Effects of Ketamine Infusion on Oxygenation in Patients with Chronic Obstructive Pulmonary Disease Undergoing Lung Cancer Surgery.

OBJECTIVE: Ketamine changes respiratory mechanics, provides airway relaxation, and alleviates bronchospasm in patients with pulmonary disease. This study investigated the effect of a continuous infusion of ketamine during thoracic surgery on arterial oxygenation (PaO2/FiO2) and the shunt fraction (Qs/Qt) in patients with chronic obstructive pulmonary disease. METHODS: Thirty patients older than 40 years, diagnosed with chronic obstructive pulmonary disease, and undergoing lobectomy were recruited for this study. Patients were allocated randomly to 1 of 2 groups. At the induction of anaesthesia, group K received intravenous (iv) 1 mg kg-1 ketamine as a bolus and followed by 0.5 mg kg-1 h-1 infusion until the end of the operation. Group S received the same amount of 0.9% saline as a bolus at induction and followed by a 0.5-mL kg-1 h-1 infusion of 0.9% saline until the end of the operation. PaO2 and PaCO2 values, FiO2 levels, PaO2/FiO2 ratio, peak airway pressure (Ppeak), plateau airway pressure (Pplat), dynamic compliance, and shunt fraction (Qs/Qt) were recorded during two-lung ventilation as a baseline and at 30 (one-lung ventilation, OLV-30) and 60 (OLV-60) minutes during one-lung ventilation. RESULTS: PaO2, PaCO2, PaO2/FiO2 values, and Qs/Qt ratio were similar between the 2 groups at OLV-30 minute (P = .36, P = .29, P = .34). However, at OLV-60 minute, PaO2, PaO2/FiO2 values were significantly increased, and Qs/Qt ratios were significantly decreased in group K than in group S (P = .016, P = .011, P = .016). CONCLUSIONS: Our data suggest that a continuous infusion of ketamine and desflurane inhalation in patients with chronic obstructive pulmonary disease during one-lung ventilation increase arterial oxygenation (PaO2/FiO2) and decrease shunt fraction.

Safety of an Inactivated SARS-CoV-2 Vaccine Among Healthcare Workers in Turkey: An Online Survey

Background: As vaccination against coronavirus disase-19 (COVID-19) evolves, hesitancy has become a problematic issue that has gradually spread worldwide. The main reason for vaccine hesitancy is uncertainties about vaccine side effects. Aims: To evaluate the safety of an inactivated COVID-19 vaccine, CoronaVac, and determine the risk factors of emergence of side effects. Study Design: Cross-sectional study. Methods: An online questionnaire was administered via the internet to healthcare workers who received one or two doses of CoronaVac. The online survey consisted of three sections detailing sociodemographic data, COVID-19 history, and post-vaccine side effects. Side effects that occurred in the period starting from immediately after the first vaccination to the end of the 14th day after the second vaccination were recorded. Results: A total of 1628 healthcare workers responded to the online survey. Of these, 24.3% had a side effect either after the first or second dose of CoronaVac. Redness and/or pain at the inoculation site, headache, muscle and joint pains, palpitations, and dizziness were the most common side effects. Female sex, age <50 years, and thyroid disorder in the pre-vaccine period were found to be risk factors for the emergence of side effects. Blood pressure control could not be achieved in 2.2% of participants despite medication use, and permanent medication was needed in 2.5% of participants for blood pressure control. Conclusion: Almost a quarter of healthcare workers have at least one side effect after the first or second dose of CoronaVac. Female gender, age <50 years, and thyroid disorder appear to be risk factors for the occurrence of side effects.

Adulthood asthma as a consequence of childhood adversity: a systematic review of epigenetically affected genes.

There is an accumulating data that shows relation between childhood adversity and vulnerability to chronic diseases as well as epigenetic influences that in turn give rise to these diseases. Asthma is one of the chronic diseases that is influenced from genetic regulation of the inflammatory biomolecules and therefore the hypothesis in this research was childhood adversity might have caused epigenetic differentiation in the asthma-related genes in the population who had childhood trauma. To test this hypothesis, the literature was systematically reviewed to extract epigenetically modified gene data of the adults who had childhood adversity, and affected genes were further evaluated for their association with asthma. PRISMA guidelines were adopted and PubMed and Google Scholar were included in the searched databases, to evaluate epigenetic modifications in asthma-related genes of physically, emotionally or sexually abused children. After retrieving a total of 5245 articles, 36 of them were included in the study. Several genes and pathways that may contribute to pathogenesis of asthma development, increased inflammation, or response to asthma treatment were found epigenetically affected by childhood traumas. Childhood adversity, causing epigenetic changes in DNA, may lead to asthma development or influence the course of the disease and therefore should be taken into account for the prolonged health consequences.

Slug and Vimentin downregulation at the metastatic site is associated with Skip-N2 metastasis of lung adenocarcinoma.

