Comparing the diagnostic value of bronchoalveolar lavage fluid galactomannan,serum galactomannanan,and serum 1,3-β-d-glucan in non-neutropenic respiratory disease patients with invasive pulmonary aspergillosis

The incidence of invasive pulmonary aspergillosis (IPA) is increasing higher in non-neutropenic patients. This study aimed to assess the diagnostic performance of bronchoalveolar lavage fluid (BALF). Galactomannan (GM), serum GM, and 1,3-β-d-glucan (BDG) in non-neutropenic respiratory disease patients with IPA.A total of 333 non-neutropenic patients suspected IPA were recruited from Xiamen University Zhong Shan hospital between January 2016 and February 2019. One, 33, and 92 cases were diagnosed with proven, and possible IPA.BALF and serum GM were both elevated in the possible IPA group and the probable/proven IPA group (p < 0.001). BALF and serum GM showed a fair correlation in the possible IPA group (r = 0.286, p = 0.008), and moderate correlation in the probable/proven IPA group (r = 0.466, p = 0.005). When the cutoff value was 0.5, the sensitivity and negative likelihood ratio of BALF GM were superior to serum GM (78.3% vs 47.8%, 96.7% vs 91.6%). The specificity and positive likelihood ratio of BALF GM were slightly weaker than serum GM (91.8% vs 95.4%, 56.7% vs 85.0%). When the cutoff value was 1.0, the sensitivity and negative predictive value of BALF GM were better than serum GM (73.9% vs 26.1%, 94.5% vs 88.8%), and the specificity of were equivalent (99.2%). The optimal cutoff value of BALF GM was 0.6, wherein the sensitivity reached 78.3% and the specificity reached 95.4%. Given the extremely low sensitivity of serum BDG at different cutoff values (≥10 μg/mL = 5.3%, ≥20 μg/mL = 2.1%), it cannot be used as a preferred biomarker.The diagnostic performance of BALF GM was superior to other biomarkers and the optimal cutoff value was 0.6.     

Brain volume in Tanzanian children with sickle cell anaemia: A neuroimaging study

Brain injury is a common complication of sickle cell anaemia (SCA). White matter (WM) and cortical and subcortical grey matter (GM), structures may have reduced volume in patients with SCA. This study focuses on whether silent cerebral infarction (SCI), vasculopathy or anaemia affects WM and regional GM volumes in children living in Africa. Children with SCA (n = 144; aged 5–20 years; 74 male) and sibling controls (n = 53; aged 5–17 years; 29 male) underwent magnetic resonance imaging. Effects of SCI (n = 37), vasculopathy (n = 15), and haemoglobin were assessed. Compared with controls, after adjusting for age, sex and intracranial volume, patients with SCA had smaller volumes for WM and cortical, subcortical and total GM, as well as bilateral cerebellar cortex, globus pallidus, amygdala and right thalamus. Left globus pallidus volume was further reduced in patients with vasculopathy. Putamen and hippocampus volumes were larger in patients with SCA without SCI or vasculopathy than in controls. Significant positive effects of haemoglobin on regional GM volumes were confined to the controls. Patients with SCA generally have reduced GM volumes compared with controls, although some subcortical regions may be spared. SCI and vasculopathy may affect the trajectory of change in subcortical GM and WM volume. Brain volume in non-SCA children may be vulnerable to contemporaneous anaemia.     

