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1.
Sci Rep ; 14(1): 13605, 2024 06 13.
Article in English | MEDLINE | ID: mdl-38871772

ABSTRACT

The aim of this study was to characterize the systemic cytokine signature of critically ill COVID-19 patients in a high mortality setting aiming to identify biomarkers of severity, and to explore their associations with viral loads and clinical characteristics. We studied two COVID-19 critically ill patient cohorts from a referral centre located in Central Europe. The cohorts were recruited during the pre-alpha/alpha (November 2020 to April 2021) and delta (end of 2021) period respectively. We determined both the serum and bronchoalveolar SARS-CoV-2 viral load and identified the variant of concern (VoC) involved. Using a cytokine multiplex assay, we quantified systemic cytokine concentrations and analyzed their relationship with clinical findings, routine laboratory workup and pulmonary function data obtained during the ICU stay. Patients who did not survive had a significantly higher systemic and pulmonary viral load. Patients infected with the pre-alpha VoC showed a significantly lower viral load in comparison to those infected with the alpha- and delta-variants. Levels of systemic CTACK, M-CSF and IL-18 were significantly higher in non-survivors in comparison to survivors. CTACK correlated directly with APACHE II scores. We observed differences in lung compliance and the association between cytokine levels and pulmonary function, dependent on the VoC identified. An intra-cytokine analysis revealed a loss of correlation in the non-survival group in comparison to survivors in both cohorts. Critically ill COVID-19 patients exhibited a distinct systemic cytokine profile based on their survival outcomes. CTACK, M-CSF and IL-18 were identified as mortality-associated analytes independently of the VoC involved. The Intra-cytokine correlation analysis suggested the potential role of a dysregulated systemic network of inflammatory mediators in severe COVID-19 mortality.


Subject(s)
COVID-19 , Critical Illness , Cytokines , Intensive Care Units , SARS-CoV-2 , Humans , COVID-19/mortality , COVID-19/blood , Cytokines/blood , Male , Middle Aged , Female , Aged , Viral Load , Biomarkers/blood , Cohort Studies , Pandemics
2.
Medicina (Kaunas) ; 60(4)2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38674228

ABSTRACT

Background and Objectives: The COVID-19 disease has significantly burdened the healthcare system, including all units of severe patient treatment. Non-intensive care units were established to rationalize the capacity within the Intensive Care Unit (ICU) and to create a unit where patients with Acute Respiratory Distress Syndrome (ARDS) could be treated with non-invasive Continuous Positive Air Pressure (CPAP) outside the ICU. This unicentric retrospective study aimed to assess the efficacy of NIV Treatment in Patients of the fourth pandemic wave and how its application affects the frequency and mortality of ICU-treated patients at University Hospital Rijeka compared to earlier waves of the COVID-19 pandemic. Furthermore, the study showcases the effect of the Patient/Nurse ratio (P/N ratio) on overall mortality in the ICU. Materials and Methods: The study was conducted on two groups of patients with respiratory insufficiency in the second and third pandemic waves, treated in the COVID Respiratory Centre (CRC) (153 patients). We also reviewed a cohort of patients from the fourth pandemic wave who were initially hospitalized in a COVID-6 non-intensive unit from 1 October 2021 to 1 November 2022 (102 patients), and some of them escalated to CRC. Results: The introduction of the CPAP non-invasive ventilation method as a means of hypoxic respiratory failure treatment in non-intensive care units has decreased the strain, overall number of admissions, and CRC patient mortality. The overall fourth wave mortality was 29.4%, compared to the 58.2% overall mortality of the second and third waves. Conclusions: As a result, this has decreased CRC patient admissions and, by itself, overall mortality.


