Possible Role of IL-25 in Eosinophilic Lung Inflammation in Patients with Chronic Eosinophilic Pneumonia

Purpose

Interleukin (IL)-25 and IL-33 induce IL-5 production by various types of cells, such as type 2 helper T (Th2) cells and type 2 innate lymphoid cells. The number of Th2 cells and concentration of IL-5 in the bronchoalveolar lavage fluid (BALF) are increased in patients with eosinophilic pneumonia (EP). To examine the contribution of IL-25 and IL-33 to eosinophilic inflammation of the lung in humans, we evaluated IL-5, IL-25 and IL-33 levels in the BALF of patients with EP.

Methods

IL-5, IL-25, and IL-33 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP), idiopathic pulmonary fibrosis (IPF), and sarcoidosis.

Results

The absolute number of eosinophils, and IL-5 levels, but not IL-33 levels, in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. IL-25 levels in the BALF were significantly higher in patients with CEP, but not in patients with AEP, than in patients with IPF and sarcoidosis. The absolute number of eosinophils was significantly correlated with the IL-5 concentration in the BALF of patients with EP. IL-5 concentrations were significantly correlated with IL-25 concentrations in the BALF of patients with CEP, but not in patients with AEP. IL-5 levels were not correlated with IL-33 levels in the BALF of patients with EP.

Conclusions

Our findings suggest that IL-25 plays an important role via IL-5 in eosinophilic lung inflammation in patients with CEP.

     

Increased asymmetric dimethylarginine and enhanced inflammation are associated with impaired vascular reactivity in women with endometriosis

Objective

Enhanced inflammatory responses which may inhibit vascular reactivity, are associated with endometriosis development. Asymmetric dimethylarginine (ADMA), an inhibitor of endogenous nitric oxide synthase, is also implicated in endothelial dysfunction. We aimed to determine whether plasma ADMA and systemic inflammation are associated with endothelial function in women with endometriosis.

Methods

We evaluated 41 women with and 28 women without endometriosis. Plasma levels of lipids and inflammatory markers such as high sensitive-C reactive protein (hs-CRP), serum amyloid protein A (SAA), and interleukin-6 (IL-6) were measured in the two groups. We also measured levels of ADMA and symmetric dimethylarginine (SDMA). High-resolution ultrasonography measured flow-mediated vasodilation (FMD) to assess vasodilatory responses.

Results

FMD was significantly lower in women with endometriosis compared to those without endometriosis (8.39 ± 0.43% vs 10.79 ± 0.54%, P = 0.001). While plasma lipid levels did not differ significantly between groups, levels of AMDA, but not SDMA, were significantly higher in women with endometriosis (409.7 ± 10.1 pmol/L vs 383.0 ± 48.3 pmol/L, P = 0.04). Inflammatory markers were also significantly higher in these women (hs-CRP: 1053.3 ± 252.0 ng/mL vs 272.0 ± 83.3 ng/mL, P = 0.02; SAA: 8.00 ± 1.53 μg/mL vs 3.82 ± 0.42 μg/mL, P = 0.04; IL-6: 2.73 ± 0.75 pg/mL vs 1.05 ± 0.60 pg/mL, P = 0.04). FMD was negatively correlated with plasma levels of ADMA (r = −0.37, P = 0.01) and log hs-CRP (r = −0.34, P = 0.01).

Conclusion

Increased plasma ADMA levels and enhanced inflammation are associated with inhibited endothelial function in women with endometriosis.     

Efecto a largo plazo de la presión positiva automática en la vía aérea sobre la proteína C reactiva y la interleucina-6 en varones con síndrome de apnea obstructiva del sueño

Background and objectives

Obstructive sleep apnoea (OSA) has been increasingly linked to cardiovascular disease. Inflammatory processes associated with OSA may contribute to this morbidity. Some studies have reported serum levels of high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) to be increased in these patients. Primary objective: investigate the impact of short and long-term autoadjusting positive airway pressure (APAP) therapy on IL-6 and hs-CRP serum levels in patients with moderate to severe obstructive sleep apnoea. Secundary Objective: evaluate the basal hs-CRP and IL-6 levels in OSA patients and its possible relation to OSA severity, independently of confounders and compare the hs-CRP levels in OSA patients with those in community controls.

