Non-Hodgkin's lymphomas with t(11;14)(q13;q32): a subset of mantle zone/intermediate lymphocytic lymphoma?

We here describe 13 patients with non-Hodgkin's lymphoma (NHL) and a translocation t(11:14)(q13:q32). They were part of a series of 163 patients with NHL and an abnormal karyotype, serially referred to our institution between January 1984 and 1990. Patients with t(11:14) seem to present several common and interesting features. Males are more frequently affected than females, and old people more than young. They present at diagnosis with advanced disease and usually show involvement of epithelium and bone marrow. With respect to histologic diagnoses, these patients are usually considered to be of low-grade malignancies. However, most of them do very poorly, have short complete remission and frequent relapses whatever the treatment. As a whole, the median survival rate is rather low. The cytologic, histologic as well as the immunologic patterns tend to be uniform: tumours are composed of small cells and display features of mantle zone/intermediate lymphocytic lymphoma. They express high IgM and low IgD levels and more commonly bear Ig lambda light chains. They also express all pan-B antigens (except CD23) as well as the CD5 antigen, but usually lack the CD10. According to these characteristics, these tumours could be placed in between lymphocytic lymphomas (which usually express CD23) and follicular lymphomas (which commonly lack IgD and CD5 and bear CD10 as well as a t(14:18).     

Precise evaluation of liver histology by computerized morphometry shows that steatosis influences liver stiffness measured by transient elastography in chronic hepatitis C

Background

Liver stiffness evaluation (LSE) by Fibroscan is now widely used to assess liver fibrosis in chronic hepatitis C. Liver steatosis is a common lesion in chronic hepatitis C as in other chronic liver diseases, but its influence on LSE remains unclear. We aimed to precisely determine the influence of steatosis on LSE by using quantitative and precise morphometric measurements of liver histology.

Methods

650 patients with chronic hepatitis C, liver biopsy, and LSE were included. Liver specimens were evaluated by optical analysis (Metavir F and A, steatosis grading) and by computerized morphometry to determine the area (%, reflecting quantity) and fractal dimension (FD, reflecting architecture) of liver fibrosis and steatosis.

Results

The relationships between LSE and liver histology were better described using morphometry. LSE median was independently linked to fibrosis (area or FD), steatosis (area or FD), activity (serum AST), and IQR/LSE median. Steatosis area ≥4.0 % induced a 50 % increase in LSE result in patients with fibrosis area <9 %. In patients with IQR/LSE median ≤0.30, the rate of F0/1 patients misclassified as F ≥ 2 by Fibroscan was, respectively for steatosis area <4.0 and ≥4.0 %: 12.6 vs 32.4 % (p = 0.003). Steatosis level did not influence LSE median when fibrosis area was ≥9 %, and consequently did not increase the rate of F ≤ 3 patients misclassified as cirrhotic.

Conclusion

A precise evaluation of liver histology by computerized morphometry shows that liver stiffness measured by Fibroscan is linked to liver fibrosis, activity, and also steatosis. High level of steatosis induces misevaluation of liver fibrosis by Fibroscan.     

Tumoral platinum concentrations in patients treated with repeated low-dose cisplatin as a radiosensitizer

The aim of the present study was to check whether platinum (Pt) concentrations achieved in tumors with a daily low-dose schedule were close to those promoting radiosensitization. Fifteen previously untreated patients with histologically proven advanced uterine cervix tumors were studied. They received a daily irradiation 30 min after a short infusion of 5 mg cisplatin for 5 consecutive days every week. A biopsy was taken from the accessible tumor mass, 4 to 6 hr after the daily injection. Blood samples were obtained once a week, just before the daily injection (H0) and 30 min after (H30). Quantificative analysis of Pt concentrations was performed by atomic absorption spectrophotometry. Plasma and tumoral Pt concentrations exhibited a marked intersubject variability. The median tumoral Pt concentration was 1,710 mg/g. Median total and ultrafiltrable Pt concentrations in plasma taken at H0 and H30 were 231 and 360 ng/ml, and 7 and 90 ng/ml respectively. Tumoral and total plasma Pt concentrations significantly increased during the course of treatment. Present data show that tumoral Pt concentrations achieved with this CDDP schedule are in the range of tumoral Pt concentrations previously shown to promote radiosensitization (2,000 ng/g). These results suggest that this CDDP radiosensitization regimen might be started with higher CDDP doses in order to reach earlier radiosensitizing Pt tumoral concentrations. © 1996 Wiley-Liss, Inc.     

