Comparison of monocyte human leukocyte antigen-DR expression and stimulated tumor necrosis factor alpha production as outcome predictors in severe sepsis: A prospective observational study

BACKGROUND: Identifying patients in the immunosuppressive phase of sepsis is essential for development of immunomodulatory therapies. Little data exists comparing the ability of the two most well-studied markers of sepsis-induced immunosuppression, human leukocyte antigen (HLA)-DR expression and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-ɑ) production, to predict mortality and morbidity. The purpose of this study was to compare HLA-DR expression and LPS-induced TNF-ɑ production as predictors of 28-day mortality and acquisition of secondary infections in adult septic patients. METHODS: A single-center, prospective observational study of 83 adult septic patients admitted to a medical or surgical intensive care unit. Blood samples were collected at three time points during the septic course (days 1–2, days 3–4, and days 6–8 after sepsis diagnosis) and assayed for HLA-DR expression and LPS-induced TNF-ɑ production. A repeated measures mixed model analysis was used to compare values of these immunological markers among survivors and non-survivors and among those who did and did not develop a secondary infection. RESULTS: Twenty-five patients (30.1 %) died within 28 days of sepsis diagnosis. HLA-DR expression was significantly lower in non-survivors as compared to survivors on days 3–4 (p = 0.04) and days 6–8 (p = 0.002). The change in HLA-DR from days 1–2 to days 6–8 was also lower in non-survivors (p = 0.04). Median HLA-DR expression decreased from days 1–2 to days 3–4 in patients who developed secondary infections while it increased in those without secondary infections (p = 0.054). TNF-ɑ production did not differ between survivors and non-survivors or between patients who did and did not develop a secondary infection. CONCLUSIONS: Monocyte HLA-DR expression may be a more accurate predictor of mortality and acquisition of secondary infections than LPS-stimulated TNF-ɑ production in adult medical and surgical critically ill patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1505-0) contains supplementary material, which is available to authorized users

T cells from patients with Candida sepsis display a suppressive immunophenotype

BACKGROUND: Despite appropriate therapy, Candida bloodstream infections are associated with a mortality rate of approximately 40 %. In animal models, impaired immunity due to T cell exhaustion has been implicated in fungal sepsis mortality. The purpose of this study was to determine potential mechanisms of fungal-induced immunosuppression via immunophenotyping of circulating T lymphocytes from patients with microbiologically documented Candida bloodstream infections. METHODS: Patients with blood cultures positive for any Candida species were studied. Non-septic critically ill patients with no evidence of bacterial or fungal infection were controls. T cells were analyzed via flow cytometry for cellular activation and for expression of positive and negative co-stimulatory molecules. Both the percentages of cells expressing particular immunophenotypic markers as well as the geometric mean fluorescence intensity (GMFI), a measure of expression of the number of receptors or ligands per cell, were quantitated. RESULTS: Twenty-seven patients with Candida bloodstream infections and 16 control patients were studied. Compared to control patients, CD8 T cells from patients with Candidemia had evidence of cellular activation as indicated by increased CD69 expression while CD4 T cells had decreased expression of the major positive co-stimulatory molecule CD28. CD4 and CD8 T cells from patients with Candidemia expressed markers typical of T cell exhaustion as indicated by either increased percentages of or increased MFI for programmed cell death 1 (PD-1) or its ligand (PD-L1). CONCLUSIONS: Circulating immune effector cells from patients with Candidemia display an immunophenotype consistent with immunosuppression as evidenced by T cell exhaustion and concomitant downregulation of positive co-stimulatory molecules. These findings may help explain why patients with fungal sepsis have a high mortality despite appropriate antifungal therapy. Development of immunoadjuvants that reverse T cell exhaustion and boost host immunity may offer one way to improve outcome in this highly lethal disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1182-z) contains supplementary material, which is available to authorized users

Adverse events related to ultrasound-guided regional anesthesia performed by Emergency Physicians: Systematic review protocol

The use of ultrasound-guided regional anesthesia for pain management has become increasingly prevalent in Emergency Medicine, with studies noting excellent pain control while sparing opioid use. However, the use of ultrasound-guided regional anesthesia may be hampered by concern about risks for patient harm. This systematic review protocol describes our approach to evaluate the incidence of adverse events from the use of ultrasound-guided regional anesthesia by Emergency Physicians as described in the literature. This project will also seek to document the scope of ultrasound-guided regional anesthesia applications being performed in Emergency Medicine literature, and potentially serve as a framework for future systematic reviews evaluating adverse events in Emergency Medicine

Sub-acute Tamponade and the Value of Point-of-Care Ultrasound for Rapid Diagnosis: A Case Report

Minoxidil is a strong oral vasodilator that is used to treat patients with hypertension refractory to first-line medications. We report a case of minoxidil-associated subacute cardiac tamponade diagnosed by point-of-care ultrasound (POCUS) in a hypertensive patient. A 30-year-old male with a past medical history of poorly controlled hypertension (treated with minoxidil) and chronic kidney disease presented with 2–3 days of chest pain and shortness of breath with markedly elevated blood pressures. A point-of-care transthoracic echocardiogram revealed a massive pericardial effusion with sonographic tamponade physiology. We review the risk factors for developing pericardial effusions that progress to cardiac tamponade, the utility of diagnosing these patients by POCUS, and the incidence of patients who present with sonographic signs of cardiac tamponade without hypotension

Sub-acute Tamponade and the Value of Point-of- Care Ultrasound for Rapid Diagnosis: A Case Report

Minoxidil is a strong oral vasodilator that is used to treat patients with hypertension refractoryto first-line medications. We report a case of minoxidil-associated subacute cardiac tamponadediagnosed by point-of-care ultrasound (POCUS) in a hypertensive patient. A 30-year-old male witha past medical history of poorly controlled hypertension (treated with minoxidil) and chronic kidneydisease presented with 2-3 days of chest pain and shortness of breath with markedly elevated bloodpressures. A point-of-care transthoracic echocardiogram revealed a massive pericardial effusion withsonographic tamponade physiology. We review the risk factors for developing pericardial effusionsthat progress to cardiac tamponade, the utility of diagnosing these patients by POCUS, and theincidence of patients who present with sonographic signs of cardiac tamponade without hypotension