Unicentric or multicentric castleman disease? A case report of a pelvic intraperitoneal mass in a middle aged woman

Castleman Disease is a lymphoid disorder characterized by the presence of an enlarged or abnormal lymph node/lymphatic tissue. The disease is classified into unicentric or multicentric variants. The unicentric form is a benign disorder that is usually asymptomatic and consists of a single lymphoid mass that is predominantly located in the mediastinum, but can also rarely develop in the neck or abdomen. The multicentric type involves more than one lymphatic station and is related to the presence of type B symptoms (fevers, night sweats and weight loss), HIV/HHV8 infection and increased serum IL-6 levels. We present the case of an unusual pelvic intraperitoneal manifestation of Castleman Disease in a 52-year-old caucasian woman who showed clinical, radiological, histological and laboratory findings common to both Unicentric and Multicentric Castleman Disease

CX3CR1 Polymorphisms are associated with atopy but not asthma in German children

Chemokines and their receptors are involved in many aspects of immunity. Chemokine CX3CL1, acting via its receptor CX3CR1, regulates monocyte migration and macrophage differentiation as well as T cell-dependent inflammation. Two common, nonsynonymous polymorphisms in CX3CR1 have previously been shown to alter the function of the CX3CL1/CX3CR1 pathway and were suggested to modify the risk for asthma. Using matrix-assisted laser desorption/ionization time-of-flight technology, we genotyped polymorphisms Val249Ile and Thr280Met in a cross-sectional population of German children from Munich (n = 1,159) and Dresden ( n = 1,940). For 249Ile an odds ratio of 0.77 (95% confidence interval 0.63-0.96; p = 0.017) and for 280Met an odds ratio of 0.71 ( 95% confidence interval 0.56-0.89; p = 0.004) were found with atopy in Dresden but not in Munich. Neither polymorphism was associated with asthma. Thus, amino acid changes in CX3CR1 may influence the development of atopy but not asthma in German children. Potentially, other factors such as environmental effects may modify the role of CX3CR1 polymorphisms. Copyright (c) 2007 S. Karger AG, Basel

Feasibility of short term drainage for diagnostic thoracoscopy

Background and Aim. Thoracoscopy is a diagnostic tool superior to other available techniques for the assessment of pleural effusions. There are numerous publications that describe the technique in detail but there is very little published on the optimal time of chest drain removal post procedure. Our aim was to retrospectively study all cases of diagnostic thoracoscopy and to ascertain the time of chest drain removal, length of hospital stay and associated complications. Methods. All patients who underwent thoracoscopy during a 6-year period were identified from a computerised database. Patients who received talc for pleurodesis were excluded as they required longer drainage time. A review of the remaining patients’ charts and radiology was performed to ascertain the predefined outcomes. Results. 124 patients had a diagnostic thoracoscopy. The time to chest drain removal was documented as less than four hours, four to 24 hours, 24 to 48 hours and greater than 48 hours in 66 (53.2%), 29 (23.4%), 12 (9.7%) and 17 (13.7%) of patients respectively. The median length of stay for all patients was one day (interquartile range, 1-4 days). There was a statistically significant difference in overall length of hospital stay between the early (48 hours) chest drain removal groups, p=0.0028. The overall complication rate was 15.9%. There was no statistical difference in complication rates between the two groups. Conclusion. This retrospective series demonstrates that early chest drain removal post diagnostic thoracoscopy is possible and safe. This is likely to confer economic benefits