Subject(s)
COVID-19 , Continuous Positive Airway Pressure , Humans , COVID-19/therapy , COVID-19/mortality , Continuous Positive Airway Pressure/methods , Retrospective Studies , Female , Male , Middle Aged , Aged , Intensive Care Units/statistics & numerical data , SARS-CoV-2 , Treatment Outcome , Respiratory Insufficiency/therapy , Respiratory Insufficiency/mortality , Hospital Mortality , Pandemics , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/mortality
3.
J Cardiovasc Dev Dis ; 10(5)2023 May 13.
Article in English | MEDLINE | ID: mdl-37233179

ABSTRACT

Cardiac surgery is one of the highest-risk procedures, usually involving cardiopulmonary bypass and commonly inducing endothelial injury that contributes to the development of perioperative and postoperative organ dysfunction. Substantial scientific efforts are being made to unravel the complex interaction of biomolecules involved in endothelial dysfunction to find new therapeutic targets and biomarkers and to develop therapeutic strategies to protect and restore the endothelium. This review highlights the current state-of-the-art knowledge on the structure and function of the endothelial glycocalyx and mechanisms of endothelial glycocalyx shedding in cardiac surgery. Particular emphasis is placed on potential strategies to protect and restore the endothelial glycocalyx in cardiac surgery. In addition, we have summarized and elaborated the latest evidence on conventional and potential biomarkers of endothelial dysfunction to provide a comprehensive synthesis of crucial mechanisms of endothelial dysfunction in patients undergoing cardiac surgery, and to highlight their clinical implications.

4.
Medicina (Kaunas) ; 59(1)2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36676766

ABSTRACT

Bilateral COVID-19 pneumonia is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and usually leads to life-threatening acute respiratory distress syndrome (ARDS). Treatment of patients with ARDS is difficult and usually involves protective mechanical ventilation and various types of recruitment maneuvers. A segmental lung recruitment maneuver by independent lung ventilation has been described as a successful recruitment maneuver in patients with lobar pneumonia, and may, therefore, be useful for the treatment of patients with bilateral COVID-19 pneumonia complicated by ARDS in the critical phase of the disease when all other therapeutic options have been exhausted. The aim of this case series was to present a case report of four mechanically ventilated patients with severe bilateral COVID-19 pneumonia complicated by ARDS using the segmental lung recruitment maneuver. The effect of the segmental lung recruitment maneuver was assessed by the increase in PaO2/FiO2 ratio and the lung ultrasound (LUS) scoring system (0 points-presence of sliding lungs with A-lines or one or two isolated B-lines; 1 point-moderate loss of lung ventilation with three to five B lines; 2 points-severe loss of lung ventilation with more than five B lines (B pattern); and 3 points-lung consolidation) determined 12, 24, and 48 h after segmental lung recruitment. In three of four patients with bilateral COVID-19 pneumonia complicated by ARDS, an increase in the PaO2/FiO2 ratio and an improvement in the LUS scoring system were observed 48 h after segmental lung recruitment. In conclusion, the segmental lung recruitment maneuver in patients with bilateral COVID-19 complicated by ARDS is an effective method of lung recruitment and may be a useful treatment method.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , COVID-19/complications , SARS-CoV-2 , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Lung/diagnostic imaging , Respiration, Artificial/methods
5.
Sci Rep ; 12(1): 14906, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36050403

ABSTRACT

The coronavirus disease (COVID-19) pandemic caused unprecedented research activity all around the world but publications from Central-Eastern European countries remain scarce. Therefore, our aim was to characterise the features of the pandemic in the intensive care units (ICUs) among members of the SepsEast (Central-Eastern European Sepsis Forum) initiative. We conducted a retrospective, international, multicentre study between March 2020 and February 2021. All adult patients admitted to the ICU with pneumonia caused by COVID-19 were enrolled. Data on baseline and treatment characteristics, organ support and mortality were collected. Eleven centres from six countries provided data from 2139 patients. Patient characteristics were: median 68, [IQR 60-75] years of age; males: 67%; body mass index: 30.1 [27.0-34.7]; and 88% comorbidities. Overall mortality was 55%, which increased from 2020 to 2021 (p = 0.004). The major causes of death were respiratory (37%), cardiovascular (26%) and sepsis with multiorgan failure (21%). 1061 patients received invasive mechanical ventilation (mortality: 66%) without extracorporeal membrane oxygenation (n = 54). The rest of the patients received non-invasive ventilation (n = 129), high flow nasal oxygen (n = 317), conventional oxygen therapy (n = 122), as the highest level of ventilatory support, with mortality of 50%, 39% and 22%, respectively. This is the largest COVID-19 dataset from Central-Eastern European ICUs to date. The high mortality observed especially in those receiving invasive mechanical ventilation renders the need of establishing national-international ICU registries and audits in the region that could provide high quality, transparent data, not only during the pandemic, but also on a regular basis.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Respiratory Insufficiency , Sepsis , Adult , COVID-19/epidemiology , COVID-19/therapy , Humans , Intensive Care Units , Male , Oxygen , Registries , Respiration, Artificial , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2 , Sepsis/epidemiology
6.
Viruses ; 14(9)2022 09 04.
Article in English | MEDLINE | ID: mdl-36146773

