Extracorporeal liver support techniques: a comparison.

ExtraCorporeal Liver Support (ECLS) systems were developed with the aim of supporting the liver in its detoxification function by clearing the blood from hepatic toxic molecules. We conducted a retrospective comparative analysis on patients presenting with liver failure who were treated with different extracorporeal techniques in our intensive care unit to evaluate and compare their detoxification abilities. To verify the effectiveness of the techniques, mass balance (MB) and adsorption per hour were calculated for total bilirubin (TB), direct bilirubin (DB), and bile acids (BA) from the concentrations measured. MB represents the total amount (mg or mcMol) of a molecule removed from a solution and is the only representative parameter to verify the purification effectiveness of one system as it is not affected by the continuous production of the molecules, released in the circulation from the tissues, as it is the case for the reduction rate (RR). The total adsorption per hour is calculated by the ratio between MB and the time duration and shows the adsorption ability in an hour. Our comparative study shows the superior adsorption capability of CytoSorb system regarding TB, DB, and BA, evaluated through the MB and adsorption per hour, in comparison with CPFA, MARS, Prometheus, and PAP. In conclusion, as extracorporeal purification in liver failure could be considered useful for therapeutic purposes, Cytosorb, being more performing than other systems considered, could represent the device of first choice.

Worsening of gas exchange parameters at high FiO2 in COVID-19: misleading or informative?

BACKGROUND: In COVID-19, higher than expected level of intrapulmonary shunt has been described, in association with a discrepancy between the initial relatively preserved lung mechanics and the hypoxia severity. This study aim was to measure the shunt fraction and variations of PaO2/FiO2 ratio and oxygen alveolar-arterial gradient (A-a O2) at different FiO2. METHODS: Shunt was measured by a non-invasive system during spontaneous breathing in 12 patients hospitalized at COVID-19 Semi-Intensive Care Unit of Papa Giovanni XXIII Hospital, Bergamo, Italy, between October 22 and November 23, 2020. RESULTS: Nine patients were men, mean age (±SD) 62±15 years, mean BMI 27.5±4.8 Kg/m2. Systemic hypertension, diabetes type 2 and previous myocardial infarction were referred in 33%, 17%, and 7%, respectively. Mean PaO2/FiO2 ratio was 234±66 and 11 patients presented a bilateral chest X-ray involvement. Mean shunt was 21±6%. Mainly in patients with a more severe respiratory failure, we found a progressive decrease of PaO2/FiO2 ratio with higher FiO2. Considering (A-a O2), we found a uniform tendency to increase with FiO2 increasing. Even in this case, the more severe were the patients, the higher was the slope, suggesting FiO2 insensitiveness due to a shunt effect, as strengthened by our measurements. CONCLUSION: Relying on a single evaluation of PaO2/FiO2 ratio, especially at high FiO2, could be misleading in COVID-19. We propose a two steps evaluation, the first at low SpO2 value (e.g., 92-94%) and the second one at high FiO2 (i.e., >0.7), allowing to characterize both the amendable (ventilation/perfusion mismatch), and the fixed (shunt) contribution quote of respiratory impairment, respectively.

At the peak of COVID-19 age and disease severity but not comorbidities are predictors of mortality: COVID-19 burden in Bergamo, Italy.

BACKGROUND: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak. METHODS: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020. RESULTS: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2: 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N.=171). Thirty-nine percent of patients were treated with continuous positive airway pressure (CPAP), 9.5% with noninvasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to Semi-Intensive Respiratory Care Unit, and 18.9% to Intensive Care Unit. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio [OR], 95% confidence interval [CI]: 38.91 [10.67-141.93], P<0.001; 70-77 years: 17.30 [5.40-55.38], P<0.001; 60-69 years: 3.20 [1.00-10.20], P=0.049), PaO2/FiO2<200 at presentation (3.50 [1.70-7.20], P=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], P<0.001), and blood urea value at admission (1.01 [1.00-1.02], P=0.015). CONCLUSIONS: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in COVID-19.

Effect of Hemoadsorption for Cytokine Removal in Pneumococcal and Meningococcal Sepsis.

Bacterial meningitis and septicemia are invasive bacterial diseases, representing a significant cause of morbidity and mortality worldwide. Both conditions are characterized by an impressive inflammatory response, resulting rapidly in cerebral edema, infarction, hydrocephalus, and septic shock with multiple organ failure. Despite advances in critical care, outcome and prognosis remain critical. Available adjunctive treatments to control the inflammatory response have shown encouraging results in the evolution of patients with sepsis and systemic inflammation, but meningococcal or pneumococcal infection has not been investigated. We herein report five patients with similar critical pathological conditions, characterized by pneumococcal or meningococcal sepsis and treated with hemoadsorption for cytokine removal. All patients showed a progressive stabilization in hemodynamics along with a rapid and marked reduction of catecholamine dosages, a stabilization in metabolic disorders, and less-than-expected loss of extremities. Therapy proved to be safe and well tolerated. From this first experience, extracorporeal cytokine removal seems to be a valid and safe therapy in the management of meningococcal and pneumococcal diseases and may contribute to the patient stabilization and prevention of severe sequelae. Further studies are required to confirm efficacy in a larger context.