Prescription,Compliance, and Burden Associated with Salt-Restricted Diets in Heart Failure Patients: Results from the French National OFICSel Observatory

(1) Background: There is much debate about the use of salt-restricted diet for managing heart failure (HF). Dietary guidelines are inconsistent and lack evidence. (2) Method: The OFICSel observatory collected data about adults hospitalised for HF. The data, collected using study-specific surveys, were used to describe HF management, including diets, from the cardiologists’ and patients’ perspectives. Cardiologists provided the patients’ clinical, biological, echocardiography, and treatment data, while the patients provided dietary, medical history, sociodemographic, morphometric, quality of life, and burden data (burden scale in restricted diets (BIRD) questionnaire). The differences between the diet recommended by the cardiologist, understood by the patient, and the estimated salt intake (by the patient) and diet burden were assessed. (3) Results: Between March and June 2017, 300 cardiologists enrolled 2822 patients. Most patients (90%) were recommended diets with <6 g of salt/day. Mean daily salt consumption was 4.7 g (standard deviation (SD): 2.4). Only 33% of patients complied with their recommended diet, 34% over-complied, and 19% under-complied (14% unknown). Dietary restrictions in HF patients were associated with increased burden (mean BIRD score of 8.1/48 [SD: 8.8]). (4) Conclusion: Healthcare professionals do not always follow dietary recommendations, and their patients do not always understand and comply with diets recommended. Restrictive diets in HF patients are associated with increased burden. An evidence-based approach to developing and recommending HF-specific diets is required.     

Surface triggering receptor expressed on myeloid cells 1 expression patterns in septic shock

Objective To analyze the pattern of cell-surface expression of the triggering receptor expressed on myeloid cells (TREM) 1 during septic shock.Design and setting Prospective clinical study in an adult 16-bed medical ICU.Patients and methods 25 septic shock patients, 15 patients with shock of noninfectious origin and 7 healthy volunteers. Arterial blood was drawn within 12 h of admission and subjected to flow cytometry analysis after staining with anti-TREM-1 and anti-CD14 antibodies. Repeated sampling was performed on days 2, 3, 5, 7, and 14 in septic shock patients.Results Monocytic TREM-1 expression was significantly higher in septic shock patients (mean fluorescence intensity 2.3±0.2) than in nonseptic patients (1.0±0.1), and healthy volunteers (1.0±0.1). There was no difference in monocytic TREM-1 expression between nonseptic patients and healthy volunteers or between any of the three groups with respect to TREM-1 expression on neutrophils. The time course of TREM-1 expression on monocytes diverged significantly by day 3 between survivors and ns.Conclusions The specificity of TREM-1 regulation by infection is highlighted. Moreover, surface TREM-1 expression on monocytes may prove useful in allowing the follow-up of septic patients during the course of the diseaseElectronic Supplementary Material Electronic supplementary material to this paper can be obtained by using the Springer Link server located at .     

Cytokine balance in infants undergoing cardiac operation

BACKGROUND: The control of the systemic inflammatory response taking place during cardiac operations depends on adequate antiinflammatory reaction. In this prospective study we tested the hypothesis that cytokine balance during pediatric cardiac surgical procedures would be influenced by the patients' preoperative clinical condition, defined as hypoxemia or heart failure. METHODS: Twenty infants (median age, 8 months) with hypoxemia owing to intracardiac right-to-left shunt (group 1, n = 10) or with heart failure because of intracardiac left-to-right shunt (group 2, n = 10), scheduled for elective primary corrective operation, were enrolled. Plasma levels of the proinflammatory cytokine interleukin (IL) 6, the natural antiinflammatory cytokine IL-10, and the markers of the acute-phase response, C-reactive protein and procalcitonin, were sequentially measured before, during, and after cardiac operation up to the 10th postoperative day. The ratio of IL-10 to IL-6 levels served as a marker for the individual's antiinflammatory cytokine balance. RESULTS: Group 1 showed higher preoperative IL-6 (p < 0.001), lower IL-10 levels (p < 0.02), and lower ratio of IL-10 to IL-6 levels (p < 0.001) than group 2. Preoperative C-reactive protein and procalcitonin were not detectable. In group 1, preoperative IL-6 levels inversely correlated with preoperative oxygen saturation (Spearman correlation coefficient, -0.74, p < 0.02). During cardiopulmonary bypass, IL-6 levels were higher, whereas IL-10 and ratio of IL-10 to IL-6 levels were lower in group 1 than in group 2. In all patients, postoperative IL-6 levels were positively correlated with duration of inotropic support and serum creatinine value and inversely correlated with oxygenation index and diuresis. CONCLUSIONS: Infants with hypoxemia show a preoperative inflammatory state with low antiinflammatory cytokine balance in contrast to those with heart failure. This in turn is associated with lower perioperative antiinflammatory cytokine balance and might contribute to postoperative morbidity.     

