Loukas Kakoullis

Bio: Loukas Kakoullis is an academic researcher from Nicosia General Hospital. The author has contributed to research in topics: Medicine & Internal medicine. The author has an hindex of 6, co-authored 20 publications receiving 138 citations. Previous affiliations of Loukas Kakoullis include University of Cyprus & University of Patras.

Mechanisms of Antibiotic Resistance in Important Gram-Positive and Gram-Negative Pathogens and Novel Antibiotic Solutions.

Abstract: Multidrug-resistant bacteria have on overwhelming impact on human health, as they cause over 670,000 infections and 33,000 deaths annually in the European Union alone. Of these, the vast majority of infections and deaths are caused by only a handful of species—multi-drug resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp. and Klebsiella pneumoniae. These pathogens employ a multitude of antibiotic resistance mechanisms, such as the production of antibiotic deactivating enzymes, changes in antibiotic targets, or a reduction of intracellular antibiotic concentration, which render them insusceptible to multiple antibiotics. The purpose of this review is to summarize in a clinical manner the resistance mechanisms of each of these 6 pathogens, as well as the mechanisms of recently developed antibiotics designed to overcome them. Through a basic understanding of the mechanisms of antibiotic resistance, the clinician can better comprehend and predict resistance patterns even to antibiotics not reported on the antibiogram and can subsequently select the most appropriate antibiotic for the pathogen in question.

Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge.

Abstract: Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50-66% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.

EBUS: Faster, cheaper and most effective in lung cancer staging.

Abstract: The use of endobronchial ultrasound trans-bronchial needle aspiration (EBUS-TBNA) as the initial diagnostic and staging procedure in patients with suspected, non-metastatic lung cancer has gained substantial support, and is now recommended by numerous guidelines. Whereas considerable attention has been pointed to the reductions in costs achieved by EBUS-TBNA, that has not been the case for some of its more significant benefits, namely the reduction of the diagnostic work-up time and its ability to accurately assess and restage lymph nodes, which were previously stated incorrectly by CT or PET scan. Both these benefits translate into improved outcomes for patients, as delays are reduced, futile surgeries are prevented and curable operations can be performed on patients previously excluded by CT or PET scan. Indeed, the use of EBUS as the initial diagnostic and staging procedure has been proven to significantly increase survival, compared with conventional diagnostic and staging procedures, in a pragmatic, randomised controlled trial (Navani N. et al, 2015). The instalment of EBUS will have the greatest effect on overwhelmed, suboptimally functioning national healthcare systems, by decreasing the number of required diagnostic and staging procedures, therefore reducing both treatment delays and costs. The improved selection of surgical candidates by EBUS will result in improved patient outcomes. The latest findings regarding the benefits of EBUS are outlined in this review, which, to the best of our knowledge, is the first to emphasise the impact of the procedure, both on timing and costs of lung cancer staging, as well as on survival.

Humoral Responses and Serological Assays in SARS-CoV-2 Infections.

Abstract: In December 2019, the novel betacoronavirus Severe Acute Respiratory Disease Coronavirus 2 (SARS-CoV-2) was first detected in Wuhan, China. SARS-CoV-2 has since become a pandemic virus resulting in hundreds of thousands of deaths and deep socioeconomic implications worldwide. In recent months, efforts have been directed towards detecting, tracking, and better understanding human humoral responses to SARS-CoV-2 infection. It has become critical to develop robust and reliable serological assays to characterize the abundance, neutralization efficiency, and duration of antibodies in virus-exposed individuals. Here we review the latest knowledge on humoral immune responses to SARS-CoV-2 infection, along with the benefits and limitations of currently available commercial and laboratory-based serological assays. We also highlight important serological considerations, such as antibody expression levels, stability and neutralization dynamics, as well as cross-reactivity and possible immunological back-boosting by seasonal coronaviruses. The ability to accurately detect, measure and characterize the various antibodies specific to SARS-CoV-2 is necessary for vaccine development, manage risk and exposure for healthcare and at-risk workers, and for monitoring reinfections with genetic variants and new strains of the virus. Having a thorough understanding of the benefits and cautions of standardized serological testing at a community level remains critically important in the design and implementation of future vaccination campaigns, epidemiological models of immunity, and public health measures that rely heavily on up-to-date knowledge of transmission dynamics.

Sepsis-Pathophysiology and Therapeutic Concepts.

Abstract: Sepsis is a life-threatening condition and a global disease burden. Today, the heterogeneous syndrome is defined as severe organ dysfunction caused by a dysregulated host response to infection, with renewed emphasis on immune pathophysiology. Despite all efforts of experimental and clinical research during the last three decades, the ability to positively influence course and outcome of the syndrome remains limited. Evidence-based therapy still consists of basic causal and supportive measures, while adjuvant interventions such as blood purification or targeted immunotherapy largely remain without proof of effectiveness so far. With this review, we aim to provide an overview of sepsis immune pathophysiology, to update the choice of therapeutic approaches targeting different immunological mechanisms in the course of sepsis and septic shock, and to call for a paradigm shift from the pathogen to the host response as a potentially more promising angle.