OBJECTIVE: Lung cancer displays heterogeneity both in the tumor itself and in its metastatic regions. One interesting behavior of the tumor is known as Skip N2 metastasis, which N2 lymph nodes contain tumor cells while N1 are clean. In this study, mRNA levels of epithelial mesenchymal transition (EMT) related genes in skip N2 and normal N2 involvements of non-small cell lung cancer tissues were investigated to evaluate the possible molecular background that may contribute to the pathogenesis of Skip N2 metastasis. MATERIALS AND METHODS: Eighty-three surgically resected and paraffin embedded lymph node samples of lung cancer patients were analyzed in this study, which 40 of them were Skip N2. N2 tissues were sampled from 50% tumor containing areas and total RNA was extracted. mRNA levels for 18S, E-cadherin, Vimentin, ZEB1 and SLUG were analyzed via qPCR and E-cadherin and vimentin protein levels via immunohistochemistry (IHC). Bioinformatic analysis were adopted using online datasets to evaluate significantly co-expressed genes with SLUG in lung cancer tissue samples. RESULTS: Skip-N2 patients who had adenocarcinoma subtype had better survival rates. Comparative analysis of PCR results indicated that Skip N2 tumor tissues had increased E-Cadherin/Vimentin ratio and ZEB1 mRNA expression, and significantly decreased levels of SLUG. E-cadherin IHC staining were higher in Skip N2 and Vimentin were in Non-Skip N2. TP63 had a strong correlation with SLUG expression in the bioinformatics analyses. CONCLUSION: The results indicate that, at molecular level, Skip N2 pathogenesis has different molecular background and regulation of SLUG expression may orchestrate the process.

COVID-19 patients' sera induce epithelial mesenchymal transition in cancer cells.

Covid-19 Pneumonia of SARS-CoV-2 pandemic infection, persists to have high disease burden especially in cancer patients. Increased inflammation and thromboembolic processes are blamed to influence cancer patients more than the others but due to lack of knowledge regarding the pathophysiology of the both the virus itself and the response of the host, more basic and translational disease modeling research is needed to understand Cancer-Covid-19 interaction. In this study, serum samples from the patients, who were hospitalized due to Covid-19 pneumonia, applied to different cancer cells and cytotoxicity, motility, proliferation and gene expression analysis were performed. Serum samples derived from healthy volunteers and the fetal bovine serum that is used regularly in cell culture experiments used as controls. Hospitalized Covid-19 patients who had also cancer, were retrospectively screened, and their clinical course were recorded. Overall 12 Patient (PS) and 4 healthy serums (CS) were included in the experiments. PS applied cells showed increased motility in A549 cells as well as lost cell to cell connection in MCF7 and HCT116 cells, and induced expression of VIM, ZEB1 and SNAIL2 mRNA levels. Eight cancer diagnosed patients who were hospitalized due to Covid-19 between April and September 2020 were also reviewed retrospectively, which 5 of them were dead during SARS-CoV-2 infection. Thorax CT images of the 2 patients showed increased metastatic nodules in the lungs as of January 2021. The results of the study indicate that metastasis may be one of the prolonged consequences of COVID-19 pandemic in cancer sufferers.

Predictive value of plasma copeptin level for diagnosis and mortality of pulmonary embolism.

OBJECTIVE: Early diagnosis and risk stratification may provide a better prognosis in pulmonary embolism (PE). Copeptin has emerged as a valuable predictive biomarker in various cardiovascular diseases. The aim of this study was to determine the levels of copeptin in patients with acute PE and to evaluate its relationship with disease severity and PE-related death. METHODS: Fifty-four patients and 60 healthy individuals were included in this study. Copeptin concentrations and right ventricular dysfunction were analyzed. The correlation between copeptin levels and hemodynamic and echocardiographic parameters was examined. After these first measurements, patients were evaluated with PE-related mortality at the one-year follow-up. RESULTS: The copeptin levels were higher in PE patients than in the control group (8.3 ng/mL vs 3.8 ng/mL, p<0.001). Copeptin levels were found to be significantly higher in patients with PE-related death and right ventricular dysfunction (10.2 vs 7.5 ng/ml, p=0.001; 10.5 vs 7.5 ng/ml, p=0.002, respectively). When the cut-off value of copeptin was ≥5.85, its sensitivity and specificity for predicting PE were 71.9% and 85.0%, respectively (AUC=0.762, 95% CI=0.635-0.889, p<0.001). CONCLUSIONS: The copeptin measurement had moderate sensitivity and specificity in predicting the diagnosis of PE, and the copeptin level was significantly higher in patients with PE-related death at the one-year follow-up. Copeptin may be a useful new biomarker in predicting diagnosis, risk stratification, and prognosis of PE.

