Combination antibody therapy with epratuzumab and rituximab in relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: To explore the safety and therapeutic activity of combination anti-B-cell monoclonal antibody therapy in non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Twenty-three patients with recurrent B-cell lymphoma received anti-CD22 epratuzumab 360 mg/m(2) and anti-CD20 rituximab 375 mg/m(2) monoclonal antibodies weekly for four doses each. Sixteen patients had indolent histologies (15 with follicular lymphoma) and seven had aggressive NHL (all diffuse large B-cell lymphoma [DLBCL]). Indolent patients had received a median of one (range, one to six) prior treatment, with 31% refractory to their last therapy and 81% with high-risk Follicular Lymphoma International Prognostic Index scores. Patients with DLBCL had a median of three (range, one to eight) prior regimens (14% resistant to last treatment) and 71% had high intermediate-risk or high-risk International Prognostic Index scores. All patients were rituximab na?ve. RESULTS: Treatment was well tolerated, with toxicities principally infusion-related and predominantly grade 1 or 2. Ten (67%) patients with follicular NHL achieved an objective response (OR), including nine of 15 (60%) with complete responses (CRs and unconfirmed CRs). Four of six assessable patients (67%) with DLBCL achieved an OR, including three (50%) CRs. Median time to progression for all indolent NHL patients was 17.8 months. CONCLUSION: The full-dose combination of epratuzumab with rituximab was well tolerated and had significant clinical activity in NHL, suggesting that this combination should be tested in comparison with single-agent treatment.     

Autotrophy as a predominant mode of carbon fixation in anaerobic methane-oxidizing microbial communities

The methane-rich, hydrothermally heated sediments of the Guaymas Basin are inhabited by thermophilic microorganisms, including anaerobic methane-oxidizing archaea (mainly ANME-1) and sulfate-reducing bacteria (e.g., HotSeep-1 cluster). We studied the microbial carbon flow in ANME-1/ HotSeep-1 enrichments in stable-isotope–probing experiments with and without methane. The relative incorporation of ¹³C from either dissolved inorganic carbon or methane into lipids revealed that methane-oxidizing archaea assimilated primarily inorganic carbon. This assimilation is strongly accelerated in the presence of methane. Experiments with simultaneous amendments of both ¹³C-labeled dissolved inorganic carbon and deuterated water provided further insights into production rates of individual lipids derived from members of the methane-oxidizing community as well as their carbon sources used for lipid biosynthesis. In the presence of methane, all prominent lipids carried a dual isotopic signal indicative of their origin from primarily autotrophic microbes. In the absence of methane, archaeal lipid production ceased and bacterial lipid production dropped by 90%; the lipids produced by the residual fraction of the metabolically active bacterial community predominantly carried a heterotrophic signal. Collectively our results strongly suggest that the studied ANME-1 archaea oxidize methane but assimilate inorganic carbon and should thus be classified as methane-oxidizing chemoorganoautotrophs.     

Ten‐Year Retrospective Follow‐Up Study of the TiOblast™ Dental Implant

Purpose: Long‐term results in the clinical outcome of different implant systems, including high patient numbers and a long follow‐up time, are rare. This retrospective study evaluated the cumulative survival rate of a self‐tapping, cylindrical implant system with a conical implant‐abutment connection after 10 years of prosthetic loading. Materials and Methods: A total of 516 TiOblast? implants (Astra Tech AB, Mölndal, Sweden) were placed in 108 patients. The patients were treated in the Department of Oral and Maxillofacial Surgery, Johannes Gutenberg University, Mainz, Germany, between September 1994 and May 2005. The main indications for implantation were the treatment of edentulous mandibles (74%) and partial edentulism (15%). Twenty‐three implants were placed postradiation, and a further 64 implants were irradiated after insertion. In 153 implants, a bony augmentation was conducted prior to implantation. Results: The in situ rate was 89.7% after an average implantation time of 108 months. Eighty‐three patients with 403 implants were available for investigation. Seventeen patients with 76 implants have died since 1994. Absence of osseointegration (n = 22), peri‐implantitis (n = 18), fracture of the implants (n = 9), failing of primary stability (n = 2), and implants next to tumors (n = 2) were the reasons of explantation in 26 patients. Under analysis with different implant success‐assessment criteria, the success rate showed results from 76 to 89%. Conclusion: With respect to the critical patient selection including a high number of patients with minor and major augmentations, the 10‐year clinical use of the studied implant system showed acceptable results.     

Improvement of Statin Utilization in Veterans With Diabetes Through Pharmacy Interventions

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes an effort aimed at increasing the use of statins among veterans with diabetes at a Veterans Affairs medical center in New Mexico.     

Are Dyspeptic Symptoms in Patients with Campylobacter pylori-Associated Type B Gastritis Linked to Delayed Gastric Emptying?

