Background
Isolated limb perfusion (ILP) is a regional surgical treatment for localized metastatic disease. High doses of chemotherapeutic agents are administered within an extracorporeal circulated ...isolated extremity, treating the metastasis, while systemic toxicity is avoided. To our knowledge, indexed oxygen supply/demand relationship during ILP has not previously been described. Our aim was to measure and describe oxygen metabolism, specifically oxygen delivery, consumption, and extraction, in an isolated leg/arm during ILP. Also investigate whether invasive oxygenation measurement during ILP correlates and can be used interchangeable with the non-invasive method, near infrared spectroscopy (NIRS).
Methods:
Data from 40 patients scheduled for ILP were included. At six time points blood samples were drawn during the procedure. DO2, VO2, and O2ER were calculated according to standard formulas. NIRS and hemodynamics were recorded every 10 min.
Results:
For all observations, the mean of DO2 was 190±59 ml/min/m2, VO2 was 35±8 ml/min/m2, and O2ER was 21±8%. VO2 was significantly higher in legs compared to arms (38±8 vs. 29±7 ml/min/m2, p=0.02). Repeated measures showed a significant decrease in DO2 in legs (209±65 to 180±66 ml/min/m2, p=<0.01) and in arms (252±72 to 150±57 ml/min/m2, p=<0.01). Significant increase in O2ER in arms was also found (p=0.03). Significant correlation was detected between NIRS and venous extremity oxygen saturation (SveO2) (rrm=0.568, p=<. 001, 95% CI 0.397–0.701). When comparing SveO2 and NIRS using a Bland–Altman analysis, the mean difference (bias) was 8.26±13.03 (p=<. 001) and the limit of agreement was − 17.28–33.09, with an error of 32.5%.
Conclusion:
DO2 above 170 ml/min/m2 during ILP kept O2ER below 30% for all observations. NIRS correlates significant to SveO2; however, the two methods do not agree sufficiently to work interchangeable. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04460053 and NCT03073304.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Expression of the RNA-binding motif protein 3 (RBM3) has been shown to correlate with favourable clinicopathological parameters and prognosis in several cancer diseases. The aim of this study was to ...examine the expression and prognostic ability of RBM3 in patients with testicular non-seminomatous germ cell tumours (NSGCT).
Immunohistochemical RBM3 expression was analysed in tissue microarrays with tumours from 206 patients. Chi-square test was applied to analyze associations between RBM3 expression and clinicopathological parameters. Kaplan-Meier analysis was used to assess the impact of RBM3 expression on cancer-specific survival (CSS) and failure-free survival (FFS). Cox regression proportional hazards models were used to estimate the relative risk for failure.
In the entire cohort, there was a significant association between clinical stage (p=0.044) and RBM3 expression. Weak RBM3 expression correlated with a significantly reduced FFS 79.3% versus 90.4% (p=0.019) and CSS 87.5% versus 97.3% (p=0.047). For patients with metastatic disease (n = 88), significant associations were found between RBM3 expression and IGCCC group (p=0.007). The FFS was significantly inferior for patients with low tumour-specific RBM3 expression 59.3% versus 79.0% (p=0.013), and this association remained significant in a multivariable model for patients with metastatic disease (HR=3.67; 95% CI 1.14, 11.89).
Low RBM3 expression is an independent predictor of treatment failure in metastatic NSGCT, in relation to the prognostic factors included in the International Germ Cell Consensus Classification (IGCCC). These findings suggest that RBM3 may be a potential biomarker for treatment stratification in patients with metastatic non-seminomatous germ cell tumours, and therefore merit further validation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict ...guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response.
Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for α-fetoprotein (AFP) of ≤ 7 days and/or for β-human chorionic gonadotropin (β-HCG) of ≤ 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2.
Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients.
With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.
Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous group of tumors with dismal prognosis, partially due to lack of reliable targetable and predictive biomarkers. ...RNA-binding motif protein 3 (RBM3) has previously been shown to be an independent prognostic and predictive biomarker in several types of cancer. Herein, we examined the prognostic value of RBM3 in periampullary adenocarcinoma, as well as the effects following RBM3 suppression in pancreatic cancer cells
. RBM3 mRNA levels were examined in 176 pancreatic cancer patients from The Cancer Genome Atlas. Immunohistochemical expression of RBM3 was analyzed in tissue microarrays with primary tumors and paired lymph node metastases from 175 consecutive patients with resected periampullary adenocarcinoma. Pancreatic cancer cells were transfected with anti-RBM3 siRNA
and the influence on cell viability following chemotherapy, transwell migration and invasion was assessed. The results demonstrated that high mRNA-levels of RBM3 were significantly associated with a reduced overall survival (
= 0.026). RBM3 protein expression was significantly higher in lymph node metastases than in primary tumors (
= 0.005). High RBM3 protein expression was an independent predictive factor for the effect of adjuvant chemotherapy and an independent negative prognostic factor in untreated patients (
for interactio
0.003). After siRNA suppression of RBM3
, pancreatic cancer cells displayed reduced migration and invasion compared to control, as well as a significantly increased resistance to chemotherapy. In conclusion, the strong indication of a positive response predictive effect of RBM3 expression in pancreatic cancer may be highly relevant in the clinical setting and merits further validation.
To investigate if testicular cancer survivors (TCSs) have a higher incidence of work loss compared with the population, accounting for stage, treatment and relapse.
A cohort of 2146 Swedish TCSs ...diagnosed 1995-2007 (seminoma n = 926, non-seminoma n = 1220) was identified in the SWENOTECA (Swedish-Norwegian Testicular Cancer Group) register, and matched 1:4 to population comparators. Prospectively recorded work loss data (both before and after diagnosis) were obtained from national registers through September 2013. Adjusted relative risks (RR) and 95% confidence intervals (CI) of sick leave and/or disability pension were calculated annually and overall with Poisson- and Cox regression, censoring at relapse. The mean number of annual work days lost was also estimated.
TCSs were at a modestly increased annual risk of work loss up to the third year of follow-up (RR3rd year 1.25, 95% CI 1.08, 1.43), attributed to a more pronounced risk among extensively treated patients (4 chemotherapy courses: RR3rd year 1.60, 95% CI 1.19, 2.15; > 4 courses: RR3rd year 3.70, 95% CI 2.25, 6.11). Patients on surveillance or limited treatment (radiotherapy, 1-3 chemotherapy courses) did not have an increased risk of work loss beyond the first year. TCSs receiving > 4 chemotherapy courses had higher mean number of annual days of work loss up to the 10th year post-diagnosis, and a five-fold risk of disability pension (RR 5.16, 95% CI 2.00, 10.3).
Extensively treated TCSs, but not those on surveillance or limited treatment, are at increased risk of work loss long-term, not explained by relapse. These patients may benefit from early rehabilitation initiatives.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In diseases like Alzheimer's disease and familial amyloidotic polyneuropathy (FAP) amyloid deposits co-localize with areas of neurodegeneration. FAP is associated with mutations of the plasma protein ...transthyretin (TTR). We can here show an apoptotic effect of amyloidogenic mutants of TTR on a human neuroblastoma cell line. Toxicity could be blocked by catalase indicating a free oxygen radical dependent mechanism. The toxic effect was dependent on the state of aggregation and unexpectedly mature fibrils from FAP-patients who failed to exert an apoptotic response. Morphological studies revealed a correlation between toxicity and the presence of immature amyloid. Thus, we can show that toxicity is associated with early stages of fibril formation and propose that mature full-length fibrils represent an inert end stage, which might serve as a rescue mechanism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Aims. In March 2008, the APEX facility instrument was installed on the telescope at the site of Lliano Chajnantor in northern Chile. The main objective of the paper is to introduce the new instrument ...to the radio astronomical community. It describes the hardware configuration and presents some initial results from the on-sky commissioning. Methods. The heterodyne instrument covers frequencies between 211 GHz and 1390 GHz divided into four bands. The first three bands are sideband-separating mixers operating in a single sideband mode and based on superconductor-insulator-superconductor (SIS) tunnel junctions. The fourth band is a hot-electron bolometer, waveguide balanced mixer. All bands are integrated in a closed-cycle temperature-stabilized cryostat and are cooled to 4 K. Results. We present results from noise temperature, sideband separation ratios, beam, and stability measurements performed on the telescope as a part of the receiver technical commissioning. Examples of broad extragalactic lines are also included.