Airway vascular damage in elite swimmers

We postulated that high level swimming can promote airway inflammation and thus asthma by enhancing local vascular permeability. We aimed to test this hypothesis by a cross-sectional study comparing swimmers (n = 13, 17 ± 3 years, competing 7 ± 4 years, training 18±3 h per week), asthmatic-swimmers (n = 6, 17 ± 2 years, competing 8 ± 3 years, training 16 ± 4 h per week), and asthmatics (n = 19, 14 ± 3 years).Subjects performed induced sputum and had exhaled nitric oxide, lung volumes, and airway responsiveness determined. Airway vascular permeability index was defined as the ratio of albumin in sputum and serum.Results from the multiple linear regression showed each unit change in airway vascular permeability index was associated with an increase of 0.97% (95%CI: 0.02 to 1.92; p = 0.047) in sputum eosinophilis, and of 2.64% (95%CI:0.96 to 4.31; p = 0.006) in sputum neutrophils after adjustment for confounders. In a general linear model no significant differences between airway vascular permeability between index study groups existed, after controlling for sputum eosinophilis and neutrophils.In conclusion, competitive swimmers training in chlorine-rich pools have similar levels of airway vascular permeability than asthmatics. Although competitive swimming has been associated with asthma, airway inflammation and airway hyperesponsiveness do not seem to be dependent on increased airway vascular permeability.     

The relationship between vitamin D and disease activity and functional health status in rheumatoid arthritis

We aimed to establish the relationship between serum vitamin D levels and disease activity and health status in rheumatoid arthritis. Sixty-five patients with RA fulfilling ACR criteria for the classification of rheumatoid arthritis and forty healthy controls were included in this study. Disease activity was assessed according to the Disease Activity Score including 28 joint counts. C-reactive protein (CRP, mg/dl) was determined by the nephelometric method. Erythrocyte sedimentation rate (ESR, mm/h) was determined by the Westergren method. Rheumatoid factor (RF, IU/ml) was also determined by the nephelometric method, and RF > 20 IU/ml was defined as positive. 25-OH Vitamin D EIA Kit was used to measure serum 25-OH Vitamin D levels. We found that the mean of the 25-OH D vitamin levels of the patients with RA was not different than that of controls (P = 0.936). We divided patients with RA into three groups according to DAS28 as low activity group (group 1, n = 25), moderate activity group (group 2, n = 25), and high activity group (group 3, n = 15). 25-OH vitamin D levels of the patients in the high activity group (group 3) were found to be the lowest (P < 0.001), and the patients with moderate disease activity had lower levels than those in the mild group (P = 0.033). Serum 25-OH vitamin D levels were significantly negatively correlated with DAS28, CRP, and HAQ (respectively, r = −0.431, P = 0.000, r = −0.276, P = 0.026, and r = −0.267, P = 0.031). Serum vitamin D levels in patients with RA were similar those in the healthy controls, while it significantly decreases in accordance with the disease activity and decreasing functional capacity.     

Serum levels of adhesion molecules ICAM-1 and VCAM-1 and tissue inhibitor of metalloproteinases, TIMP-1, are elevated in patients with autoimmune thyroid disorders: Relevance to vascular inflammation

Serum levels of ICAM-1 (Inter Cellular Adhesion Molecule-1), VCAM-1 (Vascular cell Adhesion Molecule-1-I), TIMP-1 (tissue inhibitor of metalloproteinases 1) and MMP-9 (Metalloproteinase 9) are well established markers of inflammation. The physiopathological link between inflammation, atherosclerosis and autoimmunity is well demonstrated. However, serum levels of these biomarkers in patients with autoimmune-mediated dysthyroidism, including their evolution after improvement of the thyroid disorder have not been assessed. So, we evaluated the circulating levels of these markers in autoimmune and in non-autoimmune-mediated dysthyroid patients, and their evolution after treatment of thyroid disease.We conducted a prospective study to evaluate these markers before and after treatment in hyperthyroid patients (n = 33; 28 patients with autoimmune disease), hypothyroid patients (n = 38; 33 patients with autoimmune disease) and euthyroid subjects (n = 33). At baseline, serum levels of ICAM-1, VCAM-1 and TIMP-1 were significantly elevated in patients with hyperthyroidism as compared to euthyroid and hypothyroid patients (respectively p = 0.0005 and p < 0.0001). In multivariate analysis, the differences remained significant for VCAM-1 and TIMP-1. Median levels of ICAM-1, VCAM-1 and TIMP-1 were significantly higher in patients with autoimmune-mediated dysthyroidism compared to euthyroid patients (respectively p < 0.0001 and p = 0.002). In hyperthyroid patients, ICAM-1, VCAM-1 and TIMP-1 concentrations fell significantly after they had become euthyroid (respectively p = 0.0006; p < 0.0001 and p = 0.0009), although VCAM-1 values remained higher than those observed in the control group (p = 0.005).We found that autoimmune-mediated dysthyroidism were associated with increased peripheral blood concentrations of VCAM-1, ICAM-1 and TIMP-1. Whether these biological abnormalities translate into increase intima remodelling and atherosclerosis remains to be studied.     

