)]. Circulating fetuin-A was positively correlated with serum triglycerides (TG) (r=0.461, p=0.047) and negatively correlated with serum globulins (r=-0.477, p=0.033) and C-reactive protein (CRP) (r=-0.604, p=0.010), while it independently predicted TG at baseline. Circulating fetuin-A did not change during the 6 months either in the whole population or in the subgroups of patients who were positive for each individual component of MetS at baseline and negative for this component at 6 months of follow-up, except for hypertriglyceridaemia [reduction of serum fetuin-A levels (p=0.046)]. The subgroup of patients with a decrease in circulating fetuin-A during the 6 months was characterized by a smaller reduction of serum globulins (p=0.003) and CRP (p=0.049). The change in serum fetuin-A levels over the 6 months was positively correlated with the change in TG (r=0.592, p=0.006) and negatively correlated with the change in serum globulins (r=-0.523, p=0.018) and CRP (r=-.494, p=0.037). CONCLUSIONS: Circulating fetuin-A predicted serum triglycerides before as well as 6 months after bariatric surgery.

Cost-effectiveness analysis of liraglutide versus sitagliptin or exenatide in patients with inadequately controlled Type 2 diabetes on oral antidiabetic drugs in Greece.

BACKGROUND: To evaluate the long-term cost-effectiveness of liraglutide versus sitagliptin or exenatide, added to oral antidiabetic drug mono- or combination therapy respectively, in patients with Type 2 diabetes in Greece. METHODS: The CORE Diabetes Model, a validated computer simulation model, was adapted to the Greek healthcare setting. Patient and intervention effects data were gathered from a clinical trial comparing liraglutide 1.2 mg once daily vs. sitagliptin 100 mg once daily, both combined with metformin, and a clinical trial comparing liraglutide 1.8 mg once daily vs. exenatide 10 µg twice daily, both as add-on to metformin, glimepiride or both. Direct costs were reported in 2013 Euros and calculated based on published and local sources. All future outcomes were discounted at 3.5% per annum, and the analysis was conducted from the perspective of a third-party payer in Greece. RESULTS: Over a patient's lifetime, treatment with liraglutide 1.2 mg vs. sitagliptin drove a mean increase in discounted life expectancy of 0.13 (SD 0.23) years and in discounted quality-adjusted life expectancy of 0.19 (0.16) quality-adjusted life years (QALYs), whereas therapy with liraglutide 1.8 mg vs. exenatide yielded increases of 0.14 (0.23) years and 0.19 (0.16) QALYs respectively. As regards lifetime direct costs, liraglutide 1.2 mg resulted in greater costs of €2797 (€1468) versus sitagliptin, and so did liraglutide 1.8 mg compared with exenatide (€1302 [€1492]). Liraglutide 1.2 and 1.8 mg doses were associated with incremental cost effectiveness ratios of €15101 and €6818 per QALY gained, respectively. CONCLUSIONS: Liraglutide is likely to be a cost-effective option for the treatment of Type 2 diabetes in a Greek setting.