Non-life-threatening sepsis: report of two cases

Streptococcus bovis is one of the nonenterococcal species included among the streptococci group D. It is part of the normal bowel flora in humans and animals, but it is also responsible for infectious diseases (10-15% of all cases of bacterial endocarditis). Many cases of bacteremia and metastatic abscesses (spleen, liver, soft tissues, bone, meninges, endocardium) caused by S. bovis were reported as associated with digestive tract diseases, mainly colonic disease, and, in particular colonic neoplasms, or chronic liver diseases. A role in carcinogenesis has been suggested for this microorganism. The authors report two cases of S. bovis sepsis, one associated with colonic neoplasm and the other with liver cirrhosis and gastric carcinoma. Discussion is focused on probable mechanisms that favor gastric colonization and systemic diffusion of S. bovis from the gut in patients with gastrointestinal neoplasms or chronic liver disease and provides clinical recommendations for patients with S. bovis infections.     

Length and clinical effectiveness of pulmonary rehabilitation in outpatients with chronic airway obstruction

STUDY OBJECTIVE: To assess the clinical effectiveness of pulmonary rehabilitation (PR) after 10 or 20 consecutive sessions in outpatients with chronic airway obstruction (CAO). DESIGN: Observational prospective cohort trial. SETTING: Outpatient clinic of a rehabilitation center. PATIENTS AND INTERVENTIONS: Twenty-five outpatients (mean age, 65 +/- 9 years [+/- SD]; FEV1, 64 +/- 12% predicted) admitted to a comprehensive PR program, including exercise training. MEASUREMENTS AND RESULTS: The load reached on a cycloergometer (maximal achieved load [W-max]), the maximal and isoload dyspnea and leg fatigue on a Borg scale, 6-min walk distance (6MWD), and the health-related quality of life as assessed using the St. George's Respiratory Questionnaire (SGRQ) [total and components score] have been recorded as outcome measures at baseline, after 10 sessions (T10), and after 20 sessions (T20). The predefined criteria of the clinically significant improvement were as follows: + 15% W-max, + 54 m at 6MWD, - 1 point at isoload dyspnea and leg fatigue, and - 4% at SGRQ scores. There was a mean significant difference between changes at T20 and T10 for 6MWD (- 42.96 m; 95% confidence interval [CI], - 57.79 to - 28.12 m; p = 0.001), total SGRQ (4.80; 95% CI, 2.29 to 7.31; p = 0.001), activity SGRQ (3.60; 95% CI, 0.48 to 6.71; p = 0.025), and symptoms SGRQ (5.96; 95% CI, 2.72 to 9.2; p = 0.001). The percentage of patients who improved was different at T20 as compared with T10 for W-max (68% and 48%, respectively; p = 0.025), 6MWD (76% and 20%, p = 0.001), and total SGRQ (64% and 36%, p = 0.008). CONCLUSIONS: A 10-session course of PR provides only limited clinically significant changes of outcome measures when compared with a 20-session course in outpatients with CAO of mild-to-moderate severity.     

L-folic acid supplementation in healthy postmenopausal women: effect on homocysteine and glycolipid metabolism

CONTEXT: Hyperhomocysteinemia as well as alterations of glycemic and lipidic metabolism are recognized as risk factors for cardiovascular diseases. OBJECTIVE: The aim of this study was to examine the effect of L-folic acid supplementation on homocysteine (Hcy) and related thiols, such as cysteine (Cys) and Cys-glycine (Cys-Glyc) pathways and their relationship to glucose, insulin, and lipidic metabolism in normoinsulinemic postmenopausal women. DESIGN: This study was a randomized placebo, not double-blind, trial. SETTING: The study was performed in an academic research center. PATIENTS OR OTHER PARTICIPANTS: Twenty healthy postmenopausal women were selected. No patient was taking drugs known to affect lipid or glucose metabolism. INTERVENTION(S): Patients underwent two hospitalizations before and after 8 wk of L-acid folic (7.5 mg/d) or placebo administration. The glycemic metabolism was studied by an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Hcy metabolism was studied by a standardized oral methionine-loading test. MAIN OUTCOME MEASURE(S): Hcy, Cys, and Cys-Glyc, basally and after a methionine loading test, were measured. Basal insulin, glucose, and peptide C levels as well as area under the curve for insulin, area under the curve for peptide, hepatic insulin extraction, and metabolic index were assayed. The total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels and the cholesterol/HDL and LDL/HDL ratios were also measured. RESULTS: The total basal Hcy concentration and the plasma postmethionine loading Hcy values were significantly decreased (P < 0.01) in L-folic acid-treated patients, whereas postmethionine loading Cys-Glyc levels were markedly increased (P < 0.02). Furthermore, L-folic acid intake induced a significant improvement in carbohydrate metabolism through an increase in fractional hepatic insulin extraction (P < 0.05) and peripheral insulin sensitivity (P < 0.02) in normoinsulinemic women. HDL levels considerably increased, inducing an improvement in other atherosclerotic indexes, such as cholesterol/HDL and LDL/HDL ratios (P < 0.03). CONCLUSIONS: These results show that folic acid supplementation lowers plasma Hcy levels and improves insulin and lipid metabolism, reducing the risk of cardiovascular disease.     