ABSTRACT

Studies assessing the dynamics and duration of antibody responses following SARS-CoV-2 infection or vaccination are an invaluable tool for vaccination schedule planning, assessment of risk groups and management of pandemics. In this study, we developed and employed ELISA assays to analyze the humoral responses to Nucleocapsid and Spike proteins in vaccinated health-care workers (HCW) and critically ill COVID-19 patients. Sera of more than 1000 HCWs and critically ill patients from the Clinical Hospital Center Rijeka were tested across a one-year period, encompassing the spread of major SARS-CoV-2 variants of concern (VOCs). We observed 97% of seroconversion in HCW cohort as well as sustained anti-Spike antibody response in vaccinees for more than 6 months. In contrast, the infection-induced anti-Nucleocapsid response was waning significantly in a six-month period. Furthermore, a substantial decrease in vaccinees' anti-Spike antibodies binding to Spike protein of Omicron VOC was also observed. Critically ill COVID-19 patients had higher levels of anti-Spike and anti-Nucleocapsid antibodies compared to HCWs. No significant differences in anti-Spike and anti-Nucleocapsid antibody levels between the critically ill COVID-19 patients that were on non-invasive oxygen supplementation and those on invasive ventilation support were observed. However, stronger anti-Spike, but not anti-Nucleocapsid, antibody response correlated with a better disease outcome in the cohort of patients on invasive ventilation support. Altogether, our results contribute to the growing pool of data on humoral responses to SARS-CoV-2 infection and vaccination.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , Cohort Studies , Critical Illness , Croatia , Health Personnel , Humans , Nucleocapsid Proteins , Spike Glycoprotein, Coronavirus
7.
Viruses ; 14(6)2022 06 14.
Article in English | MEDLINE | ID: mdl-35746764

ABSTRACT

While SARS-CoV-2 detection in sputum and swabs from the upper respiratory tract has been used as a diagnostic tool, virus quantification showed poor correlation to disease outcome and thus, poor prognostic value. Although the pulmonary compartment represents a relevant site for viral load analysis, limited data exploring the lower respiratory tract is available, and its association to clinical outcomes is relatively unknown. Using bronchoalveolar lavage (BAL) and serum samples, we quantified SARS-CoV-2 copy numbers in the pulmonary and systemic compartments of critically ill patients admitted to the intensive care unit of a COVID-19 referral hospital in Croatia during the second and third pandemic waves. Clinical data, including 30-day survival after ICU admission, were included. We found that elevated SARS-CoV-2 copy numbers in both BAL and serum samples were associated with fatal outcomes. Remarkably, the highest and earliest viral loads after initiation of mechanical ventilation support were increased in the non-survival group. Our results imply that viral loads in the lungs contribute to COVID-19 disease severity, while blood titers correlate with lung virus titers, albeit at a lower level. Moreover, they suggest that BAL SARS-CoV-2 copy number quantification at ICU admission may provide a predictive parameter of clinical COVID-19 outcomes.