Altered serum levels of human neutrophil peptides (HNP) and human beta-defensin 2 (hBD2) in Wegener's granulomatosis

Defensins are highly conserved peptides with antimicrobial and immunomodulatory functions. Due to their chemotactic properties on mononuclear cells, including dendritic cells and macrophages, defensins may contribute to granuloma formation in Wegener’s granulomatosis (WG). In order to explore whether these peptides might be involved in WG pathogenesis, sera of patients were screened to detect altered defensin levels. For this purpose, serum and EDTA-blood of patients with WG (n = 17; aged 54.8 ± 15.5 years) and age- and sex-matched healthy controls (n = 24; aged 55.5 ± 16.8 years) were collected. Levels of neutrophil α-defensins (human neutrophil peptides, HNP) and β-defensin (hBD) 2 and 3 in serum were measured by ELISA. By this means, WG patients displayed higher serum levels of hBD2 and HNP when compared to controls. Furthermore, serum hBD2 was raised in patients with meningeal granulomas (n = 4) or in those undergoing treatment with cyclophosphamide (n = 4). In order to detect whether increased gene expression in polymorphonuclear cells is responsible for the elevated defensin levels, real-time polymerase chain reaction with gene-specific primers was performed. Expression of specific mRNA in polymorphonuclear cells was observed for HNP only, but did not parallel HNP serum levels, suggesting that degranulation rather than increased gene expression may be responsible for increased HNP serum levels in WG. In conclusion, elevated serum levels of HNP and hBD2 in WG patients suggest a role for both defensins in WG pathogenesis.     

Efficacy and safety of tacrolimus for lupus nephritis: a placebo-controlled double-blind multicenter study

We evaluated the efficacy and safety of tacrolimus in patients receiving glucocorticoid therapy for lupus nephritis. Patients with persistent nephritis were randomized to receive 28 weeks of double-blind treatment with tacrolimus (3 mg/day) or placebo. The primary endpoint was the change in the lupus nephritis disease activity index (LNDAI) calculated from scores for daily urinary protein excretion, urinary red cells, serum creatinine, anti-double-stranded DNA antibody, and serum complement. Statistical analysis was performed using the full analysis set. The LNDAI was decreased by 32.9 ± 31.0% (mean ± SD) in the tacrolimus group (n = 28) and was increased by 2.3 ± 38.2% in the placebo group (n = 35) at final evaluation. There was significant improvement in the tacrolimus group. Daily urinary protein excretion showed a significant decrease in the tacrolimus group (p < 0.001). The complement (C3) level showed a significant increase in the tacrolimus group (p = 0.001). Treatment-related adverse events occurred in 92.9% of the tacrolimus group and 80.0% of the placebo group, but the difference was not significant. In patients on glucocorticoid therapy for lupus nephritis, addition of tacrolimus to basal therapy achieved significant improvement compared with placebo. Tacrolimus may therefore be a useful alternative treatment for lupus nephritis.     

