Comparison of Postoperative and Oncologic Outcomes in Laparoscopic and Open Right Colectomy for Colon Cancer: A 5-year Experience.

BACKGROUND/AIM: Laparoscopic colectomy is a procedure which is being performed for three decades and is gaining popularity continuously over the traditional open colectomy. This study was conducted in order to compare postoperative and oncologic results based on several factors in laparoscopic and open right colectomy for right colon cancer. PATIENTS AND METHODS: This is a retrospective study of right colectomy at a single institution from 2015 until 2020. The factors that were studied included postoperative values of C-reactive protein (CRP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), the number of excised lymph nodes, the use of postoperative analgesics and the length of hospital stay. RESULTS: We collected data from 21 open and 17 laparoscopic right colectomies through a 5-year period. Measurements on the second postoperative day revealed mean CRP and CPK values significantly lower in the laparoscopic group compared to the open group, while LDH levels did not affirm major differences between the two groups. The mean number of lymph nodes excised during the open procedure was superior to those harvested in the laparoscopic group. The use of analgesics throughout the entire hospital stay was a combination of pethidine and tramadol for the first three postoperative days in open procedures, while paracetamol and, occasionally, tramadol were administered upon patient request following laparoscopic procedures. The mean hospital stay was substantially shorter in the laparoscopic group compared to the open surgery group. CONCLUSION: Laparoscopic right colectomy is superior compared to open right colectomy with regards to postoperative analgesia and length of hospital stay, but also in certain postoperative laboratory values. Despite these there was no supremacy considering oncologic clearance.

Real-life Cretan asthma registry focused on severe asthma: On behalf of 'The Cretan registry of the use of Biologics in Severe Asthma'.

Asthma diagnosis and management remains a challenging task for the medical community. The aim of the present study was to present the functional and inflammatory profiles of patients with difficult-to-treat asthma in a real-life clinical setting referred to the specialized asthma clinic at the University Hospital of Heraklion. The registry included a cohort of 267 patients who were referred to the severe asthma clinic. Patients were assessed with emphasis on the history of allergies, nasal polyposis or other comorbidities. Blood testing for eosinophils counts and total and specific IgE, and pulmonary function tests were performed at baseline. The median age of patients with asthma was 55 years old, 68.5% were women and 58.3% were never smokers. The vast majority presented with late onset asthma (75.7%), whereas eight (3%) patients were on oral corticosteroids. The median number of exacerbations during the last 12 months was 1 (0-3). Furthermore, 50.7% of patients had a positive serum allergy test, the median eosinophil count was 300 (188-508.5) cells/µl of blood and median total IgE level was 117.5 (29.4-360.5) IU/ml. Patients were retrospectively grouped in the following categories: Group 1, mild-moderate asthma; group 2, patients prescribed a step 4 or 5 asthma therapy according to Global Initiative for Asthma; and group 3, patients on biologic agents. Group 1 had significantly higher FEV1% than groups 2 and 3 (93.4 vs. 79.9 and 79.4%, respectively; P<0.001). Finally, the median Asthma Control Questionnaire 7 (ACQ7) score was 1.14, with patients from groups 2 and 3 presenting higher ACQ7 scores compared with group 1 patients as expected (1.1 and 2.1 vs. 0.7, respectively; P<0.001). To the best of our knowledge, this was the first real-life asthma study in Crete that demonstrated that severe asthmatics predominantly have late-onset asthma with airflow obstruction and uncontrolled symptoms.

Case Report: Diagnosis of Myelodysplastic Syndrome in a 72-Year-Old Female With Interstitial Lung Disease.

