Germinal center B (GCB) and non-GCB cell-like diffuse large B cell lymphomas have similar outcomes following autologous haematopoietic stem cell transplantation

Patients with germinal center B cell-like (GCB) and non-GCB diffuse large B cell lymphomas (DLBCL) receiving first line therapy have distinct prognosis. We explored the differences in outcome following salvage autologous hematopoietic stem cell (HSC) transplantation between patients with GCB and non-GCB DLBCL. Forty-four patients with relapsed and 15 patients with primary refractory chemosensitive disease undergoing BEAM (BCNU [carmustine], etoposide, cytarabine, melphalan) conditioning and autologous HSC were included. Immunohistochemical analysis was performed for CD10, BCL-6, MUM1 (allowing classification into GCB and non-GCB-like DLBCL) and BCL-2. Median follow-up of survivors was 25 months; median age at the time of transplantation was 60 years (range 17–77). Thirty-two patients (54%) were classified as having GCB and 27 (46%) as having non-GCB-like DLBCL. Patients with GCB and non-GCB DLBCL did not differ in the risk of progression after HSC transplant ( P  = 0·78) or overall survival ( P  = 0·48). In multivariate analysis, only time to progression after initial treatment impacted overall survival. We conclude that patients with relapsed or primary refractory chemosensitive GCB and non-GCB-like DLBCL derive similar benefit from autologous HSC transplant.     

Marker-specific sorting of rare cells using dielectrophoresis

Current techniques in high-speed cell sorting are limited by the inherent coupling among three competing parameters of performance: throughput, purity, and rare cell recovery. Microfluidics provides an alternate strategy to decouple these parameters through the use of arrayed devices that operate in parallel. To efficiently isolate rare cells from complex mixtures, an electrokinetic sorting methodology was developed that exploits dielectrophoresis (DEP) in microfluidic channels. In this approach, the dielectrophoretic amplitude response of rare target cells is modulated by labeling cells with particles that differ in polarization response. Cell mixtures were interrogated in the DEP-activated cell sorter in a continuous-flow manner, wherein the electric fields were engineered to achieve efficient separation between the dielectrophoretically labeled and unlabeled cells. To demonstrate the efficiency of marker-specific cell separation, DEP-activated cell sorting (DACS) was applied for affinity-based enrichment of rare bacteria expressing a specific surface marker from an excess of nontarget bacteria that do not express this marker. Rare target cells were enriched by >200-fold in a single round of sorting at a single-channel throughput of 10,000 cells per second. DACS offers the potential for automated, surface marker-specific cell sorting in a disposable format that is capable of simultaneously achieving high throughput, purity, and rare cell recovery.     

Functional characterization of canine lymphocyte subsets

Summary Functional characterization of subsets of T lymphocytes is essential for transplantation studies in dogs, as it is in other species. We studied the function of T cells separated by two mouse monoclonal antibodies recognizing complementary subsets — an antibody directed to canine T cells (MdT-P1) with an up-regulating function, and an antibody directed to human CD 8 (MT811) that cross-reacts with down-regulating canine T cells. Immunorosetting with sheep red blood cells and Percoll gradient allowed us to study depleted and enriched fractions. Their function was tested in mixed lymphocyte culture (MLC), cell-mediated cytotoxicity (CML), and coculture with B cells in a hemolytic plaque assay (PFC). In MLC, MdT-P1-positive cells showed a high proliferative response, and MT811-positive cells responded poorly to allogeneic cells. Vice versa, MT811-negative cells responded strongly, and MdT-P1-negative cells were poor responders but strong stimulators. Effector cells of CML were separated following 8 days of culture and prior to mixing with target cells. Enriched and depleted fractions with either antibody showed low cytotoxic activity as compared with unseparated cells. When added to unseparated effector cells MT811-positive cells suppressed cytotoxicity. B cells were obtained by resetting with staphylococcal protein A (SPA). Their immunoglobulin production was studied following 6 days of culture stimulated by pokeweed mitogen in a reverse hemolytic plaque assay. Again, MT811-positive cells added to the culture suppressed, and MT811-negative cells enhanced immunoglobulin production. In conclusion, immunorosetting with two monoclonal antibodies allowed us to distinguish subpopulations of canine T cells with up-regulating (helper/inducer) from those with down-regulating (suppressor) activity.This work was supported by theWilhelm-Sander-Stiftung     