Vitamin D may not be a good marker of disease activity in Korean patients with systemic lupus erythematosus

Vitamin D is a pleiotrophic hormone with immunoregulatory properties. Low levels of vitamin D have been discovered in various autoimmune diseases. Here, we investigated serum vitamin D levels in Koreans with systemic lupus erythematosus (SLE) and examined whether levels correlate with disease activity of SLE. Blood samples were prospectively collected from patients with SLE (n = 104) and normal controls (NC, n = 49) during the spring from March to May 2008. The level of serum 25-hydroxyvitamin D (25(OH)D3) was measured by radioimmunoassay. The serum 25(OH)D3 levels of patients with SLE (42.49 ± 15.08 ng/ml) were significantly lower than NC (52.72 ± 15.19 ng/ml, P < 0.001). Additionally, 17 patients with SLE (16.3%) had vitamin D insufficiency, while two NC had vitamin D insufficiency (4.1%). The risk of vitamin D insufficiency was 4.6-fold increased in SLE (P = 0.032). The serum 25(OH)D3 levels, adjusted with BMI, were positively correlated only with hemoglobin (β = 0.256, P = 0.018) and serum complement 3 (β = 0.365, P = 0.002). Serum vitamin D levels were lower, and vitamin D insufficiency was more common in Korean patients with SLE, however, our study demonstrated that vitamin D levels might not be a good marker of disease activity.     

Human leucocyte antigen‐B27 subtypes in Korean patients with ankylosing spondylitis: higher B*2705 in the patient group

Aim: To investigate the distribution of human leucocyte antigen (HLA) class I antigens and B27 subtypings in a group of B27(+) ankylosing spondylitis (AS) patients and a group of B27(+) control individuals, and to compare differences in their clinical features using subtyping. Methods: At otal of 143 B27(+) AS samples and 32 B27(+) control samples were collected consecutively from two rheumatology centres in South Korea. All patients were diagnosed according to the modified New York criteria for AS. Medical records of the patients were retrospectively reviewed for demographic information, Bath disease activity index (BASDAI) scores, laboratory parameters at diagnosis and extra‐articular manifestations. Polymerase chain reaction‐sequence‐specific primer typing for the B27 subtypes was performed using the Dynal HLA‐B27 high resolution kit. Results: Whereas subtypes in Korean AS patients include B*2704 (n = 11, 7.7%) B*2705 (n = 130, 90.9%), and B*2710 (n = 2, 1.4%), those of the control groups include B*2704 (n = 11, 34.4%), B*2705 (n = 19, 59.4%), B*2710 (n = 1, 3.1%), and B*2715 (n = 1, 3.1%). The proportion of B*2705 subtypes were significantly higher in the AS group than the control group (P < 0.01). There were no differences in clinical features (peripheral arthritis, uveitis, BASDAI scores) or laboratory parameters between the two groups. Conclusion: In Korean AS patients, not in the control group, the HLA‐B*2705 subtype was higher than other subtypes, in contrast to AS patients from Japan and China. B27 subtypes in AS patients were not associated with clinical features or laboratory parameters.     

When the liver gets stiff,the tough get moving

Liver stiffness measurement (LSM) by FibroScan-determined transient elastography is a noninvasive approach to estimate liver fibrosis severity. In non-alcoholic fatty liver disease (NAFLD), advanced liver fibrosis is excluded by normal liver stiffness, but a wide range of cutoffs have been used to predict advanced liver fibrosis or cirrhosis. This may be partly because steatosis (measured by controlled attenuation parameter [CAP]) contributes to liver stiffness and also because LSM fluctuates in NAFLD. In a recent pivotal study, one-third of patients with liver stiffness > 12.0 kPa showed reversal after 4–6 months; these cases did not have advanced liver fibrosis on biopsy. We performed serial FibroScans 6–36 months apart in 73 NAFLD patients, 38 with LSM > 10 kPa at entry. Those who lost ≥ 1 kg of weight (n = 31) significantly reduced liver stiffness (3.6 ± 6.1 vs 0.53 ± 4.1 kPa, P < 0.05) and CAP score (39 ± 63 dB/m of loss vs 24 ± 65 dB/m of gain, P < 0.05) compared with those who did not (n = 29). Patients who reported increased physical activity (n = 25) also reduced liver stiffness (3.6 ± 6 vs 0.35 ± 6 kPa) and CAP (20 ± 71 dB/m of loss vs 32 ± 71 dB/m of gain). Overall, those with improved LSM were significantly more likely to have lost weight and/or improved physical activity. These effects of lifestyle adjustments partly explain why a single measurement of 12.0 kPa is not a reliable cutoff for advanced liver fibrosis in NAFLD. In addition to repeating the study after 6–12 months, documentation of response to lifestyle advice and weight reduction should be determined before assuming any cutoff indicates advanced liver fibrosis. Despite this reservation about diagnostic accuracy, we consider that measurement of liver stiffness and CAP score serve to motivate patients to enact lifestyle modifications that can improve NAFLD severity.     