Predictive value of plasma copeptin level for diagnosis and mortality of pulmonary embolism

SUMMARY OBJECTIVE: Early diagnosis and risk stratification may provide a better prognosis in pulmonary embolism (PE). Copeptin has emerged as a valuable predictive biomarker in various cardiovascular diseases. The aim of this study was to determine the levels of copeptin in patients with acute PE and to evaluate its relationship with disease severity and PE-related death. METHODS: Fifty-four patients and 60 healthy individuals were included in this study. Copeptin concentrations and right ventricular dysfunction were analyzed. The correlation between copeptin levels and hemodynamic and echocardiographic parameters was examined. After these first measurements, patients were evaluated with PE-related mortality at the one-year follow-up. RESULTS: The copeptin levels were higher in PE patients than in the control group (8.3 ng/mL vs 3.8 ng/mL, p<0.001). Copeptin levels were found to be significantly higher in patients with PE-related death and right ventricular dysfunction (10.2 vs 7.5 ng/ml, p=0.001; 10.5 vs 7.5 ng/ml, p=0.002, respectively). When the cut-off value of copeptin was ≥5.85, its sensitivity and specificity for predicting PE were 71.9% and 85.0%, respectively (AUC=0.762, 95% CI=0.635-0.889, p<0.001). CONCLUSIONS: The copeptin measurement had moderate sensitivity and specificity in predicting the diagnosis of PE, and the copeptin level was significantly higher in patients with PE-related death at the one-year follow-up. Copeptin may be a useful new biomarker in predicting diagnosis, risk stratification, and prognosis of PE.

RESUMO OBJETIVO: O diagnóstico precoce e a estratificação de risco podem proporcionar um melhor prognóstico em casos de embolia pulmonar (EP). A copeptina surgiu como um valioso biomarcador preditivo de várias doenças cardiovasculares. O objetivo deste estudo é determinar os níveis de copeptina em pacientes com EP aguda e avaliar a sua relação com a severidade da doença e mortes relacionadas à EP. MÉTODOS: Um total de 54 pacientes e 60 indivíduos saudáveis foram incluídos neste estudo. As concentrações de copeptina e disfunções ventriculares direitas foram analisadas. A correlação entre os níveis de copeptina e parâmetros ecocardiográficos e hemodinâmicos foi examinada. Após essas primeiras medições, os pacientes foram avaliados em relação à mortalidade relacionada à EP após um ano. RESULTADOS: Os níveis de copeptina foram maiores em pacientes com EP do que no grupo de controle (8,3 ng/mL vs 3,8 ng/mL, p<0,001). Os níveis de copeptina eram significativamente maiores em pacientes com mortes relacionadas à EP e disfunção ventricular direita (10,2 vs 7,5 ng/ml, p=0,001; 10,5 vs 7,5 ng/ml, p=0,002, respectivamente). Com um valor de corte ≥5,85 para a copeptina, sua sensibilidade e especificidade preditivas para EP foram 71,9% e 85,0%, respectivamente (AUC=0,762, 95% IC=0,635 - 0,889, p<0,001). CONCLUSÃO: A medição da copeptina teve sensibilidade e especificidade preditivas moderadas para o diagnóstico de EP, e o nível de copeptina foi significativamente maior em pacientes com mortes relacionadas à EP após um ano. A copeptina pode ser um novo biomarcador preditivo útil para o diagnóstico, a estratificação de risco e o prognóstico de PE.

Early propranolol treatment ameliorates endothelial dysfunction in experimental septic lung.

BACKGROUND: Recent reports have indicated an improved prognosis in sepsis with ß-blocker agents; however, the underlying action mechanism is still under debate. OBJECTIVES: The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats. MATERIAL AND METHODS: The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation. RESULTS: Serum tumor necrosis factor alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the preand post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells. CONCLUSIONS: These results suggest that the improved outcome with ß-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of ß-blockers on the endothelium may lead to a better understanding of sepsis.

The frequency of diastolic dysfunction in patients with sarcoidosis and it's relationship with HLA DRB1* alleles.

BACKGROUND: Impaired systolic function is common in sarcoidosis however the frequency of diastolic dysfunction (DD) and it's possible genetic basis has not been fully elucidated yet. The aim of this study is to evaluate the frequency of left ventricular DD(LVDD) and right ventricular DD(RVDD) and it's possible relationship between Human Leukocyte Antigen(HLA)-DRB1* alleles in patients with sarcoidosis. METHODS: Seventy seven patients (51 females, mean age 41.1±8.2yrs) without known sarcoid related or any other structured heart disease and 77 healthy controls with a similar age and gender (38.7±7.8yrs,51 females) were included in the case control study. DD was diagnosed with echocardiography. RVDD was defined as early(E)/late(A) ratio<1 or >2 on tricuspit valve. LVDD was defined as E/A ratio<1 or >2 on mitral valve, with isovolumetric relaxation time(IVRT)>90 miliseconds(msn) or deceleration rate of early diastolic flow(Edec)>220msn respectively. All patients were HLAtyped with the Sequence Specific Oligonucleotide Probe(SSOP) method. RESULTS: The frequencies of LVDDs and RVDDs were significantly higher in sarcoidosis patients than the controls (26.0% vs. 2.6% for LVDD; and 42.9% vs. 18.2% for RVDD)(p<0.05). No significant difference was found in patients according to the presence of RVDD and LVDD in terms of age, gender or respiratory function test parameters. Although the frequency of HLA DRB1* alleles were comparable among patients with RVDD, HLA DRB1*14 alleles were more frequent in patients with LVDD. CONCLUSIONS: Biventricular DD is common in patients with sarcoidosis without manifest cardiac involvement. HLA DRB1*14 allele seems to be related with LVDD in this study population.