Tegaserod does not alter fasting or meal-induced biliary tract motility

OBJECTIVE: Tegaserod is a 5-HT(4) receptor partial agonist that increases peristaltic activity of the intestinal tract. It is approved for the treatment of patients with irritable bowel syndrome with constipation (IBS-C). IBS is a chronic gastrointestinal disorder of function that is reported to be associated with an increased incidence of abdominal surgery including cholecystectomy. The effect of tegaserod on nongut digestive organs, such as the gallbladder and biliary tract, has not been previously investigated. Therefore, this study aimed to evaluate the effects of tegaserod on gallbladder contractility and on functional status of the sphincter of Oddi during both the interdigestive and the digestive periods in healthy female subjects and in female patients with IBS-C. METHODS: During a 6-wk, double-blind, placebo-controlled crossover study, gallbladder contractility and concomitant change in luminal diameter of the common hepatic duct (CHD) and the common bile duct (CBD, both proximal and distal) in response to a standard liquid meal were quantified using real-time ultrasonography. Changes in luminal diameter of the CHD and the CBD were used as a surrogate marker for sphincter of Oddi function. Ultrasound measurements were conducted every 15 min from 45 min before, to 60 min after the test meal to observe the impact of tegaserod on gallbladder volume and any concomitant change in the diameters of the CHD and the CBD that developed in response to gallbladder contraction. The ultrasound measurements of gallbladder contractility, along with the CHD and the CBD diameters, were repeated after each of the two 2-wk periods of treatment with tegaserod or placebo. The recommended dose of tegaserod (6 mg b.i.d.) for IBS-C patients was used in healthy female subjects (n = 13) and female patients with IBS-C (n = 20). Twice this dose (12 mg b.i.d.) was also evaluated in an additional 20 female patients with IBS-C. Statistical evaluations were conducted using a two-sided analysis of variance (ANOVA). RESULTS: Gallbladder contractility variables including ejection fraction, ejection rate and ejection period, fasting and residual volume, and maximal emptying, were similar after 2 wk of treatment with tegaserod 6 mg b.i.d. and placebo in healthy female subjects and female patients with IBS-C. There were no significant changes in the luminal diameters of the CHD or the CBD after tegaserod compared to placebo in any cohort. Additionally, no significant dilation (> or =7 mm in diameter) of the CHD or CBD was observed during maximal gallbladder emptying. Similar results were also observed when tegaserod was given at 12 mg b.i.d. in patients with IBS-C. Tegaserod treatment had no significant effect on plasma CCK concentration in response to the test meal. No significant abdominal pain or unexpected adverse events were reported during the study. CONCLUSIONS: This study showed no significant pharmacodynamic effect of tegaserod on gallbladder contractility or on CBD and CHD diameters as a surrogate marker of sphincter of Oddi function during both the interdigestive (fasting) and the digestive (postprandial) periods in healthy female subjects and female patients with IBS-C.     

Success,complications, and restenosis following rotational and transluminal extraction atherectomy of ostial stenoses

Our objectives were to determine procedural success, clinical complications, and follow-up restenosis rates after rotational burr and transluminal extraction atherectomy of coronary artery and saphenous vein graft ostial stenoses. Balloon angioplasty of ostial lesions has been associated with low rates of success and high rates of clinical complications and restenosis compared to nonostial lesions. Atherectomy, due to its ability to excise (extraction atherectomy) or pulverize (rotational atherectomy) atheroma and the internal elastic lamina, may result in improved procedural outcome. We retrospectively studied 101 patients with ostial stenoses treated by rotational burr and transluminal extraction atherectomy over a 3-yr period. Quantitative angiography and clinical follow-up were reviewed to determine success, complication, and restenosis rates. Rotational burr (n = 29) and transluminal extraction (n = 72) atherectomy were associated with high procedural success (93% and 90%, respectively) and a low incidence of complications (6.9% and 4.2%, respectively). Postatherectomy angiographic success was low (52% and 69%, respectively) and required adjunctive balloon angioplasty in 85% of patients overall. This lower success rate likely reflects device undersizing as the overall postatherectomy artery to device ratio was near unity (0.95). The rates of angiographic ostial restenosis remain high (39.1% and 65.9%, respectively, P < 0.05). The high rate of restenosis after transluminal extraction atherectomy was due to the higher rate of restenosis in saphenous vein grafts (80%) compared to TEC treated coronary arteries (59%). When only coronary artery lesions were compared, there was no significant difference between atherectomy device groups with respect to restenosis rates or late loss. Rotational or transluminal extraction atherectomy of ostial stenoses is associated with high procedural success rates and a low incidence of complications; however, the rates of restenosis in these lesions remain high.     

