Interferon gamma as an immune modulating adjunct therapy for invasive mucormycosis after severe burn - A case report.

Background: Mucormycosis is a deadly fungal infection that mainly affects severely immunocompromised patients. We report herein the case of a previously immunocompetent adult woman who developed invasive cutaneous mucormycosis after severe burn injuries. Interferon-gamma (IFN-γ) treatment was added after failure of conventional treatment and confirmation of a sustained profound immunodepression. The diagnosis was based on a reduced expression of HLA-DR on monocytes (mHLA-DR), NK lymphopenia and a high proportion of immature neutrophils. The immune-related alterations were longitudinally monitored using panels of immune-related biomarkers. Results: Initiation of IFN-γ was associated with a rapid clinical improvement and a subsequent healing of mucormycosis infection, with no residual fungi at the surgical wound repair. The serial immunological assessment showed sharp improvements of immune parameters: a rapid recovery of mHLA-DR and of transcriptomic markers for T-cell proliferation. The patient survived and was later discharged from the ICU. Conclusion: The treatment with recombinant IFN-γ participated to the resolution of a progressively invasive mucormycosis infection, with rapid improvement in immune parameters. In the era of precision medicine in the ICU, availability of comprehensive immune monitoring tools could help guiding management of refractory infections and provide rationale for immune stimulation strategies in these high risk patients.

A stratification strategy to predict secondary infection in critical illness-induced immune dysfunction: the REALIST score.

BACKGROUND: Although multiple individual immune parameters have been demonstrated to predict the occurrence of secondary infection after critical illness, significant questions remain with regards to the selection, timing and clinical utility of such immune monitoring tests. RESEARCH QUESTION: As a sub-study of the REALISM study, the REALIST score was developed as a pragmatic approach to help clinicians better identify and stratify patients at high risk for secondary infection, using a simple set of relatively available and technically robust biomarkers. STUDY DESIGN AND METHODS: This is a sub-study of a single-centre prospective cohort study of immune profiling in critically ill adults admitted after severe trauma, major surgery or sepsis/septic shock. For the REALIST score, five immune parameters were pre-emptively selected based on their clinical applicability and technical robustness. Predictive power of different parameters and combinations of parameters was assessed. The main outcome of interest was the occurrence of secondary infection within 30 days. RESULTS: After excluding statistically redundant and poorly predictive parameters, three parameters remained in the REALIST score: mHLA-DR, percentage of immature (CD10- CD16-) neutrophils and serum IL-10 level. In the cohort of interest (n = 189), incidence of secondary infection at day 30 increased from 8% for patients with REALIST score of 0 to 46% in patients with a score of 3 abnormal parameters, measured ad D5-7. When adjusted for a priori identified clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5-7), a higher REALIST score was independently associated with increased risk of secondary infection (42 events (22.2%), adjusted HR 3.22 (1.09-9.50), p = 0.034) and mortality (10 events (5.3%), p = 0.001). INTERPRETATION: We derived and presented the REALIST score, a simple and pragmatic stratification strategy which provides clinicians with a clear assessment of the immune status of their patients. This new tool could help optimize care of these individuals and could contribute in designing future trials of immune stimulation strategies.

Potential risks in using midodrine for persistent hypotension after cardiac surgery: a comparative cohort study.

BACKGROUND: Persistent hypotension is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). Midodrine, an orally administered alpha agonist, could potentially reduce intravenous vasopressor use and accelerate ICU discharge of otherwise stable patients. The main objective of this study was to explore the clinical impacts of administering midodrine in patients with persistent hypotension after CPB. Our hypothesis was that midodrine would safely accelerate ICU discharge and be associated with more days free from ICU at 30 days. RESULTS: We performed a retrospective cohort study that included all consecutive patients having received midodrine while being on vasopressor support in the ICU within the first week after cardiac surgery with CPB, between January 2014 and January 2018 at the Montreal Heart Institute. A contemporary propensity score matched control group that included patients who presented similarly prolonged hypotension after cardiac surgery was formed. After matching, 74 pairs of patients (1:1) fulfilled inclusion criteria for the study and control groups. Midodrine use was associated with fewer days free from ICU (25.8 [23.7-27.1] vs 27.2 [25.9-28] days, p = 0.002), higher mortality (10 (13.5%) vs 1 (1.4%), p = 0.036) and longer ICU length of stay (99 [68-146] vs 68 [48-99] hours, p = 0.001). There was no difference in length of intravenous vasopressors (63 [40-87] vs 44 [26-66] hours, p = 0.052), rate of ICU readmission (6 (8.1%) vs 2 (2.7%), p = 0.092) and occurrence of severe kidney injury (11 (14.9%) vs 10 (13.5%) patients, p = 0.462) between groups. CONCLUSION: The administration of midodrine for sustained hypotension after cardiac surgery with CPB was associated with fewer days free from ICU and higher mortality. Routine prescription of midodrine to hasten ICU discharge after cardiac surgery should be used with caution until further prospective studies are conducted.

