Antitumorigenic Effect of Cannabidiol in Lung Cancer: What Do We Know So Far?­A Mini Review

Lung cancer remains a major factor contributing to morbidity and mortality worldwide. cannabidiol (CBD) and Δ9-tetrahydrocannabinol could serve as a specific treatment for lung cancer, owing to their essential role in lung cancer cell apoptosis. This review evaluated the antitumorigenic mechanisms of CBD in lung cancer cells. We searched the databases MEDLINE, clinicaltrials.gov, Cochrane Central Register of Controlled Trials, and Google Scholar using specific terms. Of 246 studies screened, nine were included and assessed using the ToxRTool. All the selected studies were conducted in vitro, and four of which also had an in vivo content. The most common cell line used in all the studies was A549; however, some studies contained other cell lines, including H460 and H358. Our findings suggested that CBD has direct antineoplastic effects on lung cancer cells through various mechanisms mediated by cannabinoid receptors or independent of these receptors. All studies were referred to an in vitro model; hence, further research in animals is required.

Soluble urokinase plasminogen activator receptor (suPAR) in the emergency department: An update.

Background: The biomarker soluble urokinase plasminogen activator receptor (suPAR) is an indicator of inflammation which is increased in a variety of chronic and acute disease states. Its most promising application in the emergency setting is to aid in the prognostic stratification of patients by identifying those at high risk of deterioration. This is a narrative review of studies evaluating the use of suPAR. Methods: We conducted a Medline search for studies on the use of suPAR in patients acutely admitted to the emergency department. Results: 25 original studies were included in the review. suPAR as a marker of inflammation has been used alone or combined to other inflammatory biomarkers in the assessment of patients suffering from various acute and chronic diseases in an emergency setting. As it is non-specific, it may increase in infectious disease, malignancy or acute coronary syndromes among other conditions, but quantitative suPAR levels correlate with disease severity. It may be useful for the identification of high risk patients regardless of underlying pathology. Conclusion: As the ideal biomarker in the emergency setting has not been identified yet, suPAR may be a promising addition to the established biomarkers for the initial assessment of patients in this setting. Additional research is necessary to evaluate the usefulness of suPAR guided management algorithms.

Presepsin as a Diagnostic and Prognostic Biomarker in Sepsis.

Sepsis is a condition characterized by high morbidity and mortality which is commonly encountered in an emergency and critical care setting. Despite a substantial body of research, the ideal biomarker for the diagnosis and prognostic stratification of septic patients remains unknown. This review aimed to summarize the publications referring to the validity of the biomarker presepsin when used for the detection, monitoring and prognosis in patients suffering with sepsis. This work is a narrative review based on a PubMed/Medline search conducted in order to identify all relevant publications referring to the use of presepsin in sepsis. Search was not limited by year of publication so all articles archived in the database would be retrieved. No article from before 2010 was identified. A total of 57 publications of the last decade were included, all of which support the use of presepsin as a biomarker for the assessment of septic patients. It has been used alone or in combination with commonly used biomarkers in the evaluation of patients with sepsis in settings such as the emergency department and the intensive care unit. It is useful in the initial workup of patients with suspected sepsis in the emergency setting and may be a predictive factor of mortality and the most severe complication of sepsis. Presepsin seems to be a valuable tool for the laboratory workup of sepsis, especially when used in conjunction with other biomarkers and clinical rating scores with an established role in this population. Further research is needed to evaluate the clinical implications of utilizing presepsin measurements in the workup of sepsis.

Soluble Urokinase Plasminogen Activator Receptor as a Diagnostic and Prognostic Biomarker in Cardiac Disease.

