Delta Variant in the COVID-19 Pandemic: A Comparative Study on Clinical Outcomes Based on Vaccination Status.

BACKGROUND: As the global battle against the COVID-19 pandemic endures, the spread of the Delta variant has introduced nuanced challenges, prompting a nuanced examination. MATERIALS AND METHODS: We performed a multilevel logistic regression analysis encompassing 197 patients, comprising 44 vaccinated individuals (V group) and 153 unvaccinated counterparts (UV). These patients, afflicted with the Delta variant of SARS-CoV-2, were hospitalized between October 2021 and February 2022 at the COVID-19 department of a University Centre in Cluj-Napoca, Romania. We compared patient characteristics, CT lung involvement, Padua score, oxygen saturation (O2 saturation), ventilation requirements, dynamics of arterial blood gas (ABG) parameters, ICU admission rates, and mortality rates between the two groups. RESULTS: The UV group exhibited a statistically significant (p < 0.05) proclivity toward developing a more severe form of infection, marked by elevated rates of lung involvement, oxygen requirement, ICU admission, and mortality. CONCLUSION: Our findings underscore the substantial efficacy of the vaccine in diminishing the incidence of severe disease, lowering the rates of ICU admissions, and mitigating mortality among hospitalized patients.

The Role of Lung Microbiome in Fibrotic Interstitial Lung Disease-A Systematic Review.

Interstitial Lung Disease (ILD) involves lung disorders marked by chronic inflammation and fibrosis. ILDs include pathologies like idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), hypersensitivity pneumonitis (HP) or sarcoidosis. Existing data covers pathogenesis, diagnosis (especially using high-resolution computed tomography), and treatments like antifibrotic agents. Despite progress, ILD diagnosis and management remains challenging with significant morbidity and mortality. Recent focus is on Progressive Fibrosing ILD (PF-ILD), characterized by worsening symptoms and fibrosis on HRCT. Prevalence is around 30%, excluding IPF, with a poor prognosis. Early diagnosis is crucial for optimizing outcomes in PF-ILD individuals. The lung microbiome comprises all the microorganisms that are in the respiratory tract. Relatively recent research try to evaluate its role in respiratory disease. Healthy lungs have a diverse microbial community. An imbalance in bacterial composition, changes in bacterial metabolic activities, or changes in bacterial distribution within the lung termed dysbiosis is linked to conditions like COPD, asthma and ILDs. We conducted a systematic review of three important scientific data base using a focused search strategy to see how the lung microbiome is involved in the progression of ILDs. Results showed that some differences in the composition and quality of the lung microbiome exist in ILDs that show progressive fibrosing phenotype. The results seem to suggest that the lung microbiota could be involved in ILD progression, but more studies showing its exact pathophysiological mechanisms are needed.

Opioids in Treatment of Refractory Dyspnea in Chronic Obstructive Pulmonary Disease: Yes, No or Maybe.

Chronic Obstructive Pulmonary Disease (COPD) is a complex condition with significant impact on prognosis, especially in advanced stages where symptom burden becomes critical. Breathlessness affects patients' quality of life, and despite various therapeutic strategies, the role of opioids in palliative care for COPD remains under investigation. The acceptance of a therapeutic trial of different types of opioids is increasing not only in end-of-life situations but also for stable COPD patients experiencing intolerable refractory breathlessness despite optimal conventional therapy. Recent clinical trials have raised questions about the overall clinical benefit of opioids in addressing breathlessness in COPD, prompting the need to clarify inconsistencies and identify specific subgroups that may benefit from opioid therapy. In the clinical setting, it is crucial to understand the attributes of patients who exhibit positive responses to opioids and what type of opioids could have a positive impact. This research paper aims to offer an update of the most recent evidence of opioid treatment in managing breathlessness among individuals with COPD with a head-to-head evaluation of the supporting and opposing proof in the medical literature.

Laboratory Diagnostics Accuracy for COVID-19 versus Post-COVID-19 Syndrome in Lung Disease Patients with Multimorbidity.