Subject(s)
COVID-19 , SARS-CoV-2 , Critical Illness , Humans , Lung , Viral Load
8.
BMC Med ; 20(1): 102, 2022 03 03.
Article in English | MEDLINE | ID: mdl-35236358

ABSTRACT

BACKGROUND: The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and immediately classified as a variant of concern (VOC), since it shows substantially more mutations in the spike protein than any previous variant, especially in the receptor-binding domain (RBD). We analyzed the binding of the Omicron RBD to the human angiotensin-converting enzyme-2 receptor (ACE2) and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta, or Delta RBD variants. METHODS: All RBDs were produced in insect cells. RBD binding to ACE2 was analyzed by ELISA and microscale thermophoresis (MST). Similarly, sera from 27 COVID-19 patients, 81 vaccinated individuals, and 34 booster recipients were titrated by ELISA on RBDs from the original Wuhan strain, Beta, Delta, and Omicron VOCs. In addition, the neutralization efficacy of authentic SARS-CoV-2 wild type (D614G), Delta, and Omicron by sera from 2× or 3× BNT162b2-vaccinated persons was analyzed. RESULTS: Surprisingly, the Omicron RBD showed a somewhat weaker binding to ACE2 compared to Beta and Delta, arguing that improved ACE2 binding is not a likely driver of Omicron evolution. Serum antibody titers were significantly lower against Omicron RBD compared to the original Wuhan strain. A 2.6× reduction in Omicron RBD binding was observed for serum of 2× BNT162b2-vaccinated persons. Neutralization of Omicron SARS-CoV-2 was completely diminished in our setup. CONCLUSION: These results indicate an immune escape focused on neutralizing antibodies. Nevertheless, a boost vaccination increased the level of anti-RBD antibodies against Omicron, and neutralization of authentic Omicron SARS-CoV-2 was at least partially restored. This study adds evidence that current vaccination protocols may be less efficient against the Omicron variant.


Subject(s)
COVID-19 , BNT162 Vaccine , COVID-19/prevention & control , Humans , Pandemics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
10.
Viruses ; 13(12)2021 12 02.
Article in English | MEDLINE | ID: mdl-34960682

ABSTRACT

During COVID-19 pandemics, the availability of testing has often been a limiting factor during patient admissions into the hospital. To circumvent this problem, we adapted an existing diagnostic assay, Seegene Allplex SARS-CoV-2, into a point-of-care-style direct qPCR (POC dqPCR) assay and implemented it in the Emergency Department of Clinical Hospital Center Rijeka, Croatia. In a 4-month analysis, we tested over 10,000 patients and demonstrated that POC-dqPCR is robust and reliable and can be successfully implemented in emergency departments and similar near-patient settings and can be performed by medical personnel with little prior experience in qPCR.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Emergency Service, Hospital , Point-of-Care Testing , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , Croatia/epidemiology , Humans , RNA, Viral/genetics , Reproducibility of Results , SARS-CoV-2/genetics , Sensitivity and Specificity
11.
Bosn J Basic Med Sci ; 21(1): 93-97, 2021 Feb 01.
Article in English | MEDLINE | ID: mdl-33128869

ABSTRACT

In many areas of the world, critical care providers caring for COVID-19 patients lacked specific knowledge and were exposed to the abundance of new and unfiltered information. With support from the World Health Organization, we created a multimodal tele-education intervention to rapidly share critical care knowledge related to COVID-19 targeting providers in a region of Southeastern Europe. We delivered 60-minute weekly interactive tele-education sessions over YouTubeTM between March 2020 and May 2020, supplemented by a dedicated webpage. The intervention was reinforced using a secure social media platform (ViberTM), providing continuous rapid knowledge exchange among faculty and learners. A high level of engagement was observed, with over 2000 clinicians participating and actively interacting over a 6-week period. Surveyed participants were highly satisfied with the intervention. Tele-education interventions using social media platforms are feasible, low-cost, and effective methods to share knowledge during the COVID-19 pandemic.


Subject(s)
Access to Information , COVID-19/epidemiology , Critical Care/organization & administration , Education, Medical, Continuing/methods , Inservice Training/methods , Pandemics , Social Media , Europe , Humans , Surveys and Questionnaires , World Health Organization
12.
Medicine (Baltimore) ; 99(20): e19966, 2020 May.
Article in English | MEDLINE | ID: mdl-32443298