Serum homocystein level and vascular thrombosis in patients with Behçet disease

Objective: Behçet disease (BD) is a multisystemic inflammatory disorder of unknown aetiology that in some patients will present with thrombosis. However, the mechanism of thrombosis is unknown. In this study, we investigate the correlation between homocystein level in BD patients with vascular thrombosis. Patient and methods: One hundred and twenty‐three patients who fullfilled the criteria of the International Study Group for BD (n = 77, 62.6% females and n = 46, 37.4% males) were included in this cross‐sectional study. Patients were divided into two groups: with thrombosis (n = 23, 18.7%) and without thrombosis (n = 100, 81.3%). All patients underwent colour Doppler sonography for documentation of vascular thrombosis. Serum homocystein was measured by ELISA method, folate and B12 were measured by radioimmunoassay. Results: Patients with vascular involvement, vein and/or arterial thrombosis were enrolled. Mean serum homocystein level was significantly higher in the group with thrombosis (P = 0.012) and in male patients than females (18.10 ± 5.5 vs. 13.21 ± 4.1). In multiple regression analysis, the only factors that persisted for thrombosis were age and sex (P = 0.02, P < 0.0001, respectively). Serum folate and B12 were not correlated with thrombosis in BD. Conclusions: In this study, we found that mean homocystein levels were higher in BD patients with thrombosis and it may have a role in the process of thrombosis in BD.     

Urokinase‐type plasminogen activator system and human cationic antimicrobial protein 18 in serum and induced sputum of patients with chronic obstructive pulmonary disease

Background and objective: There is increasing evidence that the innate immune system plays an important role in the pathogenesis of COPD. The objective of this study was to quantify several innate immune biomarkers in serum and induced sputum of COPD patients, and healthy non‐smokers and smokers. Methods: Serum and induced sputum levels of urokinase‐type plasminogen activator (uPA), urokinase‐type plasminogen activator receptor (uPAR), urokinase‐type plasminogen activator inhibitor (PAI‐1) and human cationic antimicrobial protein 18 (CAP18) were measured by ELISA, in 13 patients with stage I or stage II COPD (COPD I + II), 15 patients with stage III or stage IV COPD (COPD III + IV), 18 healthy non‐smokers and 14 healthy smokers. In addition, membrane‐bound uPAR in peripheral blood and induced sputum was assessed by flow cytometry. Results: Levels of uPAR, PAI‐1 and CAP18 were elevated in induced sputum of COPD I + II and COPD III + IV patients, compared with healthy non‐smokers (P < 0.05) and healthy smokers (P < 0.05). uPAR, PAI‐1 and CAP18 levels were significantly higher in COPD III + IV patients compared with COPD I + II patients (P < 0.05). The expression of uPAR on induced sputum neutrophils and macrophages was significantly higher in COPD patients compared with healthy non‐smokers (P < 0.05) and healthy smokers (P < 0.05). Sputum uPAR and CAP18 levels showed significant inverse correlations with FEV₁% and 6MWD, and significant positive correlations with St. George's Respiratory Questionnaire scores. Conclusions: In COPD patients, increased induced sputum levels of uPAR, PAI‐1 and CAP18 were associated with airflow limitation, health status and exercise tolerance, suggesting that these biomarkers may be implicated in the pathogenesis of COPD.     