Pulmonary mucormycosis in a patient with acute liver failure: A case report and systematic review of the literature.

PURPOSE: Pulmonary mucormycosis is a highly lethal invasive fungal infection usually found in immunocompromised patients. We report herein the case of an adult woman who developed pulmonary mucormycosis with possible systemic dissemination after recovering from acute liver failure secondary to acetaminophen overdose. RESULTS: Our case developed an invasive pulmonary mucormycosis with probable systemic dissemination. She did not suffer from any immunocompromising disease other than severe acute liver failure. She did not survive the disease, although she received appropriate antifungal treatment. We also performed a systematic review of the literature on pulmonary mucormycosis, with or without dissemination, in immunocompetent patients. We found 16 cases of pulmonary or disseminated mucormycosis in immunocompetent patients. Fifty-seven percent of them died and none occurred after an acute liver failure episode. CONCLUSION: This case report is the first one to present an invasive pulmonary mucormycosis infection after acute liver failure in an adult patient. The clinical course of this disease is highly lethal, even in immunocompetent adults.

Noninvasive Administration of Inhaled Epoprostenol and Inhaled Milrinone in Extubated, Spontaneously Breathing Patients With Right Ventricular Failure and Portal Hypertension: A Report of 2 Cases.

We describe the cases of 2 patients free from mechanical ventilation after a cardiac surgery with systemic venous congestion from right ventricular (RV) failure. Management of these patients included RV preload reduction with diuretics and RV afterload reduction with inhaled pulmonary vasodilators. Noninvasive combination of inhaled epoprostenol and inhaled milrinone through the AirLife filtered nebulizer system (CareFusion) was used. Reduction of splanchnic venous congestion was assessed by Doppler portal flow pulsatility.

Noninvasive Administration of Inhaled Nitric Oxide and its Hemodynamic Effects in Patients With Acute Right Ventricular Dysfunction.

OBJECTIVE: The authors aimed to assess the hemodynamic effects and demonstrate the feasibility of inhaled nitric oxide (iNO) in hemodynamically unstable patients with acute right ventricular (RV) dysfunction and to explore the safety profile of this approach. DESIGN: Retrospective cohort study. SETTING: Intensive care unit (ICU) of 2 tertiary care centers between January 2013 and 2017. PARTICIPANTS: All patients with RV dysfunction in whom iNO was initiated without invasive mechanical ventilation. INTERVENTION: Noninvasive administration of iNO. MEASUREMENTS AND MAIN RESULTS: Eighteen patients received the intervention during the study period; 8 of these patients had a pulmonary artery catheter and 2 had a pulse contour analysis device. Median (interquartile range) iNO concentration was 20 (20-20) ppm, and therapy duration was 24 (12-46) hours. Most patients received iNO through nasal prongs (66.7%) or a high-flow nasal cannula (27.8%). Within 1 hour, iNO reduced pulmonary vascular resistance from 219.1 to 165.4 dyn•s/cm5 (n = 7; p < 0.001), mean pulmonary artery pressure from 28.4 to 25.3 mmHg (n = 8; p = 0.01), and central venous pressure from 17.5 to 13.1 mmHg (n = 16; p = 0.001). Indexed cardiac output increased from 2.0 to 2.6 L/min/m2 (n = 9; p = 0.004). ICU mortality was 27.78%, and median ICU length of stay was 7 (5-9) days. Two significant bleeding episodes requiring intervention and 1 acute kidney injury occurred during iNO therapy. No headache was reported. CONCLUSION: Noninvasively administered iNO was associated with favorable hemodynamic effects in ICU patients with acute RV dysfunction. These results suggest the safety and feasibility of this therapy for which further prospective study is warranted.

Henoch-Schonlein purpura in pregnancy: A case report.

Henoch-Schonlein purpura is a relatively common pediatric vasculitis. Very few cases of Henoch-Schonlein purpura during pregnancy have been described. Henoch-Schonlein purpura is variable in its presentation, from completely benign to possibly catastrophic complications. This rarely encountered condition in adults can also be a recurrence of a previous childhood disease. We present a case of a pregnant 40-year-old woman with Henoch-Schonlein purpura, resulting in a viable birth with no fetal complications. Her presentation is discussed in detail and a general presentation of Henoch-Schonlein purpura is explored, with particular attention to its rare onset during pregnancy.

Point-of-Care Ultrasonography to Assess Portal Vein Pulsatility and the Effect of Inhaled Milrinone and Epoprostenol in Severe Right Ventricular Failure: A Report of 2 Cases.

