(2017). Carotid body resection for sympathetic modulation in systolic heart failure -results from first-in-man study. ABSTRACT AimsAugmented reflex responses from peripheral chemoreceptors, which are mainly localized in the carotid bodies (CB), characterize patients with systolic heart failure (HF) and contribute to adrenergic hyperactivation. We investigated whether surgical resection of CB in these patients can be performed safely to decrease sympathetic tone. Methods and resultsWe studied 10 male patients with systolic HF (age: 59±3 years, left ventricular ejection fraction: 27±7%) who underwent unilateral right-sided CB resection (4 patients) or bilateral CB resection (6 patients).Primary endpoints of the study were changes in muscle sympathetic nerve activity (MSNA) and peripheral chemosensitivity measured as ventilatory response to hypoxia from baseline to 1 month post-CB resection. Safety analysis included analysis of arterial blood gas and oxygenation at night through 2 months post-procedure and adverse events assessed up to 12-months.At 1-month visit, CB resection was associated with a significant decrease in both MSNA (86.6±3.1 vs.79.7±4.2 bursts/100 beats, p=0.03) and in peripheral chemosensitivity (1.35±0.19 vs. 0.41±0.17 L/min/SpO2, p=0.005). It also resulted in improved exercise tolerance. Amongst some patients with bilateral CB resection there was a trend towards worsening of oxygen saturation at night, which in one case required therapy with non-invasive ventilation. ConclusionWe present first-in-man evidence that CB resection in patients with systolic HF is associated with decrease in sympathetic activity. Bilateral procedure may carry a risk of worsening oxygenation at night.CB modulation constitutes an interesting research avenue, but careful consideration of the balance between safety and efficacy is necessary before further clinical trials.

IntroductionLung cancer is a major cause of mortality and morbidity worldwide. Galectin-3 is multifunctional protein, which is involved in regulation of cell growth, cell adhesion, cell proliferation, angiogenesis and apoptosis. Cyclin D1 together with other cyclin plays an important role in cell cycle control. Cyclin D1 regulates the G1-to-S phase transition. The aim of this study was the evaluation of correlations between clinicopathological findings and cyclin D1 and galectin-3 expression in non-small cell lung cancer (NSCLC). We wanted also to analyze the prognostic value of cyclin D1 and galectin-3 expression. Moreover we tried to evaluate the correlations between galectin-3 and cyclin D1 expression in tumor tissue.Materials and methodsWe used the immunochemistry method to investigate the expression of galectin-3 and cyclin D1 in the paraffin-embedded tumor tissue of 47 patients (32 men and 15 women; mean age 59.34 ± 8.90). years. We used monoclonal antibodies to cyclin D1 (NCL-L-cyclin D1-GM clone P2D11F11 NOVO CASTRA) and to galectin-3 (mouse monoclonal antibody NCL-GAL3 NOVO CASTRA).ResultsGalectin-3 expression was positive in 18 cases (38.29%) and cyclin D1 in 39 (82.97%). We showed only weak trend, that galectin-3 expression was lower in patients without lymph node involvement (p = 0.07) and cyclin D1 expression was higher in this group (p = 0.080). We didn't reveal differences in cyclin D1 and galectin-3 expression in SCC and adenocarcinoma patients. We didn't demonstrated also differences in galectin-3 and cyclin D1 expression depending on disease stage. Moreover we analyzed the prognostic value of cyclin D1 expression and galectin-3 in all examinated patients and separately in SCC and in adenocarcinoma and in all stages, but we didn't find any statistical differences. We demonstrated that in galectin-3 positive tumors cyclin D1 expression was higher (96.55% vs 61.11%, Chi2 Yatesa 7.53, p = 0.0061) and we revealed negative correlation between cyclin D1 and galectin-3 expression (R Spearman -0.458, p = 0.0011). In squamous cell lung cancer we didn't observed correlations between these both examinated markers (R = -0.158, p = 0.460), and in adenocarcinoma the negative correlation was very strong (R = -0.829 p = 0.000132).ConclusionsWe didn't reveal any important correlations between clinicopathological findings and galectin-3 and cyclin D1 expression and in non small cell lung cancer. We didn't observed also prognostic value of cyclin D1 or galectin-3 expression. But we showed higher cyclin D1 expression in galectin-3 negative tumor tissues. We revealed also differences in correlations between galectin-3 and cyclin D1 expression in two main histopathological types of NSCLC.

Pneumocystis jirovecii is an opportunistic fungus causing Pneumocystis pneumonia primarily in immunosuppressed patients. However, immunocompetent individuals may become colonized and, as asymptomatic carriers, serve as reservoirs of the pathogen. Moreover, these asymptomatic carriers are at higher risk of developing pneumonia if favorable conditions occur. This study aimed to determine the prevalence of P. jirovecii in patients with various pulmonary diseases and to characterize the genetic diversity of organisms circulating in the studied population. Bronchial washing specimens from 105 patients were tested for presence of P. jirovecii using nested polymerase chain reaction (PCR) targeting the mtLSU rRNA gene, as well as immunofluorescence microscopy. Multilocus sequence typing involving analysis of three loci-mtLSU rRNA, CYB, and SOD-was used for genotyping analysis. P. jirovecii DNA was detected in 17 (16.2%) patients. Amplification of the SOD locus was successful only in five cases (29.4% of the positive patients), while mtLSU rRNA and CYB were genotyped in all positive samples. Therefore, combined genotypes were identified based only on mtLSU rRNA and CYB loci. Eight different genotypes were identified, with Pj 1 and Pj 2 being the most prevalent (29.4% of patients each). There was no statistical correlation between these genotypes and demographic or clinical data; however, we found that infection with mutant CYB strains occurred only in patients diagnosed with lung cancer. Of the potential predictors examined, only immunosuppressive treatment was significantly associated with colonization. In conclusion, patients with various respiratory diseases, especially when immunosuppressed, are at risk of Pneumocystis colonization.

