Elevated level of serum human epididymis protein 4 (HE4) predicts disease severity and mortality in COVID-19 pneumonia.

BACKGROUND: We retrospectively analyzed serum level of human epididymis protein 4 (HE4) as a pulmonary inflammatory biomarker in patients with COVID-19 pneumonia in association with disease severity and outcome. METHODS: Ninety-nine (40 critically ill, 40 severe and 19 mild) COVID-19 patients and as controls 25 age- and sex-matched non-COVID-19 bacterial sepsis subjects were included. Serum HE4 was measured by an immunoassay (Architect® i1000SR, Abbott) in the baseline samples of all study participants obtained at intensive care unit (ICU) admission or during outpatient clinic visit and follow-up sera were available in case of 30 COVID-19 subjects with life-threating conditions. Associations were studied between serum HE4, routinely available laboratory parameters, clinical characteristics, and disease progression. RESULTS: Baseline HE4 level was significantly higher (P < 0.0001) in critically ill (524.7 [300.1-1153.0] pmol/L) than severe COVID-19 subjects (157.4 [85.2-336.9] pmol/L) and in mild SARS-CoV-2 infection (46.7 [39.1-57.2] pmol/L). Similarly increased HE4 concentrations were found in bacterial sepsis (1118.0 [418.3-1953.0] pmol/L, P = 0.056) compared to critically ill COVID-19 individuals. Serum HE4 levels significantly correlated with age, SOFA-score, inflammation-dependent biomarkers, and the degree of lung manifestation evaluated by chest CT examination in ICU COVID-19 individuals. Based on ROC-AUC curve analysis, baseline HE4 independently indicated the severity of COVID-19 with an AUC value of 0.816 (95% CI [0.723-0.908]; P < 0.0001), while binary logistic regression test found HE4 as an independent prognostic parameter for death (OR: 10.618 [2.331-48.354]; P = 0.002). Furthermore, COVID-19 non-survivors showed much higher baseline HE4 levels without a substantial change under treatment vs. survivors (P < 0.0001). Finally, pre-treatment HE4 level of ≥ 331.7 pmol/L effectively predicted a larger risk for mortality (Log-Rank P < 0.0001) due to severe COVID-19 pneumonia. CONCLUSION: Elevated serum HE4 level at ICU admission highly correlates with COVID-19 severity and predicts disease outcome.

Comparison of Different Vascular Biomarkers for Predicting In-Hospital Mortality in Severe SARS-CoV-2 Infection.

Severe SARS-CoV-2 elicits a hyper-inflammatory response that results in intravascular inflammation with endothelial injury, which contributes to increased mortality in COVID-19. To predict the outcome of severe SARS-CoV-2 infection, we analyzed the baseline level of different biomarkers of vascular disorders in COVID-19 subjects upon intensive care unit (ICU) admission and prior to any vaccination. A total of 70 severe COVID-19 patients (37 survivors and 33 non-survivors) were included with 16 age- and sex-matched controls. Vascular dysfunction was monitored via soluble VCAM-1, E-selectin, ACE2 and Lp-PLA2, while abnormal platelet activation was evaluated by soluble P-selectin and CD40L in parallel. These results were correlated with routine laboratory parameters and disease outcomes. Among these parameters, VCAM-1 and ACE2 showed significantly higher serum levels in COVID-19 patients with early death vs. convalescent subjects. VCAM-1 was significantly correlated with the Horowitz index (r = 0.3115) and IL-6 (r = 0.4599), while ACE2 was related to E-selectin (r = 0.4143) and CD40L (r = 0.2948). Lp-PLA2 was altered in none of these COVID-19 subcohorts and showed no relationship with the other parameters. Finally, the pre-treatment level of VCAM-1 (≥1420 ng/mL) and ACE2 activity (≥45.2 µU/mL) predicted a larger risk for mortality (Log-Rank p = 0.0031 and p = 0.0117, respectively). Vascular dysfunction with endothelial cell activation is linked to lethal COVID-19, and highly elevated soluble VCAM-1 and ACE2 at admission to ICU may predict unfavorable outcomes.

Circulating ACE2 activity predicts mortality and disease severity in hospitalized COVID-19 patients.

