Differential diagnoses of suspected Lyme borreliosis or post-Lyme-disease syndrome

The symptoms of Lyme borreliosis are similar to those of a variety of autoimmune musculoskeletal diseases. Persistence of complaints is frequently interpreted as unsuccessful antibiotic treatment of Borrelia-associated infections. However, such refractory cases are rare, and re-evaluation of differential diagnoses helps to avoid the substantial risk of long-term antibiotic therapy. In this study, we analyzed patients who presented to our rheumatology unit with previous suspected or diagnosed Lyme borreliosis. Eighty-six patients from a 3.5-year period were evaluated. The mean age of patients was 49.2 ± 17.2 years; 60% (n = 52) reported a tick bite and 33% (n = 28) an erythema. Forty-seven percent (n = 39) had positive enzyme-linked immunoassay results and Western blots (Mikrogen, Martinsried, Germany). All but 12 patients had already received antibiotic treatment previously. Nine percent (n = 8) had ongoing or recent Lyme borreliosis. Twenty-nine percent (n = 25) showed clinical symptoms and radiographic changes compatible with degenerative disorders of the cervical and/or lumbar spine. These patients were significantly older when compared to the other patients (59.3 ± 13.7 years vs 46.1 ± 17.2 years, p = 0.001). Seventeen percent (n = 16) had arthropathies related to psoriasis or rheumatoid arthritis. Twelve percent (n = 10) were positive for the HLA B27 antigen. Other diseases were less frequent. Six patients (7%) could not be diagnosed conclusively, and four of these patients had negative Borrelia immunoassay results. In conclusion, Borrelia-associated diseases were rare in this study. Differential diagnoses helped to initiate a successful disease-specific therapeutic strategy.     

Diagnostic value of procalcitonin in pleural effusions

This study was to determine the diagnostic value of procalcitonin (PCT) in the differentiation of infectious and non-infectious causes of pleural effusion. From January 2005 to April 2005, we measured the PCT levels of pleural effusion from 76 patients using an immunoluminometric assay. The types of pleural infusions studied were para-pneumonic effusion (n = 26), empyema (n = 7), tuberculous pleurisy (n = 8), malignant pleural effusion (n = 25) and transudative pleural effusion (n = 8). The PCT levels were low in transudative pleural effusions (0.188 ± 0.077 ng/mL) and tuberculous pleurisy (0.130 ± 0.069 ng/mL), but high in empyema (5.147 ± 3.056 ng/mL), para-pneumonic effusion (1.091 ± 0.355 ng/mL), and malignant pleural effusion (0.241 ± 0.071 ng/mL). The receiver-operating characteristic curve analysis for an optimal discrimination between empyema and para-pneumonic effusion from non-para-pneumonic effusion could be performed at a cut-off point of 0.18 ng/mL with area under the curve of 0.776 (sensitivity: 69.7%, specificity: 72.1%). The correlation was found between pleural effusion PCT and serum PCT levels in 16 patients (r ² = 0.967, p < 0.001). In conclusion, a high pleural effusion PCT level suggests the presence of empyema and para-pneumonic effusion.     

Interrelationships between interleukin (IL)-1, IL-6 and IL-8 in synovial fluid of various arthropathies

High levels of many cytokines, including interleukin (IL)-1, IL-6 and IL-8, were found in various arthropathies suggesting that they play a role in the pathogenesis of disease, although their relationship with the type and activity of disease is still not clear. The synovial fluid (SF) of 24 patients with rheumatoid arthritis (RA), 19 with psoriatic arthritis (PA) and 33 with osteoarthritis (OA) was analyzed for IL-1, IL-6 and IL-8. The highest concentration of the three cytokines was found in the SF of RA. IL- detectable levels (>-20 pg/ml) were observed in 8/24 (33.3%) patients with RA, in one patient with PA but in no patient with OA.IL-6 (mean±SD) (1610.37±1781.65 pg/ml) was higher in RA than in PA (672.47±867.40 pg/ml,p=0.043) and OA (89.45±120.52 pg/ml,p=0.0001). IL-8 (1042.72±698.64 pg/ml) was higher in RA than in PA (660.36±625.11 pg/ml,p=0.03) and OA (89.9±45.88 pg/ml,p=0.0001). A correlation between IL-1, IL-6 and IL-8 was found in RA. In all patients a correlation between IL-6 and IL-8 levels was found; moreover, these two cytokines were associated with SF indices of inflammation, such as white blood cells (WBC) count and total protein (TP) concentration.Out findings suggest that these interrelationships play a role in the evolution of more severe erosive arthropathy such as RA.     

