IV thrombolysis represents the most effective acute stroke therapy. However, it is almost exclusively performed in stroke centers and is not available in most community areas. The Telemedical Pilot ...Project for Integrative Stroke Care (TEMPiS) was started in February 2003. Twelve community hospitals with no or very limited stroke thrombolysis experience and two stroke centers were connected via a network providing online neurologic examination and transfer of neuroradiologic scans. Following recently published preliminary results on acute phase safety of telethrombolysis, the present study reports on its long-term functional outcome.
Modified Rankin Scale (mRS), Barthel Index (BI), and mortality rate were prospectively collected 3 and 6 months after IV thrombolysis in patients of community network hospitals (telemedical group) and the stroke centers. Values of 95/100 for the BI and 0/1 for the mRS were defined as a favorable outcome.
Over the first 22 months, 170 patients were treated with tPA in the telemedical hospitals and 132 in the stroke center hospitals. Mortality rates were 11.2% vs 11.5% at 3 months (p = 0.55) and 14.2% vs 13% at 6 months (p = 0.45). A good functional outcome after 6 months was found in 39.5% of the telemedical hospitals vs 30.9% of the stroke centers (p = 0.10) for the mRS and 47.1% vs 44.8% (p = 0.44) regarding the BI.
Mortality rates and functional outcomes for telemedicine-linked community hospitals and stroke centers were similar and comparable to the results from randomized trials.
•A PBPK model was derived describing uptake of PFOS from contaminated fodder into consumption milk.•Almost all PFOS is eliminated through the milk.•PFOS elimination rate is low.•Single pollution ...events may lead to reaching the TDI in the vulnerable population.•Other exposure routes in the food chain should be quantified as well.
Dietary intake is the predominant route for human exposure to perfluorooctane sulfonic acid (PFOS). Single pollution events may thus affect human exposure if polluted ground and water is used to produce animal feed or food. In this study, a physiologically based pharmacokinetic (PBPK-) model is derived that describes the uptake of PFOS from contaminated feed by cows and its subsequent elimination through the cows’ milk. Parameter values of the model were estimated by fitting to experimental data of a cow feeding trial. Model calculations showed that almost all PFOS ingested is excreted through the cows’ milk. The elimination rate, however, was low as the estimated half-life in the cow was 56days and it may, thus, take a long time after an initial pollution event to produce PFOS-free milk. The derived model can be used to estimate the transfer of PFOS through the dairy food chain and can be used for comparison of various contamination routes.
To compare the diagnostic performance of PET with the amyloid ligand Pittsburgh compound B (PiB-PET) to fluorodeoxyglucose (FDG-PET) in discriminating between Alzheimer disease (AD) and ...frontotemporal lobar degeneration (FTLD).
Patients meeting clinical criteria for AD (n = 62) and FTLD (n = 45) underwent PiB and FDG-PET. PiB scans were classified as positive or negative by 2 visual raters blinded to clinical diagnosis, and using a quantitative threshold derived from controls (n = 25). FDG scans were visually rated as consistent with AD or FTLD, and quantitatively classified based on the region of lowest metabolism relative to controls.
PiB visual reads had a higher sensitivity for AD (89.5% average between raters) than FDG visual reads (77.5%) with similar specificity (PiB 83%, FDG 84%). When scans were classified quantitatively, PiB had higher sensitivity (89% vs 73%) while FDG had higher specificity (83% vs 98%). On receiver operating characteristic analysis, areas under the curve for PiB (0.888) and FDG (0.910) were similar. Interrater agreement was higher for PiB (κ = 0.96) than FDG (κ = 0.72), as was agreement between visual and quantitative classification (PiB κ = 0.88-0.92; FDG κ = 0.64-0.68). In patients with known histopathology, overall classification accuracy (2 visual and 1 quantitative classification per patient) was 97% for PiB (n = 12 patients) and 87% for FDG (n = 10).
PiB and FDG showed similar accuracy in discriminating AD and FTLD. PiB was more sensitive when interpreted qualitatively or quantitatively. FDG was more specific, but only when scans were classified quantitatively. PiB slightly outperformed FDG in patients with known histopathology.
The foundations of the Patagonian icefields Fürst, Johannes J.; Farías-Barahona, David; Blindow, Norbert ...