ABSTRACT

It is increasingly recognized that modulation of brain inflammation may uncover new potential therapeutic strategies for stroke. Recent studies have shifted focus from immunological implications in ischemic stroke to a more devastating form; the hemorrhagic stroke.The aim of this study was to investigate the neuroinflammatory response in cerebrospinal fluid in patients with primary intracerebral hemorrhage (ICH) associated with intraventricular hemorrhage (IVH) in the presence of low-dose recombinant tissue plasminogen activator (rt-PA).This retrospective study included 88 adults with primary ICH associated with IVH. Patients were divided into 2 groups: rt-PA group and non-rt-PA group, which received normal standard of care for this diagnosis. The rt-PA group was treated via catheter-based clot lysis using low-dose rt-PA injected through the external ventricular drain (EVD) system, and the non-rt-PA group was treated with saline applied to EVD system in equivalent volume. Cerebrospinal fluid samples from rt-PA were obtained from the EVD system at 4 time points: once before the drug administration, and then on day 1, 3, and 7. No attempt at randomization was made. The decision to inject rt-PA was based on the preference of the primary attending neurologist and the ability to obtain consent. Temporal interleukin-1 beta and transforming growth factor beta concentration changes were analyzed and compared between the 2 groups.The concentration of interleukin-1 beta was significantly lower in the rt-PA group than in the non-rt-PA group on day 7. In addition, the concentration of transforming growth factor beta was significantly higher in the rt-PA group than in the non-rt-PA group on day 1. There was a significant difference in interleukin-1 beta concentration between days 0 and 1 in comparison to day 3 in the rt-PA group, and between day 0 in comparison to day 3 and 7 in the non-rt-PA group. We also observed a significant difference in transforming growth factor beta concentration between days 0 and 1 and between days 3 and 7.The different pattern of pro- and anti-inflammatory cytokines in patients with ICH associated with IVH suggest distinct characteristics of secondary brain injury depending on the treatment modality.


Subject(s)
Cerebral Intraventricular Hemorrhage/drug therapy , Fibrinolytic Agents/administration & dosage , Interleukin-1beta/cerebrospinal fluid , Tissue Plasminogen Activator/administration & dosage , Transforming Growth Factor beta/cerebrospinal fluid , Adult , Aged , Cerebral Intraventricular Hemorrhage/cerebrospinal fluid , Female , Humans , Infusions, Intraventricular , Male , Middle Aged , Retrospective Studies
14.
J Clin Monit Comput ; 34(6): 1259-1264, 2020 Dec.
Article in English | MEDLINE | ID: mdl-31823209

ABSTRACT

Quantification of B-lines on lung ultrasonographs is operator-dependent and considered a semi-quantitative method. To avoid this variability, we designed a software algorithm for counting B-lines. We compared the number of B-lines obtained in real-time by observers with three different levels of experience and by the software algorithm, and analyzed intra-rater variability in terms of the estimated number of B-lines in two successive examinations. Forty mechanically ventilated adult (≥ 18 years) intensive care unit patients were included in this prospective study. All patients underwent two consecutive ultrasound examinations for B-lines detection by three human observers (OB1 = high, OB2 = medium, OB3 = low level of experience) and by the software (OBS). Ultrasound scans were obtained on the anterior right and left thoracic side along the midclavicular line, in the second and fourth intercostal space; B-lines counting for each position lasted 10 s. To assess intra-observer variability, a second ultrasound scan was obtained 15-30 min after the first scan. For all lung zones, the intraclass correlation for B-lines counting between OB1 and OB2 was 0.663; between OB1 and OB3, 0.559; and between OB1 and OBS, 0.710. OBS had a better concordance coefficient (0.752) between the first and the second measurements than did the human observers. Our results show that the software algorithm for B-lines counting is a potentially promising alternative when observers have little lung ultrasound experience.