Acute fibrinous and organizing pneumonia (AFOP) is an entity that can be secondary to various conditions leading to lung injury, such as infections, malignancies, and various autoimmune conditions or idiopathic interstitial lung disease, when no obvious underlying cause is identified. Myelodysplastic syndromes (MDS), on the other hand, are a spectrum of clonal myeloid disorders, with a higher risk of acute leukemia, characterized by ineffective bone marrow (BM) hematopoiesis and, thus, peripheral blood (PB) cytopenias. Immune deregulation is thought to take part in the pathophysiology of the disease, including abnormal T and/or B cell responses, innate immunity, and cytokine expression. In the literature, there are a few case reports of patients with MDS that have presented pulmonary infiltrates and were diagnosed as having AFOP or organizing pneumonia (OP). It is rare, though, to have isolated pulmonary infiltrates without Sweet's syndrome or even the pulmonary infiltrates to precede the diagnosis and treatment of MDS, which was our case. We present a 72-year-old female developing new lung infiltrates refractory to antibiotic treatment that responded well to corticosteroids and was histologically described as having OP. The treatment was gradually successfully switched to mycophenolate mofetil (MMF). The patient was later diagnosed with MDS. This interesting case report suggests firstly that a diagnosis of AFOP or OP should alert the clinician to search for an underlying cause including MDS and vice versa, the use of systemic steroids should not be postponed, and, finally, that MMF can successfully be used in these patients.

Enhanced IL-1ß Release Following NLRP3 and AIM2 Inflammasome Stimulation Is Linked to mtROS in Airway Macrophages in Pulmonary Fibrosis.

Fibrotic Interstitial lung diseases (ILDs) are complex disorders of variable clinical behaviour. The majority of them cause significant morbidity, whilst Idiopathic Pulmonary Fibrosis (IPF) is recognised as the most relentless. NLRP3, AIM2, and NLRC4 inflammasomes are multiprotein complexes driving IL-1ß release; a proinflammatory and profibrotic cytokine. Several pathogenetic factors associated with IPF are identified as inflammasome activators, including increases in mtROS and bacterial burden. Mitochondrial oxidation and alterations in bacterial burden in IPF and other ILDs may lead to augmented inflammasome activity in airway macrophages (AMs). IPF (n=14), non-IPF-ILDs (n=12) patients and healthy subjects (n=12) were prospectively recruited and AMs were isolated from bronchoalveolar lavage. IL-1ß release resulting from NLRP3, AIM2 and NLRC4 inflammasomes stimulation in AMs were determined and baseline levels of mitochondrial ROS and microbial burden were also measured. Our results showed that NLRP3 was more inducible in IPF and other ILDs compared to controls. Additionally, following AIM2 activation IL-1ß release was significantly higher in IPF compared to controls, whereas similar trends were observed in Non-IPF-ILDs. NLRC4 activation was similar across groups. mtROS was significantly associated with heightened NLRP3 and AIM2 activation, and mitochondrial antioxidant treatment limited inflammasome activation. Importantly, microbial burden was linked to baseline IL-1ß release and AIM2 and IL-18 relative expression independently of mtROS. In conclusion, the above findings suggested a link between the overactivation of NLRP3 and AIM2 inflammasomes, driven by mitochondrial oxidation, in the pathogenesis of lung fibrosis while changes in the microbiota may prime the inflammasome in the lungs.