Local and systemic application of tranexamic acid in heart valve surgery: a prospective,randomized, double blind LOST study

The study was performed to examine a possible augmentation of systemic administration of tranexamic acid by the additional topical application during heart valve surgery in the post-aprotinin era. One-hundred patients were enrolled in the study and all the patients were given tranexamic acid intravenously. The participants were randomized into two groups (A, n = 49; B, n = 51), and before commencing the sternal suturing, the study solution (group A: 250 ml of normal saline + tranexamic acid 2.5 g, placebo group B: 250 ml of normal saline) was poured into the pericardial cavity. The cumulative blood loss (geometric means [95% confidence intervals]) 4 h after the surgery was 86.1 [56.1, 132.2] ml in group A, and 135.4 [94.3, 194.4] in group B, test for equality of geometric means P = 0.107, test for equality of variances P = 0.059. Eight hours after the surgery, the blood loss was 199.4 [153.4, 259.2] ml in group A, 261.7 [205.1, 334.0] ml in group B, P = 0.130 and P = 0.050, respectively. Twenty-four hours postoperatively the blood loss was 504.2 [436.0, 583.0] ml in group A, 569.7 [476.0, 681.7] ml in group B, P = 0.293 and P = 0.014, respectively. The proportion of patients transfused postoperatively by fresh frozen plasma differed significantly between the two study groups (group A: n = 21, group B: n = 36, P = 0.008). Our hypothesis is supported by a significant difference in the inter-group variance of blood loss and the proportion of patients requiring fresh frozen plasma; however evident differences in mean postoperative blood loss were not statistically significant.     

Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitis B virus infection in Caucasians

Aim

Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitis B virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population.

Method

A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitis B envelope antigen (HBeAg) negative chronic hepatitis B (n = 255), with HBeAg positive chronic hepatitis B (n = 99) and with HBeAg negative HBV infection (n = 228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n = 195) and in healthy controls (n = 160).

Results

In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR = 1.75, 95% CI 1.04–2.94, p = 0.034), with an increased likelihood of HBeAg negative chronic infection (OR = 1.93, 95% CI 1.05–3.54, p = 0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07–3.39, p = 0.029) in male patients.

Conclusion

The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.     

Obstructive sleep apnea is the triggering factor for massive hemoptysis

Purpose

The purpose of this study was to investigate the prevalence of obstructive sleep apnea (OSA) in patients with hemoptysis.

Methods

Files of patients who had undergone bronchial arterial embolization due to hemoptysis between 1 December 2009 and 2015 were evaluated and interviews of patients were conducted until 1 June 2016. Pittsburgh Sleep Quality Index (PSQI), STOP and STOP-BANG surveys were administered. OSA risk was determined with Berlin Questionnaire.

Results

Study group consisted of 53 patients and 58 control subjects. Mean age was 46.94 ± 14.36 and 41.97 ± 12.92 in patient and control group, respectively. Of these patients, seven had re-embolization procedure because of recurrence of hemoptysis. High OSA risk was more common among patients with hemoptysis (24.5%, n = 13) than the control group (8.6%, n = 5) (p = 0.023). Percentage of high risk OSA patients with massive hemoptysis, nonmassive hemoptysis, and control subjects was 29.7% (n = 11), 12.5% (n = 2), and 8.6% (n = 5), respectively (p = 0.022). There were more high OSA risk subjects among patients with idiopathic hemoptysis 44.4% (four out of nine), while 20.5% (nine out of 53) patients with a known etiology had high risk (p = 0.127). The number of patients with high OSA risk was also higher in patients who required a second embolization procedure (four out of seven, 57.1%), while 19.6% of patients without need for re-embolization had high risk (p = 0.031).

Conclusions

OSA is found to be a risk factor for hemoptysis and also may provoke massive hemoptysis. It seems reasonable to consider OSA as an underlying condition in idiopathic hemoptysis. OSA may contribute to embolization failure.