The laboratory tests and identification of risk factors such as comorbidities are essential in the management, treatment and prognosis of patients with chronic respiratory diseases. Performing rigorous monitoring among patients with post-COVID-19 syndrome and early identification of risk factors associated with poor prognosis are crucial in improving patient outcomes. In the present study, 182 patients diagnosed with COVID-19 and PCI during 2020-2022 were included. A clinical and epidemiological evaluation was performed for each patient. Laboratory tests at admission included complete blood count, Erythrocyte Sedimentation Rate (ESR) and biochemical tests. Receiver operating curve (ROC) and area under the curve (AUC) were calculated to compare the diagnostic performance of each parameter. Regarding comorbidities, arterial hypertension, diabetes mellitus and obesity were the most frequent ones. In the case of chronic lung diseases, asthma and Chronic Obstructive Pulmonary Disease (COPD) were the most frequent. Pleurisy was found especially in patients with PCI Variations in serum LDH values were observed, especially in severe forms of COVID-19 in 2020, with a mean value of 481.44 U/L, compared to patients with PCI, whose mean values (122 U/L) were within the biological range of reference. High neutrophil/lymphocyte ratio (NLR) values quantified in this study were especially associated with moderate and severe forms of COVID-19 and also PCI. The Spearman correlation coefficient was determined to measure the correlations between the clinical parameters of all investigated subjects. A value of p < 0.05 was considered statistically significant. The statistical results indicated that serum lactate dehydrogenase (LDH), glucose and C-reactive protein (CRP) are sensitive markers with a diagnostic role in COVID-19, and lymphocyte (Ly) count, CRP, ESR and glucose were evidenced to be target markers in PCI. LDH values were observed to be statistically significant (p < 0.005) in patients with COVID-19 and obesity evaluated in 2021, while Ly count was statistically significant (p = 0.05) in patients with PCI and arterial hypertension. Regarding comorbidities, it has been observed that obesity, arterial hypertension and cardiovascular diseases represent risk factors in COVID-19/PCI, associated especially with the severe forms of the disease.

Non-Pharmacological Intervention for Personalizing Sleep Quality through Gentle Rocking Motion.

INTRODUCTION: Achieving restorative sleep is crucial for overall well-being, yet sleep difficulties affect a substantial portion of the adult population. Sleep disturbances are associated with diminished quality of life, physical complaints, cognitive impairment, and emotional regulation challenges. OBJECTIVE: This study explores the influence of an innovative experimental bed designed to generate rocking motions on sleep parameters. METHODS: A prospective observational study enrolled 60 adult participants, assessing their sleep on a regular stationary bed and the Inoveris bed, providing gentle rocking movements. Polysomnography was conducted, recording electroencephalography, electrooculogram, electromyogram, respiratory effort, and other parameters. RESULTS: The rocking bed significantly increased total sleep time (TST) and reduced N1 sleep stage duration (p < 0.001). Participants also experienced a quicker transition to the N2 sleep stage (p = 0.01), indicative of a faster shift from wakefulness to deeper sleep. Additionally, rocking led to a higher percentage of N1 sleep stages (p = 0.01) and a significant increase in N3 sleep stage duration (p = 0.004). While some results lacked statistical significance, notable trends in the rocking bed group have clinical relevance, consistently improving sleep parameters, including increased TST. The rocking bed also showed a trend towards higher sleep efficiency (SE) and sleep duration percentage, hinting at a potential overall enhancement in sleep quality. CONCLUSION: This study contributes valuable insights into the potential benefits of rocking motions on sleep architecture. Despite variations in outcomes across studies, our results underscore the potential of rocking beds as a non-pharmacological intervention for enhancing sleep quality. Notable improvements in total sleep time (TST), N1 sleep stage reduction, and accelerated transitions to deeper sleep stages highlight the clinical relevance of rocking interventions. Further research, collaboration, and addressing the identified limitations will advance our understanding of the therapeutic applications of rocking motions in sleep science.