Innovative haematological parameters for early diagnosis of sepsis in adult patients admitted in intensive care unit.

AIMS: This study was aimed to investigate the role of erythrocyte, platelet and reticulocyte (RET) parameters, measured by new haematological analyser Sysmex XN and C reactive protein (CRP), for early diagnosis of sepsis during intensive care unit (ICU) stay. METHODS: The study population consisted of 62 ICU patients, 21 of whom developed sepsis during ICU stay and 41 who did not. The performance for early diagnosing of sepsis was calculated as area under the curve (AUC) of receiver operating characteristics curves analysis. RESULTS: Compared with CRP (AUC 0.81), immature platelet fraction (IPF) (AUC 0.82) showed comparable efficiency for identifying the onset of sepsis. The association with the risk of developing sepsis during ICU stay was also assessed. One day before the onset of sepsis, a decreased of RET% was significantly associated with the risk of developing sepsis (OR=0.35, 95% CI 0.14 to 0.87), whereas an increased of IPF absolute value (IPF#) was significantly associated with the risk of developing sepsis (OR=1.13, 95% CI 1.03 to 1.24) 2 days before the onset of sepsis. The value of CRP was not predictive of sepsis at either time points. CONCLUSIONS: IPF# and RET% may provide valuable clinical information for predicting the risk of developing sepsis, thus allowing early management of patients before the onset of clinically evident systemic infections.

The role of open abdomen in non-trauma patient: WSES Consensus Paper.

The open abdomen (OA) is defined as intentional decision to leave the fascial edges of the abdomen un-approximated after laparotomy (laparostomy). The abdominal contents are potentially exposed and therefore must be protected with a temporary coverage, which is referred to as temporal abdominal closure (TAC). OA use remains widely debated with many specific details deserving detailed assessment and clarification. To date, in patients with intra-abdominal emergencies, the OA has not been formally endorsed for routine utilization; although, utilization is seemingly increasing. Therefore, the World Society of Emergency Surgery (WSES), Abdominal Compartment Society (WSACS) and the Donegal Research Academy united a worldwide group of experts in an international consensus conference to review and thereafter propose the basis for evidence-directed utilization of OA management in non-trauma emergency surgery and critically ill patients. In addition to utilization recommendations, questions with insufficient evidence urgently requiring future study were identified.

Clinical significance of cell population data (CPD) on Sysmex XN-9000 in septic patients with our without liver impairment.

BACKGROUND: This study evaluated the clinical significance of cell population data (CPD) parameters obtained on Sysmex XN-9000 in septic patients admitted to intensive care unit (ICU) and stratified according to liver function. METHODS: The study population consisted in 84 patients, 44 of whom did not develop sepsis (NS), whereas the remaining 40 developed sepsis (SE) (n=24) or septic shock (SS) (n=16). Two hundred ostensibly healthy blood donors [healthy subjects (HS)], undergoing routine blood testing before a regular blood donation, were studied. RESULTS: Except for neutrophils and lymphocytes cell size (NE-FCS and LY-Z), all other CPD values were significantly different in ICU patients compared to HS. Neutrophils and monocytes fluorescence intensity (NE-SFL and MO-X) values were significantly higher in SS compared to sepsis and not develop sepsis patients. The value of many parameters was also different according to liver function. Overall, MO-X and neutrophils fluorescence intensity (NE-SFL) exhibited the best performance for diagnosing sepsis in all patients (AUC, 0.75 and 0.72), as well as in those with (AUC, 0.95 and 0.89) or without (AUC, 0.72 for both) liver impairment. These parameters were also significantly correlated with Sequential Organ Failure Assessment (SOFA) score. CONCLUSIONS: This study suggested that some novel CPD parameters (namely NE-SFL and MO-X) may provide useful information for diagnosis and management of sepsis.

Extended leukocyte differential count and C-reactive protein in septic patients with liver impairment: diagnostic approach to evaluate sepsis in intensive care unit.