Patients and methods

This is a prospective study including 98 male patients with moderate to severe OSA confirmed by domiciliary sleep study. Malignancy and chronic inflammatory diseases were exclusion criteria. hs-CRP and IL-6 serum levels were evaluated before APAP, 9 days and 6 months after therapy. Community controls (n=103) were selected using random digit dialling, and matched by age and body mass index (BMI) for comparison of hs-CRP levels at baseline.

Results

The studied population had a mean age of 55.3±10.7 years, mean BMI 33.2±5.0 kg/m², mean apnoea-hypopnoea index 51.7±21.3/h and mean desaturation index 86.3±5.3/h. The APAP compliance was good: 91.27%±20.45 days usage and 5.76±1.59 h/night of usage.Mean basal hs-CRP and IL-6 serum values were 0.52±0.53 μg/l and 17.7±22.5 μg/l, respectively. CRP levels at baseline correlated significantly with apnoea-hypopnoea index, desaturation index and minimum nocturnal oxygen saturation. IL-6 levels at baseline correlated significantly and negatively with minimum nocturnal oxygen saturation. When adjusting for confounding factors found in this study, all these relations lost significance.CRP is significantly increased in patients when compared to controls (p=0.002) and when considering hs-CRP cardiovascular risk stratified categories, cases had significantly more patients at high risk of cardiovascular events than controls (p=0.002).After adjustment for BMI and arterial hypertension, cases had an almost twofold moderate risk of cardiovascular events and more than a twofold severe risk of cardiovascular events when compared to controls.We found no significant difference between hs-CRP and IL-6 concentrations pre-treatment and in two moments post-treatment (9 days and 6 months) (CRP: p=0.720 and p=0.387, respectively; IL-6: p=0.266 and p=0.238, respectively).

Conclusions

OSA is associated with a low-grade inflammatory process; hs-CRP serum levels are elevated in OSA patients when comparing to community controls, independently of age and BMI and the former have a significantly higher risk of cardiovascular events when compared to the latter. There was no significant decrease of both inflamatory mediators (hs-CRP, IL-6) after short and long-term APAP therapy.     

Ischemia-Modified Albumin: Could It Be a New Oxidative Stress Biomarker for Colorectal Carcinoma?

Background/Aims

An impaired oxidative/antioxidative status plays an important role in the pathogenesis of many diseases, including cancer. The aim of this study was to evaluate the levels of the novel marker ischemia-modified albumin (IMA) and albumin-adjusted IMA (Adj-IMA) in patients with colorectal cancer (CRC) and look for the associations of these with the total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI).

Methods

Forty patients with CRC (19 females and 21 males; mean age, 56.5±2.1 years) and 39 age- and sex-matched healthy people (22 females and 17 males; mean age, 56.0±1.7 years) were included in this study. Serum levels of IMA, TAS, and TOS were analyzed, and the OSI was calculated.

Results

Serum IMA, TOS, and OSI levels were significantly higher in patients with CRC than in controls (p<0.0001), whereas TAS levels were significantly lower in CRC patients (p=0.03). There was no significant difference in serum Adj-IMA levels between groups (p=0.32).

Conclusions

In this study, the oxidative/antioxidant status was impaired in favor of oxidative stress in CRC patients. This observation was not confirmed by IMA measurement. Further studies are needed to establish the relationship between IMA and oxidative stress parameters in CRC and other cancers.     

Changes in healthy elderly women's physical performance: a 3-year follow-up

Background

Inflammatory states, hypovitaminosis D and secondary hyperparathyroidism may have a role in the age-related loss of muscle mass, and physical performance in healthy old people. The aim of this study is to investigate changes in muscle mass, strength and physical performance in healthy, active elderly females over a 3-year follow-up, correlating them with any inflammatory states and PTH and 25-hydroxyvitamin D (25-OHD) levels.

Methods

One hundred healthy females over 65 years of age routinely attending a twice-weekly mild fitness program were eligible for the study. Clinical history, serum parameters, body composition by DEXA, handgrip strength, knee extensor isometric/isotonic strength and functional performance measured using the Short Physical Performance Battery (SPPB) were evaluated at the baseline and after 3 years.