Patients with idiopathic pulmonary fibrosis with and without obstructive sleep apnea: differences in clinical characteristics, clinical outcomes, and the effect of PAP treatment.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) in patients with idiopathic pulmonary fibrosis (IPF) is associated with worse mortality and clinical outcome. We aimed to assess differences between patients with IPF with and without OSA and the effect of positive airway pressure treatment on sleep and overall life quality, morbidity, and mortality in these patients. METHODS: Forty-five patients with newly diagnosed IPF underwent polysomnography. Using an apnea-hypopnea index ≥ 15 events/h for OSA diagnosis resulted in 16 patients with IPF and 29 with IPF-OSA. The patients completed the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Functional Outcomes in Sleep Questionnaire, Fatigue Severity Scale, Short Form-36 life questionnaire, and Beck Depression Inventory before and at the end of the follow-up period. RESULTS: Patients with IPF-OSA showed the most severe functional impairments in questionnaires, especially for General Health component of the Short Form-36 life questionnaire (37 vs 58, P = .03). At the 7-year follow-up, 16 (36%) patients had died, 6 (38%) in the IPF group and 10 (35%) in IPF-OSA group. Patients with ≥6-hour positive airway pressure use had better survival compared with patients with <6-hour use (P = .04). Significant improvement was also observed in Epworth Sleepiness Scale (3 vs 6, P = .03), Pittsburgh Sleep Quality Index (5 vs 8, P = .01), and Fatigue Severity Scale (37 vs 48, P = .008) score in patients with ≥4-hour positive airway pressure use. CONCLUSIONS: OSA plays a significant role on clinical features and quality of life in patients with IPF. Effective positive airway pressure treatment results in a significant improvement in sleepiness, fatigue, sleep quality, and mortality. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: CPAP Therapy in Patients With Idiopathic Pulmonary Fibrosis and Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/record/NCT01637831; Identifier: NCT01637831.

Use of mucolytics in COPD: A Delphi consensus study.

BACKGROUND: International guidelines recommend mucolytic agents as add-on therapy in selected patients with COPD because they may reduce exacerbations and improve health status. As the evidence varies among mucolytic agents, we used the Delphi method to assess consensus amongst an international panel of COPD experts on mucolytics use in COPD. METHODS: 53 COPD experts from 12 countries were asked to complete an online questionnaire and rate their agreement with 15 statements using a 5-point scale. The mucolytic agents evaluated were carbocysteine, erdosteine and N-acetylcysteine (NAC). Data were collected anonymously and consensus presented using descriptive statistics. RESULTS: The 47 respondents reached consensus on the statements. They agreed that regular treatment with mucolytic agents effectively reduces the frequency of exacerbations, reduces the duration of mild-to-moderate exacerbations, and can increase the time to first exacerbation and symptom-free time in COPD patients. Consensus was consistently highest for erdosteine. The experts agreed that all three mucolytics display antioxidant and anti-inflammatory activity. Erdosteine and NAC were thought to improve the efficacy of some classes of antibacterial drugs. All three mucolytics were considered effective for the short-term treatment of symptoms of acute exacerbations when added to other drugs. The panel agreed that approved doses of mucolytic agents have favorable side-effect profiles and can be recommended for regular use in patients with a bronchitic phenotype. CONCLUSIONS: Consensus findings support the wider use of mucolytic agents as add-on therapy for COPD. However, the differences in pharmacological actions and clinical effectiveness must be considered when deciding which mucolytic to use.

Solitary cerebellum metastasis from gastric adenocarcinoma. A rare case report.

INTRODUCTION: The present study reports a case of signet-ring gastric adenocarcinoma with isolated cerebellum metastasis 2 years after gastrectomy. PRESENTATION OF A CASE: Brain metastases originating from gastric cancer are rare accounting for 2.1-3.3% of all brain tumors registered in Japan. There are no established therapeutic strategies for brain metastases, which accordingly have a poor prognosis. We present here a 69 year old female patient who was diagnosed with solitary cerebellum metastasis 2 years after treatment for gastric adenocarcinoma. The primary gastric cancer was treated by laparotomy with distal gastrectomy and D2 lymphadenectomy. It was diagnosed as a signet ring gastric adenocarcinoma on histopathological examination of the surgical specimen. Two years postoperatively the patient reported back to our clinic complaining of vomiting, persistent headache and instability. MRI of the head showed an enhanced tumor in the left hemisphere of cerebellum and surrounding edematous changes on T1-enhanced imaging. Given the medical history brain metastasis was the first thought in differential diagnosis. Surgical resection was chosen as treatment. DISCUSSION: Until recently there are only two large studies that refer to metastatic brain tumors from primary gastric cancer. Besides that, official treatment guidelines for these cases do not exist. Treatment options include surgical resection (SR), whole brain radiotherapy (WBRT), steroids, chemotherapy or a combination. CONCLUSION: A solitary cerebellum metastasis from primary gastric adenocarcinoma is a very rare presentation. Early detection of metastatic lesion and successful treatment is challenging.