Communications earth & environment,
12/2024, Letnik:
5, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract The two vast Patagonian icefields are a global hotspot for ice-loss. However, not much is known about the total ice volume they store - let alone its spatial distribution. One reason is that ...the abundant record of direct thickness measurements has never been systematically exploited. Here, this record is combined with remotely-sensed information on past ice thickness mapped from glacier retreat. Both datasets are incorporated in a state-of-the-art, mass-conservation approach to produce a well-informed map of the basal topography beneath the icefields. Its major asset is the reliability increase of thicknesses values along the many marine- and lake-terminating glaciers. For these, frontal ice-discharge is notably lower than previously reported. This finding implies that direct climatic control was more influential for past ice loss. We redact a total volume for both icefields in 2000 of 5351 km 3 . Despite the wealth of observations used in this assessment, relative volume uncertainties remain elevated.
Ischaemic digital ulcers (DUs) are common in patients with systemic sclerosis (SSc) and are a cause of disease-related morbidity. In an earlier trial, treatment with bosentan, an oral endothelin ...receptor antagonist, reduced the occurrence of new DUs by 48%. The present study (RAPIDS-2, for 'RAndomized, double-blind, Placebo-controlled study with bosentan on healing and prevention of Ischemic Digital ulcers in patients with systemic Sclerosis') was conducted to more fully evaluate the effects of bosentan treatment on DUs associated with SSc.
This double-blind, placebo-controlled trial conducted at 41 centres in Europe and North America randomised 188 patients with SSc with at least 1 active DU ('cardinal ulcer') to bosentan 62.5 mg twice daily for 4 weeks and 125 mg twice daily thereafter for 20 weeks (n=98) or matching placebo (n=90; total 24 weeks). The two primary end points were the number of new DUs and the time to healing of the cardinal ulcer. Secondary end points included pain, disability and safety.
Over 24 weeks, bosentan treatment was associated with a 30% reduction in the number of new DUs compared with placebo (mean ± standard error: 1.9±0.2 vs 2.7±0.3 new ulcers; p=0.04). This effect was greater in patients who entered the trial with more DUs. There was no difference between treatments in healing rate of the cardinal ulcer or secondary end points of pain and disability. Peripheral oedema and elevated aminotransferases were associated with bosentan treatment.
Bosentan treatment reduced the occurrence of new DUs in patients with SSc but had no effect on DU healing. Bosentan was well tolerated and may be a useful adjunct in the management of patients with SSc with recurrent DUs.
Summary Background Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe. The aim in the COlorectal cancer Laparoscopic ...or Open Resection (COLOR II) trial was to compare laparoscopic and open surgery in patients with rectal cancer. Methods A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries. Patients (aged ≥18 years) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were randomly assigned to either laparoscopic or open surgery in a 2:1 ratio, stratified by centre, location of tumour, and preoperative radiotherapy. The study was not masked. Secondary (short-term) outcomes—including operative findings, complications, mortality, and results at pathological examination—are reported here. Analysis was by modified intention to treat, excluding those patients with post-randomisation exclusion criteria and for whom data were not available. This study is registered with ClinicalTrials.gov , number NCT00297791. Findings The study was undertaken between Jan 20, 2004, and May 4, 2010. 1103 patients were randomly assigned to the laparoscopic (n=739) and open surgery groups (n=364), and 1044 were eligible for analyses (699 and 345, respectively). Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group (median 200 mL IQR 100–400 vs 400 mL 200–700, p<0·0001); however, laparoscopic procedures took longer (240 min 184–300 vs 188 min 150–240; p<0·0001). In the laparoscopic surgery group, bowel function returned sooner (2·0 days 1·0–3·0 vs 3·0 days 2·0–4·0; p<0·0001) and hospital stay was shorter (8·0 days 6·0–13·0 vs 9·0 days 7·0–14·0; p=0·036). Macroscopically, completeness of the resection was not different between groups (589 88% of 666 vs 303 92% of 331; p=0·250). Positive circumferential resection margin (<2 mm) was noted in 56 (10%) of 588 patients in the laparoscopic surgery group and 30 (10%) of 300 in the open surgery group (p=0·850). Median tumour distance to distal resection margin did not differ significantly between the groups (3·0 cm IQR 2·0–4·8 vs 3·0 cm 1·8–5·0, respectively; p=0·676). In the laparoscopic and open surgery groups, morbidity (278 40% of 697 vs 128 37% of 345, respectively; p=0·424) and mortality (eight 1% of 699 vs six 2% of 345, respectively; p=0·409) within 28 days after surgery were similar. Interpretation In selected patients with rectal cancer treated by skilled surgeons, laparoscopic surgery resulted in similar safety, resection margins, and completeness of resection to that of open surgery, and recovery was improved after laparoscopic surgery. Results for the primary endpoint—locoregional recurrence—are expected by the end of 2013. Funding Ethicon Endo-Surgery Europe, Swedish Cancer Foundation, West Gothia Region, Sahlgrenska University Hospital.