Results

After 3 years, the women had a significant decrease in weight (?:−0.8 ± 3.1 kg; p < 0.05) and height (?:−0.4 ± 0,6 cm; p < 0.001), while their BMI and body composition parameters did not change. Only IL-6 (?: 0.6 ± 2.0; p < 0.01) and PTH (?: 30.7 ± 29.2 ng/L; p < 0.001) increased significantly, while there were no changes in 25-OHD levels. There was a significant decrease in all the SPPB results and in muscle strength. ? PTH only correlated with the variation in 4-meter walking speed (r: 0.41; p < 0.01).

Conclusions

With advancing age, physical performance declines even in healthy, active females despite a spare of muscle mass. The increase in PTH seems to have a role in this decline, that could be clarified by further investigations.     

La stretta correlazione tra la funzione ventricolare destra valutata all’ecografia tridimensionale e la capacità funzionale nei pazienti con cardiomiopatia dilatativa

Objectives

The aim of the study was to detect if right ventricular (RV) ejection fraction assessed by real-time 3D echocardiography (RT3DE) could predict patients with dilated cardiomyopathy (DCM) with greater functional impairment in response to cardiopulmonary exercise.

Materials and methods

55 chronic heart failure patients with DCM (56.5 ± 9.1 years; 40 males; 30 ischaemic; NYHA class III: 40) and 30 healthy controls underwent both left ventricular (LV) and RV analysis by RT3DE. Post-processing software provided data of RT3DE systolic dyssynchrony index (SDI) of 16 LV segments, and of both LV and RV ejection fraction. Cardiac magnetic resonance was performed in a subgroup of 20 DCM patients to confirm RT3DE measurements. DCM patients underwent also bicycle cardiopulmonary exercise test with evaluation of VO₂ peak (percentage of the predicted value), VE/VCO₂ slope and circulatory power (CP).

Results

In DCM patients mean LV ejection fraction was 29.8 ± 4.6%. RT3DE LV SDI was 8.4.4 ± 4.2, and RV ejection fraction was 51.3 ± 4.6%. By cardiopulmonary test, mean VO₂ peak was 15.2 ± 4.4 mL/kg/min, and mean CP was 2.1 ± 0.8. By univariable analysis, RV ejection fraction directly correlated with VO₂ peak % (r = 0,55; p < 0.0001) and inversely with VE/VCO₂ slope (r = –0.42; p < 0.001). By multivariable analysis, SDI (beta coefficient = –0.46; p < 0.001) and 3D RV ejection fraction (beta coefficient = 0.42; p < 0.001) emerged as the only independent determinant of VO₂ peak % during cardiopulmonary test.

Conclusions

Impaired RV function in DCM patients is independently associated with worse ability to perform aerobic exercise.     

Serum prolidase activity,oxidative stress,and nitric oxide levels in patients with bladder cancer

Objectives

Prolidase is a member of the matrix metalloproteinase family. It plays a major role in collagen turnover, matrix remodeling and cell growth. Nitric oxide (NO) regulates many processes such as collagen synthesis and matrix remodeling. Thus, NO may augment angiogenesis, tumor invasion, and metastasis. The aim of this study was to investigate total antioxidant status (TAS), malondialdehyde (MDA) and NO levels in patients with bladder cancer and to determine their relationship with prolidase activity.

Design and methods

Thirty-five patients with bladder cancer and 32 controls were enrolled. Serum TAS, MDA, prolidase activity and NO levels were determined.

Results

Serum prolidase activity, NO levels and MDA levels were significantly higher in bladder cancer than controls (all, P < 0.05), while TAS levels were significantly lower (P < 0.05).

Conclusions

Our results show that increased prolidase seems to be associated with increased NO levels and oxidative stress along with decreased antioxidant levels in bladder cancer.

     

Non traditional risk factors of carotid atherosclerosis in rheumatoid arthritis

Introduction

Cardiovascular events are markedly increased in rheumatoid arthritis, and they remain poorly understood.

Aim of work

To investigate inflammatory markers, markers of endothelial dysfunction, antioxidant vitamins and rheumatoid arthritis-related factors as non traditional risk factors for occurrence of carotid atherosclerosis in rheumatoid arthritis patients.