This review summarizes the published literature referring to the use and validity of the biomarker soluble urokinase plasminogen activator receptor (suPAR) when used for the assessment of patients with cardiac diseases. It is measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples. In cardiology a cut-off value range of 3.5 - 4.5 ng/mL has been commonly utilized. Different cut-off values may be applied based on the measuring kit used, the patient population and the clinical setting. A PubMed/Medline search was conducted aiming to identify all publications relevant to the use of suPAR in patients with cardiac diseases. A total of 39 studies were included in this review. suPAR as a marker of inflammation has been used more extensively in recent years, alone or in combination with other biomarkers of inflammation and cardiac pathology in the assessment of patients with acute and chronic cardiac diseases. suPAR is closely related to the pathophysiology of cardiac disease, and a number of publications encourages its use as a valuable biomarker in the assessment of patients presenting to the cardiology service. It may be most valuable in the risk assessment of patients with acute coronary syndromes and congestive heart failure, as suPAR elevation may be an independent predictor of mortality in these conditions. In conclusion, among several biomarkers used for clinical entities with underlying inflammatory pathophysiology including cardiac diseases, suPAR is a novel attractive index for the prognostic risk stratification of cardiac patients. More research is warranted to confirm its diagnostic and prognostic validity, alone or combined with other cardiac and inflammatory biomarkers.

Correlation of Positive Blood Cultures with Peripherally Inserted Central Catheter Line Infection in Oncology Patients.

INTRODUCTION: The use of peripherally inserted central catheter (PICC) lines offers several advantages compared to traditional central venous catheters (CVCs) as the insertion procedure is minimally invasive, they may be retained safely for longer periods of time, and their use is associated with fewer catheter-related infections. Their use in patients suffering from a malignant disease is common but may pose a greater risk of complications due to the severe immunosuppression associated with treatment. This study was conducted to evaluate the safety of PICC lines in this group. METHODS: This was a retrospective study of oncology patients being treated in a Mediterranean tertiary center. Patients with PICC lines were enrolled in the study if a positive blood culture necessitated the removal of the PICC and subsequent culture of the PICC tip. A comparison was conducted between patients with positive and negative PICC cultures. RESULTS: Thirty patients were included, four of whom had a positive PICC culture. The most commonly isolated pathogens were coagulase-negative Staphylococci and Corynebacteria. No statistically significant difference was noted in white blood cell (WBC) counts, C-reactive protein (CRP), and Michigan PICC central line associated bloodstream infection (MPC) score between the two groups. Staphylococcus epidermidis was the most commonly isolated pathogen. DISCUSSION: Though limited by a small sample size and the retrospective design, the findings of this study seem to corroborate existing literature on the subject which suggests that the use of PICC lines in oncology patients is feasible and does not pose unacceptable risk. Further research is indicated to determine subgroups which may be at greater risk of PICC related infections.

Neuropsychiatric Effects of Antiviral Drugs.

The adverse events of antiviral drugs are dose-dependent and often reversible. The nervous system is often affected and to date, many studies have been published regarding the central nervous system toxicity of antiviral agents. They may cause significant neuropsychiatric complications, which range from mild symptoms such as irritability and difficulty sleeping to severe complications such as depression, psychosis, and painful peripheral neuropathy, side effects which may necessitate discontinuation of treatment. The pathogenetic mechanisms may involve molecular targets common to other centrally active drugs, including human monoamine oxidase-A (MAO-A), serotonin receptors, gamma-aminobutyric acid (GABA) GABA-A receptors, 5-HT2A and 5-HT2C receptors and others. Notable examples include oseltamivir which may act as MAO inhibitor and efavirenz, which has an affinity for serotonin 5-HT2 and GABA-A receptors, the serotonin transporter, the MAO enzyme, and the vesicular monoamine transporter, with subjective effects which may be similar to those of the psychedelic hallucinogen lysergic acid diethylamide (LSD). Other antiviral drugs with prominent nervous system effects include nucleoside reverse transcriptase inhibitors, which are associated with the development of peripheral neuropathy after prolonged use (an effect strongly associated with older drugs which have since fallen into disfavor such as stavudine) and interferons, which may cause depression. Clinicians should be familiar with such adverse effects in order to recognise them promptly once they occur and manage them appropriately.

Prognosis of COVID-19: Changes in laboratory parameters.

