Serum Adipokine Levels in Patients Considered for Lung Transplantation.

The aim of the study was to investigate serum concentration of visfatin, irisin, and omentin in patients diagnosed as having end-stage lung diseases who qualified for lung transplantation (LTx) and to find the relationship between adipokine levels and clinical status. MATERIAL AND METHODS: The study population consisted of 23 consecutive patients (10 patients diagnosed as having cystic fibrosis, 6 patients diagnosed as having chronic obstructive pulmonary disease, and 7 patients diagnosed as having idiopathic pulmonary fibrosis) who qualified for LTx. Patients performed pulmonary function tests; visfatin, irisin, and omentin serum levels were assessed using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Mean visfatin serum level was 4.99 ± 3.83 pg/mL; mean irisin serum level was 2.82 ± 0.24 ng/mL; mean omentin serum level was 389.99 ± 320.85 ng/mL. Mean distance in 6-minute walk test (6MWT) was 310.62 ± 147.09 m. Average partial pressure of oxygen (pO2) was 55.79 ± 10.33 mm Hg, forced expiratory volume (FEV1) was 26.25 ± 22.38%, and forced vital capacity (FVC) was 56.95 ± 21.91% of a due value. There was no statistically significant correlation between adipokine levels and 6MWT, pO2, FEV1, and FVC in patients waiting for LTx, regardless of underlying lung disease. Significant difference between patients was noted only in 6MWT, FEV1, and pO2 in connection to lung disease. CONCLUSION: Our findings indicate that adipokines may not have a statistically significant effect on parameters of pulmonary function. Results require further investigation on a larger study group, especially comparison of adipokine serum levels between groups of overweight patients, obese patients, and patients with normal weight who qualify for LTx.

Immunosuppressive Treatment and Its Effect on the Occurrence of Pneumocystis jiroveci, Mycoplasma pneumoniae, Chlamydophila pnemoniae, and Legionella pneumophila Infections/Colonizations Among Lung Transplant Recipients.

BACKGROUND: The aim of the study was to assess the frequency of infections caused by Pneumocystis jiroveci, Chlamydophila pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae among lung transplant recipients in the context of immunosuppression. METHODS: The study group consisted of 94 patients (37 women and 57 men; mean age 42.03 years) transplanted between 2009 and 2016 at the Silesia Center for Heart Diseases (SCCS). Immunosuppressive treatment (induction and maintenance therapy) was assessed. The immunofluorescence methods were used to detect the P. jiroveci, L. pneumophila, C. pneumoniae, and M. pneumoniae antigens in samples obtained from the respiratory tract. RESULTS: Thirty-two of 94 graft recipients developed atypical or opportunistic infection. The median time of its occurrence was 178 days after transplantation. P. jiroveci was responsible for 84.38% of first infections. Five patients developed infection with P. jiroveci and C. pneumoniae. None of the infections occurred during induction of immunosuppression. An opportunistic or atypical infection developed in 19.35% of the patients treated with a tacrolimus-based regimen, and in 43.33% of patients on a cyclosporine-based regimen. CONCLUSION: Infection with P. jiroveci is a recognized problem after lung transplantation and should be monitored. The percentage of infected patients is higher in patients treated with a cyclosporine-based regimen in comparison to those treated with tacrolimus.

Bacterial Infections During Hospital Stay and Their Impact on Mortality After Lung Transplantation: A Single-Center Study.

INTRODUCTION: The aim of the study was to assess the impact of bacterial infection during hospital stay on long-term follow-up. MATERIALS AND METHODS: This was a retrospective single-center study of 97 recipients of lung transplantations performed between December 2004 and June 2016 at a single center. Information about age, sex, underlying lung disease, and date and type of procedure was gathered from patients' charts. Immunosuppressive treatment has been analyzed individually among the cohort. Microbiological evaluation included the presence of infection, bacterial species in recipients and donors, as well as type of biological material. RESULTS: During a mean hospitalization time of 57 days (range 4-398 days), 67 patients (69%) were diagnosed with bacterial infection. There were 120 episodes of infection caused by 32 species of bacteria. The most common were Pseudomonas aeruginosa (27%), Acinetobacter baumanii (21%), Klebsiella pneumoniae (10%) and Stenotrophomonas maltophilia (11%). Analysis revealed that 39 patients developed bronchiolitis obliterans syndrome (43%). Patients with A baumanii had a lower probability of survival than the rest of the population (P < .05). Patients treated with mammalian target of rapamycin inhibitors had a higher probability of survival. CONCLUSIONS: Infection with A baumanii affects lung transplant recipients' survival. Incorporating sirolimus could be beneficial for the lung transplant recipients' survival.