COVID-19 "Nightmare": Perceived Stress, Emotional Distress, and Burnout Syndrome among Medical Staff after One Year of the COVID-19 Pandemic.

(1) After one year of treating patients with SARS-CoV-2 infection, physical exhaustion is added to emotional stress and burnout syndrome. (2) By applying specific questionnaires, we evaluated healthcare workers who handled patients infected with SARS-CoV-2in terms of disease perception, perceived stress, emotional distress, and burnout syndrome after one year of the COVID-19 pandemic and compared them with staff who did not handle infected patients. (3) A total of 165 persons were evaluated, with 79 working in the COVID-19 department and 86 working in the non-COVID-19 department. No statistically significant differences were found in the perceived stress scores, emotional distress (functional or dysfunctional), and disease perception among the COVID-19 and non-COVID-19 groups. Also, we did not find any differences between the COVID-19 and non-COVID-19 departments concerning their total Maslach scores-50 in the COVID-19 department and 51 in the non-COVID-19 department, p = 0480-so a moderate level of burnout in the two groups. The only statistical difference was in the Maslach depersonalization scores, which were higher among COVID-19 workers (p = 0.024). (4) In our center, there was no statistically significant difference in perceived stress or emotional distress. The level of burnout syndrome seems to be the same among the two groups, regardless if they worked withCOVID-19-infected patients or not.

IL-6 and Neutrophil/Lymphocyte Ratio as Markers of ICU Admittance in SARS-CoV-2 Patients with Diabetes.

Inflammation along with coagulation disturbances has an essential role in the evolution towards a severe disease in patients with the coronavirus disease 2019 (COVID-19). This study aimed to evaluate inflammatory and coagulation biomarkers when predicting the need to visit an intensive care unit (ICU) in diabetes mellitus (DM) patients. In a retrospective study, laboratory parameters were examined for 366 participants: ICU = 90, of which 44 patients had DM and no ICU admittance = 276. The ability of inflammatory and coagulation markers to distinguish the severity of COVID-19 was determined using univariate and multivariate regression analysis. In all patients, lactate dehydrogenase was the only predictor for ICU admittance in the multivariate analysis. In the DM group, the results showed that the interleukin (IL)-6 and neutrophil/lymphocyte ratio (NLR) values at admission could predict the need for ICU admittance. Even though there were significant differences between the ICU and no ICU admittance groups regarding the coagulation markers, they could not predict the severity of the disease in DM patients. The present study showed for the first time that the IL-6 and NLR admission values could predict ICU admittance in DM patients. This finding could help clinicians manage the infection more easily if the COVID-19 pandemic strikes again.

Prognosis Predictive Markers in Patients with Chronic Obstructive Pulmonary Disease and COVID-19.

Some studies have reported that chronic respiratory illnesses in patients with COVID-19 result in an increase in hospitalization and death rates, while other studies reported to the contrary. The present research aims to determine if a predictive model (developed by combing different clinical, imaging, or blood markers) could be established for patients with both chronic obstructive pulmonary disease (COPD) and COVID-19, in order to be able to foresee the outcomes of these patients. A prospective observational cohort of 165 patients with both diseases was analyzed in terms of clinical characteristics, blood tests, and chest computed tomography results. The beta-coefficients from the logistic regression were used to create a score based on the significant identified markers for poor outcomes (transfers to an intensive care unit (ICU) for mechanical ventilation, or death). The severity of COVID-19, renal failure, diabetes, smoking status (current or previous), the requirement for oxygen therapy upon admission, high lactate dehydrogenase (LDH) and C-reactive protein level (CRP readings), and low eosinophil and lymphocyte counts were all identified as being indicators of a poor prognosis. Higher mortality was linked to the occurrence of renal failure, the number of affected lobes, the need for oxygen therapy upon hospital admission, high LDH, and low lymphocyte levels. Patients had an 86.4% chance of dying if their mortality scores were -2.80 or lower, based on the predictive model. The factors that were linked to a poor prognosis in patients who had both COPD and COVID-19 were the same as those that were linked to a poor prognosis in patients who had only COVID-19.