Subject(s)
Algorithms , Point-of-Care Systems , Adult , Humans , Lung/diagnostic imaging , Observer Variation , Prospective Studies , Reproducibility of Results , Software , Ultrasonography
15.
Heart Surg Forum ; 22(3): E218-E224, 2019 05 22.
Article in English | MEDLINE | ID: mdl-31237547

ABSTRACT

BACKGROUND: Coronary artery bypass grafting (CABG) surgery continues to be the gold standard for treating the patients with coronary artery disease. CABG surgery can be performed on or off cardiopulmonary bypass, termed as on-pump or off-pump CABG, respectively. It has been shown that CABG surgery, preferably on-pump CABG surgery, leads to the changes of cell immunity during perioperative and early postoperative period. The mechanisms of regulation of the immune response in patients during and early after surgical revascularization are not fully understood. The aim of this study was to investigate the influence of carbohydrate preoperative oral feeding on frequency and perforin expression in peripheral blood lymphocytes in patients after on- or off-pump CABG surgery in early postoperative period. PATIENTS AND METHODS: In this prospective clinical study, 80 patients scheduled for CABG surgery were included in the study. The patients were randomly allocated into four groups (20 in each group): patients in Group 1 underwent on-pump CABG and did not receive carbohydrate preoperative oral feeding; patients in Group 2 underwent on-pump CABG and were preoperatively fed; patients in Group 3 underwent off-pump CABG and did not receive carbohydrate preoperative oral feeding; while patients in Group 4 underwent off-pump CABG and received carbohydrate preoperative oral feeding. Blood samples were collected immediately before (T1), 24 (T2) and 72 (T3) hours after the surgery. Peripheral blood mononuclear cells were isolated by gradient centrifugation and simultaneously labelled by antigens using fluorochrome-conjugated monoclonal antibodies. Frequency of T lymphocytes, NK and NKT cells, their subsets as well as their perforin expression were detected, and analyzed by flow cytometry. RESULTS: There was significant decrease in frequency of CD3+ and CD3+CD4+ cells, as well as perforin expressing CD3+CD8+ cells in patients who underwent on-pump CABG in comparison to patients who underwent off-pump CABG 24 hours after the surgery. Carbohydrate preoperative oral feeding did not effect changes in lymphocytes subpopulations and perforin expression at any time point. CONCLUSION: Decreases of CD3+ cells on account of CD3+CD4+ subsets, and perforin expressing cells on account of CD3+CD8+ perforin+ cells were found in patients who had undergone on-pump CABG, but not in patients who had undergone off-pump CABG surgery, irrespectively of carbohydrate preoperative oral feeding.


Subject(s)
Coronary Artery Bypass , Coronary Artery Disease/blood , Coronary Artery Disease/surgery , Dietary Carbohydrates/administration & dosage , Leukocytes, Mononuclear/metabolism , Perforin/blood , Aged , Cardiopulmonary Bypass , Enteral Nutrition , Female , Humans , Male , Middle Aged , Preoperative Care , Prospective Studies
16.
J Neurotrauma ; 36(2): 190-200, 2019 01 15.
Article in English | MEDLINE | ID: mdl-29690821

ABSTRACT

Extracellular vesicles (EVs) are membranous nanostructures that can indicate undergoing processes in organs and thus help in diagnostics and prognostics. They are secreted by all cells, contained in body fluids, and able to transfer proteins, lipids and nucleic acids to distant cells. Intracranial EVs were shown to change their composition after severe traumatic brain injury (TBI) and therefore to have biomarker potential to evaluate brain events. Properties of intracranial EVs early after TBI, however, have not been characterized. Here, we assessed cerebrospinal fluid (CSF) up to seven days after isolated severe TBI for physical properties of EVs and their proteins associated with neuroregeneration. These findings were compared with healthy controls and correlated to patient outcome. The study included 17 patients with TBI and 18 healthy controls. EVs in TBI-CSF were visualized by electron microscopy and confirmed by immunoblotting for membrane associated Flotillin-1 and Flotillin-2. Using nanoparticle tracking analysis, we detected the highest range in EV concentration at day 1 after injury and significantly increased EV size at days 4-7. CSF concentrations of neuroregeneration associated proteins Flotillin-1, ADP-ribosylation Factor 6 (Arf6), and Ras-related protein Rab7a (Rab7a) were monitored by enzyme-linked immunosorbent assays. Flotillin-1 was detected solely in TBI-CSF in about one third of tested patients. Unfavorable outcomes included decreasing Arf6 concentrations and a delayed Rab7a concentration increase in CSF. CSF concentrations of Arf6 and Rab7a were negatively correlated. Our data suggest that the brain response within several days after severe TBI includes shedding of EVs associated with neuroplasticity. Extended studies with a larger number of participants and CSF collected at shorter intervals are necessary to further evaluate neuroregeneration biomarker potential of Rab7a, Arf6, and Flotillin-1.


