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ObjectiveTo assess the efficacy and safety of endoscopic resection of large colorectal polyps.DesignRelevant publications were identified in MEDLINE/EMBASE/Cochrane Central Register for the period 1966–2014. Studies in which ≥20 mm colorectal neoplastic lesions were treated with endoscopic resection were included. Rates of postendoscopic resection surgery due to non-curative resection or adverse events, as well as the rates of complete endoscopic removal, invasive cancer, adverse events, recurrence and mortality, were extracted. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was produced based on random effect models. I2 statistic was used to describe the variation across studies due to heterogeneity. Meta-regression analysis was also performed.Results50 studies including 6442 patients and 6779 large polyps were included in the analyses. Overall, 503 out of 6442 patients (pooled rate: 8%, 95% CI 7% to 10%, I2=78.6%) underwent surgery due to non-curative endoscopic resection, and 31/6442 (pooled rate: 1%, 95% CI 0.7% to 1.4%, I2=0%) to adverse events. Invasive cancer at histology, non-curative endoscopic resection, synchronous lesions and recurrence accounted for 58%, 28%, 2.2% and 5.9% of all the surgeries, respectively. Endoscopic perforation occurred in 96/6595 (1.5%, 95% CI 1.2% to 1.7%) polyps, while bleeding in 423/6474 (6.5%, 95% CI 5.9% to 7.1%). Overall, 5334 patients entered in surveillance, 502/5836 (8.6%, 95% CI 7.9% to 9.3%) being lost at follow-up. Endoscopic recurrence was detected in 735/5334 patients (13.8%, 95% CI 12.9% to 14.7%), being an invasive cancer in 14/5334 (0.3%, 95% CI 0.1% to 0.4%). Endoscopic treatment was successful in 664/735 cases (90.3%, 95% CI 88.2% to 92.5%). Mortality related with management of large polyps was reported in 5/6278 cases (0.08%, 95% CI 0.01% to 0.15%).ConclusionsEndoscopic resection of large polyps appeared to be an extremely effective and safe intervention. However, an adequate endoscopic surveillance is necessary for its long-term efficacy.

High-intensity interval resistance training (HIIRT) is an increasingly popular exercise program that provides positive results with short sessions. This study aimed to evaluate whether an HIIRT session causes muscle and kidney damage. Fifty-eight healthy volunteers (median age 24 years, 50% women) participated in this study and performed a HIIRT session. The Borg CR10 scale for pain (CR10P) and blood and urine samples were collected before (baseline) and 2 and 24 hours after the HIIRT session. Blood samples were analyzed for serum creatinine (SCr), creatine kinase (CK) and myoglobin. Urine samples were assessed for creatinine, neutrophil gelatinase-associated lipocalin, interleukin 18, calbindin, microalbuminuria, trefoil factor-3 and β-2 microglobulin. CR10P had a significant increase at 2 and 24 hours post-workout, and CK increased significantly at 2 hours and increased further at 24 hours. Myoglobin increased significantly at 2 hours and remained elevated at 24 hours. SCr increased modestly but significantly at 24 hours only in men. Three men met the KDIGO diagnostic criteria for acute kidney injury. The urinary kidney injury biomarkers increased significantly at 2 hours and returned to the baseline values 24 hours after HIIRT. A single HIIRT session caused early and significant elevations in CK, myoglobin, SCr, microalbuminuria and urinary biomarkers indicative of kidney tubular injury, suggesting the occurrence of muscle and kidney damage.

The changes in rainfall erosivity have been investigated using the rainfall erosivity factor ( R ) proposed for USLE by Wischmeier and Smith ( R W-S ) and some simplified indexes (the Fournier index modified by Arnoldus, F , a regional index spatial independent, R Fr , and a regional index spatial dependent, R Fs ) estimated by indirect approaches. The analysis has been carried out over 48 rainfall stations located in Calabria (Southern Italy) using data collected in the period 1936–2012 and divided in three sub-periods. The series of the erosivity indexes and of some precipitation variables have been analyzed for evidence of trends using standard methods. The simplified indexes suggested a general underestimation of the rainfall erosivity with respect to R W-S . The mean underestimation ranged between 23 and 54 % for R Fr and from 10 to 15 % for R Fs . Both the sign and the magnitude of the trends were different for the different stations depending on the variable and sub-period considered. In general, the erosivity increased during the period 1936–1955 (1 st sub-period) and during the more recent sub-period (1992–2012, 3 rd sub-period), whereas it decreased during 1958–1977 (2 nd sub-period). The evidence of trends was generally higher for R W-S than for R Fr and R Fs . Focusing on the most recent sub-period (3 rd sub-period), all the variables analyzed showed mainly increasing trends but with different magnitude. More particularly, R W-S showed a mean increment of 29 %; F , R Fr and R Fs increased by 11, 15 and 18 %, respectively; the maximum intensity of 0.5-h precipitation increased by 5 %; and the annual precipitation increased by 22 %. Consequently, it remains difficult to define which precipitation variable plays the dominant role in the temporal variation of rainfall erosivity in the region. However, the overall results suggest that the indexes estimated by indirect procedures ( F , R Fr , and R Fs ) should be used with caution for climate change analysis, despite they are used for practical purposes considering they are based on easily available information.