An Overview of the Factors Involved in Biofilm Production by the Enterococcus Genus.

Enterococcus species are known for their ability to form biofilms, which contributes to their survival in extreme environments and involvement in persistent bacterial infections, especially in the case of multi-drug-resistant strains. This review aims to provide a comprehensive understanding of the mechanisms underlying biofilm formation in clinically important species such as Enterococcus faecalis and the less studied but increasingly multi-drug-resistant Enterococcus faecium, and explores potential strategies for their eradication. Biofilm formation in Enterococcus involves a complex interplay of genes and virulence factors, including gelatinase, cytolysin, Secreted antigen A, pili, microbial surface components that recognize adhesive matrix molecules (MSCRAMMs), and DNA release. Quorum sensing, a process of intercellular communication, mediated by peptide pheromones such as Cob, Ccf, and Cpd, plays a crucial role in coordinating biofilm development by targeting gene expression and regulation. Additionally, the regulation of extracellular DNA (eDNA) release has emerged as a fundamental component in biofilm formation. In E. faecalis, the autolysin N-acetylglucosaminidase and proteases such as gelatinase and serin protease are key players in this process, influencing biofilm development and virulence. Targeting eDNA may offer a promising avenue for intervention in biofilm-producing E. faecalis infections. Overall, gaining insights into the intricate mechanisms of biofilm formation in Enterococcus may provide directions for anti-biofilm therapeutic research, with the purpose of reducing the burden of Enterococcus-associated infections.

The Management of Obstructive Sleep Apnea Patients during the COVID-19 Pandemic as a Public Health Problem-Interactions with Sleep Efficacy and Mental Health.

With the onset of the COVID-19 outbreak, it was stipulated that patients with obstructive sleep apnea (OSA) may have a greater risk of morbidity and mortality and may even experience changes in their mental health. The aim of the current study is to evaluate how patients managed their disease (sleep apnea) during the COVID-19 pandemic, to determine if continuous positive airway pressure (CPAP) usage changed after the beginning of the pandemic, to compare the stress level with the baseline, and to observe if any modifications are related to their individual characteristics. The present studies highlight the level of anxiety, which was high among patients with OSA during the COVID-19 pandemic (p < 0.05), with its influence on weight control (62.5% of patients with high levels of stress gained weight) and sleep schedule (82.6% reported a change in sleep schedule). Patients with severe OSA and high levels of stress increased their CPAP usage (354.5 min/night vs. 399.5 min/night during the pandemic, p < 0.05). To conclude, in OSA patients, the presence of the pandemic led to a greater level of anxiety, changes in sleep schedule and weight gain because of job loss, isolation, and emotional changes, influencing mental health. A possible solution, telemedicine, could become a cornerstone in the management of these patients.

Assessment of Some Risk Factors and Biological Predictors in the Post COVID-19 Syndrome in Asthmatic Patients.

Long COVID-19 or post-COVID infection (PCI) refers to the prolongation of symptoms in people who have been infected with the SARS-CoV-2 virus. Some meta-analysis studies have shown that patients with comorbidities, such as diabetes, obesity or hypertension, have severe complications after infection with the SARS-CoV-2 virus. The presence of chronic respiratory diseases such as bronchial asthma, COPD, pulmonary hypertension or cystic fibrosis increases the risk of developing severe forms of the COVID-19 disease. The risk of developing the severe form of COVID-19 was observed in patients with bronchial asthma being treated with corticosteroids, but also in those hospitalized with severe asthma. The biological variables determined in patients with PCI infection showed changes, especially in the hematological parameters, but also in some inflammatory markers. The aim of this study was to investigate some biological predictors in post-COVID-19 infection in patients with asthma and various comorbidities. In the case of patients diagnosed with moderate and severe forms of COVID-19, the variation in biological tests has shown high concentrations for serum glucose, lactate dehydrogenase and C-reactive protein. Additionally, the calculation of the relative risk (RR) based on the associated comorbidities in patients with PCI points to higher values for patients with asthma, hypertension, diabetes and obesity (RR moderate/severe form = 0.98/1.52), compared to patients with PCI and asthma (RR moderate/severe form = 0.36/0.63). Based on the statistical results, it can be concluded that the alanine aminotransferase (ALT) activity (p = 0.006) and the age of patients (p = 0.001) are the variables that contribute the most to the separation of the four classes of comorbidities considered.