Lymphocyte subtypes CD3+, CD19+, CD16+CD56+, CD4+, CD8+, and CD3+HLA-DR+ in peripheral blood obtained from patients after thoracic organ transplantation.

INTRODUCTION: The aim of this study was to assess peripheral blood lymphocyte subtypes (CD3+, CD19+, CD16+CD56+, CD4+, CD8+, and CD3+HLA-DR+) obtained from thoracic organ recipients at various periods after transplantation. MATERIAL AND METHODS: Seventeen patients after lung transplantation (LT) and 5 patients after heart transplantation (HT) included 13 males (76.5%) and 4 females (23.5%) of overall mean age at the time of transplantation of 46.7±11.55 years and mean body mass index of 21.1±4. Lymphocyte phenotypes were estimated using Simultest IMK Plus. RESULTS: A significant decrease in lymphocytes of the majority of subtypes was observed at 1 year posttransplantation compared with normal ranges: CD19+ B lymphocytes in 56% of patients, CD8+ T cells among 48% and CD16+CD56+ natural killer elements, 56%. In contrast, there were increased numbers of activated lymphocytes (CD3+HLA-DR+). Beyond the 1-year observation, we observed a trend to normalize parameters among the majority of subjects. CONCLUSION: A clear tendency to a decrease number of peripheral blood lymphocytes of various subtypes was observed among thoracic organ recipients in the first year posttransplantation with the exception of activated HLA-DR+ cells. After the first year, there was slow restoration of lymphocytes.

Procalcitonin serum concentration in lung transplant recipients during mold colonization or infection.

BACKGROUND: This publication attempted to evaluate the frequency of mold colonization and infection and the procalcitonin serum concentrations (PCT) among lung transplant recipients. METHODS AND MATERIALS: We included 49 patients (36 males and 13 females) of mean age at transplantation of 47.1±13.6 years. Molds were isolated using routine microbiologic methods. PCT (ng/mL) was measured using an immunoluminescence assay with values below 0.5 showing no probability of infection, 0.5 to 2.0, a moderate infection risk; 2.0 to 10, a high infection risk; and above 10 high sepsis risk. RESULTS: Twenty-four (49%) patients revealed the presence of molds in material from the lower respiratory tract (sputum, tracheal, or tracheobronchial aspirate), mini-bronchoalveolar lavage. Aspergillus species was isolated in 14 (28.6%) patients, Penicillium in 7 (14.3%) patients, and Zygomycetes fungi in 9 (18.4%) patients. The average PCT value from 61 examinations of PCT during fungal isolation was 0.5±0.7 ng/mL. However, when the studied group was categorized according to the PCT range, the rates for the groups were no infection (n=30; 49.2%), moderate (n=20; 32.8%), high (n=9; 14.8%) and high sepsis risk (n=2; 3.3%). CONCLUSIONS: The mold colonization of transplanted lung is a frequent complication and should be considered even in the case of proper prophylaxis. Procalcitonin might be the marker helpful in mold infection diagnosis.

Visfatin serum levels in chronic hepatitis C patients.

Visfatin is a new adipokine involved in several processes. The data concerning visfatin in chronic hepatitis C (CHC) is small. To assess visfatin serum concentration and to study its association with biochemical and morphological features in CHC. Seventy nonobese patients with CHC (Group 1) confirmed by the presence of serum hepatitis C virus (HCV)-RNA and 20 healthy volunteers (Group 2), similar in age and BMI with normal fasting glucose and lipid profile were included. Visfatin was significantly increased in Group 1 compared with Group 2 (55.6 +/- 23.1 vs 23.7 +/- 3.8 ng/mL; P < 0.001). Visfatin was negatively associated with necro-inflammatory activity grade (r = -0.36; P = 0.007). The lowest levels were found in patients with the most advanced inflammation: grades 3-4 - 46.8 +/- 17.1, grade 2 - 52.6 +/- 18.4 and grade 1 - 75.2 +/- 27.6 ng/mL; P = 0.017. A significant difference was also shown comparing patients with minimal inflammatory activity to the rest of the cohort (P = 0.009). Visfatin receiver operating characteristic curve analysis for different necro-inflammatory activity - grade 1 vs grades 3-4 with area under the curve 0.81 indicated a good discriminant power for differentiation of moderate/severe inflammation, with the cut-off set at 57.6 ng/mL (sensitivity 75%, specificity 90%, positive predictive value 0.90, negative predictive value 0.75). Serum visfatin concentration increases significantly in CHC patients. These findings suggest that visfatin is important in the pathogenesis of the inflammatory process in CHC. Visfatin may play a dual role as a pro-inflammatory or/and protective factor. The measurement of visfatin serum concentration may serve as an additional tool in distinguishing more advanced grades of the necro-inflammatory activity.

