Prognostic bioindicators in severe COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity. MATERIALS AND METHODS: Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups. RESULTS: In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95. CONCLUSIONS: Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients.

Incidence and risk factors for respiratory tract bacterial colonization and infection in lung transplant recipients.

To evaluate incidence of and risk factors for respiratory bacterial colonization and infections within 30 days from lung transplantation (LT). We retrospectively analyzed microbiological and clinical data from 94 patients transplanted for indications other than cystic fibrosis, focusing on the occurrence of bacterial respiratory colonization or infection during 1 month of follow-up after LT. Thirty-three percent of patients developed lower respiratory bacterial colonization. Bilateral LT and chronic heart diseases were independently associated to a higher risk of overall bacterial colonization. Peptic diseases conferred a higher risk of multi-drug resistant (MDR) colonization, while longer duration of aerosol prophylaxis was associated with a lower risk. Overall, 35% of lung recipients developed bacterial pneumonia. COPD (when compared to idiopathic pulmonary fibrosis, IPF) and higher BMI were associated to a lower risk of bacterial infection. A higher risk of MDR infection was observed in IPF and in patients with pre-transplant colonization and infections. The risk of post-LT respiratory infections could be stratified by considering several factors (indication for LT, type of LT, presence of certain comorbidities, and microbiologic assessment before LT). A wider use of early nebulized therapies could be useful to prevent MDR colonization, thus potentially lowering infectious risk.

The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence.

PURPOSE: Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli. METHODS: IL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA. RESULTS: Baseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression. CONCLUSION: Sildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level.

Correction to: Practical approach to diastolic dysfunction in light of the new guidelines and clinical applications in the operating room and in the intensive care.

In the original article [1], the authors noticed a typographical error in Figure 2. The top left box should have included "E/A <0.8 and E <50 cm/s". Please see below the corrected figure.

Practical approach to diastolic dysfunction in light of the new guidelines and clinical applications in the operating room and in the intensive care.

There is growing evidence both in the perioperative period and in the field of intensive care (ICU) on the association between left ventricular diastolic dysfunction (LVDD) and worse outcomes in patients. The recent American Society of Echocardiography and European Association of Cardiovascular Imaging joint recommendations have tried to simplify the diagnosis and the grading of LVDD. However, both an often unknown pre-morbid LV diastolic function and the presence of several confounders-i.e., use of vasopressors, positive pressure ventilation, volume loading-make the proposed parameters difficult to interpret, especially in the ICU. Among the proposed parameters for diagnosis and grading of LVDD, the two tissue Doppler imaging-derived variables e' and E/e' seem most reliable. However, these are not devoid of limitations. In the present review, we aim at rationalizing the applicability of the recent recommendations to the perioperative and ICU areas, discussing the clinical meaning and echocardiographic findings of different grades of LVDD, describing the impact of LVDD on patients' outcomes and providing some hints on the management of patients with LVDD.

Case Report: Aortic Valve Replacement After JARVIK 2000 Left Ventricular Assist Device Implantation in Long-Time Survivor With Severe Aortic Valve Regurgitation.

BACKGROUND: There are limited clinical records in the literature regarding aortic valve replacement in left ventricular assist device (L-VAD) patients. Previously we had two cases of severe aortic valve regurgitation in patients with L-VAD support treated with Corvalve prosthesis insertion and Amplatzer closure procedure. Both patients died a few days after the procedure from complications not related to the procedure itself. PATIENT HISTORY: The patient was a male with previous coronary artery bypass graft surgery in 2001 that was complicated with postischemic dilated cardiomyopathy with severe heart failure (ejection fraction [EF], 20%). Cardiac resynchronization therapy was biventricular-pacemaker and cardiac defibrillator implantation in 2009 for recurrent ventricular arrhythmia. L-VAD implantation (Jarvik 2000) with graft apposition in descending thoracic aorta through left thoracotomy access and retro-auricolar cable was performed in October 2013. In 2015 the patient underwent surgical aortic valve replacement with bioprothesis due to progressive worsening of the aortic valve regurgitation. The Jarvik 2000 outflow was occluded with vascular ball occluder inserted via right axillary artery under fluoroscopy before CEC installation. The recovery was without major complications. DISCUSSION: Long-time survivors with Jarvik 2000 are increasing in number and such late complication is expected to become a main future issue. Our previous experience with the interventional approach was delusive. Due to the fatal consequences in similar patients with nonsurgical approaches, we opted for surgical aortic valve replacement. At the moment, the international literature does not describe safe approaches regarding aortic valve replacement in patients with Jarvik 2000 L-VAD. This case shows that surgical valve replacement could be managed with success according to the described specific technique.

