The effect of inhaled corticosteroids on bronchoalveolar lavage cells and IL-8 levels in stable COPD patients

Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammatory process in the large and small airways, as well as in the lung parenchyma. Although the role of oral corticosteroids in the management of acute exacerbations of COPD is well documented, its role in stable COPD is not clear. We examined the anti-inflammatory effect of inhaled budesonide on the percentage of neutrophils and on interleukin-8 (IL-8) levels in bronchoalveolar lavage (BAL) and their correlation with spirometry and symptom scores. Twenty-six patients with stable COPD were randomised, in a double-blinded, placebo-controlled trial with either 800 microg of inhaled budesonide or placebo for a 6-month period. The budesonide-treated subjects had significant reductions in IL-8 levels in the BAL after therapy (mean+/-sem, 1.53+/-0.72 at baseline vs. 0.70+/-0.48 ng/ml at 6 months, P=0.004) and a reduction in the mean percentages of neutrophils (17.16+/-2.67% vs. 13.25+/-2.28% P=0.002). The improvement in sputum production was of borderline (P=0.058) significance but there was no improvement in lung function. In stable patients with COPD, treatment with inhaled budesonide for a period of 6 months has a positive effect on markers of lung inflammation, as assessed by reduction in percentage neutrophils and IL-8 concentration in BAL.     

The role of angiotensin converting enzyme genotype in coronary artery ectasia

Coronary artery ectasia (CAE) is characterised by irregular, diffuse, saccular, or fusiform dilatation of the coronary arteries. Although the underlying mechanisms are not fully understood, CAE is considered to be an original form of vascular remodelling in response to atherosclerosis. However, it is not clear why some patients develop CAE while most do not. Experimental data suggest that activation of the renin angiotensin system may lead to an increased inflammatory response in the vessel wall or to an activation of matrix metalloproteinases. In addition, an insertion/deletion (ID) polymorphism of angiotensin converting enzyme (ACE) has been associated with coronary vascular tone and the development of aneurysms. Accordingly, we hypothesised that the gene polymorphism of ACE may be a potential factor influencing the genesis of CAE. We retrospectively evaluated 112 patients who underwent coronary angiography. ACE ID genotype was determined in two groups of patients. Group 1 consisted of 56 patients who were found to have CAE. Group 2 consisted of 56 patients with significant coronary artery disease (CAD) (> 50% stenosis in any of the major epicardial coronary arteries or their branches) but without any evidence of coronary ectasia. Polymerase Chain Reaction (PCR) was used to detect ACE genotype. The ratio of DD genotype was found to be greater in group 1 than group in 2 (39% versus 18%, respectively, P < 0.05). When assessed according to the presence of the I allele, it was greater was greater in group 2 than in group 1 (82.1% versus 60.7%, respectively, P < 0.05). The results indicate that an ACE DD genotype may be a risk factor for CAE.     

Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair

The error-free repair of double-stranded DNA breaks by homologous recombination requires processing of broken ends. These processed ends are substrates for assembly of DNA strand exchange proteins that mediate DNA strand invasion. Here, we establish that human BLM helicase, a member of the RecQ family, stimulates the nucleolytic activity of human exonuclease 1 (hExo1), a 5′→3′ double-stranded DNA exonuclease. The stimulation is specific because other RecQ homologs fail to stimulate hExo1. Stimulation of DNA resection by hExo1 is independent of BLM helicase activity and is, instead, mediated by an interaction between the 2 proteins. Finally, we show that DNA ends resected by hExo1 and BLM are used by human Rad51, but not its yeast or bacterial counterparts, to promote homologous DNA pairing. This in vitro system recapitulates initial steps of homologous recombination and provides biochemical evidence for a role of BLM and Exo1 in the initiation of recombinational DNA repair.     

Wide QRS Complex and Lateral ST-T Segment Abnormality Are Associated With Worse Clinical Outcomes in COVID-19 Patients

BackgroundThe information on electrocardiographic features of patients with coronavirus disease 2019 (COVID-19) is limited. Our aim was to determine if baseline electrocardiographic features of hospitalized COVID-19 patients are associated with markers of myocardial injury and clinical outcomes.MethodsIn this retrospective, single center cohort study, we included 223 hospitalized patients with laboratory-confirmed COVID-19. Clinical, electrocardiographic and laboratory data were collected and analyzed. Primary composite endpoint of mortality, need for invasive mechanical ventilation, or admission to the intensive care unit was assessed.ResultsForty patients (17.9%) reached the primary composite endpoint. Patients with the primary composite endpoint were more likely to have wide QRS complex (>120 ms) and lateral ST-T segment abnormality. The multivariable Cox regression showed increasing odds of the primary composite endpoint associated with acute respiratory distress syndrome (odds ratio 7.76, 95% CI 2.67–22.59; p < 0.001), acute cardiac injury (odds ratio 3.14, 95% CI 1.26–7.99; p = 0.016), high flow oxygen therapy (odds ratio 2.43, 95% CI 1.05–5.62; p = 0.037) and QRS duration longer than >120 ms (odds ratio 3.62, 95% CI 1.39–9.380; p = 0.008) Patients with a wide QRS complex (>120 ms) had significantly higher median level of troponin T and pro-BNP than those without it. Patients with abnormality of lateral ST-T segment had significantly higher median level of troponin T and pro-BNP than patients without.ConclusionsThe presence of QRS duration longer than 120 ms and lateral ST-T segment abnormality were associated with worse clinical outcomes and higher levels of myocardial injury biomarkers.     