Serum C-reactive Protein (CRP) Levels in Cancer Patients are Linked with Tumor Burden and are Reduced by Anti-hypertensive Medication

High levels of CRP relate with advanced disease and poor prognosis of cancer patients. CRP serum levels were measured in 684 cancer patients who had undergone complete surgery or inoperable patients. Patients with inoperable tumors had significantly higher CRP levels (1.21 ± 2.2 vs. 0.40 ± 0.4 mg/dL; p < 0.0001). No association with gender, diabetes, autoimmune disease, thyroid disease or allergy was noted. Significantly higher CRP levels were noted in operated patients with hypertension (0.55 ± 0.5 vs. 0.35 ± 0.4; p = 0.001), coronary disease (0.73 ± 0.8 vs. 0.39 ± 0.4; p = 0.01) and obesity (0.51 ± 0.5 vs. 0.37 ± 0.4; p = 0.04). On the contrary, analysis in the group of inoperable patients showed that hypertensive patients had significantly lower CRP levels (0.64 ± 1.0 vs. 1.36 ± 2.4; p = 0.008). Although the tumor itself is the main factor defining increased CRP levels in cancer patients, hypertension, coronary disease and obesity are also linked with high CRP levels. Anti-hypertensive drugs appear as potent suppressors of the tumor-induced CRP production.     

Fibrinogen Beta-Chain -C148T Polymorphism is Associated with Increased Fibrinogen, C-Reactive Protein, and Interleukin-6 in Patients Undergoing Coronary Artery Bypass Grafting

The fibrinogen beta-chain (FGB) -C148T polymorphism is linked with plasma fibrinogen concentration in the general population. We examined whether the -C148T polymorphism is associated with pre- and early postoperative levels of fibrinogen, C-reactive protein (CRP), and interleukin-6 (IL-6) in 243 consecutive patients undergoing coronary artery bypass grafting (CABG) surgery. Plasma inflammatory markers were measured prior to and 5–7 days after surgery. The -C148T polymorphism was analyzed with the restriction fragment-length polymorphism method. The genotype distribution was as follows: CC—142 (58%), CT—85 (35%), and TT—16 (7%). Carriers of the -148T allele had higher preoperative plasma fibrinogen (4.42 ± 0.14 vs. 4.07 ± 0.11 mg/L, p = 0.04) and CRP levels (7.49 ± 1.2 vs. 4.26 ± 1.0 mg/L, p = 0.04) compared with non-carriers; 5 to 7 days after CABG, patients carrying -148T allele had increased CRP (70.4 ± 5.0 vs. 51.6 ± 4.25 mg/L, p = 0.005) and IL-6 levels (22.34 ± 2.64 vs. 15.53 ± 2.28 pg/L, p = 0.05), but not fibrinogen, compared with the remaining subjects. In-hospital nonfatal stroke occurred more frequently in -148T allele carriers (4% vs. 0%, p = 0.02). No genotype-associated differences were found in the occurrence of postoperative myocardial infarction and death. Presence of the -148T allele has also been associated with longer intensive care stay and intubation time (p = 0.01). Multivariate analysis identified the CT+TT genotype as an independent predictor of pre- and postoperative CRP levels. The results indicate that the presence of the -148T FGB allele determines higher pre- and postoperative levels of inflammatory markers, which might be associated with in-hospital clinical outcomes.     