BACKGROUND: Sepsis is still a major cause of death in intensive care units (ICUs) worldwide. Patients with liver impairment express an imbalanced cytokine response which alters common sepsis biphasic nature. Cytokines measurement is expensive, often unavailable, whereas leukocytes (WBC) evaluation performed through hematology analyzers can provide a practical strategy for monitoring inflammatory response. METHODS: A total of 200 healthy subjects (HS) and 84 patients (18 with, 66 without liver impairment) admitted to ICU, were assessed for International Sepsis Definitions, Sequential Organ Failure Assessment (SOFA) and Model for End-Stage Liver Disease (MELD) scores. We tested 1,022 peripheral blood samples using Sysmex XN-9000, estimating diagnostic accuracy of leukocyte differential count and nontraditional parameters through receiver operating characteristics (ROC) curves analysis compared to clinical classification. RESULTS: Median value of all-leukocyte parameters was different in ICU patients compared to HS. Leukocytes, neutrophils (NE) and immature granulocytes (IGs) in sepsis and septic shock (SS) were higher than no sepsis (NS), with an area under the curve: 0.81, 0.82 and 0.78 respectively. Lymphocytes (LY) and monocytes (MO) were significantly associated with liver impairment. CONCLUSIONS: Diagnostic accuracy of all-leukocyte parameters may provide valuable information for diagnosis and follow-up of sepsis in ICU patients, especially those with liver impairment.

Management of hemodynamically unstable pelvic trauma: results of the first Italian consensus conference (cooperative guidelines of the Italian Society of Surgery, the Italian Association of Hospital Surgeons, the Multi-specialist Italian Society of Young Surgeons, the Italian Society of Emergency Surgery and Trauma, the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care, the Italian Society of Orthopaedics and Traumatology, the Italian Society of Emergency Medicine, the Italian Society of Medical Radiology -Section of Vascular and Interventional Radiology- and the World Society of Emergency Surgery).

Hemodynamically Unstable Pelvic Trauma is a major problem in blunt traumatic injury. No cosensus has been reached in literature on the optimal treatment of this condition. We present the results of the First Italian Consensus Conference on Pelvic Trauma which took place in Bergamo on April 13 2013. An extensive review of the literature has been undertaken by the Organizing Committee (OC) and forwarded to the Scientific Committee (SC) and the Panel (JP). Members of them were appointed by surgery, critical care, radiology, emergency medicine and orthopedics Italian and International societies: the Italian Society of Surgery, the Italian Association of Hospital Surgeons, the Multi-specialist Italian Society of Young Surgeons, the Italian Society of Emergency Surgery and Trauma, the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care, the Italian Society of Orthopaedics and Traumatology, the Italian Society of Emergency Medicine, the Italian Society of Medical Radiology, Section of Vascular and Interventional Radiology and the World Society of Emergency Surgery. From November 2012 to January 2013 the SC undertook the critical revision and prepared the presentation to the audience and the Panel on the day of the Conference. Then 3 recommendations were presented according to the 3 submitted questions. The Panel voted the recommendations after discussion and amendments with the audience. Later on a email debate took place until December 2013 to reach a unanimous consent. We present results on the 3 following questions: which hemodynamically unstable patient needs an extraperitoneal pelvic packing? Which hemodynamically unstable patient needs an external fixation? Which hemodynamically unstable patient needs emergent angiography? No longer angiography is considered the first therapeutic maneuver in such a patient. Preperitoneal pelvic packing and external fixation, preceded by pelvic binder have a pivotal role in the management of these patients.Hemodynamically Unstable Pelvic Trauma is a frequent death cause among people who sustain blunt trauma. We present the results of the First Italian Consensus Conference.

In vitro activity of Amphotericin B against zygomycetes isolated from deep mycoses: a comparative study between incubation in aerobic and hyperbaric atmosphere.

Many case reports suggest that the use of hyperbaric oxygen therapy associated with surgical and medical approaches may contribute to restricting the growth of zygomycetes in patient tissue. The primary aim of this study was to obtain data concerning the in vitro susceptibility of 22 zygomycetes to antifungals such as amphotericin B and posaconazole, and to compare the in vitro development of these fungi in aerobic normobaric versus hyperoxic normobaric and hyperbaric atmosphere. None of the zygomycetes grew after 24-hour and 72-hour incubation in a hyperoxic hyperbaric (2 or 3 ATA) atmosphere. However, when plates were maintained at room temperature in aerobic conditions, colonies were observed from 36-96 h after inoculation, while minimum inhibitory concentration (MIC) values remained the same. This preliminary in vitro study focuses on the in vitro examination of combination therapies to potentiate antifungal activity. Both hyperoxic hyperbaric conditions and a single antifungal agent, as well as combinations of different antifungal drugs were used. Results suggest an impressive in vitro fungistatic activity of the hyperoxic hyperbaric atmosphere, even if the antifungal effect is strictly time-dependent using these incubation conditions.

Scedosporium apiospermum post-traumatic cranial infection.

Scedosporium apiospermum is an environmental mould. Human infection caused by this organism is described more and more often. However, only a few case reports demonstrate its role as a telluric contaminant in patients affected by traumatism. This report is the case of a severe post traumatic infection by S. apiospermum in an immunocompetent young man. Surgical drainage associated with systemic therapy was successful.