INTRODUCTION: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) emerged in China and has become a global threat. Comparison of hematological parameters between mild and severe cases of SARS-CoV 2 is so far limited, but significant differences in parameters such as interleukin-6, d-dimers, glucose, fibrinogen and C-reactive protein have been already reported. PURPOSE: In this study we analyzed the changes observed in easily measured blood biomarkers in the patients and provided evidence of how these markers can be used as prognostic factors of the disease. METHODS: Demographic characteristics, detailed medical history, and laboratory findings of all enrolled SARS-CoV 2 infection positive patients who were referred to Patras University Hospital from the period of March 4th 2020 (when first confirmed case in Greece appeared in our hospital) until April 4th 2020 were extracted from electronic medical records and analyzed. RESULTS: We provided evidence that some very common laboratory values can be used as independent predictive factors in SARS-CoV 2 infection. Despite the retrospective nature of this study and the small number of subjects analyzed, we showed that NLR, LDH, d-dimers, CRP, fibrinogen and ferritin can be used early at the patient's first visit for SARS-CoV 2 infection symptoms and can predict the severity of infection. CONCLUSION: More studies are warranted to further objectively confirm the clinical value of prognostic factors related to SARS-CoV 2 and establish an easy-to-get panel of laboratory findings for evaluating the disease severity.

Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain.

Even though the early reports from China provided advance warning of what was to come, the COVID-19 pandemic has spread throughout the world with devastating consequences. Emergency measures are being implemented to reduce the magnitude of the public health crisis, prevent healthcare facilities from becoming overwhelmed and reduce the death toll of the disease. Containment strategies to mitigate viral transmission and emergency measures to increase the capacity of each country to provide intensive care are at the forefront of the public health management of the epidemic, even though the detrimental social and psychological effects of quarantine are evident on a global scale. Optimal management of critically ill patients with COVID-19 is also unclear, and the initial suggestion for early intubation as in typical ARDS may have caused significant harm. The management of mild cases of confirmed infection is another point of controversy, as drugs which may be repurposed for COVID-19 treatment have significant, potentially irreversible toxic effects and their use in mild cases of a viral illness which is typically self-limited may be harmful.

Intubation and mechanical ventilation of patients with COVID-19: what should we tell them?

Severe COVID-19 illness is characterised by the development of Acute Respiratory Distress Syndrome (ARDS), for which the mainstay of treatment is represented by mechanical ventilation. Mortality associated with ARDS due to other causes is in the range of 40-60%, but currently available data are not yet sufficient to draw safe conclusions on the prognosis of COVID-19 patients who require mechanical ventilation. Based on data from cohorts of the related coronavirus-associated illnesses, that is to say Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), prognosis would seem to be worse than ARDS due to other causes such as trauma and other infections. Discussion of prognosis is central to obtaining informed consent for intubation, but in the absence of definitive data it is not clear exactly what this discussion should entail.

Prevalence, Contribution to Disease Burden and Management of Comorbid Depression and Anxiety in Chronic Obstructive Pulmonary Disease: A Narrative Review.

Mental health issues such as depression and anxiety are common comorbidities of individuals suffering from chronic obstructive pulmonary disease (COPD), though they are frequently underdiagnosed and consequently undertreated. To that end we sought to identify the impact of co-morbid anxiety and depression in COPD patients and evaluate recent evidence regarding the management of such cases. A Pubmed search was conducted for relevant original articles with emphasis on the past 5 years. The studies we identified indicate that psychiatric comorbidity negatively impacts the prognosis of COPD, as it is associated with reduced adherence to treatment, reduced physical activity and a general reduction in quality of life, in turn leading to more frequent exacerbations and increased severity of exacerbations (which are more likely to require hospitalization), resulting in increased mortality. Despite the evidence showing a high prevalence and exceedingly negative impact of depression and anxiety in patients with COPD, very few clinical trials (for both pharmacological and psychological treatments) with small sample sizes have been conducted in this population. As treatment for co-morbid mental health conditions may reduce mortality, interventions to ensure prompt identification of mental health issues and subsequent initiation of treatment are warranted.

Review of the association between periodontitis and chronic obstructive pulmonary disease in smokers.