Subject(s)
Biomarkers/cerebrospinal fluid , Brain Injuries, Traumatic/cerebrospinal fluid , Extracellular Vesicles , ADP-Ribosylation Factor 6 , Adult , Aged , Aged, 80 and over , Brain Injuries, Traumatic/physiopathology , Female , Humans , Male , Middle Aged , Nerve Regeneration/physiology , Recovery of Function/physiology , Young Adult
17.
Injury ; 48 Suppl 5: S1-S7, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29122114

ABSTRACT

INTRODUCTION: Trauma with multiple injuries is associated with a high risk of complications, which may be related to excessive stimulation of inflammatory and anti-inflammatory responses. Although the effects of polytrauma on the immune response have been well established at the cellular and molecular levels, there is little information about the changes in the cytolytic potential of immunocompetent cells, including expression of cytotoxic molecules such as perforin. Therefore, the objective of the present study was to analyse and compare differences in the frequency and perforin expression of leukocyte subpopulations in the peripheral blood of patients with lower limb fracture, thoracic injury, and simultaneous lower limb fracture and thoracic injury. PATIENTS AND METHODS: Forty-five patients with trauma injury (15 patients with lower limb injury, 15 patients with thoracic injury, and 15 patients with simultaneous lower limb and thoracic injury) were included in the study. Peripheral blood of 15 sex- and age-matched healthy volunteers served as the control group. Peripheral blood samples were taken from all subjects included in the study and peripheral blood mononuclear cells were isolated by gradient centrifugation. The frequency of T lymphocytes, natural killer (NK) and NK T cells, and their subsets, as well as their perforin expression levels were simultaneously detected and analysed by flow cytometry. RESULTS: There was a statistically significant decrease in the frequency of T lymphocytes, NK and NK T cells as well as perforin expression in the patients with simultaneous lower limb and thoracic injury compared with the other two groups, with a predominantly marked decrease in NK and NK T cells. CONCLUSION: The decrease in the frequency and cytotoxic potential of peripheral blood lymphocytes is related to the severity of trauma injury, which can explain the underlying mechanism contributing to complication occurrence.


Subject(s)
Fractures, Bone/immunology , Lower Extremity/injuries , Lymphocyte Subsets/immunology , Multiple Trauma/immunology , Perforin/metabolism , Systemic Inflammatory Response Syndrome/physiopathology , Thoracic Injuries/immunology , Adult , Female , Flow Cytometry , Fractures, Bone/physiopathology , Gene Expression Regulation , Humans , Immunity, Cellular/physiology , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Male , Middle Aged , Multiple Trauma/physiopathology , Perforin/analysis , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
18.
Injury ; 46(11): 2103-7, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25840790

ABSTRACT

BACKGROUND: Chest tube malfunction, after the tube thoracostomy, is often the result of an inappropriate chest tube tip position. The aim of this study was to analyse the precision of chest tube placement using the targeted wire guide technique (TWG technique) with curve dilator and to compare it to the classical surgical technique (CS technique). MATERIALS AND METHODS: In this clinical study 80 patients with an indication for thoracic drainage, due to pneumothorax or pleural effusion were included. Experimental group contained 39 patients whose chest tube was placed using the TWG technique. The control group contained 41 patients whose chest tube was placed using the CS technique. RESULTS: The comparison of the outcomes of the two techniques applied suggests that the TWG technique was significantly more successful in achieving adequate (precise) chest tube placement, irrespective of patient diagnosis (TWG vs. CS in all patients, 78.4% vs. 36.6%, p<0.001). In the pleural effusion group, TWG and CS had success rates of 78.2% and 37.5% (p=0.005), respectively, while in pneumothorax group, TWG and CS had success rates of 78.6% and 35.3% (p=0.029), respectively. CONCLUSIONS: Using a curved dilator and the TWG technique for the thoracic drainage procedure we found statistically significant advantage to the TWG technique in comparison to the CS technique (78% vs. 37%) regarding precise chest tube placement within the pleural cavity. Introducing the materials and technique used in this clinical trial into clinical practice may improve the quality of thoracic drainage, including residual volume of air and/or fluid, poor functioning of the chest tube, and, as a consequence of both, prolonged hospitalisation.