OBJECTIVES: Angiotensin-converting enzyme 2 (ACE2) represents the primary receptor for SARS-CoV-2 to enter endothelial cells. Here we investigated circulating ACE2 activity to predict the severity and mortality of COVID-19. METHODS: Serum ACE2 activity was measured in COVID-19 (110 critically ill and 66 severely ill subjects at hospital admission and 106 follow-up samples) and in 32 non-COVID-19 severe sepsis patients. Associations between ACE2, inflammation-dependent biomarkers, pre-existing comorbidities, and clinical outcomes were studied. RESULTS: Initial ACE2 activity was significantly higher in critically ill COVID-19 patients (54.4 [36.7-90.8] mU/L) than in severe COVID-19 (34.5 [25.2-48.7] mU/L; P<0.0001) and non-COVID-19 sepsis patients (40.9 [21.4-65.7] mU/L; P=0.0260) regardless of comorbidities. Circulating ACE2 activity correlated with inflammatory biomarkers and was further elevated during the hospital stay in critically ill patients. Based on ROC-curve analysis and logistic regression test, baseline ACE2 independently indicated the severity of COVID-19 with an AUC value of 0.701 (95% CI [0.621-0.781], P<0.0001). Furthermore, non-survivors showed higher serum ACE2 activity vs. survivors at hospital admission (P<0.0001). Finally, high ACE2 activity (≥45.4 mU/L) predicted a higher risk (65 vs. 37%) for 30-day mortality (Log-Rank P<0.0001). CONCLUSIONS: Serum ACE2 activity correlates with COVID-19 severity and predicts mortality.

Beneficial effects of theophylline infusions in surgical patients with intra-abdominal hypertension.

BACKGROUND: Intra-abdominal hypertension (IAH) can cause high mortality. Recently, we found that IAH was associated with increased serum levels of adenosine and interleukin 10. Our present "hypothesis-generated study" was based on the above mentioned results. MATERIALS AND METHODS: In this uncontrolled clinical trial, a total of 78 patients with IAH were enrolled representing a 13-20 mmHg range of intra-abdominal pressure (IAP). Patients requiring surgical abdominal decompression were excluded. Patients were treated with the following protocols: standard supportive therapy (ST, n = 38) or ST plus infusion with the adenosine receptor antagonist theophylline (T, n = 40). Over the 5-day measurement period, IAP was monitored continuously and serum adenosine concentration and other clinical and laboratory measurements were monitored daily. Mortality was followed for the first 30 days following the diagnosis of IAH. RESULTS: Mortality of ST patients was 55%, which is compatible to other studies. Serum adenosine concentration was found to be directly proportional to IAP. Of the 40 patients receiving T treatment, survival was 100%. An increased survival related to theophylline infusion correlated with improving serum concentrations of IL-10, urea, and creatinine, as well as 24-h urine output, fluid balance, mean arterial pressure, and O(2)Sat. CONCLUSIONS: Adenosine receptor antagonism with T following IAH diagnosis resulted in markedly reduced mortality in patients with moderated IAH (<20 mmHg). Theophylline-associated mortality reduction may be related to improved renal perfusion and improved MAP, presumably caused by adenosine receptor blockade. Because this study was not a randomized controlled study, these compelling observations require further multicentric clinical confirmation.

[Successful treatment of retrohepatic inferior vena cava injury: report of two cases]. / Retrohepaticus vena cava sérülés két sikeresen operált esete.

UNLABELLED: Authors present two cases of successfully operated patients with retrohepatic inferior vena cava (IVC) injury. In the first case a 79 year old female patient suffered from multiple stab wounds in the area of the 4th segment of the right lung as well as in the retrohepatic region in close proximity to the IVC. At the time of the first surgery the IVC injury was not identified. During a second operation, however, the IVC was isolated from the liver using an anterior dissection of the parenchyma with finger-fracture technique and the injury was oversawn finally. Successful haemostasis of the liver was achieved by packing of the perihepatic space, which was removed three days later. In the second case a 25 year-old male patient had suffered blunt abdominal trauma. He underwent laparotomy and packing on the site of the hepatic injury, which had to be repeated seven more times. Later on, another urgent laparotomy was carried out for recurring intraabdominal bleeding and bile leakage, and cholecystectomy was performed due to gallbladder perforation. Another two days later a further emergency laparotomy was indicated for ongoing intraabdominal bleeding, when the bleeding source - an injury (3 mm in diameter) of the retrohepatic IVC - was oversawn. After relatively long postoperative stay both patients were fully recovered and discharged from hospital. CONCLUSIONS: penetrating injuries of the IVC are associated with high mortality rate of approximately 78%. Proper management of these injuries requires experience in both vascular and liver surgery. Retrohepatic IVC injury needs to be considered in the differential diagnosis of ongoing bleeding in penetrating or blunt liver trauma. Packing of the liver is a reliable haemostatic method if bleeding persists due to division of the liver parenchyma.

