Modulation of peripheral immune responses by paclitaxel–ifosfamide–cisplatin chemotherapy in advanced non-small-cell lung cancer

Purpose

The aim of this study was to assess systemic immunological responses in non-small-cell lung cancer (NSCLC) patients with stage III/IV disease during treatment with paclitaxel–ifosfamide–cisplatin (TIP) chemotherapy.

Methods

Peripheral blood mononuclear cells (PBMCs) collected from healthy donors (HD) (n = 20) and chemotherapy-naive NSCLC patients treated with TIP (n = 32) were tested for production of IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10, IL-12 and IL-2 upon polyclonal stimulation with anti-CD3 mAb. They were further assessed over a treatment period of twelve weeks (i.e., four treatment cycles).

Results

PBMCs from NSCLC patients produced higher IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10 and IL-12 levels, whereas IL-2 exhibited lower values compared to HD (p < 0.001 for all parameters). Of interest, patients who responded to treatment had significantly higher increases in IL-2 (p < 0.001) and significantly higher decreases in IL-1 (p < 0.001), TNF-α (p < 0.001), TNF-β (p < 0.001), IL-6 (p = 0.02), IL-8 (p < 0.001), IL-10 (p < 0.001) and IL-12 (p < 0.001) levels. Non-responders revealed post-therapeutically a significantly higher increase in IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10 and IL-12 secretion and a significantly higher decrease in IL-2 levels (p < 0.001 for all parameters). Patients who responded to treatment and had a significantly higher increase in IL-2 showed a significantly longer median survival (p value < 0.001, 26 vs. 7.5 months).

Conclusion

Our study indicates that monitoring cytokine dynamics in patients with advanced NSCLC and especially those of IL-2 in peripheral blood components in vitro could be used as a predictor of treatment-related outcome and overall survival in NSCLC.     

The Effect of Synbiotics on Acute Radiation-Induced Diarrhea and Its Association with Mucosal Inflammatory and Adaptive Responses in Rats

Background

Previous clinical studies advocated that probiotics beneficially affect acute radiation-induced diarrhea. These encouraging results were attributed to the restoration of the intestinal flora; however, there is lack of evidence if and how probiotics influence the underlying pathophysiological mechanisms.

Aims

The present study was conducted to investigate the potential supporting role of a synbiotic preparation (combination of pro- and pre-biotics) on experimentally-induced acute radiation diarrhea from the perspective of mucosal inflammation and histological injury.

Methods

Ninety adult Wistar rats were randomly assigned into six groups. Group A (non-irradiated), group B (non-irradiated/synbiotic supplemented), group C (irradiated), and group D (irradiated/synbiotic supplemented) were followed up to a week after the beginning of the experiment. Group E (irradiated) and group F (irradiated/synbiotic supplemented) were followed up for four days. On the last day of the experiments tissues were harvested for structural and molecular assessments.

Results

Synbiotic administration could not avert the occurrence of diarrhea, but significantly attenuated its severity. This effect was associated with the significant downregulation of neutrophil accumulation and lipid peroxidation during the acute phase. During the subacute phase, synbiotic treatment significantly improved both the histological profile and radiation mucositis. These mechanisms significantly contributed to the rehabilitation of the intestinal absorptive function as further indicated from the significantly reduced weight loss.

Conclusions

Given the optimization of the intestinal flora exerted by synbiotics, the resolution of diarrhea relies on the suppression of the “reactive” and the augmentation of “regenerative” components of acute radiation-induced intestinal response.     