Naive CD4+ T lymphocytes express high levels of Bcl-2 after highly active antiretroviral therapy for HIV infection

The mechanism causing the increasing number of peripheral T cells after highly active antiretroviral therapy (HAART) is still unclear. The bcl-2 oncogene prevents spontaneous apoptosis (SA) in lymphocytes. Spontaneous apoptosis could be a determinant of HIV immunodeficiency and can be reversed by HAART including protease inhibitors (PI-HAART). The aims of our study were to measure Bcl-2 protein expression in memory (CD45RO+) and naive (CD45RO-) CD4+ and CD8+ T lymphocytes of HIV+ patients and to correlate it with efficacy of PI-HAART. Forty-nine HIV+ patients (cases) and 26 HIV- individuals (controls) were evaluated. Patients receiving PI-HAART, and who had undetectable HIV plasma viral load (VL-, n = 21), had higher levels of Bcl-2 than did VL+ patients (n = 28), both in CD4+ cells (p < 0.0001) and in CD8+ cells (p < 0.001). VL+ patients had lower Bcl-2 levels than did controls in CD8+ cells (p = 0.02), but not in CD4+ cells (p > 0.05). Interestingly, VL- patients had higher Bcl-2 expression than did controls both in CD4+ cells (p < 0.0001) and in CD8+ cells (p = 0.03). In a subcohort of the same patients, Bcl-2 was significantly higher in VL- patients (n = 10) than in controls (n = 12), both in naive CD4+ cells (p < 0.0001) and in naive CD8+ cells (p = 0.01). Naive CD4+ cells had higher Bcl-2 expression in VL- than in VL+ patients (p = 0.01). In a subsequent longitudinal study of nine HIV patients, naive CD4+ cells increased after effective PI-HAART (p = 0.03), which paralleled an increase in Bcl-2 expression in the same cells (p = 0.02). In conclusion, upregulation of bcl-2 could be a mechanism of immune reconstitution of naive CD4+ T cells induced by PI-HAART.     

CagA antigen of Helicobacter pylori and coronary instability: insight from a clinico-pathological study and a meta-analysis of 4241 cases

BackgroundCytotoxin-associated gene-A (CagA) antigen is expressed by some virulent strains of Helicobacter pylori (H. pylori). The role of CagA antigen in coronary instability is unknown. We performed a clinico-pathological study and a meta-analysis in the attempt to shed new light on this complex issue.MethodsIn the clinico-pathological study, 38 patients with unstable angina (UA), 25 patients with stable angina (SA), 21 patients with normal coronary arteries (NCA) and 50 age and sex matched healthy volunteers were enrolled. Serology for CagA was assessed in all patients. Specimens of atherosclerotic plaques were obtained from all patients by directional coronary atherectomy, and prepared for immunohistochemistry using anti-CagA monoclonal antibodies. The meta-analysis includes 9 studies assessing the association between seropositivity to CagA strains and acute coronary events.ResultsThe titre of anti-CagA antibodies was significantly higher in patients with unstable angina (161 ± 90 RU/ml) compared to those with stable angina (83 ± 59 RU/ml p < 0.02), NCA (47.3 ± 29 RU/ml p < 0.01) and healthy controls (73 ± 69 p < 0.02). Anti-CagA antibodies recognized antigens localized inside coronary atherosclerotic plaques in all specimens from both stable and unstable patients. In the meta-analysis, seropositivity to CagA was significantly associated with the occurrence of acute coronary events with an odds ratio (OR) of 1.34 (95% CI, 1.15–1.58, p = 0.0003).ConclusionsTaken together these findings suggest that in a subset of patients with unstable angina, an intense immune response against CagA-positive H. pylori strains might be critical to precipitate coronary instability mediated by antigen mimicry between CagA antigen and a protein contained in coronary atherosclerotic plaques.     

Endothelial Dysfunction in Early Systemic Lupus Erythematosus Patients and Controls Without Previous Cardiovascular Events

Objective

To assess the prevalence and risk factors for endothelial dysfunction detected by peripheral artery tonometry in systemic lupus erythematosus patients with early disease without cardiovascular disease and risk factors.