Objectives: Encephalitozoon spp. and Enterocytozoon bieneusi are intracellular parasitic fungi from the phylum Microsporidia, which initially localize to the intestine. As opportunistic pathogens, Encephalitozoon spp. in particular can disseminate to the respiratory tract, among other locations. Patients on life-long immunosuppression are at higher risk of such infections, mostly symptomatic. Methods: Sputum samples and bronchial washings from 72 renal transplant recipients and 105 patients with various respiratory diseases were screened for Encephalitozoon spp. and E. bieneusi by microscopic examination and genus-specific nested PCR followed by genotyping. Results: A total of 8.3% (6/72) of immunosuppressed renal transplant recipients and 1.9% (2/105) of patients with various respiratory diseases, both immunocompetent and immunosuppressed, were positive for respiratory microsporidial infection. All six transplant recipients were Encephalitozoon cuniculi-positive by PCR/sequencing and five of them suffered from respiratory symptoms. The presence of microsporidial spores was also confirmed microscopically in three of the transplant recipients. Of the two immunocompetent patients with various respiratory diseases, one had an E. cuniculi infection, while the second had an E. bieneusi infection. Conclusions: Life-long immunosuppression in renal transplant recipients increases the risk of respiratory infection by E. cuniculi. Microsporidia should be screened in respiratory samples of these patients, particularly when they have respiratory symptoms.

Pneumocystis jirovecii is an opportunistic fungus occurring in human lungs. The group at highest risk consists of HIV-infected and non-HIV-infected immunosuppressed individuals. In these patients, P. jirovecii infection may lead to Pneumocystis pneumonia; it may, however, persist also in an asymptomatic form. This study aimed to determine the prevalence of P. jirovecii and potential risk factors for infection in a group of renal transplant recipients and to characterize the genetic diversity of this fungus in the studied population. Sputum specimens from 72 patients were tested for presence of P. jirovecii using immunofluorescence microscopy, as well as nested PCR targeting the mtLSU rRNA gene. Genotyping involving analysis of four loci—mtLSU rRNA, CYB, DHPS, and SOD—was used to characterize the diversity of the detected organisms. Pneumocystis DNA was detected in eight (11.11%) patients. It has been shown that low eosinophil count and dual immunosuppressive treatment combining prednisone and calcineurin inhibitors are potential risk factors for colonization. Analysis of genotype distribution showed an association of the wild-type genotype of mtLSU rRNA with lower average age of patients and shorter time after kidney transplantation. Furthermore, CYB 2 genotype was detected only in patients with the ongoing prophylaxis regimen. In conclusion, renal transplant recipients are at risk of Pneumocystis colonization even a long time after transplantation. The present preliminary study identifies specific polymorphisms that appear to be correlated with certain patient characteristics and highlights the need for deeper investigation of these associations in renal transplant recipients.

There are more than 200 different diseases classed as interstitial lung diseases (ILDs). For epidemiological and practical purposes, ILDs are classified into diseases of known and unknown etiology. The aim of this review is to evaluate our current knowledge about the efficacy and safety of pulmonary rehabilitation (PR) in patients with ILDs. Other issues, such as ILD pathogenesis, prevalence and comorbidity, are also elaborated in the review. Pulmonary rehabilitation is an important part of comprehensive care for patients with ILDs. In comparison to PR for patients with chronic pulmonary obstructive disease (COPD), the number of clinical studies concerning PR for patients with ILDs is small. The majority of trials have been performed in relatively small groups of patients. The principles of PR in this group of patients are the same as for patients with COPD. Exercise-induced desaturation is frequently observed during PR, which is the main source of complications in patients with ILDs. Major differences between ILD and COPD patients include poorer exercise tolerance and faster development of respiratory failure in patients with ILDs.

Introduction:Chronic inflammation in asthmatic airways leads to bronchial hyper-responsiveness (BHR) and the development of structural changes. Important features of remodeling include the formation of subepithelial fibrosis due to increased collagen deposition in the reticular basement membrane. Transforming growth factor (TGF)-β might be a central mediator of tissue fibrosis and remodeling.Materials and Methods:Immunohistochemistry was used to measure collagen III deposition and TGF-β1 expression in biopsies from patients with long-standing asthma treated with inhaled corticosteroids, patients with recently diagnosed asthma, and control subjects. Computer-assisted image analysis was used to evaluate total basement membrane (TBM) thickness.Results:Asthmatics, particularly those with long-standing asthma, had thicker TBMs than healthy subjects. Collagen III deposition was comparable in the studied groups. BHR was not correlated with features of mucosal inflammation and was lower in steroid-treated patients with long-standing asthma than in subjects with newly diagnosed asthma untreated with steroids. Epithelial TGF-β1 expression negatively correlated with collagen III deposition and TBM thickness.Conclusions:The study showed that TBM thickness, but not collagen III deposition, could be a differentiating marker of asthmatics of different disease duration and treatment. The lack of correlation between BHR and features of mucosal inflammation suggests the complexity of BHR development. Corticosteroids can reduce BHR in asthmatics, but it seems to be less effective in reducing subepithelial fibrosis. The role of epithelial TGF-β1 needs to be further investigated since the possibility that it plays a protective and anti-inflammatory role in asthmatic airways cannot be excluded.

suggests the need to adopt management strategies, including active surveillance, for leishmaniasis in the region. These actions would facilitate the successful implementation of guidelines from the ongoing National Kala-azar Elimination Programme in India. Acknowledgments We are grateful to Abidha Suresh and Jessu S. Mathew for their technical help and to the Directorate of Health Services, Government of Kerala, India, for facilitating the study.