Profiling of Lactate Dehydrogenase Isoenzymes in COVID-19 Disease.

INTRODUCTION: Serum total lactate dehydrogenase (LDH) activity was elevated and showed a positive correlation with disease severity and outcome in severe COVID-19 disease. However, it is still unknown whether the relative abundance or calculated activity of any LDH isoenzyme is predominately increased in COVID-19 subjects. METHODS: Twenty-two consecutive patients suffered from moderate or severe COVID-19 pneumonia were recruited into this study who showed enhanced total LDH activity. The ratio of LDH isoenzyme activities was further investigated using gel electrophoresis (Hydragel®, Sebia) with densitometric evaluation. Calculated activity values of these isoenzymes were correlated with routine laboratory parameters, the degree of lung parenchymal affection based on chest CT and clinical outcome. RESULTS: Total LDH activity was raised in the range of 272-2141 U/L and significantly correlated with calculated LDH-3 and LDH-4 activities (r=0.765, P=0.0001; and r=0.783, P=0.0001, respectively). In contrast, the relative abundance of neither LDH isoenzyme was exclusively abnormal in COVID-19 patients. Calculated activity of LDH-3 and LDH-4 demonstrated a modest but statistically significant association with serum ferritin (r=0.437, P=0.042; r=0.505, P=0.016, respectively). When the relationship between the severity of pulmonary affection by SARS-CoV-2 infection and relative abundance of LDH isoenzymes was studied, a larger ratio of mid-zone fractions was observed in the presence of ≥ 50% lung parenchymal involvement. Finally, regardless of LDH isoenzyme pattern, abnormal relative ratio of LDH-4 and higher calculated LDH-3 and LDH-4 activity values were detected in subjects with unfavorable outcome. CONCLUSION: No characteristic profile of LDH isoenzymes can be detected in COVID-19 pneumonia, however, elevated activities of LDH-3 and LDH-4 are associated with worse clinical outcomes.

A dramatic rise in serum ACE2 activity in a critically ill COVID-19 patient.

Endothelial cells express surface angiotensin-converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that promotes the infection of endothelial cells showing activation and damage. Bronchoalveolar lavage fluid from coronavirus disease-2019 (COVID-19) subjects showed a critical imbalance in the renin-angiotensin-aldosterone system with the upregulated expression of ACE2. Recently, intravenous recombinant ACE2 was reported as an effective therapy in severe COVID-19 by blocking the viral entry to target cells. Here, we present a case of a critically ill COVID-19 patient with acute respiratory distress syndrome where circulating ACE2 was first measured to monitor disease prognosis. ACE2 activity increased about 40-fold over the normal range and showed a distinct time course as compared to 2-3-fold higher levels of endothelium biomarkers. Although the level of soluble E-selectin followed the clinical status of our patient similar to ferritin and IL-6 levels, the dramatic rise in serum ACE2 activity may act as an endogenous nonspecific protective mechanism against SARS-CoV-2 infection that preceded the recovery of our patient.

Up-to-date management of acute traumatic bleeding and coagulopathy / Az akut traumás vérzés és véralvadási zavar korszeru ellátása.

Major trauma is a frequent cause of death, and is the leading cause of death in the younger agegroups. Severe bleeding is often responsible for early mortality. The background of the latter is the trauma-induced coagulopathy (TIC), which - often very early - develops after the onset of bleeding. The high amount of blood products, i.e., massive transfusion administered during the management of traumatic bleeding can result in severe, even fatal complications. Modern, aggressive management of masssive traumatic bleeding is effective in reducing exsanguination and mortality or late complications. This method also fits into the concept of Patient Blood Management. This review deals with the up-to-date, goal-directed, preventive management of traumatic bleeding and coagulopathy, with emphasis on theoretical grounds. The aim is to present the essence of this management method also to those who are not directly involved in this activity. Orv Hetil. 2020; 161(37): 1599-1605.

Challenges of intensive care and anesthesiology related to COVID-19 pandemic. Practical considerations / [Az aneszteziológiai és intenzív ellátás kihívásai a COVID­19-fertozéssel kapcsolatban. Gyakorlati ajánlás]

Due to the coronavirus epidemic, healthcare systems face growing challenges all around the world nowadays. These challenges are the most critical in the field of intensive treatment and anesthesiology. One of the most important prerequisites of effective critical care treatment is preserving the involved healthcare workers from the infection, by providing them with detailed practical advices on the preventive measures and treatment strategies. The aim of the present review is to summarize the most important related knowledge available from previous experiences. Orv Hetil. 2020; 161(17): 652­659.