The prognostic significance of beta(2)-microglobulin in patients with Hodgkin's lymphoma

BACKGROUND AND OBJECTIVES: Serum beta(2)-microglobulin (s beta(2)m) is an established prognostic factor for multiple myeloma and non-Hodgkin's lymphoma, but only limited data suggest an adverse prognostic significance for Hodgkin's lymphoma (HL). This study was undertaken to examine the impact of s beta(2)m on the prognosis of patients with HL. DESIGN AND METHODS: s beta(2)m was measured by a radioimmunoassay (upper normal limit 2.4 mg/L), in pretreatment serum samples of 232 patients with HL, who were then treated with ABVD or equivalent regimens with or without radiotherapy. Multivariate survival analysis was based on Cox's proportional hazards model. RESULTS: Main patients' characteristics: median age 30.5 years (14-78); 58% males; 68% nodular sclerosis, 20% mixed cellularity and 12% lymphocyte predominance; 34% B-symptoms; 24% Ann Arbor stage I, 49% II, 18% III and 9% IV. Elevated s beta(2)m levels were detected in 65/232 patients (28%) and correlated with older age (p<0.001), mixed cellularity (p=0.03), B-symptoms (p=0.002), advanced stage (p=0.02), > or = 5 involved sites (p=0.02), inguinal/iliac involvement (p=0.009), lymphocytopenia (p=0.002) and elevated lactate dehydrogenase (p=0.01). The 7-year failure free survival (FFS) was 75% vs. 72% for patients with normal vs. elevated s beta(2)m (p=0.15). The corresponding 7-year overall survival (OS) rates were 86% vs. 52% (p=0.003). In multivariate analysis, elevated s beta(2)m was not predictive of FFS, but was independently associated with inferior OS (p=0.01), along with the number of involved sites (p<0.001). INTERPRETATION AND CONCLUSIONS: s beta(2)m is not a potent prognostic factor for FFS in optimally treated patients with HL. However s beta(2)m may be predictive of OS, probably due to its effect on the timing of treatment failure.     

Comparison of murine leukemia virus, human immunodeficiency virus, and adeno-associated virus vectors for gene transfer in multiple myeloma: lentiviral vectors demonstrate a striking capacity to transduce low-proliferating primary tumor cells

Genetic modification of primary tumor cells by gene transfer is of major interest to study the role of specific genes in the biology of a given malignancy and to modify tumor cells for therapeutic use. Multiple myeloma (MM) is a low-proliferating cancer, with often less than 1% of the cells in the S phase of the cell cycle. As primary myeloma cells are notoriously difficult to transduce, we conducted a comparison of various viral vectors, known to integrate the transgene of interest into the target genome, for their ability to stably promote the expression of an enhanced green fluorescent protein (EGFP) transgene. We compared three murine leukemia virus-based vectors, differing only in their viral envelope, a human immunodeficiency virus (HIV)-based vector pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G), and an adeno-associated virus type 2 vector. Transduction characteristics of these vectors were evaluated in human myeloma cell lines and in primary myeloma cells. Unequivocally, we observed that the VSV-G/HIV vector was the most efficient vector for transducing the cell lines and the only one able to transduce primary myeloma cells reproducibly. The mean percentage of transduced primary myeloma cells was 43.6% (range, 16.3-77.6%), with one round of infection at a low multiplicity of infection, including MM cell samples with less than 1% of cells in the S phase. A quantitative polymerase chain reaction assay demonstrated that this more efficient EGFP expression was associated with a higher GFP copy number in the targeted cell. We propose that lentiviral vectors should be used for transduction of nonproliferating primary tumor cells such as myeloma cells.