Gastrointestinal microbiota: A predictor of COVID-19 severity?

Coronavirus disease 2019 (COVID-19), caused by a severe acute respiratory syndrome coronavirus 2 infection, has raised serious concerns worldwide over the past 3 years. The severity and clinical course of COVID-19 depends on many factors (e.g., associated comorbidities, age, etc) and may have various clinical and imaging findings, which raises management concerns. Gut microbiota composition is known to influence respiratory disease, and respiratory viral infection can also influence gut microbiota. Gut and lung microbiota and their relationship (gut-lung axis) can act as modulators of inflammation. Modulating the intestinal microbiota, by improving its composition and diversity through nutraceutical agents, can have a positive impact in the prophylaxis/treatment of COVID-19.

The role of 3D speckle tracking echocardiography in the diagnosis of obstructive sleep apnea and its severity.

There is a consistent relationship between obstructive sleep apnea (OSA) and cardiovascular diseases. It is already recognized that OSA may influence the geometry and function of the right ventricle (RV). This has encouraged the development of echocardiographic evaluation for screening of OSA and its severity. Three-dimensional speckle tracking echocardiography (3D STE) is in assumption better, compared with 2D STE, because it overcomes the standard 2D echo limitations. Thus, the purpose of our study is to evaluate whether 3D STE measurements, could predict the positive diagnosis and severity of OSA. We enrolled 69 patients with OSA and 37 healthy volunteers who underwent a cardiorespiratory sleep study. 2DE was performed in all patients. RVEF and 3D RVGLS were measured by 3DSTE. NT pro BNP plasma level was also assessed in all participants. 3D RV GLS (- 13.5% vs. - 22.3%, p < 0.001) and 3D RVEF (31.9% vs. 50%, p < 0.001) were reduced in patients with OSA, compared with normal individuals. 3D Strain parameters showed better correlation to standard 2D variables, than 3D RVEF. Except for NT pro BNP (p = 0.059), all parameters served to distinguish between severe and mild-moderate cases of OSA. 3D STE may be a reliable and accurate method for predicting OSA. Consequently, 3D RV GLS is a good tool of assessing the RV global function in OSA, because it correlates well with other established measurements of RV systolic function. Furthermore, 3D RV GLS was a precise parameter in identifying severe cases of OSA, while NT pro BNP showed no association.

Therapeutic Efficacy and Outcomes of Remdesivir versus Remdesivir with Tocilizumab in Severe SARS-CoV-2 Infection.

The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated many challenges to find an effective drug combination for hospitalized patients with severe forms of coronavirus disease 2019 (COVID-19) pneumonia. We conducted a retrospective cohort study, including 182 patients with severe COVID-19 pneumonia hospitalized between March and October 2021 in a Pneumology Hospital from Cluj-Napoca, Romania. Among patients treated with standard of care, 100 patients received remdesivir (R group) and 82 patients received the combination of remdesivir plus tocilizumab (RT group). We compared the clinical outcomes, the inflammatory markers, superinfections, oxygen requirement, intensive care unit (ICU) admission and mortality rate before drug administration and 7 days after in R group and RT group. Borg score and oxygen support showed an improvement in the R group (p < 0.005). Neutrophiles, C-reactive protein (CRP) and serum ferritin levels decreased significantly in RT group but with a higher rate of superinfection in this group. ICU admission and death did not differ significantly between groups. The combination of remdesivir plus tocilizumab led to a significantly improvement in the inflammatory markers and a decrease in the oxygen requirement. Although the superinfection rate was higher in RT group than in R group, no significant difference was found in the ICU admission and mortality rate between the groups.