First World Report of Internal Power Cable Repair in Left Ventricular Assist Device Jarvik 2000: Case Report.

BACKGROUND: There are limited clinical reports concerning internal power cable fixing in left ventricular assist device (L-VAD) patients. Actually there are no reports in the literature about Jarvik 2000 internal cable repair. We show the first description of a technique for surgical reparation of such a fatal complication. PATIENT HISTORY: The patient was a 62-year-old woman who had L-VAD implantation (Jarvik 2000) with outflow graft apposition in descending thoracic aorta through left thoracotomy access, in 2009. She arrived urgently on January 25, 2014 for Jarvik 2000 dysfunction correlated with head movements. The neck X-rays revealed the rupture of one of the nine power cables located inside the neck and the damaging of two more cables nearby to be ruptured. On the same day she got pump failure due to the final interruption of the remaining two cables, we were obliged to install femoro-femoral extracorporeal membrane oxygenation (ECMO) assistance, to repair the power cables, approaching them through a pacemaker extension cable. The L-VAD outflow was occluded with vascular ball occluder inserted via right axillary artery under fluoroscopy before ECMO installation. At the end the ECMO assistance was interrupted and the Jarvik 2000 was turned back on. The patient was dismissed from the hospital 12 days after the procedure. DISCUSSION: At the moment the international literature is poor regarding this issue. This case provides evidence that in emergency conditions ECMO assistance is mandatory and a hybrid surgical and radiological approach could help to repair the damage in safe conditions.

Microcirculatory changes in children undergoing cardiac surgery: a prospective observational study.

BACKGROUND: The effects of cardiac surgery on the microcirculation of children are unknown. The aim of this study was to assess the microcirculatory changes in children undergoing surgery for correction of congenital heart disease. METHODS: We used a videomicroscope (Sidestream Dark Field, SDF) in a convenience sample of 24 children

Moderate-degree acidosis is an independent determinant of postoperative bleeding in cardiac surgery.

BACKGROUND: Acidosis is a well-known factor leading to coagulopathy. It has been widely explored as a risk factor for severe bleeding in trauma patients. However, no information with respect to acidosis as a determinant of postoperative bleeding in cardiac surgery patients exists. The aim of this study was to investigate the role of acidosis and hyperlactatemia (HL) in determining postoperative bleeding and need for surgical revision in cardiac surgery patients. METHODS: We carried out a retrospective analysis on 4521 patients receiving cardiac operations in two institutions. For each patient the preoperative data and operative profile was available. Arterial blood gas analysis data at the arrival in the intensive care unit were analyzed to investigate the association between acidosis (pH<7.35), HL (>4.0 mMol/L) and postoperative bleeding and surgical revision rate. RESULTS: After correction for the potential confounders, both acidosis (P=0.001) and HL (P=0.001) were significantly associated with the amount of postoperative bleeding. HL was an independent risk factor for postoperative bleeding even in absence of acidosis. Overall, surgical revision rate was 5.6% in patients with HL and no acidosis; 7.7% in patients with acidosis and HL, and 7.2% in patients with acidosis and no HL. All these values are significantly (P=0.001) higher than the ones in patients without acidosis/HL (2%). CONCLUSIONS: Even a moderate degree of postoperative acidosis is associated with a greater postoperative bleeding and surgical revision rate in cardiac surgery patients. Correction of acidosis with bicarbonate does not lead to an improvement of the postoperative bleeding asset.

Brain injury after cardiac surgery.

In patients undergoing cardiac surgery, postoperative brain injury significantly contributes to increase morbidity and mortality and has negative consequences on quality of life and costs. Moreover, over the past years, compelling medical and technological improvements have allowed an even older patients' population, with several comorbidities, to be treated with cardiac surgery; however, the risk of brain injury after such interventions is also increased in these patients. With the aim of improving post-operative neurological outcome, a variety of neuromonitoring methods and devices have been introduced in clinical practice. These techniques allow the assessment of a number of parameters, such as cerebral blood flow, brain embolic events, cerebral cortical activity, depth of anesthesia and brain oxygenation. Some of them have been used to optimize the hemodynamic management of such patients and to select specific therapeutic interventions. Also, various pharmacological and non-pharmacological approaches have been proposed to minimize the incidence of brain injury in this setting. In this review we describe the risk factors and mechanisms of cerebral injury after cardiac surgery and focus on monitoring techniques and clinical strategies that could help clinicians to minimize the incidence of brain injury.