ObjectiveAlthough split regimen is associated with higher adenoma detection and is recommended for elective colonoscopy, its adoption remains suboptimal. The identification of patient-related barriers may improve its implementation. Our aim was to assess patients' attitude towards split regimen and patient-related factors associated with its uptake.DesignIn a multicentre, prospective study, outpatients undergoing colonoscopy from 8:00 to 14:00 were given written instructions for 4 L polyethylene glycol bowel preparation, offering the choice between split-dose and day-before regimens and emphasising the superiority of split regimen on colonoscopy outcomes. Uptake of split regimen and association with patient-related factors were explored by a 20-item questionnaire.ResultsOf the 1447 patients (mean age 59.2±13.5 years, men 54.3%), 61.7% and 38.3% chose a split-dose and day-before regimens, respectively. A linear correlation was observed between time of colonoscopy appointments and split-dose uptake, from 27.3% in 8:00 patients to 96% in 14:00 patients (p<0.001, χ2 for linear trend). At multivariate analysis, colonoscopy appointment before 10:00 (OR 0.14, 95% CI 0.11 to 0.18), travel time to endoscopy service >1 h (OR 0.55, 95% CI 0.38 to 0.79), low education level (OR 0.72, 95% CI 0.54 to 0.96) and female gender (OR 0.74, 95% CI 0.58 to 0.95) were inversely correlated with the uptake of split-dose. Overall, the risk of travel interruption and faecal incontinence was slightly increased in split regimen patients (3.0% vs 1.4% and 1.5% vs 0.9%, respectively; p=NS). Split regimen was an independent predictor of adequate colon cleansing (OR 3.34, 95% CI 2.40 to 4.63) and polyp detection (OR 1.46, 95% CI 1.11 to 1.92).ConclusionPatient attitude towards split regimen is suboptimal, especially for early morning examinations. Interventions to improve patient compliance (ie, policies to reorganise colonoscopy timetable, educational initiatives for patient and healthcare providers) should be considered.Trial registration numberNCT02287051; pre-result.

Background:Tapering of tumor necrosis factor inhibitor (TNFi) treatment in patients who have reached sustained remission is debated in current guidelines, and further data are needed regarding the long-term consequences of such strategies.Objectives:To assess the 3-year effects of tapering and withdrawal of TNFi versus continuing stable TNFi on disease activity flare, radiographic joint damage and remission status among RA patients in sustained remission.Methods:ARCTIC REWIND was a randomized, multicenter, open-label, non-inferiority trial including RA patients in sustained remission for ≥12 months on stable TNFi therapy, with no swollen joints at inclusion. Patients were randomized 1:1 to tapering to withdrawal of TNFi (four months half-dose, thereafter withdrawal) or continue stable TNFi therapy, with scheduled visits every four months for 3 years. Full-dose TNFi therapy was reinstated if a flare occurred. The primary endpoint of the current study was flare in disease activity over 3 years. A flare was defined as a combination of DAS>1.6 (loss of remission status), an increase in DAS ≥0.6 units (change above minimal detectable change) and ≥2 swollen joints, or if the physician and patient agreed that a clinically significant flare had occurred. Secondary endpoints included remission status (ACR/EULAR Boolean 2.0 and DAS), 3-year change in radiographic joint damage assessed by van der Heijde modified Sharp Score, medication use and adverse events (AE). Data were analysed in the per protocol population adjusting for center as a stratification factor. Flare-free survival was evaluated by Kaplan-Meier and risk of flare by Cox regression, remission status and radiographic change by logistic and linear regression.Results:Of 99 randomised patients, 92 received the allocated therapy, and 80 (87%) completed 3-year follow-up. Mean baseline DAS (SD) was 0.8 (0.3) in the tapering TNFi group, and 0.9 (0.4) in the stable TNFi group. csDMARD co-medication was used by 89% in the tapering group and 91% in the stable group. After 3 years, 25% (95% CI: 13 to 38) remained flare-free in the tapering TNFi group compared to 85% (70 to 93) in the stable TNFi group (Figure 1), with corresponding hazard ratio for flare of 9.4 (3.9 to 22.8), p<0.0001. Most patients regained DAS remission within the next visit after a flare (84% in the tapering group, 67% in the stable group). We observed significantly lower Boolean 2.0 remission rates in the tapering TNFi group than the stable TNFi group throughout the study