Hardware in the Loop Testing of an Iodine-Fed Hall Thruster

CUBESATS are relatively new spacecraft platforms that are typically deployed from a launch vehicle as a secondary payload,1 providing low-cost access to space for a wide range of end-users. These satellites are comprised of building blocks having dimensions of 10x10x10 cm cu and a mass of 1.33 kg (a 1-U size). While providing low-cost access to space, a major operational limitation is the lack of a propulsion system that can fit within a CubeSat and is capable of executing high delta v maneuvers. This makes it difficult to use CubeSats on missions requiring certain types of maneuvers (i.e. formation flying, spacecraft rendezvous). Recently, work has been performed investigating the use of iodine as a propellant for Hall-effect thrusters (HETs) 2 that could subsequently be used to provide a high specific impulse path to CubeSat propulsion. Iodine stores as a dense solid at very low pressures, making it acceptable as a propellant on a secondary payload. It has exceptionally high Isp (density times specific impulse), making it an enabling technology for small satellite near-term applications and providing the potential for systems-level advantages over mid-term high power electric propulsion options. Iodine flow can also be thermally regulated, subliming at relatively low temperature ( less than100 C) to yield I2 vapor at or below 50 torr. At low power, the measured performance of an iodine-fed HET is very similar to that of a state-of-the-art xenon-fed thruster. Just as importantly, the current-voltage discharge characteristics of low power iodine-fed and xenon-fed thrusters are remarkably similar, potentially reducing development and qualifications costs by making it possible to use an already-qualified xenon-HET PPU in an iodine-fed system. Finally, a cold surface can be installed in a vacuum test chamber on which expended iodine propellant can deposit. In addition, the temperature doesn't have to be extremely cold to maintain a low vapor pressure in the vacuum chamber (it is under 10(exp -6) torr at -75 C), making it possible to 'cryopump' the propellant with lower-cost recirculating refrigerant-based systems as opposed to using liquid nitrogen or low temperature gaseous helium cryopanels. In the present paper, we describe testing performed using an iodine-fed 200 W Hall thruster mounted to a thrust stand and operated in conjunction with MSFCs Small Projects Rapid Integration and Test Environment (SPRITE) Portable Hardware In the Loop (PHIL) hardware. This work is performed in support of the iodine satellite (iSAT) project, which aims to fly a 200-W iodine-fed thruster on a 12-U CubeSat. The SPRITE PHIL hardware allows a given vehicle to do a checkout of its avionics algorithm by allowing it to monitor and feed data to simulated sensors and effectors in a digital environment. These data are then used to determine the attitude of the vehicle and a separate computer is used to interpret the data set and visualize it using a 3D graphical interface. The PHIL hardware allows the testing of the vehicles bus by providing 'real' hardware interfaces (in the case of this test a real RS422 bus) and specific components can be modeled to show their interactions with the avionics algorithm (e.g. a thruster model). For the iSAT project the PHIL is used to visualize the operating cycle of the thruster and the subsequent effect this thrusting has on the attitude of the satellite over a given period of time. The test is controlled using software running on an Andrews Space Cortex 160 flight computer. This computer is the current baseline for a full iSAT mission. While the test could be conducted with a lab computer and software, the team chose to exercise the propulsion system with a representative CubeSat-class computer. For purposes of this test, the "flight" software monitored the propulsion and PPU systems, controlled operation of the thruster, and provided thruster state data to the PHIL simulation. Commands to operate the thruster were initiated from an operator's workstation outside the vacuum chamber and passed through the Cortex 160 to exercise portions of the flight avionics. Two custom-designed pieces of electronics hardware have been designed to operate the propellant feed system. One piece of hardware is an auxiliary board that controls a latch valve, proportional flow control valves (PFCVs) and valve heaters as well as measuring pressures, temperatures and PFCV feedback voltage. An onboard FPGA provides a serial link for issuing commands and manages all lower level input-output functions. The other piece of hardware is a power distribution board, which accepts a standard bus voltage input and converts this voltage into all the different current-voltage types required to operate the auxiliary board. These electronics boards are located in the vacuum chamber near the thruster, exposing this hardware to both the vacuum and plasma environments they would encounter during a mission, with these components communicating to the flight computer through an RS-422 interface. The auxiliary board FPGA provides a 28V MOSFET switch circuit with a 20ms pulse to open or close the iodine propellant feed system latch valve. The FPGA provides a pulse width modulation (PWM) signal to a DC/DC boost converter to produce the 12-120V needed for control of the proportional flow control valve. There are eight MOSFET-switched heating circuits in the system. Heaters are 28V and located in the latch valve, PFCV, propellant tank and propellant feed lines. Both the latch valve and PFCV have thermistors built into them for temperature monitoring. There are also seven resistance temperature device (RTD) circuits on the auxiliary board that can be used to measure the propellant tank and feedline temperatures. The signals are conditioned and sent to an analog to digital converter (ADC), which is directly commanded and controlled by the FPGA

Developmental regulation of apical endocytosis controls epithelial patterning in vertebrate tubular organs

© 2015 Macmillan Publishers Limited. Epithelial organs develop through tightly coordinated events of cell proliferation and differentiation in which endocytosis plays a major role. Despite recent advances, how endocytosis regulates the development of vertebrate organs is still unknown. Here we describe a mechanism that facilitates the apical availability of endosomal SNARE receptors for epithelial morphogenesis through the developmental upregulation of plasmolipin (pllp) in a highly endocytic segment of the zebrafish posterior midgut. The protein PLLP (Pllp in fish) recruits the clathrin adaptor EpsinR to sort the SNARE machinery of the endolysosomal pathway into the subapical compartment, which is a switch for polarized endocytosis. Furthermore, PLLP expression induces apical Crumbs internalization and the activation of the Notch signalling pathway, both crucial steps in the acquisition of cell polarity and differentiation of epithelial cells. We thus postulate that differential apical endosomal SNARE sorting is a mechanism that regulates epithelial patterning.MINECO (BFU2011-22622) and CONSOLIDER (CSD2009-00016); Fundación Obra Social `La Caixa' PhD fellowship. G.A. was supported by the Amarouto Program for senior researchers from the Comunidad Autónoma de Madrid.Peer Reviewe

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity

Rituximab plus bendamustine as front-line treatment in frail elderly (>70 years) patients with diffuse large b-cell non-hodgkin lymphoma: A phase ii multicenter study of the fondazione italiana linfomi