How to target temperature after cardiac arrest: insights from a randomized clinical trial.

Implementation of treatments able to improve survival and neurological recovery of cardiac arrest (CA) survivors is a major clinical challenge. More than ten years ago, two pivotal trials showed that application of therapeutic hypothermia (TH, 32-34 °C) to patients resuscitated from an out-of-hospital CA (OHCA) with an initial shockable rhythm significantly ameliorated their outcome. Since then, TH has been used also for non-shockable rhythms and for in-hospital CA to some extent, even if the quality of evidence supporting TH in such situations remained very low. The objective of this randomized, controlled, multicenter study (named "Targeted Temperature Management" TTM study) was to compare two different strategies of temperature control after CA; patients were randomized to be treated either at 33 °C or at 36 °C for 24 hours, while fever was accurately avoided for the first 3 days since randomization. Inclusion criteria were: Glasgow Coma Score <8, presumed cardiac origin of arrest, randomization occurring within the first 4 hours from the return of spontaneous circulation. Patients were excluded if they had an unwitnessed arrest with asystole as the initial rhythm, suspected or known acute intracranial hemorrhage or stroke, and a body temperature of less than 30 °C. A specific algorithm was used to decide for withdrawal of care in patients remaining comatose after 72 hours since normothermia was achieved. The primary outcome was 6-month mortality. After the enrollment of 939 patients, the authors did not find any significant difference between groups in primary outcome (235/473 [50%] and 225/466 [48%] of patients died in 33 °C and 36 °C group, respectively; HR for death if in the 33 °C group, 1.06 [95% CI 0.89 to 1.28; P=0.51]). Similarly, the analysis of the composite outcome of death or poor neurologic function yielded similar results between the two groups. This is the largest study evaluating the effects of two different strategies of temperature management after CA. Some important concerns have been raised on the real benefit of keeping CA patients at 33 °C and major changes in clinical practice are expected. We discussed herein the main differences with previous randomized trials and tried to identify possible explanations for these findings.

Development of acute kidney injury during continuous infusion of vancomycin in septic patients.

PURPOSE: Few data are available on the occurrence of renal failure during continuous infusion of vancomycin in critically ill patients. METHODS: We reviewed the data of all patients admitted to the intensive care unit (ICU) between January 2008 and December 2009 in whom vancomycin was given as a continuous infusion for more than 48 h in the absence of renal replacement therapy. We collected data on the doses of vancomycin and blood concentrations during therapy. Acute kidney injury (AKI) was defined as a daily urine output <0.5 ml/kg/h and/or an increase in the serum creatinine of ≥0.3 mg/dl from baseline levels during vancomycin therapy or within 72 h after its discontinuation. Multivariable logistic regression analysis was performed to identify predictors of AKI. RESULTS: Of 207 patients who met the inclusion criteria, 50 (24 %) developed AKI. These patients were more severely ill, had lower creatinine clearance at admission, were more frequently exposed to other nephrotoxic agents, had a longer duration of therapy, and had higher concentrations of vancomycin during the first 3 days of treatment (C(mean)). The C(mean) was independently associated with early AKI (within 48 h from the onset of therapy) and the duration of vancomycin administration with late AKI. CONCLUSIONS: AKI occurred in almost 25 % of critically ill patients treated with a continuous infusion of vancomycin. Vancomycin concentrations and duration of therapy were the strongest variables associated with the development of early and late AKI during therapy, respectively.

Echocardiography and pulse contour analysis to assess cardiac output in trauma patients.

BACKGROUND: Echocardiography is a valuable technique to assess cardiac output (CO) in trauma patients, but it does not allow a continuous bedside monitoring. Beat-to-beat CO assessment can be obtained by other techniques, including the pulse contour method MostCare. The aim of our study was to compare CO obtained with MostCare (MC-CO) with CO estimated by transthoracic echocardiography (TTE-CO) in trauma patients. METHODS: Forty-nine patients with blunt trauma admitted to an intensive care unit and requiring hemodynamic optimization within 24 hours from admission were studied. TTE-CO and MC-CO were estimated simultaneously at baseline, after a fluid challenge and after the start of vasoactive drug therapy. RESULTS: One hundred sixteen paired CO values were obtained. TTE-CO values ranged from 2.9 to 7.6 L·min(-1), and MC-CO ranged from 2.8 to 8.2 L·min(-1). The correlation between the two methods was 0.94 (95% confidence interval [CI]=0.89 to 0.97; P<0.001). The mean bias was -0.06 L·min(-1) with limits of agreements (LoA) of -0.94 to 0.82 L·min(-1) (lower 95% CI, -1.16 to -0.72; upper 95% CI, 0.60 to 1.04) and a percentage error of 18%. Changes in CO showed a correlation of 0.91 (95% CI=0.87 to 0.95; P<0.001), a mean bias of -0.01 L·min(-1) with LoA of -0.67 to 0.65 L·min(-1) (lower 95% CI, -0.83 to -0.51; upper 95% CI, 0.48 to 0.81). CONCLUSION: CO measured by MostCare showed good agreement with CO obtained by transthoracic echocardiography. Pulse contour analysis can complement echocardiography in evaluating hemodynamics in trauma patients.