     

Effects of plant stanol esters on serum cholesterol concentrations, relative markers of cholesterol metabolism and endothelial function in type 1 diabetes

We investigated the effect of plant stanol esters (STAEST) on serum total and LDL cholesterol concentrations and endothelial function in subjects with type 1 diabetes (T1D). In addition, the changes in the relative serum markers of cholesterol metabolism were recorded. In a parallel, randomized, double-blind study the intervention group (n = 11) consumed STAEST spread (2 g/day stanols) and the control group (n = 8) the same spread containing no added stanols for 12 weeks. At baseline, brachial artery diameter was negatively correlated with serum HDL cholesterol concentration (r = −0.476, P < 0.05), but not with total or LDL cholesterol concentrations or serum non-cholesterol sterol ratios to cholesterol. Flow-mediated dilatation was positively associated with serum absorption marker ratios to cholesterol, significantly so with the sitosterol ratio (r = 0.467, P < 0.05). During the intervention, serum total and LDL cholesterol concentrations were reduced by 4.9 and 6.9% from baseline in the STAEST group, and by 10.8 and 16.1% from controls, respectively (P < 0.05 for all). No significant changes in HDL cholesterol and serum triglyceride concentrations were found. The STAEST consumption reduced serum campesterol and sitosterol ratios by 17–21% (P < 0.05) from baseline, but the relative serum synthesis markers were not changed. Brachial artery diameter and flow-mediated dilatation did not change during the investigation. In conclusion, STAEST significantly reduced serum total and LDL cholesterol concentrations and serum plant sterol ratios without affecting HDL and triglyceride concentrations in subjects with T1D. STAEST had no effect on endothelial function.     

Cost and occurrence of thrombocytopenia in patients receiving venous thromboembolism prophylaxis following major orthopaedic surgeries

Background Many factors impact the choice of anticoagulant used for venous thromboembolism prophylaxis following orthopaedic surgery. Thrombocytopenia (TCP) is an important factor from both clinical and economic perspectives, warranting assessment between the available agents. Thus, a retrospective cohort analysis was conducted to: (1) report the occurrence of TCP in a treatment and no treatment group, (2) evaluate the impact of anticoagulant choice on TCP within the treatment group, and (3) assess the clinical and economic implications of TCP in the treatment group. Methods Administrative claims from a hospital database were used to identify patients with hip replacement, knee replacement, or hip fracture surgery. The treatment group (n = 144,806) included patients receiving one of the following injectable anticoagulants post-operatively: dalteparin (n = 16,109); enoxaparin (n = 97,827); fondaparinux (n = 12,532); or unfractionated heparin (UFH) (n = 18,338). The no treatment group consisted of patients who did not receive one of the four injectable anticoagulants (n = 112,574) post-operatively. Outcomes were assessed for the hospitalization period plus 2 months post-discharge while controlling for relevant demographic and clinical characteristics. Results The occurrence of TCP was 1.0% in the no treatment group and 1.7% in the treatment group. Within the treatment group, patients who received dalteparin, enoxaparin, and UFH were significantly more likely to experience coded thrombocytopenia than those in the no treatment group. The risk of TCP among patients who received fondaparinux was not significantly different from the no treatment cohort (odds ratio [OR] = 1.15, 95% CI: 0.96–1.37, P = 0.13). Patients in the treatment group with coded TCP had 22% higher adjusted mean total healthcare costs (relative cost difference) compared to those without ($19,134 vs. $15,400, respectively, P < 0.0001), greater mean length of stay (LOS) (8.4 vs. 5.7, respectively), and a greater likelihood of experiencing a venous thromboembolic (VTE) event (6.1% vs. 2.4%, respectively). Conclusion Patients treated with fondaparinux did not have a significant increase in the risk of TCP compared to patients not on prophylaxis. In contrast, the risk was increased in those treated with enoxaparin, dalteparin, and UFH compared to the patients not on prophylaxis. Patients in the treatment group with coded TCP experienced more thrombotic events, incurred greater per patient healthcare costs, and experienced longer LOS than patients without coded TCP. Therefore, the risk of TCP should be considered when evaluating the profile of injectable anticoagulants since TCP may have important clinical and economic implications.     