Chemerin, vaspin and insulin resistance in chronic hepatitis C.

Adipocytokine profile seems to play a distinct role in the pathogenesis of chronic hepatitis C (CHC). Chemerin and vaspin are recently described adipocytokines with various suggested functions and potential to modulate inflammatory response and insulin resistance (IR). We assessed chemerin, vaspin and leptin serum concentration and studied their association with IR laboratory and morphological features in patients with hepatitis C. The study included 40 patients with hepatitis C and 20 healthy volunteers, similar in age and body mass index (43.6 +/- 11.6 vs 40.9 +/- 11.8 years and 25.0 +/- 4.1 vs 23.9 +/- 3.3 kg/m(2), respectively). Patients had to have a normal lipid profile, and diabetes was an exclusion criteria. Serum chemerin and leptin levels and IR were significantly higher in patients with hepatitis C when compared to the controls (P = 0.02, P = 0.02 and P = 0.02, respectively), whereas vaspin level was significantly decreased (P = 0.01). Serum chemerin was negatively associated with necro-inflammatory grade (r = (-0.49), P = 0.01). The lowest levels of serum chemerin were found in patients with moderate/severe inflammation (P = 0.03). Serum leptin tended to be up-regulated in patients with minimal inflammatory activity. Serum vaspin was higher, although not significantly, when fibrosis was more advanced. IR was positively associated with fibrosis stage (r = 0.33, P = 0.03). Serum chemerin and leptin were related to each other (r = 0.45, P = 0.02).Our findings support a complex interaction between the analysed adipokines and pathogenesis of inflammatory process in CHC. The role of chemerin and vaspin in pathogenesis of inflammatory response should be further investigated.

What else distinguishes cellular rejection grade 1A from 0? Annexin V and BCL in elective biopsies received from heart transplant recipients.

BACKGROUND: Despite morphologic differences of lymphocytes aggregation between nonrejection (0 on the International Society for Heart and Lung Transplantation [ISHLT] scale) and moderate focal cellular rejection (1a, ISHLT), genetic and clinical differences have not been shown in Cardiac Allograft Rejection Gene Observation (CARGO) studies. Therefore, we sought to compare the expression of selected antigens associated with apoptosis in heart transplant recipients in the context of grade 0 versus grade 1a cellular rejection episodes. We assessed the expression of annexin V, a nonspecific apoptosis marker, Bcl-2 as opposed to antiapoptotic activity of Bcl-xL and Bcl-xL/S. MATERIALS AND METHODS: We retrospectively examined 17 heart transplant patients (2 women and 15 men) of overall mean age of 46.2 +/- 13.9 years and body mass index of 25.7 +/- 3.2. Ten biopsies showed rejection grade 0 and the other 10, grade 1a on the ISHLT scale, comprising groups A and B, respectively. Endomyocardial biopsy specimens were processed using routine immunohistochemical methods. The expression of apoptotic molecules was assessed according to the IHC method: 0, the lack of expression; 1, trace; 2, distinct; and 3, strong. A correlation was analyzed between particular molecular expressions. RESULTS: We observed a significant increase in Bcl-2 expression associated with rejection. The expression of other antigens did not show a significant tendency. No correlation was noted among group A, whereas in group B those were significant strong and negative correlations with Bcl-2 and Bcl-xL/S. CONCLUSION: Bcl-2 expression corresponded to the morphologic progression of graft rejection as opposed to Bcl-xL/S activity.

Mixed cellular and humoral acute rejection in elective biopsies from heart transplant recipients.

