Follicular lymphoma international prognostic index

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs 120 g/L), number of nodal areas (> 4 vs 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk ( 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.      

Short-Chain Fatty Acids Induce Cytoskeletal and Extracellular Protein Modifications Associated with Modulation of Proliferation on Primary Culture of Rat Intestinal Smooth Muscle Cells

Short-chain fatty acids are the main end products of bacterial fermentation of carbohydrates. Their role on the metabolism and biology of colonocytes is now well characterized. However, the functional consequences of their presence on intestinal smooth muscle cells remain poorly studied. We aimed to assess the effect of different short-chain fatty acids on ileal and colonic smooth muscle cells in primary culture and on A7R5 line. Butyrate (above 0.1 mM) inhibited A7R5 cell proliferation, while at low concentration (0.05 to 0.5 mM) butyrate significantly stimulated the proliferation of ileal and colonic myocytes in primary culture. An inhibition was observed at higher concentrations. Collagenous and noncollagenous protein synthesis was stimulated by butyrate. Moreover, butyrate stimulated actin and myosin expression. Thus, butyrate, which is produced by dietary fiber fermentation, may affect intestinal muscles by directly acting at the molecular level on myocytes.     

Doppler reference values of the fetal vertebral and middle cerebral arteries,at 19–41 weeks gestation

Objectives: Blood flow to the fetal brain is supplied by two vascular systems: the vertebral artery (VA) and the internal carotid artery with its anatomical continuation, the middle cerebral artery (ICA/MCA). In this work, our aim was to establish consistent reference values for the comparative study of both arterial systems.

Methods: The study group consisted of 2323 Doppler examinations of the VA, MCA and UA performed on 2323 single pregnancies between 19 and 41 weeks. These values were afterwards used to calculate the pulsatility index (PI), peak systolic velocity (PSV) and cerebro-placental ratio (CPR) percentiles.

Results: The VA and MCA PI reached maximum values at the end of the second trimester and decreased afterwards due to an increase in the diastolic flow. Conversely, the VA and MCA PSV increased progressively until the end of pregnancy. Regarding the VA and MCA CPR values, they were higher in the middle of the third trimester and decreased afterwards.

Conclusions: In both arterial systems, Doppler reference values have been calculated for the PI, PSV and CPR, being available for future comparative studies.     

Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow’s milk

Background

Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy. However, its pathogenesis remains poorly understood and biomarkers are lacking. We aimed to perform in-depth characterization of humoral and cellular immune responses in children with cow’s milk (CM)-FPIES and investigated whether there is a FPIES metabolomic signature.

Methods

Children with CM-FPIES and control subjects with an IgE-mediated CM allergy (IgE-CMA), both avoiding CM, were recruited on the day of an oral food challenge. Blood samples were collected before the challenge. Total and specific levels of IgE, IgG1-4, IgA, IgM and IgD to various whey and casein allergens and to their gastroduodenal digestion products were measured in plasma, using plasma from CM-tolerant peanut allergic patients (IgE-PA, not avoiding CM) as additional controls. Cytokine secretion and cellular proliferation were analyzed after stimulation of PBMC with different CM allergens. Metabolomic profiles were obtained for plasma samples using liquid chromatography coupled to high-resolution mass spectrometry.

Results

Nine children with CM-FPIES and 12 control subjects (6 IgE-CMA and 6 IgE-PA) were included. In children with CM-FPIES, total Ig concentrations were lower than in control subjects, specific Ig against CM components were weak to undetectable, and no specific IgE against CM digestion products were detected. Moreover, in CM-FPIES patients, we did not find any Th cell proliferation or associated cytokine secretion after allergen reactivation, whereas such responses were clearly found in children with IgE-CMA. Plasma metabolic profiles were different between CM allergic patients, with significantly lower concentrations of various fatty acids and higher concentrations of primary metabolites such as amino acids in CM-FPIES compared to IgE-CMA patients.

Conclusions

In CM-FPIES, both humoral and cellular specific immune responses are weak or absent, and this is not related to CM avoidance. A metabolomic signature was identified in patients with CM-FPIES that may be useful for the diagnosis and management of this disease.

     

Benign and malignant vascular tumors of the liver in adults

Vascular tumors of the liver in adult patients include cavernous hemangioma, a common benign tumor; epithelioid hemangioendothelioma, a rare, usually low-grade malignant tumor; and angiosarcoma, a rare and very aggressive tumor. All these primary mesenchymal tumors develop on a normal liver and may also affect other organs. Their pathogenesis remains largely unknown. Hepatic tumors are increasingly detected incidentally due to widespread use of modern abdominal imaging techniques. Therefore, reliable noninvasive characterization and differentiation of such liver tumors is of major importance for clinical practice. Hemangioma follows a benign course, and a nonoperative approach for the majority of these lesions is recommended. A definitive diagnosis of epithelioid hemangioendothelioma and angiosarcoma requires histopathologic examination. Liver transplantation at an early stage has greatly improved the prognosis of epithelioid hemangioendothelioma. The prognosis of angiosarcoma remains dismal. Designing a worldwide database that contains all data about patients with these rare diseases is recommended.     