period (Figure 2), adjusted risk difference 0-36 months -24% (-33 to -15), p<0.0001 (Boolean 1.0 revealed similar results). The median radiographic changes after 3 years were minimal; 0.5 (95% CI: 0.0 to 2.0) in the tapering group versus 0.5 (0.0 to 1.5) in the stable group, with no significant difference between groups, p-value=0.6. Systemic glucocorticoids (≥1 treatment period during the study) were used by 23% in the tapering TNFi group and 13% in the stable TNFi group during the study, while 10% switched to other types of TNFi or JAK inhibitor treatment in the tapering group, and 11% in the stable group. AE/serious AE occurred in 81%/21% of the patients in the tapering group, and 87%/11% of the patients in the stable group.Conclusion:A large majority of RA patients in remission tapering TNFi to withdrawal experienced a flare within three years, while a minority of patients receiving stable TNFi treatment flared over the same time period. Even though most patients regained remission within the next visit after a flare, TNFi tapering was associated with significantly lower Boolean 2.0 remission rates throughout the study. These findings do not support tapering of TNFi treatment among RA patients in sustained remission.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Kaja E. Kjørholt: None declared, Nina Paulshus Sundlisæter: None declared, Anna-Birgitte Aga AbbVie, Lilly, Novartis, Pfizer, Joe Sexton: None declared, Inge C. Olsen Dilafor AB, EU Commission, Åse Lexberg: None declared, Tor Magne Madland Boehringer 2022, Hallvard Fremstad: None declared, Christian A. Høili: None declared, Gunnstein Bakland UCB (Organizing meeting), Cristina Spada Advisory board UCB, Hilde Haukeland Advisory borad for UCB Pharma x2 in 2022., Inger M. Hansen: None declared, Ellen Moholt: None declared, Karen Holten: None declared, Till Uhlig Lilys, Galapagos, Pfizer and UCB, Lilly, Galapagos, Pfizer and UCB, Tore K. Kvien Grünenthal, Janssen, Sandoz, AbbVie, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sandoz, UCB, AbbVie, BMS, Novartis, Pfizer, UCB, Daniel H. Solomon Royalties on several UpToDate chapters on NSAIDs and coxibs. CARRA; unpaid board member., CorEvitas, Horizon, Janssen, Moderna and Novartis provide research support through contracts with Brigham and Women’s Hospital for unrelated work., Désirée van der Heijde Director of Imaging Rheumatology, AbbVie, BMS, Galapagos, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, Takeda UCB Pharma., Espen A. Haavardsholm Pfizer, UCB, AbbVie, Participation on a Data Safety Monitoring Board or Advisory Board for Pfizer, AbbVie, Boehringer, Ingelheim, Eli Lilly, Galapagos, Gilead, Novartis, Siri Lillegraven: None declared.

BackgroundTapering of disease modifying antirheumatic drugs (DMARDs) to achieve drug-free remission is a goal for the growing group of rheumatoid arthritis (RA) patients in remission. However, the long-term effects of tapering or withdrawal of DMARDs remain unclear.ObjectivesTo compare the 3-year clinical and radiographic outcomes of three conventional synthetic DMARD (csDMARD) treatment strategies (continued stable treatment, half-dose treatment and tapering to withdrawal) among patients in sustained RA remission.MethodsARCTIC REWIND was a randomized, multicenter, open-label, clinical trial enrolling 160 RA patients in sustained remission for ≥1 year on stable csDMARD therapy from 10 different Norwegian rheumatology departments.(1) At baseline, patients were randomized 2:1:1 to stable csDMARDs, half-dose csDMARDs, or half-dose csDMARDs for one year, followed by withdrawal of all csDMARDs (“tapering to withdrawal”). The primary endpoint was absence of disease activity flare over the 3-year study period. A flare was defined as a combination of disease activity score (DAS)>1.6, an increase in DAS ≥0.6 units since the previous visit and ≥2 swollen joints, or if the physician and patient agreed that a clinically significant flare had occurred. Full-dose csDMARD treatment was reinstated upon flare. Secondary endpoints included remission (DAS, ACR/EULAR Boolean) at 1, 2 and 3 years, and 3-year change in radiographic joint damage evaluated by van der Heijde-Sharp score (vdHSS). Data were analyzed using Kaplan-Meier, Mann-Whitney test, Cox and mixed effect logistic regression, with stratification or adjustment for study center.ResultsOf 156 patients who received the allocated treatment strategy, 139 patients completed 3-years follow-up without major protocol violation. Mean baseline methotrexate dose/week was 19.0 mg in the stable group, 19.4 mg in half-dose, and 