Release of cardiac troponin I from viable cardiomyocytes is mediated by integrin stimulation

Elevated cardiac troponin-I (cTnI) levels have been demonstrated in serum of patients without acute coronary syndromes, potentially via a stretch-related process. We hypothesize that this cTnI release from viable cardiomyocytes is mediated by stimulation of stretch-responsive integrins. Cultured cardiomyocytes were treated with (1) Gly–Arg–Gly–Asp–Ser (GRGDS, n = 22) to stimulate integrins, (2) Ser–Asp–Gly–Arg–Gly (SDGRG, n = 8) that does not stimulate integrins, or (3) phosphate-buffered saline (control, n = 38). Cells and media were analyzed for intact cTnI, cTnI degradation products, and matrix metalloproteinase (MMP)-2. Cell viability was examined by assay of lactate dehydrogenase (LDH) activity and by nuclear staining with propidium iodide. GRGDS-induced integrin stimulation caused increased release of intact cTnI (9.6 ± 3.0%) as compared to SDGRG-treated cardiomyocytes (4.5 ± 0.8%, p < 0.001) and control (3.0 ± 3.4%, p < 0.001). LDH release from GRGDS-treated cardiomyocytes (15.9 ± 3.8%) equalled that from controls (15.2 ± 2.3%, p = n.s.), indicating that the GRGDS-induced release of cTnI is not due to cell necrosis. This result was confirmed by nuclear staining with propidium iodide. Integrin stimulation increased the intracellular and extracellular MMP2 activity as compared to controls (both p < 0.05). However, despite the ability of active MMP2 to degrade cTnI in vitro, integrin stimulation in cardiomyocytes was not associated with cTnI degradation. The present study demonstrates that intact cTnI can be released from viable cardiomyocytes by stimulation of stretch-responsive integrins.     

Performance of two commercial blood IFN-γ release assays for the detection of Mycobacterium tuberculosis infection in patient candidates for anti-TNF-α treatment

The reactivation of latent tuberculosis (TB) is a major complication of tumor necrosis factor (TNF)-α inhibitors. Screening for TB infection is recommended before anti-TNF therapy is initiated; however, the use of tuberculin skin testing (TST) is controversial, due to the high rate of false-negative results in patients receiving immunosuppressive treatment. To compare the performance of two commercial interferon (IFN)-γ release assays (IGRA), T-SPOT.TB (TS-TB) and QuantiFERON-TB Gold “In-tube” (QFT-GIT), with TST for the detection of TB infection in patients due to start anti-TNF therapy, 69 human immunodeficiency virus (HIV)-negative Italian patients (mean age: 45.2 ± 12.6 years; male=39) were enrolled between September 2005 to August 2006. Patients affected by rheumatoid arthritis (n = 18), psoriatic arthritis (n = 26), ulcerous rectocolitis (n = 6), and Crohn’s disease (n = 19) were tested simultaneously with TST, TS-TB, and QFT-GIT. Overall, 26% of patients were positive by TST, 30.4% by TS-TB, and 31.8% by QFT-GIT. Agreement with TST was similar (κ = 0.21, p = 0.0002 and κ = 0.26, p < 0.001, respectively). In 11 TST-negative cases, IFN-γ release assays were positive. In addition, in seven Mantoux-positive cases with no TB risk factors, TST result agreement was achieved with at least one blood test. Indeterminate results were detected in 5.8% and 2.8% of cases, respectively, with TS-TB and with QFT-GIT (p = not significant [ns]). In conclusion, our results suggest that IGRAs may be helpful for screening purposes in patient candidates for anti-TNF therapy to confirm positive TST results and in selected cases when false-negative results are suspected. The utility of blood tests in patients with low or no TB risk remains to be assessed.     