This article describes 2 patients with severe acute right ventricular failure causing circulatory shock. Portal vein pulsatility assessed by bedside ultrasonography suggested clinically relevant venous congestion. Management included cardiac preload reduction and combined inhalation of milrinone and epoprostenol to reduce right ventricular afterload. Portal vein ultrasonography may be useful in assessing right ventricular function in the acutely ill patient.

A morphometric 3D model of coronary artery bypass graft dysfunction with multidetector computed tomography.

OBJECTIVE: The objective was to assess, with computed tomography (CT) angiography, quantitative morphological parameters of a composite coronary artery bypass grafting (CABG) strategy and to correlate these with graft dysfunction. FINDINGS: Forty patients [median postoperative time, 32 (14-51) months] underwent CT angiography. Graft patency was assessed, and specific quantitative morphological parameters of the graft were collected. Graft segments had an overall patency rate of 93% (78/84). Two specific morphological parameters were found to be associated with graft dysfunction. CONCLUSION: A CT morphometric model can be used to identify quantitative 3D parameters associated with graft dysfunction. Such an approach could help in developing and improving CABG designs.

A novel composite coronary bypass graft strategy: the saphenous vein bridge--a pilot study.

OBJECTIVES: The aim of this pilot study was to describe and assess the safety of a novel composite graft technique for coronary artery bypass grafting (CABG) surgery. A saphenous vein is grafted to the left anterior descending artery (LAD) and other anterolateral coronary arteries, creating a saphenous vein bridge (SVB) and the left internal mammary artery (LIMA) is anastomosed to the SVB, distributing the blood flow distally (LIMA-SVB). METHODS: All patients who underwent CABG with the LIMA-SVB between 2005 and 2008 at our centre were enrolled in this study. Perioperative data were retrospectively collected from hospital charts, and the clinical follow-up was completed by telephone interview. Graft patency was assessed by computed tomography angiography (CTA) in patients with the longest follow-up time (n = 20). RESULTS: A total of 256 patients (mean age: 67 ± 12 years; 79% male) received 4.0 ± 1.0 grafts, including 2.2 ± 0.4 distal grafts provided by the LIMA-SVB. Nine (3.5%) deaths and 4 (1.6%) myocardial infarctions (MIs) were noted in the perioperative period. With a median follow-up time of 36 months [inter-quartile range 31-44], 1 (0.5%) MI and 2 (1.0%) strokes were reported. At 51 months post-surgery [47-53], CTA demonstrated a LIMA pedicle (n = 20) and SVB (n = 42) patency rate of 100 and 93%, respectively. Specifically, the LIMA-SVB patency rate was 100% to the LAD and 85% to diagonal arteries. Aortocoronary vein grafts (n = 38) patency rate in the same patients was 87%. CONCLUSIONS: Revascularization of the anterolateral territory using the LIMA-SVB is a promising approach considering its clinical safety and favourable patency rate results. A prospective randomized clinical trial is underway to compare this technique to conventional CABG.

Composite versus conventional coronary artery bypass grafting strategy for the anterolateral territory: study protocol for a randomized controlled trial.

BACKGROUND: In severe coronary artery disease, coronary artery bypass grafting (CABG) surgery is indicated to re-establish an adequate blood supply to the ischemic myocardium. Effectiveness of CABG surgery for symptom relief and mortality decrease should therefore depend on bypass graft patency. As bypass using a left internal mammary artery (LIMA)-to-left anterior descending coronary artery (LAD) anastomosis allows the best results in terms of graft patency, we designed a new surgical technique using a saphenous vein graft as a venous bridge to distribute the LIMA flow to the cardiac anterolateral territory. This novel strategy could extend the patency benefits associated to the LIMA. Other potential benefits of this technique include easier surgical technique, possibility to use saphenous vein grafts as vein patch angioplasty, shorter saphenous vein grafts requirement and reduced or eliminated manipulations of the ascendant aorta (and associated stroke risk). METHODS/DESIGN: Between July 2012 and 2016, 200 patients undergoing a primary isolated CABG surgery using cardiopulmonary bypass with a LAD bypass graft and at least another target on the anterolateral territory will be randomized (1:1) according to 1) the new composite strategy and 2) the conventional strategy with a LIMA-to-LAD anastomosis and revascularization of the other anterolateral target(s) with a separated aorto-coronary saphenous vein graft. The primary objective of the trial is to assess whether the composite strategy allows non-inferior anterolateral graft patency index (proportion of non-occluded CABGs out of the total number of CABGs) compared to the conventional technique. The primary outcome is the anterolateral graft patency index, evaluated at one year by 256-slice computed tomography angiography. Ten years of clinical follow-up is planned to assess clinical outcomes including death, myocardial infarction and need for revascularization. DISCUSSION: This non-inferiority trial has the potential to advance the adult cardiac surgery field, given the potential benefits associated with the composite grafting strategy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585285.