Diagnostic yield and therapeutic implications of capsule endoscopy in obscure gastrointestinal bleeding

AIM: The main aim of this study was to evaluate efficacy and therapeutic impact of capsule endoscopy (CE) in obscure gastrointestinal bleeding (OGIB). In addition, we evaluated the software of automatic detection of red zones (SBI, Given Imaging). PATIENTS AND METHODS: From June 2002 to June 2003, thirty-five patients with OGIB underwent capsule endoscopy after negative upper and lower digestive endoscopy. Capsule endoscopy was performed following a 12-hour fasting period and some received 2 L of PEG the night before for bowel preparation. RESULTS: CE was performed for occult (N=18) or overt (N=17) OGIB. Potentially bleeding lesions were found in 16/35 patients (45.7%). Lesions were angiodysplasias (N=8), ulcerations (N=4), tumors (N=2) and active bleeding without visible lesion (N=2). Lesions were located in gastric antrum (N=1), duodenum (N=2) and jejuno-ileum (N=13). Endoscopic (N=10), surgical (N=2) or medical (N=1) treatments were performed in 13/35 (37%). SBI was retrospectively evaluated in 24 patients with sensitivity, specificity, positive and negative predictive value of respectively 45%, 73%, 50% and 69%. CE retention during 10 days occurred in a patient with a small bowel NSAID-induced stricture. CONCLUSION: CE is a safe and effective procedure in the management of OGIB and had a therapeutic impact in more than one third of patients.     

Palmoplantar keratosis associated with keratitis: hereditary hypertyrosinemia treated by diet

The authors report the cases of two unrelated children 16 and 5 years of age respectively, affected with hypertyrosinaemia type II. This condition is characterized by palmo-plantar hyperkeratosis associated with a herpetiform keratitis. The diagnosis is based on the finding of hypertyrosinaemia and hypertyrosyluria, and may be confirmed by their biopsy findings of a cytoplasmic tyrosine amino-transferase deficiency. It is a hereditary autosomal recessive disease. A low phenylalanine and tyrosine diet produced a spectacular improvement but the ocular complications could have been avoided by an earlier diagnosis.     

Antibiotic-resistant soil bacteria in transgenic plant fields

Understanding the prevalence and polymorphism of antibiotic resistance genes in soil bacteria and their potential to be transferred horizontally is required to evaluate the likelihood and ecological (and possibly clinical) consequences of the transfer of these genes from transgenic plants to soil bacteria. In this study, we combined culture-dependent and -independent approaches to study the prevalence and diversity of bla genes in soil bacteria and the potential impact that a 10-successive-year culture of the transgenic Bt176 corn, which has a blaTEM marker gene, could have had on the soil bacterial community. The bla gene encoding resistance to ampicillin belongs to the beta-lactam antibiotic family, which is widely used in medicine but is readily compromised by bacterial antibiotic resistance. Our results indicate that soil bacteria are naturally resistant to a broad spectrum of beta-lactam antibiotics, including the third cephalosporin generation, which has a slightly stronger discriminating effect on soil isolates than other cephalosporins. These high resistance levels for a wide range of antibiotics are partly due to the polymorphism of bla genes, which occur frequently among soil bacteria. The blaTEM116 gene of the transgenic corn Bt176 investigated here is among those frequently found, thus reducing any risk of introducing a new bacterial resistance trait from the transgenic material. In addition, no significant differences were observed in bacterial antibiotic-resistance levels between transgenic and nontransgenic corn fields, although the bacterial populations were different.     

Unexpected discovery of 2 cases of hepatocyte nuclear factor 1α-mutated infracentimetric adenomatosis

We present 2 cases of hepatocyte nuclear factor 1α （HNF1α）-mutated adenomatosis, discovered for reasons unrelated to this disease, and identified using immunohistochemical methods. These new tools may further our understanding of the link between adenomas/adenomatosis subtypes and their complications, and their association with other abnormalities.     

Cardiovascular impact of exercise and drug therapy in older hypertensives with coronary heart disease: PREHACOR study

Our aim in this study was to examine the relationship between regular exercise and major cardiovascular events in hypertensive elderly with established coronary heart disease (CHD) in the primary care setting. The PREHACOR study recruited 3193 hypertensive patients, aged 74 ± 6 years, 67% male, with CHD. Regular exercise assessed by questionnaire was defined as recreational activity >20 min/day, >3 times/week. Endpoints at 6 months were new cardiovascular events (NCEs: myocardial infarction and hospitalization for stroke, unstable angina, congestive heart failure, or coronary revascularization). New cardiovascular events occurred in 376 patients (11.8%), with 17 deaths (0.5%). New cardiovascular events patients were older, with higher body mass index, and were more likely to have diabetes, arrhythmia, history of congestive heart failure, and noncardiac organ damage than non-NCE patients. Blood pressure was significantly and similarly reduced in both groups. Multivariate logistic regression associated NCEs positively and independently with a history of congestive heart failure (odds ratio [OR] 2.50; confidence interval [CI] = 1.9–3.23), noncardiac target organ damage (OR 1.51; CI = 1.20–1.90), and beta-blocker use (OR 1.28; CI = 1.02–1.59), and inversely and independently with combination low-dose angiotensin converting enzyme inhibitor + diuretic therapy (OR 0.66; CI = 0.45–0.95) and regular exercise (OR 0.70; CI = 0.54–0.90). Regular exercise is significantly associated with fewer major cardiovascular events in hypertensive elderly subjects with established CHD.