Polymorphisms of Genes for Programmed Cell Death 1 Ligands in Patients with Rheumatoid Arthritis

To investigate the role of ligands for programmed cell death 1 (PD-L) in the pathogenesis of rheumatoid arthritis (RA), 129 patients with RA and 125 unrelated healthy controls were enrolled in this study. The PD-L1 and PD-L2 polymorphisms were determined by the method of polymerase chain reaction (PCR)/direct sequencing or PCR/reaction fragment length polymorphisms. The genotype distributions of PD-L1 6777 C/G were not significantly different between the patients with RA and healthy controls. There was also no significant difference in the allele frequencies of PD-L1 6777 C/G polymorphisms between the patients with RA and controls. Similar findings could also be found in the phenotypes and alleles frequencies of PD-L2 47103 C/T and 47139 T/C polymorphisms between the patients with RA and controls. The patients with PD-L1 6777 G had higher prevalence of rheumatoid nodule in comparison with those without PD-L1 6777 G (p = 0.005, OR = 4.0, 95% CI = 1.5–10.9). In contrast, the PD-L2 47103 C/T and 47139 T/C polymorphisms were not related to the occurrence of rheumatoid nodule. This study demonstrated that the PD-L1 and PD-L2 polymorphisms were not associated with susceptibility to RA in Taiwan. PD-L1 6777 G was associated with the prevalence of rheumatoid nodule. Shu-Chen Wang and Chia-Hui Lin contributed equally to this work.     

Subacute Inflammatory Activation in Subjects with Acute Coronary Syndrome and Left Ventricular Dysfunction

Several lines of evidence indicate that increased inflammatory cytokine levels can be used for risk prediction in patients with acute coronary syndrome (ACS). This study therefore aimed to evaluate correlations between levels of soluble interleukin (IL)-2 receptor (sIL-2r), IL-6, and IL-8 and in-hospital incidence of acute heart failure (AHF) and left ventricular (LV) systolic dysfunction in the subacute phase of ACS. In 48 consecutive patients with ACS, circulating levels of sIL-2r, IL-6, and IL-8 were ascertained 72–96 h after onset of symptoms. Clinical data, LV function, and in-hospital incidence of AHF were also evaluated. IL-8 levels were significantly higher in patients with pulmonary edema (1,829 ± 2,496 vs 456 ± 624 pg/ml, p < 0.05); sIL-2r, IL-6, and IL-8 levels were increased proportionally to Killip class (r = 0.35, p < 0.05; r = 0.48, r = 0.47, p < 0.01) and in patients with LV ejection fraction (LVEF) < 30%. Levels of sIL-2r were inversely related to LVEF in subjects with acute myocardial infarction (r = −0.51, p < 0.05). Soluble IL-2r and IL-8 levels were related to mitral regurgitation severity (r = 0.34, p < 0.05; r = 0.37, p < 0.05). Levels of sIL-2 were proportional to LV end-diastolic diameter (r = 0.49, p < 0.001) and LV end-systolic diameter (r = 0.58, p < 0.001). Number of cytokines with circulating values above upper level of normal was significantly correlated with Killip class and LVEF (r = 0.40, r = −0.38, p < 0.05). sIL-2r, IL-6, and IL-8 are increased in patients with ACS and systolic dysfunction or AHF. These data suggest that inflammatory cytokine activity detectable in peripheral blood may be useful in identifying subjects with a worse clinical course.     

The Analysis of Tryptase in Serum of Sarcoidosis Patients

Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by activation of macrophages and T lymphocytes. Relatively little is known about the role of mast cells and their mediators in the pathogenesis of sarcoidosis. Tryptase is an enzyme produced by activated mast cells, regarded as a marker of mast cell activation. To analyse tryptase concentrations in serum of sarcoidosis patients in an attempt to define the role of tryptase and mast cells in the pathogenesis of sarcoidosis and to evaluate the potential of tryptase as marker of disease severity. Quantitative analysis of tryptase concentrations was performed in serum of patients with stable sarcoidosis (n = 12), progressive sarcoidosis (n = 23) and controls (n = 13). Patients enrolled in the study had been monitored at Siena Regional Referral Centre for Sarcoidosis from onset for at least 12 months. Significantly higher concentrations of tryptase were found in peripheral blood of sarcoidosis patients (6.08 ± 3.98 μg/l) than controls (2.96 ± 1.75μg/l; p = 0.012). Patients with progressive disease showed the highest tryptase concentrations in serum. Tryptase and mast cells may be involved in the immunopathogenesis of sarcoidosis and further studies are required to understand if tryptase may represent a marker of sarcoidosis severity.     