Patients and methods

Thirty RA patients were included in this study. All of them were females and their ages ranged from 23 to 62 years with a mean of 43.95 ± 7.2 years. All of them were subjected to full history taking, thorough clinical examination, laboratory investigations, disease activity assessment, bone erosion assessment by Modified Larsen score and functional assessment by health assessment questionnaire (HAQ) score. Carotid Duplex was done to measure the intima-media thickness (IMT) and carotid plaques. The patients who proved to have carotid atherosclerosis by ultrasound were subjected to ultrasound examination of brachial artery flow mediated dilatation (FMD) to confirm presence of endothelial dysfunction in those patients.

Results

Ten out of 30 RA patients (33.3%) had carotid atherosclerosis in whom there was impaired FMD denoting endothelial dysfunction. Among those patients, the risk factors that associated with occurrence of carotid atherosclerosis included higher levels of inflammatory markers (CRP, ESR and IL-6) and VCAM-1 (a marker of endothelial dysfunction), lower levels of antioxidant vitamins A and E, and RA-related factors as longer duration of disease, increased RF titer, increased HAQ-score, bone erosion, duration of prednisone use and prednisone cumulative dose.

Conclusion

The prevalence of carotid atherosclerosis in rheumatoid arthritis patients was 33.3%. Among those patients, a statistically significant association was found between occurrence of carotid atherosclerosis and inflammatory markers, endothelial dysfunction, antioxidant vitamins and rheumatoid arthritis related factors.     

Decreased circulating lipoprotein-associated phospholipase A2 levels are associated with coronary plaque regression in patients with acute coronary syndrome

Objective

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vascular-specific inflammatory enzyme, of which increases are associated with cardiovascular events. However, the relationship between circulating Lp-PLA2 levels and coronary plaque volume has not been clarified in patients with acute coronary syndrome (ACS).

Methods

We studied 40 patients with ACS (age, 61.4 ± 8.0 years; male, 87.5%; statin use, 45.0%) who had undergone successful percutaneous coronary intervention (PCI). Plaque volume (PV) in non-culprit sites of PCI lesions was precisely determined using grayscale intravascular ultrasound (IVUS) at onset and at six months later. We then analyzed associations among PV, lipid profiles and Lp-PLA2 levels.

Results

Circulating Lp-PLA2 levels and PV significantly decreased between baseline and six months of follow-up (458.6 ± 166.7 IU/L vs. 378.4 ± 158.5 IU/L, p < 0.001 and 82.2 ± 34.8 mm³ vs. 77.3 ± 33.1 mm³, p < 0.001, respectively). The % change in PV positively and significantly correlated with % change in LDL-C and in the LDL-C/HDL-C ratio (r = 0.444, p = 0.004 and r = 0.462, p = 0.003, respectively). Furthermore, % changes in Lp-PLA2 and in PV correlated even more closely (r = 0.496, p = 0.001). The absolute change in PV also significantly correlated with the change in Lp-PLA2 levels (r = 0.404, p = 0.009).

Conclusions

Circulating Lp-PLA2 levels are associated with changes in coronary plaque determined by IVUS in patients with ACS.     

Surgical repair and biological therapy for fecal incontinence in Crohn's disease involving both sphincter defects and complex fistulas

Background and aims

Surgeons have traditionally tried to avoid any complex surgical procedures in Crohn's patients with complex perianal diseases because of the fear of complications, worsening the patient's condition and risking an eventual proctectomy. The introduction of biological therapy has changed the management of Crohn's disease. This study assesses the long-term success of addressing defects in anal sphincter and complex fistula when patients receive anti-TNF-α antibodies.

Methods

Ten consecutive patients were prospectively scheduled for induction therapy with 5 mg/kg Infliximab at week 0, 2 and 6 and maintenance every 8 weeks associated with azathioprine. Elective surgery was performed conducting a simultaneous approach to the sphincter defect and fistula tracts. Outcomes were long-term continence, complications which were assessed by a Wexner's score along with a complementary questionnaire. Statistical analysis was performed using general linear model of repeated measures.

Results

Three patients had complications related to surgery: two abscesses and low intersphincteric fistula and one case of rectal stenosis causing fecal urgency. There was no suture dehiscence. Wexner's score improved at 12 months (10.0 ± 2.4 vs. 18.0 ± 2.6; p = 0.003) and over time (48 month 9.5 ± 2.8; p = 0.001). These scores were significantly worse when patients had urgency before treatment (12.8 ± 1.2 vs. 9.5 ± 2.8; p = 0.03) but not when the urgency appeared later. No patient remained incontinent to solid stools. Three patients had occasional incontinence to liquid stools associated to disease reactivation.