Influence of age on symptoms and laboratory findings at presentation in patients with influenza-associated pneumonia

Influenza virus infection is a major respiratory infectious disease that generally induces pneumonia. The clinical manifestations of influenza virus infection and community-acquired pneumonia (CAP) differ between elderly persons and younger adults. To determine the clinical features of influenza-associated pneumonia, we studied 21 adult patients with influenza-associated pneumonia, as indicated by positive test results for influenza virus antigen. At presentation, the higher-age patients (≥75 years; n = 12) with influenza-associated pneumonia had lower body temperature than did the lower-age (<75 years) patients (n = 9). Conversely, the laboratory data indicated significantly higher C-reactive protein (CRP) concentration in higher-age patients than that in lower-age patients. None of the 18 patients undergoing neuraminidase inhibitor therapy died, but two of three patients who did not receive this therapy died from complications of advanced pneumonia. In this study, vaccination did not appear to be an important factor for prevention of pneumonia. High-age patients with CAP have lower body temperature, raising the possibility that diagnosis and treatment may be delayed in these patients. Increased CRP levels in these patients at presentation, however, could contribute to early detection of this serious pulmonary complication.     

Prognostic factors in patients in the terminal phase of haematological malignancies who are receiving home medical care

Although there are many prognostic models for patients in the terminal phase of solid tumours, a reliable prognostic scoring system in patients in the terminal phase of haematological malignancies (HM) has not been established. We retrospectively evaluated 180 patients in the terminal phase of HM who were receiving home medical care (HMC). Multivariate analyses revealed that clinician's estimate, consciousness, loss of appetite, dyspnoea, neutrophil count, lymphocyte count, and lactate dehydrogenase were associated with overall survival (OS). Based on this result, we developed a novel prognostic scoring system, the Japan palliative haematological oncology prognostic estimates, in which four risk groups were shown to clearly differ in survival (p < 0.001): a low-risk group (n = 41, median OS of 434 days), an intermediate-low-risk group (n = 80, median OS of 112 days), an intermediate-high-risk group (n = 38, median OS of 31.5 days), and a high-risk group (n = 21, median OS of 10 days). This is the first investigation of prognostic factors that influence the OS of patients in the terminal phase of HM who are receiving HMC. Providing patients with reliable information about their prognosis is important for them to consider how to spend their remaining life.     

Clinical significance of serum interleukin‐8 and soluble tumor necrosis factor‐like weak inducer of apoptosis levels in patients with diabetic nephropathy

Aims/Introduction

Recent studies suggest that chronic inflammatory responses are important in the development of diabetic nephropathy (DN). Various inflammatory and angiogenesis molecules affect the pathogenesis and progression of DN. Inflammation damages the microcirculation and causes kidney damage. In the present study, we studied changes in interleukin‐8 (IL‐8) and soluble tumor necrosis factor‐like weak inducer of apoptosis (sTWEAK) levels in patients with DN, and investigated the clinical significance of these two inflammatory factors.

Materials and Methods

Participants were categorized into healthy controls (n = 30) and patients with type 2 diabetes mellitus (n = 124). The type 2 diabetes mellitus group was further subdivided into the normoalbuminuria (n = 34), microalbuminuria (MAU; n = 46,) and proteinuria (MaAU; n = 44,) groups. Patients with DN were included in the MAU and MaAU groups. Total cholesterol, triglyceride, low‐density lipoprotein cholesterol, glycosylated hemoglobin, fasting blood glucose, 2‐h postprandial blood glucose, blood urea nitrogen, serum creatinine, 24‐h urine microalbumin, IL‐8 and sTWEAK levels were measured. Logistic regression was used to analyze the factors associated with proteinuria.

Results

In the healthy controls, normoalbuminuria, MAU and MaAU groups, we found that IL‐8 levels increased, whereas sTWEAK levels decreased (P < 0.05). IL‐8 might be an independent risk factor and serum sTWEAK a protective factor for MAU and MaAU. Serum levels of sTWEAK, IL‐8 and microalbumin were significantly correlated in the MAU and MaAU groups.

Conclusions

Serum IL‐8 and sTWEAK levels might be markers that can be used for an early diagnosis of DN.