Lung resection for non-small cell lung cancer after prophylactic coronary angioplasty and stenting: short- and long-term results.

AIM: Recent studies have reported a high incidence of perioperative in-stent trombosis with myocardial infarction (MI), in patients undergoing non-cardiac surgery, early after coronary angioplasty and stenting. The short and long-term results of surgery for non-small cell lung cancer (NSCLC) after prophylatic coronary angioplasty and stenting were analyzed. METHODS: Prospective collected data were examined for postoperative complications and long-term survival in 16 consecutive patients who underwent mayor lung resection for NSCLC after prophylactic coronary angioplasty and stenting for significant coronary artery disease , from 2001 to 2008. One and two non-drug-eluting stents were placed in 75% or (25% of the patient, respectively. All patients had four weeks of dual antiplatelet therapy, that was discontinued 5 days prior to surgery and replaced by low molecular weight heparin. Patients were keep sedated and intubated overnight, according to our protocol. RESULTS: There were no postoperative deaths nor MI. A patient experienced pulmonary embolism with moderate troponin release and underwent coronary angiography that showed patency of the stent. Two patients developed postoperative bleeding complications haemothorax requiring a re-thoracotomy in 1, gastric bleeding requiring blood transfusion in 1. At the mean follow-up of 30 months (range 3-95), none of the patients showed evidence of myocardial ischemia, while 5 (31%) patients died, mostly (N.=4) due to distant metastasis. The five-year survival rate was 53%. CONCLUSION: In contrast to previous reports, lung resection after prophylactic coronary angioplasty and stenting is a safe and effective treatment for NSCLC and myocardial ischemia. The application of a refined protocol could be the key factor for improved results.

Vasopressors in shock: too early to move away from catecholamines?

Adrenergic and non-adrenergic vasopressor agents can be used to correct hypotension in shock states. For a similar increase in arterial pressure, these agents may be associated with different haemodynamic, metabolic, endocrinological or immunological effects. But how relevant are these differences? Do these affect the outcome of patients with shock? Large-scale randomized trials comparing the effects of different vasopressor agents are scarce. Data on potential alternatives, and especially vasopressin, are even more scarce. Over-interpretation of the data, and especially of data obtained in subgroups, is common. Analysis of subgroups may be useful to address mechanisms and to raise hypotheses. However, subgroup analysis is often biased by confounding factors, especially when subgroup categorization is defined by response to therapy and not by intrinsic patient or disease characteristics. In this issue of the British Journal of Pharmacology, Bracht and colleagues present their interpretation of data from trials comparing vasopressin with noradrenaline in patients with septic shock. Here, we present an alternative interpretation.

When, where and how to initiate hypothermia after adult cardiac arrest.

Therapeutich hypothermia (TH) has been shown to improve neurological outcome and survival after witnessed cardiac arrest (CA) that is due to ventricular fibrillation. Although TH is widely used following witnessed CA as well as all forms of initial rhythm, the mortality rate after CA remains unacceptably high, and additional study is needed to understand when and how to implement hypothermia in the post-resuscitation phase. Experimental studies have emphasized the importance of initiating cooling soon after the return of spontaneous circulation (ROSC) or even during cardiopulmonary resuscitation (CPR). Clinical studies have shown that pre-hospital induction of hypothermia is feasible and has no major adverse events-even when used intra-arrest-and may provide some additional benefits compared to delayed in-hospital cooling. Thus, hypothermia use should not be limited to the Intensive Care Unit but can be initiated in the field/ambulance or in the Emergency Department, then continued after hospital admission- even during specific procedures such as coronary angiography-as part of the global management of CA patients. Various methods (both non-invasive and invasive) are available to achieve and maintain the target temperature; however, only some of these methods-which include cold fluids, ice packs, iced pads and helmet and trans-nasal cooling- are easily deployed in the pre-hospital setting.