Methods

All the consecutive adult lupus patients, with a disease duration <5 years, seen in our hospital from December 2014 to March 2016 were considered. We excluded patients with any history of cardiovascular disease or risk factors possibly affecting peripheral artery tonometry. Enrolled patients were matched for sex, age, body mass index, and blood pressure with healthy controls with the same exclusion criteria. Patients and controls received a transthoracic Doppler echocardiogram and an evaluation of endothelial function by peripheral artery tonometry.

Results

Twenty patients (100% female) with a median disease duration of 14 months (range 1–58 months), a mean ± SD age of 42 ± 15 years, and a mean ± SD age at diagnosis of 40 ± 16 years were enrolled and matched with 20 controls. Peripheral artery tonometry showed a significantly higher prevalence of endothelial dysfunction (P = 0.003) and vascular stiffness (P = 0.02), while echocardiography detected a significantly higher prevalence of left ventricular concentric remodeling (P = 0.003), grade I diastolic dysfunction (P = 0.047), and subclinical increase of filling pressures (P = 0.039) in lupus patients compared to controls. Among lupus patients, no features were associated with endothelial dysfunction.

Conclusion

A high rate of endothelial dysfunction and vascular stiffness occurs in early lupus patients without cardiovascular risk factors and disease. Larger studies are needed to confirm our results and to look for patients’ characteristics possibly associated with these abnormalities.

     

Differential expression of miR-144* as a novel fecal-based diagnostic marker for colorectal cancer

Background

MicroRNAs (miRNA) are tiny, noncoding, small, endogenous RNAs that play major roles in neoplastic transformation and could therefore offer a better quantitative and noninvasive method for the diagnosis and prognosis of colorectal cancer (CRC) using feces. In the present study, we screened feces for 648 miRNAs and analyzed the role of miR-144* as a potential CRC diagnostic marker.

Methods

Fecal miRNA expression was profiled with RT-pre-amplification-qPCR, and the stability was determined using both endogenous and exogenous miRNA by RT-qPCR. ROC analysis was performed to enhance the diagnosing power of the CRC patients?? fecal specimens.

Results

We detected 39% of all the miRNAs screened in feces. Endogenous miRNAs are more stable over time and temperature, while exogenous miRNAs degraded rapidly. miR-144* was overexpressed in feces, suggesting that it could be a potent candidate diagnostic marker for CRC detection, with a sensitivity of 74% and a specificity of 87% (n?=?75, p?Conclusions We demonstrated that miRNAs are stable in the fecal microenvironment, and that, among them, miR-144* represents a novel fecal-based diagnostic marker for CRC screening. Nevertheless, our data need to be validated in a large cohort of subjects.     

Preclinical development of novel humanised ROR1 targeting chimeric antigen receptor T cells and bispecific T-cell engagers

Background

Immunotherapy with chimeric antigen receptor (CAR) T cells and bispecific T-cell engagers (BiTEs) has shown impressive efficacy against CD19+ malignancies, but translation to other tumour targets is not possible. In this regard, receptor tyrosine kinase like orphan receptor 1 (ROR1) is an attractive therapeutic target that is present on a range of haematological and solid malignancies, as well as cancer stem cells, but importantly with limited expression on normal adult tissues. Our aim, through iterative optimisation, was to generate novel humanised ROR1 single chain variable fragments (scFv) that enable efficient targeting of ROR1 on tumour cells without toxicity.

De novo AML patients with favourable–intermediate karyotype may benefit from the addition of low-dose gemtuzumab ozogamicin (GO) to fludarabine, Ara-C and idarubicin (FLAI): a contribution to the reopened “GO question”

We report the final results of a prospective trial testing the combination of fludarabine, Ara-C and idarubicin (FLAI) followed by low-dose gemtuzumab ozogamicin (FLAI-GO) in 85 patients aged 60 years or more with CD33+ acute myeloid leukaemia (AML). Median age was 68 years (60–82); karyotype was unfavourable in 21 patients (24 %), intermediate in 63 (74 %) and favourable in 1 (2 %). There were five therapy-related deaths. Of the 80 evaluable patients, 47 achieved complete response (CR) (58 %); CR rates were 65 and 32 % in good-intermediate/poor karyotype patients, respectively. Median length of CR was 7 months (3–76). The cumulative incidence of relapse was 84 % with an actuarial survival of 50.3 % at 1 year and 14.4 % at 2 years. The study control population is an unselected consecutive historic cohort of 104 patients treated with the FLAI regimen, who were matched for age and prognostic factors. CR rates after FLAI-GO and FLAI were comparable. However, patients with de novo AML and intermediate–favourable karyotype receiving GO had a significantly lower risk of relapse at 2 years as compared to patients not receiving GO (n?=?77) (40 vs 80 %, p?=?0.01) and significantly better disease-free survival (p?=?0.018) and overall survival (p?=?0.022).