NLRP3/Caspase-1 inflammasome activation is decreased in alveolar macrophages in patients with lung cancer.

Lung cancer (LC) remains the leading cause of cancer-related mortality. The interaction of cancer cells with their microenvironment, results in tumor escape or elimination. Alveolar macrophages (AMs) play a significant role in lung immunoregulation, however their role in LC has been outshined by the study of tumor associated macrophages. Inflammasomes are key components of innate immune responses and can exert either tumor-suppressive or oncogenic functions, while their role in lung cancer is largely unknown. We thus investigated the NLRP3 pathway in Bronchoalveolar Lavage derived alveolar macrophages and peripheral blood leukocytes from patients with primary lung cancer and healthy individuals. IL-1ß and IL-18 secretion was significantly higher in unstimulated peripheral blood leukocytes from LC patients, while IL-1ß secretion could be further increased upon NLRP3 stimulation. In contrast, in LC AMs, we observed a different profile of IL-1ß secretion, characterized mainly by the impairment of IL-1ß production in NLRP3 stimulated cells. AMs also exhibited an impaired TLR4/LPS pathway as shown by the reduced induction of IL-6 and TNF-α. Our results support the hypothesis of tumour induced immunosuppression in the lung microenvironment and may provide novel targets for cancer immunotherapy.

Investigation of key autophagy-and mitophagy-related proteins and gene expression in BALF cells from patients with IPF and RA-ILD.

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung disease with a poor prognosis and limited therapeutic options. Over the past decade, research efforts have focused on the pathogenetic mechanisms involved in this enigmatic lung disease. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease often complicated by the development of interstitial lung disease (ILD), leading to high mortality and morbidity. Autophagy is a process regulating the turnover of subcellular components and organelles, and represents a major cellular homeostatic mechanism. Recent evidence suggests a role of autophagy and mitochondrial dysfunction in the development of IPF, focusing on lung fibroblasts and epithelial cells. The aim of this study was to examine the mRNA levels of molecules involved inthe autophagy pathway in bronchoalveolar lavage fluid (BALF)­derived cellsfrom patients with IPF in comparison topatients with RA demonstrating lung involvement (ILD) by RT-qPCR. The significant upregulation of BECLIN1 was observed in patients with RA-ILD compared with those with IPF. Other genes involved in the autophagy pathway were also examined, such as Unc-51 like autophagy activating kinase 1 (ULK1), BCL2 interacting protein 3 (BNIP3) and p62. No differences in the mRNA expression levels of these genes were observed. As regards the selective degradation of mitochondria and mitophagy, similar PTEN-induced putative kinase 1 (PINK1) and PARKIN; E3 ubiquitin ligase (PRKN) expression, as well as PINK1 protein levels, were observed. On the whole, the findings of this study demonstrate an increased expression of BECLIN1 in BALF cells from patients with RA-ILD compared with those from patients with IPF, while similar levels in other key molecules implicating in the autophagy pathway were observed in patients with IPF and RA-ILD.

Upregulation of citrullination pathway: From Autoimmune to Idiopathic Lung Fibrosis.

BACKGROUND: Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear. METHODS: We evaluated PADI2 and PADI4 mRNA expression in bronchoalveolar lavage fluid (BALF) cells of 59 patients with IPF, 27 patients RA-ILD and 10 healthy controls. PADI 2 and 4 expression was analyzed by western blot and immunohistochemistry. Citrullinated protein levels were also quantified. RESULTS: PADI4 mRNA and protein levels were higher in RA-ILD and IPF than controls. Furthermore, PADI4 mRNA levels showed an increase among smokers in RA-ILD. PADI4 expression was detected in granulocytes and macrophages in all groups, with the strongest cytoplasmic expression observed in granulocytes in RA-ILD and IPF. PADI2 mRNA and immunostaining of BAL cells, were similar in all groups among smokers. Overall, stronger staining was observed in current smokers. Citrullinated peptides were significantly increased in IPF compared to RA-ILD and controls. In RA-ILD, protein citrullination strongly correlated with PADI4 expression and anti-citrullinated protein antibodies (ACPAs). CONCLUSIONS: These results suggest that the citrullination pathway is upregulated in IPF and in RA-ILD.