Barriers to interferon-alpha therapy are higher in intravenous drug users than in other patients with acute hepatitis C

BACKGROUND/AIMS: Treatment with interferon-alpha (IFN-alpha) may eradicate HCV in most acute hepatitis C patients, thus preventing chronic hepatitis and avoiding less efficacious combination therapy. METHODS: In a prospective study, we evaluated the impact of barriers to successful start and completion of treatment of acute and subacute (<12 months from infection) hepatitis C with pegylated IFN-alpha2b, 1.5 microg/kg, QW, for 24 weeks. RESULTS: Out of 27 patients (22 were active intravenous drug users [IVDU]), 5 cleared HCV spontaneously. Antiviral treatment was indicated in 22 patients: six refused therapy for fear of side effects, whereas two others were lost to observation. Eight patients completed the treatment or received >80% of the scheduled drug: seven (88%) were sustained virological responders 24 weeks after the end of treatment. Six patients (all IVDU) stopped prematurely due to side effects: only one had a sustained virological response. Based on an intent-to-treat analysis, and considering all 14 patients in whom at least one dose of drug was administered, only 8 (57%) became sustained virological responders. CONCLUSIONS: Treatment of acute hepatitis C with pegylated IFN-alpha is highly beneficial, but its effectiveness is affected by a poor rate of acceptance and/or adherence to currently available regimens, especially in IVDU and women.     

Effect of nutrition counselling with a digital job aid on child dietary diversity: Analysis of secondary outcomes from a cluster randomised controlled trial in rural Bangladesh

Adequate dietary diversity among infants is often suboptimal in developing countries. We assessed the impact of nutrition counselling using a digital job aid on dietary diversity of children aged 6–23 months using data from a cluster randomised controlled trial in Bangladesh. The trial had five arms, each with 25 clusters. The four intervention arms provided counselling using a digital job aid and different prenatal and post-natal combinations of lipid-based supplements and the comparison arm with usual practice. We enrolled 1500 pregnant women and followed them until the children reached their second birthday. We developed a tablet-based system for intervention delivery, data collection and project supervision. We combined the four intervention arms (n = 855), in which community health workers (CHWs) provided age-appropriate complementary feeding counselling, to compare against the comparison arm (n = 403). We calculated the outcome indicators from the children's 24-h dietary recalls. Overall, the intervention increased the mean dietary diversity score by 0.09 (95% confidence interval [CI]: 0.2–0.16) and odds of minimum dietary diversity by 18% (95% CI: 0.99–1.40). However, there was a significant interaction on the effect of the intervention on dietary diversity by age. The mean dietary diversity score was 0.24 (95% CI: 0.11–0.37) higher in the intervention than in the comparison arm at 9 months and 0.14 (95% CI: 0.01–27) at 12 months of age. The intervention effect was non-significant at an older age. Overall, consumption of flesh food was 1.32 times higher in the intervention arm (odds ratio [OR] 1.32, 95% CI: 1.11–1.57) in 6–23 months of age. The intervention significantly improved child dietary diversity score in households with mild and moderate food insecurity by 0.27 (95% CI: 0.06–0.49) and 0.16 (0.05–27), respectively, but not with food-secure and severely food-insecure households. Although the study did not evaluate the impact of digital job aid alone, the findings indicate the utility of nutrition counselling by CHWs using a digital job aid to improve child feeding practices in broader programmes.     

Emergency pediatric radiology imaging trends for non-COVID-19-related illnesses through different stages of the pandemic

Emergency Radiology - To evaluate how the COVID-19 pandemic affected the imaging utilization patterns for non-COVID-19-related illness in a pediatric emergency department (ED). We retrospectively...     

Imaging technologies and techniques

Equipment manufacturers provide contrast-specific detection techniques that have excellent sensitivity and excellent agent-to-tissue specificity along with helpful tools that improve workflow efficiency dramatically. Excellent contrast agents have been approved for LV opacification and are available worldwide. Techniques designed for low-MI imaging offer real-time acquisition capabilities and lead to faster examinations. Techniques designed for medium-MI imaging offer better sensitivity than low-MI techniques while maintaining the benefit of rapid image acquisition. Techniques designed for high-MI imaging offer the best sensitivity with longer acquisition times. These techniques are viable means for imaging contrast agents tailored to clinical needs. Progress by contrast agent manufacturers, equipment manufacturers, and physicians will continue to drive improvements in the areas of detection and clinical workflow for improved patient care.