The Effects of High Dose Pravastatin and Low Dose Pravastatin and Ezetimibe Combination Therapy on Lipid,Glucose Metabolism and Inflammation

Objective Coronary artery disease (CAD) is presently the major cause of mortality and morbidity. Anti-hyperlipidemic treatment is one of the main treatment steps in the management of CAD. Statins are the cornerstones in this treatment. Ezetimibe can be reliably used, when statins prove ineffective in treatment, or to reduce their side effects. In the present study we examined the effects of high-dose pravastatin (40 mg) and low-dose pravastatin (10 mg) + ezetimibe (10 mg) combination therapy on lipid and glucose mechanism, as well as inflammation. Methods This study registered 100 cases. Of the cases, 50 [57.1 ± 11.1 years (24 (48%) females and 26 (52%) males)] were administered 40 mg/day pravastatin (group 1) and 50 [53.2 ± 12.2 years (27 (54%) females and 23 (46%) males)] were administered 10 mg pravastatin + 10 mg ezetimibe (group 2). Results In group 1, total cholesterol fell from 231.1 ± 83.5 mg/dl to 211.3 ± 37.2 mg/dl (p = 0.03), triglyceride from 243.5 ± 96.8 mg/dl to 190.9 ± 55.2 mg/dl (p = 0.003), and LDL cholesterol from 165.7 ± 29.7 mg/dl to 133.4 ± 26.6 mg/dl (p = 0.02). In group 2, total cholesterol dropped from 250.9 ± 51.8 mg/dl to 187.9 ± 34.9 mg/dl (p = 0.001), triglyceride from 270.3 ± 158.9 mg/dl to 154.6 ± 60.7 mg/dl (p = 0.001), and LDL cholesterol from 158.1 ± 47.5 mg/dl to 116.9 ± 26.4 mg/dl (p = 0.001). Insulin resistance decreased from 4.05 ± 2.31 to 3.16 ± 1.90 (p = 0.07) in group 1 and from 2.96 ± 1.50 to 2.05 ± 0.55 (p = 0.009) in group 2. High sensitive C-reactive protein fell from 6.69 ± 6.11 mg/l to 3.02 ± 1.70 mg/l (p = 0.01) in group 1 and from 6.36 ± 2.06 mg/l to 2.68 ± 1.69 mg/l (p = 0.001) in group 2. Conclusion Both therapy regimes are effective. However, we found that low-dose pravastatin and ezetimibe combination therapy is more effective than high-dose pravastatin therapy on lipid metabolism, glucose metabolism and inflammation.     

Cyclin D3 gene amplification in bladder carcinoma in situ

Carcinoma in situ (CIS) is a non-papillary high-grade, potentially aggressive, and unpredictable manifestation of bladder urothelial carcinoma. The aim of this study was to assess patterns of Cyclin D3 gene amplification in Bacillus Calmette-Guerin (BCG)-treated CIS and correlate gene status with recurrence-free and progression-free survival. A sequential cohort series of 28 primary (isolated) or secondary (concomitant) bladder CIS samples in which there was enough tissue material to assess Cyclin D3 gene status by fluorescent in situ hybridization was the study group. Cyclin D3 gene amplification was present in 29% of secondary CIS; none of primary CIS samples had Cyclin D3 gene amplification. Cyclin D3 amplification was related to recurrence- (p = 0.046) and progression-free survival (p = 0.002). Type of bladder CIS (primary vs. secondary) was unrelated to recurrence- or progression-free survival in the current series. Cox’s regression analysis selected Cyclin D3 as an independent predictor of progression-free survival (p = 0.041, relative risk = 61.503, 95% confidence interval = 1.1–274.710). None of primary CIS cases recurred on follow-up; nine secondary CIS recurred and four of them progressed to invasive bladder carcinoma HG T1 (n = 1), T2b N0M0 (n = 1), T3b N1M0 (n = 1) and T4aN1M1 (n = 1). Mean recurrence ± SD (months) occurred at 19.5 ± 2.06 (95% (confidence interval (CI)), 15.5–23.6); mean progression (months) occurred at 23.8 ± 1.46 (95% (CI), 20.9–26.7). Our study suggests that Cyclin D3 gene amplification might be a predictor of aggressiveness in BCG-treated CIS.     