[Cost differences in the treatment of severe sepsis between survivors and non-survivors on the first day of intensive care admission]. / A súlyos szepszis kezelésének elsô napi költsége az intenzív osztályon a gyógyult és a meghalt betegek összehasonlításában.

BACKGROUND: Patients admitted to intensive care unit with severe sepsis have high mortality and use significant resources. AIMS: Determination of variable cost differences on day 1 between survivors and non-survivors of severe sepsis in Hungary. METHODS: A sample of 6 intensive care units (ICU) included 70 patients who were admitted with severe sepsis to their ICU. Retrospective data collection of resource consumption for 24 hours following ICU admission using medical and nursing records. 59 different resource uses were collected separately for radiology, biochemistry and disposables. Blood products and drugs/fluids were collected individually. The authors identified the price of each resource for the cost calculation. RESULTS: The ICU mortality of severe sepsis in our sample was found to be 64%, the average length of stay for survivors was 19.9 (SD +/- 11.4) and for non-survivors was 13.0 (SD +/- 8.5). Mean ICU variable cost on day 1 of severe sepsis was HUF 60 957 (247 Euro), more for non-survivors (HUF 70 835 vs. 40 108, p = 0.020). The use of blood products is higher in non-survivors ( p = 0.047) and so is the use of drugs/fluids ( p = 0.003). The use of more colloids ( p = 0.016) and more expensive antibiotics ( p = 0.021) was responsible for the higher drugs/fluids spending in non-survivors. CONCLUSION: The mortality of severe sepsis is high and the cost of sepsis treatment is low in Hungary compared to international data. Non-survivors cost almost twice as much even on day 1, this warrants the need for early diagnosis and adequate treatment.

[Surveillance results of nosocomial infections of the ICU in Kenézy Hospital, based on two years data]. / Nosocomialis surveillance eredményei a Kenézy Gyula Kórház Intenzív Osztályán, két év adatai alapján.

INTRODUCTION: According to data in the literature, the number of nosocomial infections in the ICU is far higher than in non-ICU patients. As a result of improving lifesaving technologies, the risk of nosocomial infections increases in ICUs. Utilization of epidemiological methods is recommended for the detection and follow up of nosocomial infections. AIMS: Prospective surveillance to assess the epidemiology of nosocomial infections in an ICU. METHODS: Kenézy Hospital is a country hospital with 1637 beds and a 16-bed central ICU. During the investigated period (01. 04. 2004-31. 03. 2006) 1490 patients, with a total 8058 ICU days, were hospitalised in the mixed medical-surgical ICU. The commonest primary diagnosis were respiratory failure, multiple trauma and head injury. Surveillance was performed by a trained infection control nurse and was supervised by an infection control physician and infectious disease physician. CDC definitions were used to define nosocomial infections. RESULTS: A total of 194 nosocomial infections in 134 patients were detected during the study period. The overall incidence and incidence density of nosocomial infections were 13.0 per 100 patients and 24.0 per 1000 patient-days. Respiratory tract infections (44.3%) were the most frequent nosocomial infection, followed by urinary tract (21.1%) and bloodstream infections (20.1%). CONCLUSIONS: Nosocomial surveillance is useful in detecting nosocomial infections in ICU. A multidisciplinary approach and partnership between the physicians and infection control nurses is needed. Patient-to-nurse ratio is an independent risk factor for nosocomial infections in intensive care, this must be kept in mind when planning rationalization of the number of nursing staff.

[Necrotising fasciitis in hyper-IgE syndrome]. / Fasciitis necrotisans hyper-IgE-szindrómában.

Hyper-IgE syndrome is a rare primary immunodeficiency disease characterized by recurrent staphylococcal skin abscesses, chronic eczematoid dermatitis, pneumonia, pneumatoceles, and extreme elevation of serum IgE. The most common pathogens are S. aureus, and C. albicans. Abnormalities of dentition, bone manifestations, and connective tissue disorders are also common features of the disease. The authors report here a 19-year-old female with hyper-IgE syndrome who developed necrotising fasciitis and toxic shock syndrome. Methicillin resistant S. aureus and S. pyogenes cultured from the skin lesions. Association of hyper-IgE syndrome with necrotising fasciitis is a rarity in the medical literature. In addition to the case report, the authors describe here the major immunologic and clinical manifestations of hyper-IgE syndrome.