Acute exacerbation of COPD: is it the "stroke of the lungs"?

Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide. Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality. This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease. A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD). Exacerbations and comorbidities contribute to the overall severity in individual patients. Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease. In this review, we focus on the evidence that supports the claim that AECOPD is the "stroke of the lungs". AECOPD can be viewed as: a Semicolon or disease's full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment.

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung.

In this study we investigated the implication of NLRP3 inflammasomes in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-usual interstitial pneumonia (RA-UIP).NLRP3 inflammasome activation at baseline and following stimulation with lipopolysaccharide/ATP was evaluated by measuring interleukin (IL)-1ß and IL-18 levels released in the bronchoalveolar lavage fluid (BALF) fluid and by cultures of BALF cells. IL-1ß and IL-18 levels were significantly elevated in the BALF and BALF macrophage cultures from RA-UIP patients, consistent with pre-existing inflammasome activation in these patients. In contrast, in IPF, BALF levels of IL-1ß were significantly less elevated relative to RA-UIP and IL-18 was lower than controls. Furthermore, upon inflammasome stimulation, IPF BALF macrophage cultures failed to upregulate IL-1ß and partly IL-18 secretion, in contrast to controls, which showed robust IL-1ß and IL-18 upregulation. Interestingly, RA-UIP BALF cell cultures treated with lipopolysaccharide/ATP showed a potent stimulation of IL-18 secretion but not IL-1ß, the latter being already elevated in the unstimulated cultures, while examination of the intracellular IL-1ß levels in RA-UIP BALF cells upon NLRP3 inflammasome stimulation showed a significant upregulation of IL-1ß suggesting the NLRP3 pathway could be further activated.Taken together, our results suggest distinct inflammasome activation profiles between autoimmune and idiopathic lung fibrosis.

Gastrointestinal Stromal Tumors (GIST): A Prospective Analysis and an Update on Biomarkers and Current Treatment Concepts.

Gastrointestinal stromal tumors (GIST) are the most common sarcomas of the gastrointestinal tract, with transformation typically driven by activating mutations of cKIT and less commonly platelet-derived growth factor receptor alpha (PDGFRA). Successful targeting of tyrosine-protein kinase Kit with imatinib, a tyrosine kinase inhibitor, has had a major impact in the survival of patients with GIST in both the adjuvant and metastatic setting. A recent modification of treatment guidelines for patients with localized, high-risk GIST extended the adjuvant treatment duration from 1 year to 3 years. In this paper, we review the clinical data of patients with GIST treated in the Oncology Outpatient Unit of "Attikon" University Hospital and aim to assess which patients are eligible for prolongation of adjuvant imatinib therapy as currently suggested by treatment recommendations.

Managing comorbidities in COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities. COPD exacerbations and comorbidities contribute to the overall severity in individual patients. Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age. Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations. However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide. This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale. Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases. All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases. In this review, we focus on the major comorbidities that affect COPD patients. We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs. We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.

The prevalence of obstructive sleep apnea-hypopnea syndrome-related symptoms and their relation to airflow limitation in an elderly population receiving home care.