Predictors of New-Onset Diabetes in Hospitalized Patients with SARS-CoV-2 Infection.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is one of the world's most disruptive health crises. The presence of diabetes plays an important role in the severity of the infection, and a rise in newly diagnosed diabetes cases has been identified. The aim of this retrospective study was to determine the incidence of new-onset diabetes (NOD) and predictive factors with their cut-off values for patients hospitalized with COVID-19. All patients (n = 219) hospitalized for COVID-19 during three consecutive months were included. NOD was diagnosed in 26.48% of patients. The severity of the infection, hospital admission values for fasting plasma glucose, lactate dehydrogenase (LDH), PaO2/FiO2 ratio, the peak values for leucocytes, neutrophils, C-reactive protein, triglycerides, and the need for care in the intensive care unit were predictors for the occurrence of NOD in univariate analysis, while only LDH level remained a significant predictor in the multivariable analysis. In conclusion, the results of the study showed a high incidence of NOD in patients hospitalized with COVID-19 and identified LDH levels at hospital admission as a significant predictor of NOD during SARS-CoV-2 infection. However, the persistence of NOD after the COVID-19 infection is not known, therefore, the results must be interpreted with caution.

Change in Neuroticism and Extraversion among Pre-University Education Employees during the COVID-19 Pandemic.

Background and objectives: Since the first reports of SARS-CoV-2 infection cases in China, the virus has rapidly spread to many countries, including Romania. In Romania, schools were closed in March 2020 to prevent the virus from spreading; since then, they have been sporadically opened, but only for a short time. Teachers had to adopt online education methods, experiencing real difficulties in their attempts to maintain high-quality teaching, as a result of social distancing from students and colleagues. The current study aimed to evaluate the burden on the neuroticism states of employees in the pre-university education system during the COVID-19 pandemic. Materials and Methods: A prospective study was conducted, in which personality trait data from 138 employees were collected via a questionnaire (EPI, Eysenck Personality Inventory), which measured extraversion-introversion and neuroticism scores before and during the COVID-19 pandemic. Initially, 150 subjects were invited to participate in the study, although 12 of them refused to participate. Based on the questionnaire not being fully filled in a further three subjects were excluded from the study, leaving a total of 135, of which 115 were woman and 20 were men. Results: The results demonstrate that the subjects included in the study expressed higher neuroticism during the COVID-19 pandemic than in the pre-pandemic period. This change could promote more stress and depression symptoms. Subjects with high school education had significantly lower neuroticism scores over time than those with university education (p = 0.006). Furthermore, we found extraversion scores to be statistically significant in our population (p = 0.022). Conclusion: The gender and living environment of the teachers were not significantly associated with the reduction in the extraversion score, but were more frequently found among older persons and in subjects without higher education. Subjects of Hungarian ethnicity had lower extraversion scores than those of Romanian ethnicity.

Obesity Impact on SARS-CoV-2 Infection: Pros and Cons "Obesity Paradox"-A Systematic Review.

BACKGROUND: During the last years, the COVID-19 pandemic meets the pandemic generated by obesity, raising many questions regarding the outcomes of those with severe forms of infection. METHODS: The present systematic review summarises and analyses the data providing evidence for or against the "obesity-paradox" in COVID-19 patients. After applying the inclusion and exclusion criteria, 23 studies were included. We also analysed the presumably underlying basic mechanisms. RESULTS: The patients with a body mass index (BMI) of 30-40 kg/m2 presented severe symptoms that led to intensive care unit (ICU) admission but not increased death rate. Those with a higher degree of obesity, with a BMI higher than 40 kg/m2, led to a rise in the death rate, particularly in young patients. Obesity was associated with a higher rate of ICU admission but was not determined as an independent predictor of increased mortality. In contrast, some studies suggest a strong association between obesity or morbid obesity and the risk of death. CONCLUSIONS: The existence of "obesity-paradox" cannot be stated; our study presents obesity as a critical risk factor in the evolution of COVID-19.

Multivariate Analysis of the Predicted Probability of Smoking Behavior of Foster Care Minors: Results of a Study from Romania.