Antioxidants: Classification, Natural Sources, Activity/Capacity Measurements, and Usefulness for the Synthesis of Nanoparticles.

Abstract: Natural extracts are the source of many antioxidant substances. They have proven useful not only as supplements preventing diseases caused by oxidative stress and food additives preventing oxidation but also as system components for the production of metallic nanoparticles by the so-called green synthesis. This is important given the drastically increased demand for nanomaterials in biomedical fields. The source of ecological technology for producing nanoparticles can be plants or microorganisms (yeast, algae, cyanobacteria, fungi, and bacteria). This review presents recently published research on the green synthesis of nanoparticles. The conditions of biosynthesis and possible mechanisms of nanoparticle formation with the participation of bacteria are presented. The potential of natural extracts for biogenic synthesis depends on the content of reducing substances. The assessment of the antioxidant activity of extracts as multicomponent mixtures is still a challenge for analytical chemistry. There is still no universal test for measuring total antioxidant capacity (TAC). There are many in vitro chemical tests that quantify the antioxidant scavenging activity of free radicals and their ability to chelate metals and that reduce free radical damage. This paper presents the classification of antioxidants and non-enzymatic methods of testing antioxidant capacity in vitro, with particular emphasis on methods based on nanoparticles. Examples of recent studies on the antioxidant activity of natural extracts obtained from different species such as plants, fungi, bacteria, algae, lichens, actinomycetes were collected, giving evaluation methods, reference antioxidants, and details on the preparation of extracts.

Can Melatonin Be a Potential "Silver Bullet" in Treating COVID-19 Patients?

Abstract: The therapeutic potential of melatonin as a chronobiotic cytoprotective agent to counteract the consequences of COVID-19 infections has been advocated. Because of its wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound, melatonin could be unique in impairing the consequences of SARS-CoV-2 infection. Moreover, indirect evidence points out to a possible antiviral action of melatonin by interfering with SARS-CoV-2/angiotensin-converting enzyme 2 association. Melatonin is also an effective chronobiotic agent to reverse the circadian disruption of social isolation and to control delirium in severely affected patients. As a cytoprotector, melatonin serves to combat several comorbidities such as diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases, which aggravate COVID-19 disease. In view of evidence on the occurrence of neurological sequels in COVID-19-infected patients, another putative application of melatonin emerges based on its neuroprotective properties. Since melatonin is an effective means to control cognitive decay in minimal cognitive impairment, its therapeutic significance for the neurological sequels of SARS-CoV-2 infection should be considered. Finally, yet importantly, exogenous melatonin can be an adjuvant capable of augmenting the efficacy of anti-SARS-CoV-2 vaccines. We discuss in this review the experimental evidence suggesting that melatonin is a potential “silver bullet” in the COVID 19 pandemic.

The clinical efficacy of intravenous IgM-enriched immunoglobulin (pentaglobin) in sepsis or septic shock: a meta-analysis with trial sequential analysis

Abstract: Sepsis is characterized by a complex immune response. This meta-analysis evaluated the clinical effectiveness of intravenous IgM-enriched immunoglobulin (IVIgGM) in patients with sepsis and septic shock. Four databases, PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase, were systematically searched from inception to June 2018 to update the 2013 edition of the Cochrane review by two investigators, who independently selected studies, extracted relevant data, and evaluated study quality. Data were subjected to a meta-analysis and trial sequential analysis (TSA) for the primary and secondary outcomes. Level of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale. Nineteen studies comprising 1530 patients were included in this meta-analysis. Pooled analyses showed that the use of IVIgGM reduced the mortality risk of septic patients (relative risk 0.60; 95% confidence interval [CI] 0.52–0.69, I2 = 0%). TSA showed that IVIgGM had a significant effect on mortality. Additionally, the meta-analysis suggested that use of IVIgGM shortened length of mechanical ventilation (mean difference − 3.16 days; 95% CI − 5.71 to − 0.61 days) and did not shorten length of stay in the intensive care unit (mean difference − 0.38 days; 95% CI − 3.55 to 2.80 days). The GRADE scale showed that the certainty of the body of evidence was low for both benefits and IVIgGM. Administration of IVIgGM to adult septic patients may be associated with reduced mortality. Treatment effects tended to be smaller or less consistent when including only those studies deemed adequate for each indicator. The available evidence is not clearly sufficient to support the widespread use of IVIgGM in the treatment of sepsis. Trial registration PROSPERO registration number: CRD42018084120. Registered on 11 February 2018.