Conclusion

Surgical repair and immunomodulator therapy with infliximab could be an option in incontinent patients with Crohn's disease involving both a sphincter defect and severe or refractory fistulas.     

Asymptomatic carotid plaque rupture with unexpected thrombosis over a non-canonical vulnerable lesion

Objective

Several studies have demonstrated that carotid plaque rupture and thrombosis represent the most important factors correlated with the onset of acute cerebrovascular symptoms. Nevertheless, ruptured thrombotic plaques have been described also in asymptomatic patients. What still needs to be clarified is why a plaque rupture leads either to an acute ischemic syndrome or, in a minor group of patients, remains asymptomatic. The purpose of this study was to systematically compare the histologic features of thrombotic plaques both in asymptomatic and symptomatic patients in order to identify specific findings that could explain the peculiar clinical behavior that characterizes each of the clinical settings.

Methods

A total of 157 thrombotic plaques from 60 asymptomatic patients and 97 with major stroke who consecutively underwent CEA were serially sectioned and studied by histology.

Results

A minute cap disruption very frequently characterizes thrombotic plaques of asymptomatic patients and it was always smaller than large ulcers observed in thrombotic symptomatic plaques (651 ± 687 μm vs. 4150 ± 3526, p = 0.001). In asymptomatics this typical feature was associated with fewer inflammatory cells (20.1 ± 8.8 vs. 33.9 ± 26.1 cells × hpf, p = 0.001), smaller lipidic–necrotic core (33.9% ± 2.9% vs. 42.0% ± 2.4%; p = 0.04) and larger calcification (16.2 ± 12.8% vs. 8.1 ± 12.2%, p = 0.02). Symptomatic patients with thrombotic plaques showed higher incidence of metabolic syndrome (p = 0.002) and moderate-high Framingham risk scores (p = 0.001) comparing to asymptomatic individuals.

Conclusion

The transformation from a stable to a vulnerable plaque is a gradual process in the natural history of the disease and plaque rupture is an event not necessarily occurring at a late phase but also at earlier one. In this case, the rupture will be most likely smaller and clinically asymptomatic.     

Atherosclerosis in an Indian cohort of rheumatoid arthritis with low disease activity and its correlation with inflammatory markers

Background

Patients of rheumatoid arthritis (RA) have close association with an increased risk of cardiovascular disease. The earliest stage of atherosclerosis is exhibited by endothelial dysfunction, which is an expression of a systemic phenomenon.

Objective

To evaluate the effect of inflammation of RA on endothelial function and its correlation with inflammatory markers, in young patients RA with low disease activity and without traditional cardiovascular risk factors by measuring endothelial reactivity.

Methods

Flow-mediated vasodilatation (FMV), assessed by non-invasive ultrasound on the brachial artery, was evaluated in 50 young to middle aged patients with RA (age between 18 and 55 years) with disease activity score ≤3.2, without overt cardiovascular disease, at the age of 50 years, and sex matched healthy controls.

Results

Mean FMV was found significantly lower in RA patients than in controls ([4.03±1.9 vs. 8.7±1.7]%; P < 0.001), and it was inversely related to C-reactive protein level (r = −0.415; P < 0.01) expressed at the value measured at the time of ultrasound evaluation.

Conclusions

RA patients, young to middle aged, having low disease activity, free from overt cardiovascular disease and cardiovascular risk factors, have an altered endothelial reactivity that seemed to be primarily related to the inflammatory state of the disease.     

Pulmonary surfactant-associated proteins and inflammatory factors in obstructive sleep apnea

Purpose

Pulmonary surfactant (PS) plays roles in promoting the removal of the liquid, host defense, and immune regulation in the tracheal, bronchial, and alveoli epithelium. PS protein expression level can be regulated by oxygen levels and related free radicals. Obstructive sleep apnea (OSA) is featured with oxygen free radical production for damaging epithelial tissues and thus may affect PS production. The study was to explore the relationship between PS protein and OSA severity.

Methods

We collected serum and bronchoalveolar lavage fluid (BALF) samples from 35 OSA patients and 22 healthy subjects. PS-associated proteins and inflammatory factors, including surfactant proteins, HIF-1α, NF-κB, and IL-6, were analyzed. Regression analysis was performed to reveal the relationship between biochemical factors and clinical indexes recorded during PSG monitor.