BACKGROUND: There are a multitude of factors that influence smoking status, and minors from the social protection system are a vulnerable category in terms of smoking. METHODS: The objective of this research was to assess the degree of smoking dependence and to identify potential predictors of smoking status in foster care teenagers. Smoker status was confirmed by dosing CO in the exhaled air, and the degree of dependence was assessed using the Fagerström score. We performed a multivariate logistic regression analysis. RESULTS: From the 275 foster care minors, 22.5% were current smokers. Exhaled CO was not influenced by general demographic factors, was associated with the frequency of smoking, and was positively correlated with the estimated number of cigarettes consumed daily and with the Fagerström score. The calculated probability of being a smoker was less than 20.4% in 75% of nonsmokers, whereas 75% of actual smokers had a predicted probability higher than 30.3%. CONCLUSIONS: In addition to age, gender, social environment, previous exposure to secondhand smoking, and residential type of foster care system, the expressed opinions regarding the health effects of tobacco use were associated with smoking in foster care teenagers.

An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance.

Implementation of precision medicine in lung cancer has benefited from intense research in the past years, developing subsequently an improved quality of life and increased overall survival of the patients. Targeted therapy has become one of the most important therapeutic innovations for the non-small cell lung cancer (NSCLC) category with anaplastic lymphoma kinase (ALK) gene rearrangement. The aim of this review is to provide a through overview of the main molecules of ALK tyrosine kinase inhibitors (TKI) with their general and particular mechanisms of resistance, the main methods of ALK gene detection, each with advantages and limits and the future perspectives currently under research which try to overcome the mechanisms of resistance. We have used two of the most reliable medical databases EMBASE and PubMed to properly select the latest and the most relevant articles for this topic. Encouraged by the promising results, the clinical practice was enriched by the approval of tyrosine kinase inhibitor molecules, three generations being developed, each one with more powerful agents than the previous ones. Unfortunately, the resistance to TKI eventually occurs and it may be induced by several mechanisms, either known or unknown. Crizotinib was the most intensely studied TKI , becoming the first molecule approved into clinical practice and although four other drugs have been broadly used (alectinib, ceritinib, brigatinib and lorlatinib) it seems that even the most recently developed one remains imperfect due to the resistance mutations that developed. There are two types of resistance generally described for the entire class and for the particular drugs, but half of them remain unknown.

Increased Vascular Endothelial Growth Factor Serum Level and the Role of +936C/T Gene Polymorphism in Chronic Obstructive Pulmonary Disease.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) represents a debilitating disease, with rising morbidity and mortality. Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis, vascular permeability, and airway remodeling. The purpose of this study was to investigate the relationship between VEGF serum levels and VEGF +936 C/T gene polymorphism (rs3025039) with COPD, for the first time in a Romanian population. Materials and Methods: In total, 120 participants from Transylvania were included in this case-control study. Serum levels of VEGF were determined using an enzyme-linked immune-sorbent assay and rs3025039 was investigated by high molecular weight genomic deoxyribonucleic acid (DNA). Spirometric values, arterial blood gas analysis, and the Six Minute Walk Test (6MWT) outcome were also determined. Results: The serum level of VEGF was higher in the COPD group versus controls (p < 0.001), with a positive correlation with the 6MWT outcome. No significant difference was observed in the VEGF serum levels between VEGF +936C/T genotypes. There was no difference in the VEGF +936C/T genotype between COPD patients and healthy subjects (chi2 test p = 0.92, OR = 1.04, 95%CI = 0.41-2.62), but the presence of the T allele was significantly linked to the presence of COPD (chi2 test p = 0.02, OR = 2.36, 95%CI = 1.12-4.97). Conclusions: Higher VEGF serum levels were found in moderate and severe COPD and were positively correlated with the distance in the 6MWT. No significant difference was found between CC, CT, and TT genotypes of rs3025039 and the presence of COPD. The presence of the T allele was found to be linked to COPD and also to the degree of airway obstruction.