Subject(s)
Catheterization/methods , Chest Tubes , Drainage/methods , Pleural Effusion/surgery , Pneumothorax/surgery , Thoracostomy/methods , Adult , Aged , Catheterization/instrumentation , Female , Humans , Male , Middle Aged , Practice Guidelines as Topic , Reproducibility of Results , Thoracostomy/instrumentation
19.
Lijec Vjesn ; 136(7-8): 179-85, 2014.
Article in Croatian | MEDLINE | ID: mdl-25327004

ABSTRACT

Nutritional status of patients significantly affects the outcome of surgical treatment, whether it's about being obese or malnutrition with loss of muscle mass. Inadequate nutritional support in the perioperative period compromises surgical procedures even in patients who are adequately nourished. In this paper, particular attention was paid to malnourished patients, and their incidence in population hospitalized in surgical wards can be high up to 30%. Special emphasis was paid to the appropriateness of preoperative fasting and to the acceptance of new knowledge in this area of treatment. The aim of this working group was to make guidelines for perioperative nutritional support with different modalities of enteral nutrition. The development of these guidelines was attended by representatives of Croatian Medical Association: Croatian Society for Digestive Surgery, Croatian Society for Clinical Nutrition, Croatian Society of Surgery, Croatian Society for Endoscopic Surgery, Croatian Trauma Society and the Croatian Society of Anesthesiology and Intensive Care. The guidelines are designed as a set of questions that arise daily in clinical practice when preparing patients for surgery and after the surgical treatment, which relate to the assessment of nutritional status, perioperative nutritional support, duration of preoperative fasting period and the selection of food intake route. Assessment of nutritional status and the use of different modes of enteral nutrition should enter into standard protocols of diagnosis and treatment in the Croatian hospitals.


Subject(s)
Malnutrition/complications , Nutritional Status , Perioperative Care/methods , Practice Guidelines as Topic , Body Mass Index , Croatia , Fasting/adverse effects , Humans , Nutritional Support , Preoperative Care/methods
20.
Hepatogastroenterology ; 60(127): 1602-6, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24634929

ABSTRACT

BACKGROUND/AIMS: Fasting period before surgery may change metabolic status of the patient and have influence on perioperative stress response. The aim of the study was to investigate effects of preoperative carbohydrate-rich beverage on stress response after laparoscopic cholecystectomy. METHODOLOGY: Patients admitted for laparoscopic cholecystectomy were included into study and they were randomized into a group that was fed prior to surgery and in a group that was in the regime of nothing by mouth from the evening one day before surgery. Concentrations of C-reactive protein and cortisol, were measured before and subsequently up to 48 h postoperatively. RESULTS: Postoperative serum C-reactive protein increased significantly in both groups, but the increase was more evident in the group with fasting protocol both 24 and 48 hours postoperatively. In fed patients cortisol concentration measured in the afternoon immediately after the operation showed physiological decline. In patients with fasting protocol postoperative cortisol values rise above the values measured in the morning. CONCLUSIONS: Preoperative feeding has advantage over overnight fasting by reducing preoperative discomfort in patients after laparoscopic cholecystectomy. In fed patients, smaller increase in C-reactive protein and better regulation of cortisol levels are an indicator of decreased perioperative stress response.


Subject(s)
Cholecystectomy, Laparoscopic/adverse effects , Dietary Carbohydrates/administration & dosage , Enteral Nutrition/methods , Stress, Physiological , Administration, Oral , Beverages , Biomarkers/blood , C-Reactive Protein/metabolism , Croatia , Double-Blind Method , Fasting , Female , Humans , Hydrocortisone/blood , Male , Middle Aged , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Postoperative Nausea and Vomiting/etiology , Postoperative Nausea and Vomiting/prevention & control , Preoperative Care , Time Factors , Treatment Outcome
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