OBJECTIVE: Acute cellular rejection in heart transplants is characterized by an active lymphocytic infiltration, whereas the humoral response shows complement deposits in myocardial tissue. Both reactions may produce hemodynamic compromise during the first months after orthotopic heart transplantation (OHT). The aim of this study was to estimate the coexistence of humoral rejection symptoms in the first posttransplant biopsy with mild/moderate cellular rejection as an additional prognostic factor. MATERIALS AND METHODS: The study group included 13 biopsies obtained from 11 men and 2 women of overall mean age of 52.6 +/- 5.3 years who displayed International Society for Heart and Lung Transplantation (ISHLT) mild/moderate rejection grades. The control group consisted of 11 biopsies obtained from 8 men and 3 women of overall mean age of 54.8 +/- 3.6 years with no signs of rejection. Complement deposits were determined immunohistochemically using anti-C4d antibodies (Quidel Corporation). RESULTS: None of the control cases showed a positive reaction, whereas 3 men in the study group of mean age of 56.1 +/- 5.8 years revealed regional positive anti-C4d expression with cellular infiltrates. This expression occurred in all myocardial components adjacent to lymphocytic infiltrations. The survival rates were comparable in both the pure cellular versus the mixed rejection groups. The relative rate of grade 3 rejection in the posttransplantation period was increased among patients with mixed types of rejection. CONCLUSIONS: The term "mixed acute rejection" should be applied to cases with coincidence of 2 forms of acute rejection. It seemed to be associated with more frequent grade 3 rejection processes upon long-term follow-up.

Frequency of Pseudomonas aeruginosa colonizations/infections in lung transplant recipients.

BACKGROUND: Lower respiratory tract infections remain a leading cause of morbidity and mortality after solid organ transplantation. The particularly increased susceptibility to infection is an especial problem in the early posttransplant period at the initial stage of immunosuppression, owing to direct contact with the hospital environment by mechanical ventilation, biopsies, injections, bronchoscopy, and bladder and vessel catheterizations exacerbated by the impaired clearance mechanisms after denervation of the transplanted lung. Airway colonization with Pseudomonas aeruginosa is common in lung transplant (LT) recipients. Therefore, we performed a retrospective analysis to address the frequency of P aeruginosa infections in our Center. MATERIALS AND METHODS: From January 2004 to December 2008, we performed 33 LT, including 4 heart-lung, 6 double, and 23 single lung transplantations. Respiratory samples were the main diagnostic material undergoing routine microbiological methods. RESULTS: P aeruginosa was isolated from 13 patients (39.4% of all 33 LT). In 10 cases (30.3%), we observed airway colonization together with lower respiratory tract infections. From 2005 to 2008, P aeruginosa was diagnosed in about 50% of LT patients each year: in 2005, 33.3%; 2006, 57.1%; 2007, 42.9%; and 2008, 40%. CONCLUSION: LT recipients in our center are at high risk for pseudomonal airway colonisation and lower respiratory tract infection that may have a significant impact on posttransplant follow-up.

Procalcitonin serum concentration during Pneumocystis jiroveci colonization or Pseudomonas aeruginosa infection/colonization in lung transplant recipients.

BACKGROUND: Allograft infection after lung transplantation (OLT) has a significant impact on outcomes and represents a diagnostic challenge. Pneumocystis jirovecii causes an opportunistic infection, life-threatening pneumonia among immunocompromised patients. Airway colonization with Pseudomonas aeruginosa is common in lung transplant recipients. The aim of the study was to evaluate procalcitonin (PCT) serum concentrations during P jiroveci and P aeruginosa colonization/infections in lung transplant recipients. MATERIALS AND METHODS: Fifteen OLT patients were retrospectively enrolled into the study (10 men and 5 women) of overall mean age of 41.4 +/- 14.6 years. In seven patients, P jiroveci cysts were diagnosed (group J) and in 13 patients, we isolated P aeruginosa (group A). In respiratory samples, P jiroveci was detected using an indirect immunofluorescence method, and P aeruginosa was isolated using routine microbiologic methods. PCT was measured using immunoluminescence assay. RESULTS: The average PCT value in group A was 0.30 +/- 0.21 and in group J, 0.88 +/- 0.43, a difference that was not significant. In group A, 3 patients (23.1%) has PCT values indicating moderate infection risk (PCT > 0.5) and one patient (7.7%), a high infection risk (PCT > 2.0 and <10). In group J, three patients (42.9%) has PCT values indicating moderate and one patient (14.3%), high infection risk. CONCLUSIONS: Bronchial tree colonization with P jiroveci as well as P aeruginosa colonization can be associated with increased PCT suggesting a general, systemic response in addition to local colonization.