Type-III interferons and rheumatoid arthritis: Correlation between interferon lambda 1 (interleukin 29) and antimutated citrullinated vimentin antibody levels

Aim: To assess serum type III or lambda (λ) interferons (IFN) levels and its clinical and laboratory associations in rheumatoid arthritis (RA). Methods: A cross-sectional study including 43 patients with RA (86% females; age 45.3?±?10.3 years) and 43 healthy individuals was performed. Clinical data including disease activity, acute-phase reactants, rheumatoid factor and anticyclic citrullinated peptide (anti-CCP) antibodies were collected. Serum IFNλ1, IFNλ2, IFNλ3, CXCL8 and anti-mutated citrullinated vimentin (anti-MCV) antibody levels were measured. Results: Patients with RA had higher IFNλ1 (113.5?±?118.6?pg/mL versus 55.9?±?122.3?pg/mL; p?<?0.0001) and IFNλ2 (245.4?±?327.7?pg/mL versus 5.1?±?11.0?pg/mL; p?=?0.009) levels than controls, but not IFNλ3 levels. Notably, IFNλ1 levels were found to be higher in both patients with active disease (124.9?±?135.9?pg/mL; p?<?0.001) and quiescent disease (99.0?±?93.7?pg/mL; p?<?0.01), while IFNλ2 levels were higher only in patients with active disease (264.0?±?356.1?pg/mL; p?=?0.02). A noteworthy association between serum IFNλ1 levels and anti-MCV antibody titers (Spearman's rho coefficient 0.36, 95% CI 0.36 to 0.61; p?=?0.02) was observed. Conclusion: Serum IFNλ1 and IFNλ2 levels are abnormally elevated in patients with RA and the former are linearly associated with circulating anti-MCV antibody levels. These results may place type-III IFN as an attractive new therapeutic target in RA.     

Modulation of the transient outward K+ current by inhibition of endothelin-A receptors in normal and hypertrophied rat hearts

Inhibition of endothelin-A (ET_A) receptors has been shown to reduce ventricular electrical abnormalities associated with cardiac failure. In this study, we investigate the effect of ET_A-receptor inhibition on the development of regional alterations of the transient outward K⁺ current (I _to) in the setting of pressure-induced left ventricular (LV) hypertrophy. Cardiac hypertrophy was induced in female Sprague–Dawley rats by stenosis of the ascending aorta (AS) for 7 days. Treatment with the selective ET_A-receptor antagonist darusentan (LU135252, 35 mg [kg body weight]⁻¹ day⁻¹) was started 1 day before the surgery. AS induced a 46% increase in the relative LV weight (p < 0.001) and caused a significant reduction in I _to (at +40 mV) in epicardial myocytes (19.5 ± 1.2 pA pF⁻¹, n = 32 vs 23.2 ± 1.2 pA pF⁻¹, n = 35, p < 0.05). Darusentan further reduced I _to in AS (15.4 ± 1.3 pA pF⁻¹, n = 37, p < 0.05) and sham-operated animals (19.8 ± 1.6 pA pF⁻¹, n = 48, ns.). The effects of AS and darusentan on I _to were significant and independent as tested by two-way analysis of variance. I _to was not affected in endocardial myocytes. These results indicate that endothelin-1 may exert a tonic effect on the magnitude of I _to in the epicardial region of the left ventricle but that ET_A-receptor activation is not necessary for the development of electrical alterations associated with pressure-induced hypertrophy.     