Introduction
The negative influence of conversion from laparoscopic to open colorectal resection on early postoperative morbidity and outcome has been demonstrated several times. In this study, we ...analyzed the conversion rate and its influence on early postoperative morbidity and short-term oncological outcome following laparoscopic rectal resections.
Methods
From January 1998 to December 2006, 300 patients underwent laparoscopic resection due to rectal carcinoma at our institution. We compared the converted patient group with the non-converted patient group regarding demographical, clinical, surgical, and histological data, compounded with the early and late postoperative results.
Results
Two hundred seventy-four (91.3%) patients underwent laparoscopic rectal resection (LR)
,
while conversion resection (CR) was necessary in 26 cases (8.6%). Conversion rate was 13% during the first 100 resections and decreased to 3% during the last 100 procedures (
p
= 0.035). Male gender, higher body mass index, and presence of T4-tumor were risk factors for conversion. Early postoperative complications were more frequent in the CR group than in the LR group. Concerning local tumor recurrence and overall survival, there was no significant difference between both groups (local recurrence, CR at 3.8% vs. LR at 4.5% and overall survival rate, CR at 76.9% vs. LR at 89.1%) after a median follow-up period of 22.5 months.
Conclusion
Conversion to an open procedure during laparoscopic rectal resection correlates with an increased postoperative morbidity, however, without impairment of the short-term oncological outcome. The conversion rate is minimized by the growing experience of the operating surgeon and, therefore, is a marker of the learning curve.
Abstract
For several decades, the origin of ultra-high-energy cosmic rays (UHECRs) has been an unsolved question of high-energy astrophysics. One approach for solving this puzzle is to correlate ...UHECRs with high-energy neutrinos, since neutrinos are a direct probe of hadronic interactions of cosmic rays and are not deflected by magnetic fields. In this paper, we present three different approaches for correlating the arrival directions of neutrinos with the arrival directions of UHECRs. The neutrino data are provided by the IceCube Neutrino Observatory and ANTARES, while the UHECR data with energies above ∼50 EeV are provided by the Pierre Auger Observatory and the Telescope Array. All experiments provide increased statistics and improved reconstructions with respect to our previous results reported in 2015. The first analysis uses a high-statistics neutrino sample optimized for point-source searches to search for excesses of neutrino clustering in the vicinity of UHECR directions. The second analysis searches for an excess of UHECRs in the direction of the highest-energy neutrinos. The third analysis searches for an excess of pairs of UHECRs and highest-energy neutrinos on different angular scales. None of the analyses have found a significant excess, and previously reported overfluctuations are reduced in significance. Based on these results, we further constrain the neutrino flux spatially correlated with UHECRs.
Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) ...evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis.
We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild N=1229 vs. moderate to severe N=354). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24.
The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P=0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P=0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P=0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P=0.002). Adverse events were mild, infrequent, and evenly distributed among the groups.
Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. (ClinicalTrials.gov number, NCT00032890.).
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Human 5-lipoxygenase (5-LO) is the key enzyme of leukotriene biosynthesis, mostly expressed in leukocytes and thus a crucial component of the innate immune system.
In this study, we ...show that 5-LO, besides its canonical function as an arachidonic acid metabolizing enzyme, is a regulator of gene expression associated with euchromatin. By Crispr-Cas9-mediated 5-LO knockout (KO) in MonoMac6 (MM6) cells and subsequent RNA-Seq analysis, we identified 5-LO regulated genes which could be clustered to immune/defense response, cell adhesion, transcription and growth/developmental processes. Analysis of differentially expressed genes identified cyclooxygenase-2 (COX2, PTGS2) and kynureninase (KYNU) as strongly regulated 5-LO target genes. 5-LO knockout affected MM6 cell adhesion and tryptophan metabolism via inhibition of the degradation of the immunoregulator kynurenine. By subsequent FAIRE-Seq and 5-LO ChIP-Seq analyses, we found an association of 5-LO with euchromatin, with prominent 5-LO binding to promoter regions in actively transcribed genes. By enrichment analysis of the ChIP-Seq results, we identified potential 5-LO interaction partners. Furthermore, 5-LO ChIP-Seq peaks resemble patterns of H3K27ac histone marks, suggesting that 5-LO recruitment mainly takes place at acetylated histones.
In summary, we demonstrate a noncanonical function of 5-LO as transcriptional regulator in monocytic cells.
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