Both periodontitis and chronic obstructive pulmonary disease (COPD) are among the most common diseases associated with smoking. These conditions frequently present alongside comorbidities including diabetes, coronary heart disease, duodenal ulcer, deep vein thrombosis, pulmonary embolism, osteoporosis and muscle atrophy. Chronic inflammation contributes to the pathology of both periodontitis and COPD, and in patients suffering from both conditions treatment of periodontitis may lead to relief from COPD symptoms as well. Smoking contributes to the underlying pathophysiology by causing local inflammation, increasing the production of proinflammatory cytokines and most importantly, by locally increasing the activity of proteolytic enzymes which degrade the extracellular matrix in both periodontal and lung interstitial tissue. The increase in protease activity and extracellular matrix degradation may explain why periodontitis and COPD comorbidity is so common, a finding which also indicates that therapeutic interventions targeting protease activity and the inflammatory response may be beneficial for both conditions.

Treatment Options for Acute Agitation in Psychiatric Patients: Theoretical and Empirical Evidence.

Acute agitation is a common presenting symptom in the emergency ward and is also dealt with on a routine basis in psychiatry. Usually a symptom of an underlying mental illness, it is considered urgent and immediate treatment is indicated. The practice of treating agitation on an acute care basis is also referred to as rapid tranquilization. A variety of psychotropic drugs and combinations thereof can be used. The decision is usually made based on availability and the clinician's experience, with the typical antipsychotic haloperidol (alone or in combination with antihistaminergic and anticholinergic drugs such as promethazine), the benzodiazepines lorazepam, diazepam and midazolam as well as a variety of atypical antipsychotics being used for this purpose. Haloperidol is associated with extrapyramidal symptoms (which can be controlled by co-administration of promethazine) and may control agitation without inducing sedation, while benzodiazepines have a more pronounced sedating activity. The atypical antipsychotics aripiprazole and ziprasidone are better tolerated, while olanzapine is also a powerful sedative. Clinical trials evaluating the efficacy of different treatment options have been conducted but they are extremely heterogenous and most have numerous methodological flaws, leading to a poor overall quality of evidence upon which guidelines for the appropriate treatment could be based. The combination of haloperidol and promethazine, which combines the sedative properties of the antihistamine with the more selective calming action of haloperidol (with a reduced risk of extrapyramidal effects compared to haloperidol alone because of the anticholinergic properties of promethazine) may be the best choice based on empirical evidence.

Prevalence of Comorbid Chronic Obstructive Pulmonary Disease in Individuals Suffering from Schizophrenia and Bipolar Disorder: A Systematic Review.

The disease burden associated with schizophrenia and bipolar disorder is substantial, with affected individuals having a shorter life expectancy and a high risk of severe physical comorbid conditions. These individuals are more likely to smoke and have a longer smoking history compared to the general population. Furthermore, use of antipsychotic drugs has also been linked to active smoking. Chronic obstructive pulmonary disease (COPD) is a respiratory condition affecting elderly individuals with a long smoking history, so it would be expected that individuals suffering from major mental disorders may exhibit a higher prevalence of COPD compared to the general population. We searched the databases Pubmed and Scopus for observational studies of at least 200 patients including at least one group suffering from schizophrenia or bipolar disorder and a comparison group of individuals at risk of COPD. The initial search, along with the data extraction process and the risk of bias assessment were carried out independently by the two reviewers. Eight studies were included. The risk of bias was substantial as most studies did not adequately address confounding variables. A pooled analysis showed a greater likelihood of suffering from comorbid COPD compared with the general population both for schizophrenic (OR 1.573, 1.439-1.720) and bipolar individuals (OR 1.551, 1.452-1.658). Based on these findings, COPD is more common in individuals suffering from major mental illness compared to the general population. Further research is required to ascertain whether smoking is the only cause and develop strategies for the prevention of COPD in these high-risk groups.

Efficacy and tolerability of vilazodone for the acute treatment of generalized anxiety disorder: A meta-analysis.