BACKGROUND: Both airflow limitation and obstructive sleep apnea-hypopnea syndrome (OSAHS)-related symptoms are most prevalent in the elderly population. Previous studies revealed significant associations between OSAHS-related symptoms and obstructive airway diseases in the general population. However, other studies showed that the frequency of OSAHS-related symptoms in patients with obstructive airway diseases decreases after the age of 60 and older. AIMS: To investigate the prevalence of OSAHS-related symptoms (snoring, breathing pauses, and excessive daytime sleepiness [EDS]) and their relations to airflow limitation, for people over 65 years old. METHODS: A full screening spirometry program was performed in a total of 490 aging participants (mean age 77.5 years - range 65-98) who were attending 16 home care settings in central Greece. Airflow limitation was assessed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric criteria (FEV1/FVC <70%). The Berlin Questionnaire and the Epworth Sleepiness Scale were used to screen individuals for OSAHS-related symptoms. Bivariate associations were described using odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Airflow limitation prevalence was 17.1% (male 24.2% and female 9.9%) and was strongly related to male gender and smoking status. The prevalence rates of frequent snoring, breathing pauses, and EDS were 28.1%, 12.9%, and 11.6%, respectively. However, participants with airflow limitation were less likely to report breathing pauses, frequent snoring, EDS, and obesity. Finally, frequent snoring was significantly more common in males than females. CONCLUSION: This study revealed decreased frequency of OSAHS-related symptoms in participants with airflow limitation suggesting that OSAHS-related symptoms and airflow limitation are not related in our elderly population.

Pain and Anxiety versus Sense of Family Support in Lung Cancer Patients.

Lung cancer is a stressful condition for both patient and family. The anxiety and pain accompanying cancer and its treatment have a significant negative influence on the patient's quality of life. The aim of this study was to investigate the correlation between anxiety, pain, and perceived family support in a sample of lung cancer patients. The sample consisted of a total of 101 lung cancer outpatients receiving treatment at the oncology department of a general hospital. Anxiety, pain (severity and impact on everyday life), and perceived family support were assessed using Spielberger's State-Trait Anxiety Inventory, the Brief Pain Inventory, and the Family Support Scale, respectively. Statistical analyses revealed correlations between anxiety, pain, and family support as perceived by the patients. The intensity of pain had a positive correlation with both state and trait anxiety and a negative correlation with family support. Anxiety (state and trait) had a significant negative correlation with family support. In conclusion, high prevalence rates of anxiety disorders were observed in lung cancer patients. Females appeared more susceptible to anxiety symptoms with a less sense of family support. A negative correlation was evidenced between family support and anxiety and a positive one between anxiety and pain.

Association of the miR-146aC>G, miR-149T>C, and miR-196a2T>C polymorphisms with gastric cancer risk and survival in the Greek population.

MicroRNAs (miRNAs) play an important role in regulating gene expression at the post-transcriptional level and are involved in numerous physiological processes. Accumulating evidence suggests that single-nucleotide polymorphisms (SNPs) in human miRNA genes may affect miRNA biogenesis pathway and influence the susceptibility to several diseases such as cancer. The aim of the study was to investigated whether three common miRNA polymorphisms [miR-146a C>G (rs2910164), miR-149 T>C (rs2292832), and miR-196a2 T>C (rs11614913)] are associated with the susceptibility and prognosis of gastric cancer (GC) in the Greek population. The three mRNA SNPs were identified in a case-control study (163 patients; 480 controls) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. We found that the risk for GC was significantly higher for the carriers of miR-149 rs2292832CC (p = 0.009) and miR-196a2 rs11614913CC (p < 0.0001) genotypes, as well as for the carriers of the rs2910164/rs2292832/rs11614913 CCC and GTC haplotype (p < 0.0001 and p = 0.03, respectively). The rs2910164/rs2292832/rs11614913 CTT and CCT haplotypes seems to have a protective role against GC (p = 0.002 and p = 0.001, respectively). Our data demonstrate that specific miRNA SNPs are associated with GC susceptibility in the Greek population.

The role of macrophages in obstructive airways disease: chronic obstructive pulmonary disease and asthma.