Results

Lower BALF and surfactant protein (except surfactant protein C or SPC) levels occurred in OSA patients (all p < 0.05 compared to control group). A strongly negative correlation was found between surfactant protein with apnea-hypopnea index (AHI) and other sleeping indexes including ODI₃ and ODI₄. Similar patterns were found in serum samples, which were strongly correlated with BALF counterparts. Surfactant proteins were further found to have negative regression with inflammatory factors such as HIF-1α, NF-κB, and IL-6.

Conclusions

This study established the relationship between PS-related protein with severity of OSA, plus their relationship with inflammatory factors. Our results provided possibly novel markers in general circulation for disease evaluation of OSA.

     

Decreased serum antioxidant capacity in patients with Wilson disease is associated with neurological symptoms

Background &; Aims

Wilson disease (WD) is an inherited disorder of copper disposition caused by an ATP7B transporter gene mutation, leading to copper accumulation in predisposed tissues. In addition to a genetic predisposition, other factors are likely to contribute to its clinical manifestation. The aim of the study was to assess whether oxidative stress affects the phenotypic manifestation of WD.

Methods

In 56 patients with WD (29 men; 26 with the hepatic form, 22 with the neurologic form, and eight asymptomatic; mean age 38.5?±?12 years), total serum antioxidant capacity (TAC) and inflammatory parameters (hs-CRP, IL-1??, IL-2, IL-6, IL-10, and TNF-??) were analyzed and related to the clinical manifestation, and mutations of the ATP7B gene. The control group for the TAC and inflammatory parameters consisted of 50 age- and gender-matched healthy individuals.

Results

WD patients had a significantly lower TAC (p?Conclusions Data from our study suggest that the increased oxidative stress contributes significantly to the clinical manifestation of WD; as a lower TAC is associated with the neurological symptoms in WD patients.     

Influence of ileal pouch anal anastomosis on bone loss in ulcerative colitis patients

Background and aim

Patients with ulcerative colitis (UC) are at an increased risk for low bone mineral density (BMD). It is unclear whether proctocolectomy with ileal pouch-anal anastomosis (IPAA) for UC alters the risk of bone loss. The aim of this study was to compare BMD in UC patients with and without IPAA.

Methods

A total of 267 patients with UC and IPAA (study group) were compared to 119 UC patients without IPAA (control group) in this cross-sectional study. The demographic and clinical variables including dual-energy X-ray absorptiometry scan results were compared. Patients were classified as having normal or low BMD, based on the criteria by the International Society for Clinical Densitometry. Univariate and multivariate analyses were performed to assess risk factors associated with low BMD. Age, gender, race, smoking status, steroid use, alcohol use, body mass index, years of absent estrogen protection, use of calcium, vitamin D supplements and disease duration were selected as covariates.

Results

83 (31.1%) had low BMD in the study group vs. 18 (15.1%) in the control group (p = 0.001). 2/13 (15.4%) had low BMD before surgery. The mean age of patients in the study and control groups were 44.7 ± 14.1 vs. 52.4 ± 17.7 years, respectively (p < 0.001). The hip BMD was lower in the study group (0.93 ± 0.17 g/cm2) than that in the control group (0.98 ± 0.17 g/cm2) (p = 0.038). Fragility fracture was documented in 23 (8.6%) patients in the study group vs. 3 (2.5%) in the control group (p = 0.038) Sixty-four (24.0%) of the study group patients were using corticosteroids after surgery in contrast to 93 (78.2%) in the control group (p < 0.001). On multivariable analyses, covariate adjusted factors associated with a low BMD in UC patients were advanced age [odds ratio (OR) 1.51 per 5 years; 95% confidence interval [CI], 1.34–1.71], low body mass index (OR = 2.37 per 5 kg/m² decrease; 95% CI, 1.68–3.36), and the presence of IPAA (OR = 6.02; 95% CI, 2.46–14.70). For the 13 IPAA patients who had information available, BMD before IPAA was low. After a median of 46 (Range 7–84) months after IPAA, BMD improved in 7/13 patients (53.8%), while it continued to be low in 6/13 (46.2%) patients.

Conclusions

Low BMD is common in patients with UC. The risk appears to persist even after colectomy and IPAA surgery suggesting that these patients need to be monitored for bone loss.     