IgA Anti-b2GPI Antibodies in Patients with Autoimmune Liver Diseases

INTRODUCTION: Recently, we reported a high prevalence of immunoglobulin G and/or immunoglobulin M anticardiolipin antibodies (aCL) in patients with autoimmune liver diseases, namely, autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC), which were independent of the respective isotypes of antibodies against beta2-glycoprotein I (anti-b2GPI). Immunoglobulin A (IgA) aCL and IgA anti-b2GPI are the least studied of the three specific isotypes either in antiphospholipid syndrome (APS) or in other conditions. METHODS: Therefore, we investigated the prevalence and clinical significance of IgA anti-b2GPI and IgA aCL by enzyme-linked immunosorbent assays in another set of Caucasian patients with autoimmune liver diseases (59 AIH, 96 PBC, and 37 PSC). The disease controls group consisted of 50 hepatitis C virus (HCV) patients, 50 hepatitis B virus (HBV), 30 alcoholic liver disease (ALD), 30 non-alcoholic steatohepatitis (NASH), and 110 healthy controls. RESULTS AND DISCUSSION: IgA anti-b2GPI prevalence was higher in AIH (50.8%) compared to PBC (p = 0.005), PSC (p = 0.008), NASH (p = 0.004), ALD (p = 0.01), and HCV (p = 0.002). The titers were also significantly higher in AIH compared to any other group of the study. IgA aCL prevalence was higher in AIH (33.9%) compared to PBC (p = 0.005), PSC (p = 0.014), NASH (p = 0.001), ALD (p = 0.004), and HCV (p < 0.001). IgA anti-b2GPI or IgA aCL were not associated with APS features in patients with liver autoimmunity. Of note, IgA anti-b2GPI and IgA aCL were associated with clinical and biochemical markers of disease severity in AIH and PBC. We demonstrated a high prevalence and high titers of IgA anti-b2GPI in patients with AIH compared to any other liver disease of the study. CONCLUSION: IgA anti-b2GPI and IgA aCL were associated with the severity and biochemical activity of AIH and PBC, but long-term prospective studies are needed to address whether this new finding is of clinical importance in AIH and PBC patients.     

Clinical significance of nuclear factor (NF)-κB levels in urothelial carcinoma of the urinary bladder

Nuclear factor (NF)-kappaB has been reported to be constitutively activated in various human neoplasms. However, its clinical significance in bladder urothelial carcinoma (UC) remains an unresolved issue. We conducted this study trying to elucidate the role of NFkappaB in bladder UC and its potential prognostic significance, by quantifying immunohistochemically the levels of p65/RelA expression in paraffin-embedded tissue from 116 patients. Some of the cases had previously been stained for cellular FLICE-like inhibitory protein (c-FLIP) and bcl-2. Seventy-four cases displayed concurrent cytoplasmic and nuclear immunoreactivity, whereas 18 only nuclear immunoexpression and 21 only cytoplasmic immunoexpression, and the remaining three cases were negative for p65/RelA. Nuclear p65/RelA expression was positively associated with tumour grade and T-category (p=0.0001 in both cases). In addition, cytoplasmic p65/RelA expression was lower in advanced T-category (p=0.0030). Moreover, p65/RelA nuclear expression was positively correlated with c-FLIP (p=0.0109) and bcl-2 (p=0.0452). p65/RelA nuclear expression adversely affected survival in both univariate and multivariate analysis in superficial (Ta-T1; p=0.0010 and p=0.0008) as well as in muscle-invasive carcinomas (T2-T4; p=0.0004 and p=0.0003). Our results demonstrate that NF-kappaB nuclear expression is correlated with histologic grade and T category in bladder UC. Moreover, NF-kappaB nuclear expression emerges as an independent prognosticator of adverse significance, conveying information beyond that obtained by standard clinicopathological prognosticators.     

C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population

It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1523 from mainland Italy. Sixty (3.7%) of 1624 mainland Italians and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the pathogenic repeat expansion. None of the 619 regionally matched control samples (1238 chromosomes) carried the expansion. Twenty-five cases (36.2%) had behavioral FTD in addition to ALS. FTD or unspecified dementia was also detected in 19 pedigrees (27.5%) in first-degree relatives of ALS patients. Cases carrying the C9ORF72 hexanucleotide expansion survived 1 year less than cases who did not carry this mutation. In conclusion, we found that C9ORF72 hexanucleotide repeat expansions represents a sizeable proportion of apparent sporadic ALS in the Italian and Sardinian population, representing by far the most common mutation in Italy and the second most common in Sardinia.     