Urinary iodine concentrations should be monitored to diagnose some thyroid gland diseases in heart transplant recipients.

BACKGROUND: According to the World Health Organization, iodine excreted in urine is a measure of its supply. According to the International Council for Control of Iodine Deficiency Disorders (ICCIDD), the urinary iodine (UI) should be >100 microg I per 1 liter of urine. Severe deficiency (SID) is diagnosed when UI is <50 microg/L and a moderate deficiency (MID) when UI is <100 microg/L. MATERIALS AND METHODS: UI analysis among 32 heart transplant recipients (26 men and 6 women); of overall mean age of 50.4 +/- 12.6 years was performed using the modified Program Against Micronutrient Malnutrition method, a spectrophotometric measurement based on the Sandell-Kolthoff reaction. Results were compared with those of thyroid stimulating hormone (TSH; microIU/mL), of free tri-iodothyronine (FT3; pg/mL), and thyroxine (FT4; ng/dL). RESULTS: The average UI among the whole group was 126.4 +/- 109.6 microg/L. SID occurred in 12 patients (37.5%) and MID in 4 (12.5%); namely, mean UI of 17.0 +/- 9.6 and 79.5 +/- 5.6, respectively. In the other 16 patients (50%), the average UI was high, namely, 220.1 +/- 72.1 IU/mL. TSH, FT3, and FT4 in the whole group were within normal ranges. However, FT4 values significantly differed when SID and MID patients were compared with those displaying the recommended UI: 0.8 +/- 0.2 and 0.9 +/- 0.1 versus 1.1 +/- 0.2 respectively (P < .05). We noted decreased values of TSH in 5 patients (15.6%) and of FT3 or FT4 in 6 subjects (18.8%). CONCLUSION: There exists significant iodine deficiency among heart transplant recipients. Measurements of urinary iodine together with thyroid gland hormones may be essential to prevent thyroid gland disturbances in these patients.

Postprandial response of ghrelin and PYY and indices of low-grade chronic inflammation in lean young women with polycystic ovary syndrome.

The aim of the study were to answer the question 1.) Whether circulating pro-inflammatory markers of endothelial dysfunction and due to chronic low-grade inflammation of obesity, are altered in untreated lean, young relatively healthy polycystic ovary syndrome (PCOS) patients in comparison with healthy controls; 2.) Whether postprandial plasma concentration pattern of ghrelin and PYY can be predictable as risk factors for atherosclerosis and depend of obesity. Forty young women with PCOS were divided in two groups: 19 lean and 21 obese. The control group included 20 lean, healthy volunteers. Plasma total and active ghrelin, total PYY and PYY(3-36), serum adiponectin and insulin were measured using RIA technique, serum sCD40L, visfatin, sP-, sE-selectins, resistin by EIA. Composition of test meal was: 527 kcal total and consisted of 24.1% fat, 54.4% carbohydrate and 21.5% protein. Total and active ghrelin and total PYY were significantly lower in obese PCOS women, whereas active ghrelin was also significantly lower in lean PCOS women compared to controls. Postprandial plasma total ghrelin levels decrease were blunted in lean and obese compared to controls (12.8 % and 18.2% vs 28.2 %). Postprandial plasma active ghrelin decreased in lean and obese PCOS groups (49.9 % and 44.1 %) and controls (63.8 %). PCOS subjects exhibited smaller rises in postprandial levels of total PYY. Postprandial plasma PYY(3-36) levels increased in obese PCOS women (30.9 %) and controls (41%), whereas lean PCOS women exhibited blunted increase (11.5%). sCD40L levels increased, whereas adiponectin decreased in PCOS groups independently, whereas rise in visfatin, sE- and sP-selectin and the fall in adiponectin was associated with obesity. sP- and sE -selectins correlated positively with obesity. In summary, our study provides the first evidence that lean untreated young PCOS women contribute to the so called "pancreatic islet adaptation to insulin resistance" because of ghrelin and PYY profiles. We confirmed existing of low-grade chronic inflammation in early stage of visceral obesity in lean PCOS patients. The lost endogenous "islet adaptation to insulin resistance" may lead to endothelial dysfunction and promote acceleration of atherosclerosis.