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FMFMET, NUK, UL, UM, UPUK
A new receiver for the Onsala 20 m antenna with the possibility of being equipped with 3 mm and 4 mm bands has been built and the 3 mm channel has been commissioned during the Spring 2014. For ...single-dish operation, the receiver uses an innovative on-source/off-source optical switch. In combination with additional optical components and within the same optical layout, the switch provides two calibration loads (for the 3 mm and 4 mm channels), sideband rejection measurement, and tuning possibilities. The optical layout of the receiver employs all cold (4 K) offset elliptical mirrors for both channels, whereas the on-off switch employs flat mirrors only. The 3 mm channel employs a sideband separation (2SB) dual polarization receiver with orthomode transducer (OMT), 4–8 GHz intermediate frequency (IF), x 2pol x upper and lower sidebands (USB + LSB). The cryostat has four optical windows made of high density polyethylene (HDPE) with anti-reflection corrugations, two for the signal and two for each frequency band cold load. The cryostat uses a two-stage cryocooler produced by Sumitomo HI RDK 408D2 with anti-vibration suspension of the cold-head to minimize impact of the vibrations on the receiver stability. The local oscillator (LO) system is based on a Gunn oscillator with aphase lock loop (PLL) and four mechanical tuners for broadband operation, providing independently tunable LO power for each polarization. This paper provides a technical description of the receiver and its technology and could be useful for instrumentation engineers and observers using the Onsala 20 m telescope.
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FMFMET, NUK, UL, UM, UPUK
Oral conditions were studied in 48 children and adolescents who, during short or long periods, had been assigned to anti‐epileptic drug treatment with carbamazepine or phenytoin. The individuals were ...diagnosed as suffering from partial seizures or generalized tonic‐clonic seizures and were distributed between three test groups according to the drug selected for treatment; patients on active carbamazepine (I) or phenytoin (II) medication, and patients previously treated with phenytoin (III). Untreated, newly diagnosed epileptics served as controls.
The results showed that individuals treated with carbamazepine for an average of 3 years displayed no intra‐oral side‐effects from the drug treatment. Compared with those on carbamazepine medication the subjects treated with phenytoin demonstrated a significantly greater number of gingival units with increased probing depths, lower saliva secretion rates and lower salivary buffer capacities. In all groups a majority of the individuals showed unsatisfactory plaque control. As a consequence of the results of the investigation it appears justified, from a dental point of view, to support carbamazepine as the first drug of choice for treatment of the types of seizures mentioned.
APEX, the Atacama PAthflnder Experiment (APEX) Telescope, is a partnership between Max Planck Institut fur Radioastronomie (in collaboration with Astronomisches Institut Ruhr Universitat Bochum ...(AIRUB)), Onsala Space Observatory and the European Southern Observatory. The telescope antenna, supplied by VERTEX Antennentechnik, is a 12 m antenna with a 17 mum rms surface accuracy operating at the Atacama Desert in the Chilean Andes at a 5100 m altitude. The APEX heterodyne facility receiver is placed in the telescope Nasmyth Cabin A. The receivers are coupled to the antenna via relay optics allowing the operation of two different Pi-type instruments and a 6-channel facility heterodyne receiver to cover approximately 210 - 1500 GHz frequency range while providing frequency independent illumination of the secondary. In this report, we present details on the optics for the APEX facility heterodyne receiver and details of its design. The report includes a very brief review of the APEX Band 1, 211 - 270 GHz, Band 2, 270 - 370 GHz, Band 3, 385 - 500 GHz, all based on sideband separation SIS mixer technology and Band T2, 1250 - 1390 GHz, a balanced waveguide HEB mixer, all developed by GARD.
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