PURPOSE: A systematic review and meta-analysis of all relevant randomized controlled trials was conducted to evaluate the safety and efficacy of vilazodone in the acute treatment of generalized anxiety disorder (GAD). METHODS: The literature was searched through all relevant databases in order to identify clinical trials on the use of vilazodone in the treatment of GAD. Once the trials were identified, data was extracted and analyzed using Revman5.3 and open meta-analyst. Assessment of continuous outcomes relied upon standardized mean difference, while binary outcomes were evaluated via relative risk, absolute risk reduction and NNT/NNH. RESULTS: A total of 3 well-designed randomized controlled trials with a duration of 10 weeks were conducted, with a total of 844 (intent to treat population) randomized to vilazodone (20-40mg, mean dose=31.42mg) and 618 to placebo. The study drug was significantly superior (p<0.001) to placebo in continuous primary outcome measures (HAMA reduction at week 8, CGI-S reduction at week 8 and CGI-I score at week 8). Binary outcome measures however are not as promising, probably reflecting a small effect size [NNT=10 (6.67, 21.28) for induction of response according to the HAMA scale and NNT=12 (7.58, 34.48) for the CGI-I scale], although statistical significance (p<0.01) was attained for both. The study drug was significantly (p<0.001) more likely than placebo to induce adverse effects and to be discontinued due to adverse effects NNH=14 (10.31, 22.22), most common of which were nausea and diarrhea. DISCUSSION: Vilazodone was superior to placebo in the short term treatment of GAD. However, due to the small effect size and high incidence of adverse events, the utility of vilazodone in the treatment of GAD remains unclear. Likelihood to be helped (HAMA response) or harmed (discontinuation due to adverse events) was inconclusive [1.4 (0.48, 3.33)], demonstrating a need for further trials and direct comparisons of vilazodone to the standard treatments for the disorder. Thus vilazodone cannot be recommended yet as a first line agent. CONCLUSION AND LIMITATIONS: Vilazodone is an effective treatment for generalized anxiety disorder, though further trials are required for a more adequate comparison with established treatments, as well as long term maintenance studies to determine the validity of claims regarding the absence of sexual side effects.

Neuropsychiatric Effects of Antimicrobial Agents.

Antimicrobial drugs used in clinical practice are selected on the basis of their selective toxicity against bacterial cells. However, all exhibit multiple offsite interactions with eukaryotic cell structures, resulting in adverse reactions during antimicrobial pharmacotherapy. A multitude of these side effects involve the nervous system as antimicrobials at clinically relevant concentrations seem to interact with many of the same molecules usually implicated in the action of psychotropic drugs. The importance of such events cannot be overstated, as the misdiagnosis of an adverse drug reaction as a symptom of a primary psychiatric or neurological disorder entails great suffering for the patient affected as well as significant costs for the healthcare system. The neuropsychiatric effects of antimicrobial drugs are extensively documented in the literature. A number of antimicrobial drugs have the potential to exert CNS effects and many are associated with stimulant, psychotomimetic and epileptogenic properties, mediated by GABA antagonism (beta-lactams, quinolones and clarithromycin), NMDA agonism (D-cycloserine, aminoglycosides, and perhaps quinolones), MAO inhibition (linezolid, metronidazole and isoniazid weakly) as well as more exotic mechanisms, as in the case of trimethoprim, isoniazid, ethambutol, rifampicin and the tetracyclines. While those effects are generally undesirable, they may also under certain circumstances be beneficial, and further research is warranted in that direction.

Effects of 5-HT-7 receptor ligands on memory and cognition.

The 5-HT7R is the most recently cloned serotonin receptor and thus one the least studied. Many drugs, experimental and in clinical use bind to 5-HT7 with high affinity, though their effects have yet to be clearly elucidated. Its physiological function, though not completely clear, is mostly associated with learning and memory, with both agonists and antagonists possessing subtle procognitive and promnesic properties. We consider it a promising area of research, though still in its infancy, which may one day lead to clinical benefits for patients with various afflictions characterised by cognitive dysfunction, particularily autism spectrum disorder, fragile X syndrome and Alzheimer's disease.