Hepatic involvement of disseminated actinomycosis

A 35-year-old woman was admitted for weight loss, fatigue, and epigastric and back pain. She had undergone uterine myomectomy 6 weeks previously, and light microscopic examination revealed actinomycosis. Radiologic examination showed 5×4×4 cm and 2×2×2 cm solid lesions in the left liver lobe. Ultrasound-guided fine-needle aspiration biopsy could not exclude the possibility of malignancy. We decided to perform an explorative laparotomy. Frozen sections indicatedEchinococcus alveolaris infection or granulomatous inflammatory disease, and left hepatic lobectomy was performed. Histologic examination revealed hepatic actinomycosis. After 6 months' penicillin treatment, there was no sign of recurrence. This case of hepatic actinomycosis following uterine infection without gross involvement of any other abdominal organ raises questions on the dissemination pathway. The other interesting feature of this case is the short interval from the presumed initiatory event to the presence of the hepatic deposits.     

Quantitative assessment of thyroid gland elasticity with shear-wave elastography in pediatric patients with Hashimoto’s thyroiditis

Objective

Hashimoto’s thyroiditis is the most common autoimmune thyroid disorder in the pediatric age range. Measurement of thyroid gland size is an essential component in evaluation and follow-up of thyroid pathologies. Along with size, tissue elasticity is becoming a more commonly used parameter in evaluation of parenchyma in inflammatory diseases. The aim of the current study was to assess thyroid parenchyma elasticity by shear-wave elastography in pediatric patients with Hashimoto’s thyroiditis; and compare the elasticity values to a normal control group.

Materials and methods

In this study; thyroid glands of 59 patients with a diagnosis of Hashimoto’s thyroiditis based on ultrasonographic and biochemical features, and 26 healthy volunteers without autoimmune thyroid disease and thyroid function disorders, were evaluated with shear-wave elastography. Patients with Hashimoto thyroiditis were further subdivided into three categories based on gray-scale ultrasonography findings as focal thyroiditis (grade 1), diffuse thyroiditis (grade 2), and fibrotic thyroid gland (grade 3).

Results

Patients with Hashimoto’s thyroiditis (n = 59) had significantly higher elasticity values (14. 9 kPa; IQR 12.9–17.8 kPa) than control subjects (10.6 kPa; IQR 9.0–11.3 kPa) (p < 0.001). Of the 59 patients with Hashimoto’s thyroiditis, 23 patients had focal thyroiditis involving less than 50% of the gland categorized as grade 1, 24 patients had diffuse involvement of the thyroid gland categorized as grade 2, and 12 patients had marked hyperechoic septations and pseudonodular appearance categorized as grade 3 on gray-scale ultrasound. Based on elastography, grade 3 patients had significantly higher elasticity values (19.7 kPa; IQR 17.8–21.5 kPa) than patients with grade 2 (15.5 kPa; IQR 14.5–17.8 kPa) and grade 1 thyroiditis (12.8 kPa; IQR 11.9–13.1 kPa) (p < 0.05). Patients with grade 2 thyroiditis had significantly higher elasticity values than those with grade 1 thyroiditis (p < 0.05).

Conclusion

Gray-scale ultrasound findings of heterogeneous echotexture and hypoechoic echogenicity reflect a longer duration of inflammation and may not be found in the initial stages of thyroiditis. Our results indicate that shear-wave elastography could be used to evaluate the degree of fibrosis in Hashimoto’s thyroiditis.

     

Retinal vessel diameters and their correlation with retinal nerve fiber layer thickness in patients with pseudoexfoliation syndrome

AIM: To compare retinal artery-vein diameters (RAVDs) of patients with pseudoexfoliation (PSX) syndrome with healthy controls and investigate the correlations between retinal nerve fiber layer (RNFL) thickness parameters and RAVDs. METHODS: Seventeen eyes with PSX and 17 eyes of age-matched controls were included in the study. All participants underwent routine ophthalmological examination, Humphrey visual field and RNFL examination by using Stratus OCT. Retinal images were obtained by using a retinal camera (Topcon 501X). RAVDs were measured from inferior nasal, inferior temporal, superior nasal and superior temporal arcuates by using IMAGEnet software. Superior, inferior, nasal, temporal and average RNFL thicknesses were recorded. RAVDs and RNFL parameters in groups and correlations were analyzed by Mann-Whitney U and Spearmann correlation tests. RESULTS: Only inferior quadrant and average RNFL thickness were detected thinner in the PSX group compared with control group (P=0.009, P=0.038, respectively). No statistically significant difference regarding RAVDs was found between two groups. CONCLUSION: RAVDs seems to be comparable in the PSX and control group. RNFL is thinner in the inferior quadrant in the PSX group. RNFL thickness and RAVDs show significant correlations in both groups. This correlation doesn’t seem to be specific to PSX.     

Familial history of cancer and lung cancer

There are many studies supporting the family history in lung cancer. In this study, we observed 1500 with lung cancer cases diagnosed between the years 1995-2000 in our clinic, and investigated family tendency of lung cancer in a control group including partners of 600 patients with family history of cancer. We conducted face-to-face interviews with 100 patients with lung cancer, and with first degree relatives of the other 1400 patients with lung cancer. There were 600 positive family history of cancer. Control populations were matches of the cancer patients with positive family history of cancer. Cases and controls were asked to report on their family history of cancer, as well as smoking status of family members. In conclusion, in 40% of 1500 patients with lung cancer, there was positive family history of lung cancer with regard to malignity. This positive family history of cancer was consisted of 51.8% lung cancer, 35.5% digestive cancer and 12.7% other cancers such as breast, larynx, prostate and bone. In control group, the value of the positive family history of lung cancer with regard to malignity was 5.0% (p< 0.001). These results support the hypothesis of a genetic susceptibility by showing that the patients with lung cancer have significantly more positive family history of lung cancer and digestive cancer.