Prediction of improvement in quality of life (QoL-AGHDA) in adults with growth hormone deficiency by normative reference limits: Data of the German KIMS cohort

Objective

The objective of the present study was to calculate sex- and age-specific normative values for health-related quality of life (HRQoL) in Germany using quantile regression. Furthermore, we investigate the estimates of these normative data to and to predict the improvement of QoL-AGHDA scores in the German KIMS cohort during growth hormone treatment.

Design

Normative data of HRQoL was assessed by quality of life assessment of growth hormone deficiency (GHD) in adults (QoL-AGHDA) in a representative sample of the German population (n = 4172). Corresponding data for 888 patients with GHD were retrieved from the German KIMS cohort (Pfizer International Metabolic Database).

Results

The overall mean QoL-AGHDA score of the general population was 4.8 ± 5.2. ANOVA indicated that variability in QoL-AGHDA scores did not differ significantly across gender (p = 0.20), whereas age was a significant predictor (p < 0.001). Given the QoL-AGHDA score distribution of the general population, we calculated reference values based on quantile regression. In KIMS patients we observed significantly higher QoL-AGHDA scores, 7.9 ± 6.5 (p < 0.001), before GH treatment. The optimal predictive QoL-AGHDA score was 6 (70th percentile) with a sensitivity of 0.57 and a specificity of 0.70 in ROC analysis. Furthermore, a baseline QoL-AGHDA score above the 70th percentile allowed predicting an improvement of QoL by GH treatment.

Conclusions

This study established normative reference values for the QoL-AGHDA in a representative sample of the German population. Based on these normative data a QoL-AGHDA cut-off value for prediction of improvement was investigated for the German population, which may facilitate clinical assessment of HRQoL response to GH replacement for patients with GHD.     

Elevated uric acid and adenosine triphosphate concentrations in bronchoalveolar lavage fluid of eosinophilic pneumonia

Background

Recent evidence has suggested that the innate immune response may play a role in the development of eosinophilic airway inflammation. We previously reported that uric acid (UA) and adenosine triphosphate (ATP), two important damage-associated molecular pattern molecules (DAMPs), activate eosinophil functions, suggesting that these molecules may be involved in the development of eosinophilic airway inflammation. The objective of this study was to measure the concentrations of DAMPs including UA and ATP in the bronchoalveolar lavage fluid (BALF) of patients with eosinophilic pneumonia (EP).

Robotic approach mitigates perioperative morbidity in obese patients following pancreaticoduodenectomy

Introduction

The aim was to evaluate the impact of obesity on perioperative outcomes in patients undergoing robotic pancreaticoduodenectomy (RPD) compared to open pancreaticoduodenectomy (OPD).

HJP272, A Novel Endothelin Receptor Antagonist,Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Hamsters

Introduction

Previous studies from this laboratory indicate that endothelin-1 (ET-1), a potent vasoconstrictor, may play an important role in lipopolysaccharide (LPS)-induced release of neutrophils from the pulmonary microvasculature. To further test this concept, Syrian hamsters were treated with a novel endothelin receptor A (ETA) antagonist (HJP272) prior to intratracheal instillation of LPS.

Methods

The effect of HJP272 on the LPS-induced inflammatory reaction was determined by measuring: (1) lung histopathological changes, (2) total neutrophils in bronchoalveolar lavage fluid (BALF), (3) expression of tumor necrosis factor receptor 1 (TNFR1) by BALF macrophages, and (4) alveolar septal cell apoptosis.

Results

Treatment with HJP272 significantly reduced each of these parameters during a 24-hr period following LPS instillation, supporting the concept that limiting the activity of ET-1 may reduce the extent of lung injury. This hypothesis was further tested by giving ET-1 prior to LPS instillation, which resulted in a marked enhancement of LPS-induced lung inflammation, as measured by BALF neutrophils and TNFR1-positive macrophages. Furthermore, the increase in neutrophils resulting from treatment with ET-1 was significantly reduced by HJP272, again demonstrating the ability of ETA receptor antagonists to limit the influx of these cells into the lung.

Conclusions

These findings suggest a potential therapeutic role for these agents in diseases where neutrophils are a significant cause of lung injury, such as bronchopneumonia, respiratory distress syndrome, and chronic obstructive pulmonary disease.