Determinants of quality of life in Greek middle-age women: a population survey

Objectives

The aim of the present study was to evaluate how sociodemographic parameters, lifestyle indicators and intensity of climacteric symptoms affect the quality of life (QOL) of Greek community dwelling middle-aged women.

Study design

This population survey included 1140 middle-aged women aged 45–65 who represented 1% of the whole female population of this age group in Greece, stratified by residential area.

Main outcome measures

Participants were asked to complete a questionnaire concerning sociodemographic and anthropometric parameters, medical history, the Utian quality of life (QOL) scale and the Greene climacteric scale rating menopausal symptoms.

Results

In the univariate analysis, normal body mass index, married status, higher education, employment, good financial status, physical exercise and a high calcium diet were associated with higher total QOL scores (p-value < 0.001). Multivariate regression analysis showed that higher total QOL scores were predicted by being married (separated/divorced/widowed: beta = −3.17, p-value = 0.008), by physical exercise (beta = 4.84 and beta = 4.57 for 1–3 h and >3 h per week respectively, p-value < 0.001) and by a good financial status (beta = 7.05, p-value < 0.001), while a higher score in the Greene scale resulted in lower total QOL scores (beta = −0.77, p-value < 0.001). Women with a better QOL were more health conscious and more probable to have utilized the public health preventive resources.

Conclusions

Menopause as a life event has no effect on the QOL of Greek middle-aged women. On the contrary, the presence and intensity of climacteric symptoms have a negative impact on all aspects of QOL. Marital and financial status, as well as physical exercise, are also significant predictors of QOL.     

Reversal of tetraplegia in a patient with haematogenous cervical epidural abscess

Pyogenic haematogenous cervical epidural abscess complicated by tetraplegia is an uncommon entity, but its clinical importance overshadows its rarity. Predisposing risk factors for spinal epidural abscess include diabetes, intravenous drug abuse, liver disease, renal failure, malignancy, HIV, infection elsewhere, rheumatoid conditions, trauma and a number of spinal interventions. Lack of recovery and death are much more frequent when complete paralysis exists since more than 24 to 48 hours. Most authors combine decompressive laminectomy and antibiotics. Anterior decompression and needle aspiration are rarely used, the former more specifically in case of anterior abscess formation. A high index of suspicion along with reliance on gadolinium-enhanced MRI is essential to diagnose the pathology and institute appropriate treatment on an individual basis. The authors report on a diabetic male patient who developed a cervical epidural abscess with tetraplegia after dental extraction. He was treated within six hours by one stage anterior/posterior decompression and fusion, with complete recovery.     

Moderately increased alcohol consumption is associated with higher pressure wave reflections and blood pressure in men

Background and aimsIncreased alcohol consumption has been associated with CVD risk. Subclinical arterial damage (SAD) precedes the onset of cardiovascular disease (CVD), and allows early identification and study of the pathophysiology of CVD. Reliable, noninvasive vascular biomarkers are available for the early detection of SAD and reclassification of CVD risk. To investigate the association of alcohol consumption with multiple SAD biomarkers and central hemodynamics in a large sample of Greek adults with CVD risk factors.Methods and resultsThis cross-sectional study was conducted with 938 participants (43.5% men) and collected data on SAD biomarkers, central hemodynamics, and dietary intake. Multiple linear regression analysis was performed according to sex after adjusting for several confounders. In men, alcohol consumption of 20–30 g/d was positively associated with mean, diastolic, and peripheral systolic blood pressure (BP). The consumption of >30 g/d was positively associated with the augmentation index. In women, no statistically significant associations were found between alcohol consumption and BP or SAD indices. No statistically significant associations were found between alcohol consumption and arterial compliance or distensibility in both sexes.ConclusionIn men even a small deviation from the current recommendation for alcohol consumption is associated with both higher BP indices and pressure wave reflections. The absence of association in women might be due to very low alcohol intake, even in the high consumption group. More studies are needed to verify our findings and establish the above associations in each sex.