Hepatoprotective Effect of Infliximab,an Anti-TNF-α Agent,on Carbon Tetrachloride-Induced Hepatic Fibrosis

To assess the effect of infliximab, an anti-tumor necrosis factor (TNF)-α agent, on the carbon tetrachloride (CCl₄)-induced hepatic fibrosis in rats. Rats were randomized into three groups (n = 9). The control group received only intraperitoneal (i.p.) olive oil. Hepatic fibrosis was induced by repeated i.p. injections of 1.5 ml/kg CCl₄ (1:3 mixture with olive oil) for 5 weeks in the remaining two groups which were also injected subcutaneous saline or 2 mg/kg infliximab. Infliximab reduced the levels of aspartate aminotransferase and alanine aminotransferase (p < 0.05 for both). The scores of hepatic necrosis, inflammation and fibrosis, and expression of α-smooth muscle actin were lower in the infliximab-treated group than the CCI₄-treated group (p < 0.01, p < 0.001, p < 0.01, p < 0.001, respectively). However, there was no significant difference in terms of liver tissue and plasma malondialdehyde, and serum TNF-α levels, while infliximab relatively reduced the level of transforming growth factor-β₁ (373.0 ± 153.1 vs. 280.8 ± 127.1 pg/ml). Treatment with infliximab attenuated the necro-inflammation and fibrogenesis in the CCI₄-induced hepatic fibrosis, and thus it might be effective as a therapeutic anti-fibrotic agent.     

The Efficiency of a Urotensin II Antagonist in an Experimental Lung Fibrosis Model

Pulmonary fibrosis is a chronic disease. Urotensin II (U-II) is a new peptide with angiogenic and profibrotic features. Therefore, we aim to evaluate the antagonism of U-II with palosuran in an animal model and plan to measure U-II, endothelin-1 (ET-1), and transforming growth factor-β1 (TGF-β1) and their association with lung fibrosis. Thirty Wistar male rats were used in the study and were divided into three groups: group 1, control; group 2, bleomycin-induced lung fibrosis group; and group 3, bleomycin-induced lung fibrosis with treatment palosuran group. U-II level (nanograms per milliliter) was 2.957 ± 0.159 in group1, 3.188 ± 0.122 in group 2, and 2.970 ± 0.165 in group 3 (p = 0.002). The ET-1 level (picograms per milliliter) was 4.486 ± 0.376 in group 1, 9.086 ± 1.850 in group 2, and 4.486 ± 0.376 in group 3 (p < 0.001). The TGF-β1 (nanograms per milliliter) level was 73.143 ± 9.96 in group 1, 84.81 ± 4.73 in group 2, and 77.86 ± 5.77 in group 3 (p = 0.006). Finally, the fibrosis score was 0.7 ± 0.48 in group 1, 4.4 ± 1.34 in group 2, and 3.2 ± 0.63 in group 3 (p < 0.001). There is a statistically significant positive relationship between fibrosis scores and the UT-II, ET-1, and TGF-β1 levels of the experimental lung fibrosis model. We believe U-II is an important mediator in lung fibrosis models, and its antagonism with palosuran could be a new treatment choice for interstitial lung fibrosis, but further studies need to be conducted to verify the findings of the current study.     