19.5 mg in the withdrawal group, and mean DAS at baseline was 0.8 in all groups. During the 3-year study period, 80.1% remained flare-free in the stable csDMARD group, 59.5% in the half-dose and 40.8% in the withdrawal group (Figure 1), with corresponding adjusted hazard ratio (aHR) for flare of 2.7 (95% CI: 1.3 to 5.5) in the half-dose group and 4.1 (2.1 to 8.0) in the withdrawal group, compared to stable csDMARD. The aHR was 1.5 (0.8 to 3.0) in the withdrawal group compared to the half-dose group. For all groups, a majority were in remission at 1, 2 and 3 years (Table 1), with the only significant group difference for ACR/EULAR Boolean remission at 3 years, with risk difference for withdrawal vs stable dose -25% (-45 to -6). Mean/median change in vdHSS after 3 years were 0.3/0.0 in the stable group, 1.0/0.5 in the half-dose group, and 0.7/0.0 in the tapering to withdrawal group, with significant difference between the stable and half-dose group, p<0.01. Sensitivity analyses in the full analysis population gave similar results.ConclusionThese 3-year data show that 41% of patients in the tapering to withdrawal arm achieved long-term drug-free remission, indicating that this is a realistic option for some RA patients in sustained remission. The two tapering strategies were associated with an increased risk of flares compared to full-dose csDMARD, and the half-dose group had more radiographic change. However, there were no differences in DAS-remission at the end of the study period. Further research identifying prognostic factors for successful tapering is needed.Reference[1]Lillegraven S et al. JAMA 2021Table 1.Remission at 12, 24 and 36 monthsStable doseHalf-doseTapered to withdrawal*DAS remission 12 months71/77 (92%)34/39 (87%)29/36 (81%) 24 months64/73 (88%)33/37 (89%)33/35 (94%) 36 months64/67 (96%)34/36 (94%)31/34 (91%)ACR/EULAR 2011 Boolean remission 12 months56/77 (73%)25/39 (64%)22/36 (61%) 24 months47/73 (64%)21/37 (57%)20/35 (57%) 36 months55/67 (82%)25/36 (69%)19/34 (56%)*12 months half-dose, thereafter withdrawalAcknowledgements:NIL.Disclosure of InterestsKaja Kjørholt: None declared, Nina Paulshus Sundlisæter: None declared, Anna-Birgitte Aga Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, Joseph Sexton: None declared, Inge Olsen: None declared, Hallvard Fremstad: None declared, Cristina Spada Consultant of: Advisory board UCB November 2022, Tor Magne Madland Speakers bureau: Cellgene (2017), Novartis (2018), Boehringer (2022), Christian A. Høili: None declared, Gunnstein Bakland Consultant of: Consultant fee from UCB, Åse Lexberg: None declared, Inger Johanne Widding Hansen: None declared, Inger M. Hansen: None declared, Hilde Haukeland Consultant of: Advisory board for UCB Pharma 2x in 2022, NovartisNorge 2017 and 2018, Abbot 2012, Maud-Kristine A Ljosa Consultant of: Advisory Board for Abbvie i 2022, Ellen Moholt: None declared, Till Uhlig Speakers bureau: Lilly, Galapagos, Pfizer, UCB, Consultant of: Lilly, Galapagos, Pfizer, UCB, Tore K. Kvien Speakers bureau: Grünenthal, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB, Grant/research support from: AbbVie, Amgen, BMS, Galapagos, Novartis, Pfizer, UCB, Daniel Solomon Grant/research support from: Abbvie, Amgen, CorEvitas, Moderna, and Janssen, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma Director of Imaging Rheumatology bv, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, Gilead, Siri Lillegraven Grant/research support from: Boehringer Ingelheim.

The investigations of the process of heat and mass transfer in the evaporation of model liquids (distilled water, alcohol mixture, kerosene TC-1) in a vacuum chamber (VC) under parametric ultrasonic influence (UI) and vacuum influence (VI) on a liquid with the purpose of using the obtained results for the development of a methods for designing the evaporation system of unused liquid residues of rocket fuel remaining in the launch vehicle (LV) tanks at the end of the mission. The initial data, variable parameters, assumptions and limitations have been determined. Experimental dependences of the temperature variation of model liquids and gas in a VC under UI under conditions of reduced pressure (up to 0.065 kPa) are obtained. The masses of evaporated model fluids and the rate of evaporation are determined. A comparative analysis of the experimental data obtained for various model liquids was carried out, which showed that the evaporation rate increases with increasing amplitude of the bath bottom vibrations, with the highest evaporation rate under the same conditions for kerosene TC-1.