We conducted a phase II study to assess activity and safety profile of bendamustine and rituximab in elderly patients with untreated diffuse large B-cell lymphoma (DLBCL) who were prospectively defined as frail using a simplified version of the Comprehensive Geriatric Assessment (CGA). Patients had to be over 70 years of age, with histologically confirmed DLBCL. Frail patients were those younger than 80 years with a frail profile at CGA or older than 80 years with an unfit profile. Treatment consisted of 4-6 courses of bendamustine [90 mg/m 2 days (d)1-2] and rituximab (375 mg/m 2 d1) administered every 28 days. Other main study end points were complete remission rate and the rate of extra-hematologic adverse events. Forty-nine patients were enrolled of whom 45 were confirmed eligible. Overall, 24 patients achieved a complete remission (53%; 95%CI: 38-68%) and the overall response rate was 62% (95%CI: 47-76%). The most frequent grade 3-4 adverse event was neutropenia (37.8%). Grade 3-4 extra-hematologic adverse events were observed in 7 patients (15.6%; 95%CI: 6.5-29.5%); the most frequent was grade 3 infection in 2 patients. With a median follow up of 33 months (range 1-52), the median progression-free survival was ten months (95%CI: 7-25). The study shows promising activity and manageable toxicity profile of BR combination as first-line therapy for patients with DLBCL who are prospectively defined as frail according to a simplified CGA, as adopted in this trial (clinicaltrials.gov identifier: 01990144)

First-line therapy with either bortezomib-melphalan-prednisone or lenalidomide-dexamethasone followed by lenalidomide for transplant-ineligible multiple myeloma patients: A pooled analysis of two randomized trials

Bortezomib-melphalan-prednisone (VMP) and continuous lenalidomide-dexamethasone (Rd) represent the standard treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (MM). To date, no randomized trial has compared VMP to Rd, and there is no evidence of the optimal treatment for newly diagnosed MM, particularly in patients with high-risk cytogenetics [del(17p), t(4;14) or t(14;16)]. We pooled together data from patients with newly diagnosed MM treated with VMP or Rd induction followed by lenalidomide maintenance 10 mg (Rd-R) enrolled in the GIMEMA-MM-03-05 and EMN01 trials, to evaluate the efficacy of these treatments in different subgroups of patients, focusing on those with standard- and high-risk cytogenetics. Overall, 474 patients were analyzed (VMP: 257 patients; Rd-R: 217 patients). No differences in progression-free survival (hazard ratio=0.96) and overall survival (hazard ratio=1.08) were observed between standard-risk patients treated with VMP or Rd-R, whereas among the high-risk patients, the probabilities of progression (hazard ratio=0.54) and death (hazard ratio=0.73) were lower in the patients treated with VMP than in those treated with Rd-R. In particular, standard-risk patients >75 years benefited less from VMP than from Rd-R (hazard ratio for progression-free survival=0.96; hazard ratio for overall survival=1.81). In this non-randomized analysis, VMP and Rd-R were equally effective in younger ( 6475 years), standard-risk patients, while older ones (>75 years) benefited more from Rd-R. In high-risk patients, VMP improved progression-free survival and overall survival irrespective of age. The source trials are registered at ClinicalTrials.gov (NCT01063179 and NCT01093196)

Low-dose oral imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide: a phase II pilot study.

NTRODUCTION: Pulmonary involvement represents a major cause of death of systemic sclerosis (SSc) patients. Recent data suggest that tyrosine kinase inhibitors, such as imatinib, may be a therapeutic option for SSc patients. However, preliminary published clinical trials were inconclusive about imatinib efficacy and showed side effects. The purpose of this study was to verify efficacy and tolerability of low-dose imatinib on interstitial lung disease in a cohort of SSc patients unresponsive to cyclophosphamide therapy. METHODS: Thirty consecutive SSc patients with active pulmonary involvement, unresponsive to cyclophosphamide, were treated with imatinib 200 mg/day for 6 months followed by a 6-month follow-up. A "good response" was defined as an increase of forced vital capacity (FVC) by more of 15% and/or increase of diffusing capacity of carbon monoxide (DLCO) >15% and PaO2 > 90% of initial value and high-resolution computed tomography (HRCT)-scan pattern unchanged or improved. RESULTS: Twenty-six patients completed the study. Three patients died and one patient was lost to follow-up. Four patients (15.32%) had a good response, 7 worsened and 15 had a stabilized lung disease. Overall, 19 (73.07%) patients had an improved or stabilized lung disease. After a 6-month follow-up, 12 (54.5%) of the 22 patients showed an improved or stabilized lung disease. CONCLUSIONS: Lung function was stabilized in a large proportion of patients unresponsive to cyclophosphamide therapy and a beneficial outcome emerged from the analysis of HRCT lung scans. There was no significant improvement of skin involvement, and the low dose was well tolerated. These data provide useful suggestions to design future randomized clinical trials for SSc therapeutics