Pulmonary <Emphasis Type="Italic">Mycobacterium simiae</Emphasis> infection: comparison with pulmonary tuberculosis

To identify the clinical and radiological features distinguishing Mycobacterium simiae respiratory infection from pulmonary tuberculosis, the demographics, underlying conditions, and clinical and radiological findings of 121 consecutive patients with pulmonary tuberculosis and 102 with M. simiae respiratory infection were compared retrospectively. In the M. simiae group, the patients were older (mean age 69 ± 16 years vs. 47 ± 21 years, p = 0.0001), with a female predominance (62% vs. 45%, p = 0.008). Only 4% were of Ethiopian origin compared to 25% of the tuberculosis group (p = 0.0001). M. simiae infection was associated with significantly higher rates of smoking history, underlying chronic obstructive pulmonary disease, zero human immunodeficiency virus (HIV) infection compared to 10% in the tuberculosis group (p = 0.001), blunted symptoms, and noncavitary infiltrates in the lower/middle lobes on chest X-ray. HIV-negative patients with M. simiae respiratory infection are distinguishable from patients with pulmonary tuberculosis by several demographic, clinical, and radiological features. These findings have important diagnostic and therapeutic implications.     

Adequacy and Diagnostic Accuracy of Aspiration vs. Capillary Fine Needle Thyroid Biopsies

Thyroid nodules can be biopsied by fine needle aspiration (FNA) or fine needle capillary (FNC) biopsies. However, there is controversy on whether one technique is superior to another. In a randomized cytopathologist-blinded cross-sectional study, 260 patients (238 females, age 43.2 ± 12.6) with nodular (82.7%) and diffuse goiter (17.3%) underwent 520 FNAs and 520 FNCs (not guided by ultrasound). Smears were scored for sample adequacy, and diagnosed as malignant, benign, suspicious, or nondiagnostic. Diagnostic accuracy was calculated based on the histological findings of 58 patients submitted to surgery. Intra-technique diagnostic accuracy and sample adequacy was seen in all samples. FNA and FNC provided similar cytological diagnosis, respectively (benign: 75.8% vs. 74.2%, p = 0.600; malignant: 3.8% vs. 3.8%, p = 0.871; suspicious: 10.4% vs. 10.8%, p = 0.913; and nondiagnostic: 10.0% vs. 11.2%, p = 0.598). Adequacy scores were similar by FNA (7.94 ± 2.84) and FNC (7.96 ± 2.81, p = 0.909). The same proportion of adequate or superior samples was seen in both techniques (91.6%). Sensitivity was equal to 85.7% for FNA and 100% for FNC. Similarly, specificity was 100% for both techniques. FNA and FNC provide the similar sample adequacy and diagnostic accuracy. The choice of technique should be based on the operator’s personal preferences and experience.     

Classical and Follicular Variant Papillary Thyroid Carcinoma: Comparison of Clinical,Ultrasonographical, Cytological,and Histopathological Features in 444 Patients

Follicular variant papillary thyroid carcinoma (FVPTC) is the most common variant of papillary thyroid carcinoma (PTC) after classical PTC (CPTC). In this study, we aimed to compare functional status, ultrasonographical features, cytological results, and histopathological characteristics of patients with CPTC and FVPTC. Preoperative thyroid functions, thyroid autoantibodies, ultrasonographical features, cytology, and histopathology results of 354 (79.9%) CPTC and 90 (20.3%) FVPTC patients were reviewed retrospectively. Sex distribution, mean age, thyroid autoantibody positivity, and thyroid dysfunctions were similar in two groups. Among 320 patients with preoperative ultrasonography (US) findings, a hypoechoic halo was observed more frequently (p = 0.003), and marginal irregularity was observed less commonly (p = 0.024) in FVPTC lesions. In CPTC, rate of malignant cytology (p = 0.001), and in FVPTC, rate of suspicious cytology (p < 0.001) were significantly higher. Histopathologically, mean tumor diameter was markedly higher in FVPTC compared to CPTC (16.89 ± 13.86 vs 10.64 ± 9.70 mm, p < 0.001), while capsular invasion and extrathyroidal spread were significantly lower in patients with FVPTC (p = 0.018 and p = 0.039, respectively). FVPTC tend to have more benign features in US and less malignant results in cytology. Higher tumor size in FVPTC might be explained by the recognition of clinical importance of these lesions after reaching particular sizes due to benign US features.