In this paper, the association of gastric Campylobacter pylori (CP) colonization with histologic findings and gastric emptying of a mixed solid-liquid meal was prospectively investigated in 43 consecutive patients with essential non-ulcer dyspepsia (ENUD). Gastric emptying was also measured in 30 symptom-free control subjects. The frequency of CP infection in patients with ENUD was 44.2%. We found a strong association between gastric CP colonization and chronic antral type B gastritis. Although gastric emptying was significantly prolonged in patients with ENUD, compared with the control group (p less than 0.05), we could not detect significant differences of gastric emptying between CP-negative and CP-positive ENUD patients, both groups disclosing a similar proportion of patients with significantly delayed gastric emptying (29.2% vs 31.6%). We therefore conclude that delayed gastric emptying of a mixed solid-liquid meal is not correlated with CP-positive chronic antral type B gastritis, and does not help to explain dyspeptic symptoms, which may possibly arise in relation to gastric CP colonization.     

Prospective pilot evaluation of a new needle prototype for endoscopic ultrasonography-guided fine-needle aspiration: comparison of cytology and histology yield

OBJECTIVES: Endoscopic ultrasonography (EUS) with the adjunct of EUS-guided fine needle aspiration has become an important diagnostic modality in gastroenterologic oncology. EUS-guided fine needle aspiration mainly relies on cytology; data are scarce that compare cytology and histology. While testing a 22-gauge prototype needle, we prospectively compared the yield for both. METHODS: Forty-two consecutive patients (27 male, 15 female; mean age 59.2 years, range: 17-90 years) were included. In each patient we aimed to make two needle passes, and if the material acquired appeared insufficient macroscopically (no in-room cytopathology was available), further passes were done. The material was sent for cytological and histological assessment. RESULTS: A median number of two passes (range: 2-3) were uneventfully performed for pancreatic lesions (n=30), mediastinal and other lymph nodes/masses (n=8) and various other lesions (n=4) and yielded adequate material for cytology, histology or at least one of the two investigations in 62, 67 and 74% of patients, respectively. No false positive results were found (specificity 100%). Sensitivities were 58.6 and 65.5%, respectively, for cytology and histology alone; combined assessment increased sensitivity to 79.3%. When adjusted values were calculated, based only on those cases with adequate material, sensitivity was 89.5% for cytology and 85.7% for histology, and increased to 100% with combined assessment. CONCLUSION: The new needle achieves sensitivities similar to those previously reported with no significant differences in sensitivity between cytology and histology. More effective tissue acquisition methods must be sought to improve overall results.     

Activism on rifapentine pricing: removing cost barriers to improve the uptake of tuberculosis research innovations

As recent advances have been made in developing tools to fight tuberculosis (TB), there is also a trend towards increasing advocacy by the civil society for TB research and access. One recent successful effort to increase access to treatment options for TB involved a collaborative effort to identify the need for and barriers to the use of rifapentine (RPT) use in the United States. Survey responses confirmed the under-utilization of RPT: 82% of survey respondents selected cost as a significant or potential barrier to use. Survey results provided data to support a year-long advocacy campaign urging the drug company Sanofi to lower the price of RPT. This campaign was based on a common evidence base built in part by the stakeholders themselves. After multiple engagements with communities and providers, Sanofi US announced on 12 December 2013 that they would drop the price of RPT to US$32 per blister pack of 32 tablets for US public health programs. While further work remains to secure access to RPT in the United States and worldwide, the lowering of the price of RPT reflects the positive impact that collaborative advocacy can accomplish, and sets an example for other drug companies to follow.     

Residual Stresses Measurements in Laser Powder Bed Fusion Using Barkhausen Noise Analysis

In recent years, the advancement of technology brought the laser powder bed fusion process to its industrialisation step. Despite all the advancements in process repeatability and general quality control, many challenges remain unsolved due to the intrinsic difficulties of the process, notably the residual stresses issue. This work aimed to assess the usability of Barkhausen noise analysis (BNA) for the residual stress in situ monitoring of laser powder bed fusion on Maraging steel 300 (18Ni-300/1.2709). After measuring the evolution of grain size distribution over process parameter changes, two series of experiments were designed. First, a setup with an external force allows to validate the working principle of BNA on the chosen material processed using LPBF. The second experiment uses on-plates samples with different residual stress states. The results show a good stability in microstructure, a prerequisite for BNA. In addition, the external load setup acknowledges that signal variation correlates with the induced stress state. Finally, the on-plate measurement shows a similar signal variation to what has been observed in the literature for residual stress variation. It is shown that BNA is a suitable method for qualitative residual stresses variation monitoring developed during the LPBF process and underlines that BNA is a promising candidate as an in situ measurement method.