Macrophages are a major cellular component of the innate immune system, and play an important role in the recognition of microbes, particulates, and immunogens and to the regulation of inflammatory responses. In the lung, macrophages react with soluble proteins that bind microbial products in order to remove pathogens and particles and to maintain the sterility of the airway tract. Chronic obstructive pulmonary disease and asthma are both obstructive airway diseases that involve chronic inflammation of the respiratory tract which contributes to disease progression. In the case of COPD, there is increasing evidence that lung macrophages orchestrate inflammation through the release of chemokines that attract neutrophils, monocytes and T cells and the release of several proteases. On the other hand, in asthma, it seems that alveolar macrophages are inappropriately activated and are implicated in the development and progression of the disease. In this review we summarize the current basic and clinical research studies which highlight the role of macrophages in asthma and COPD.

Molecular profiling of EGFR family in chronic obstructive pulmonary disease: correlation with airway obstruction.

BACKGROUND: Growth factors mediate various cellular responses to environmental stimuli. Specifically, exposure of lung epithelium to oxidative stress induced by cigarette smoke stimulates aberrant epidermal growth factor receptor (ERBB) family activation. This study's objective was to evaluate the expression of ERBB1-4 receptors in the lung tissue of smokers with or without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: ERBBs expression was measured by microarray analysis in lung tissue samples from five patients with COPD and five non-COPD smokers, and by quantitative real-time PCR in additional 20 patients with COPD (GOLD stage II), 15 non-COPD smokers and 10 nonsmoker controls. RESULTS: Microarray data analysis revealed that ERBB receptors expression was elevated in patients with COPD compared to non-COPD smokers, ranging from 1·62- to 2·45-fold, (P < 0·01). Real-time qPCR verified that patients with COPD had higher ERBB1-3 expression levels compared with non-COPD smokers (PERBB1  < 0·001; PERBB2  = 0·003; PERBB3  = 0·003) and nonsmokers (PERBB1  = 0·019; PERBB2  = 0·005; PERBB3  = 0·011). On the other hand, ERBB4 mRNA levels gradually increased from nonsmokers (0·74 ± 0·19) to non-COPD smokers (1·11 ± 0·05) to patients with COPD (1·57 ± 0·28) and were correlated with the degree of airflow obstruction (PFEV1  < 0·001). DISCUSSION: These data suggest that ERBB1-3 overexpression is not related only to smoking exposure but probably to epithelial remodelling and mucociliary system distortion, characterizing COPD. Additionally, the inverse correlation of ERBB4 with FEV1 exhibits a possible link between ERBB4 and COPD severity.

Validity of the cohort of Crete in the Seven Countries Study: A time-series study applied to the cancer mortality trend between 1960 and 2011.

We examined whether the Cretan cohort of the Seven Countries Study (SCS) is representative for the entire population in the island using cancer mortality registries. The analysis was carried out on the Cretan cohort of the SCS cancer mortality data and a similar cancer registry for the general population during a 51-year follow-up (1960-2011). Information about the causes of mortality was obtained from official death certificates and classified according to the International Classification of Diseases, 9th Revision (ICD-9). Two time-series models of mortalities from cancer, using data from the Cretan cohort and the Hellenic Statistical Office (EL. STAT), were developed using Matlab software. The existence of long-term memory in the data was tested by rescaled range analysis (Hurst-Mandelbrot). State-space reconstruction was applied to identify the simplest system that was able to re-create the present time-series. In the cohort, cancer mortalities accounted for 18.9% of total mortalities. The EL.STAT time-series analysis generated mean V statistics (95%CI) of 0.69815 (0.398-0.999) and 0.677143 (0.301-0.897) for the general population and the seven countries cohort, respectively. The embedding dimension for the EL.STAT data was equal to 1 for the general population and for the Cretan cohort (m=1). The exponent H values for the two time-series were almost equal. In the two time-series the proposed time delay of cancer mortalities was 2. The Cretan cohort of the SCS and the entire population of the island followed similar patterns of cancer mortality over time.