Репозиторий Университета

© 2019 The Royal College of Radiologists AIM: To evaluate the effect of pre-biopsy magnetic resonance imaging (MRI) on cancer diagnostic times, and to report MRI-directed pathology outcomes. MATERIALS AND METHODS: In total, 1483 patients were referred with prostate cancer suspicion during a 30-month period. Upfront MRI was performed in 745 patients: 332 MRIs in the 15 months prior to dedicated scanning slots (group 1), and 413 in the 15 months post-introduction (group 2). A further 88 patients had initial MRI following clinical assessment. Biopsy via the transrectal (TR) or transperineal (TP) approach was performed, with MRI/ultrasound fusion for MRI targets. Clinically significant cancer (csPCa) was defined as Gleason ≥3+4. Negative MRIs were defined as Likert 1–2. Per-case clinical decisions were taken to biopsy or not. RESULTS: 44.4% of patients avoided biopsy. 484/833 (58.1%) MRIs were negative; 37.4% of these patients had biopsy with a negative predictive value (NPV) of 92.8% for Gleason ≥3+4 and 98.3% for ≥4+3. Overall prostate cancer prevalence was 34.3% (24.6% csPCa). In 323 MRI-positive cases, any cancer was present in 78.9% (csPCa 60.4%). Of the 1483 patients, 1232 (83.1%) completed all diagnostic tests within 28 days. Upfront MRI patients met this standard in 621/833 (74.5%), improving from 66.9% to 81.1% with reserved slots (group 2) with a reduced diagnostic time from median 25.5 to 20.9 days. Biopsy scheduling delayed the pathway in 69.7%, with MRI responsible in 22.3%, reducing to 10.3% in group 2. TP biopsies met the 28-day standard in significantly less cases (29.7%), compared to TR (67.4%, p<0.0001). CONCLUSION: Reserved MRI slots reduces time-to-diagnosis, and upfront MRI safely avoids biopsy in a significant proportion of men, whilst maintaining expected csPCa detection rates.

© 2019, International League of Associations for Rheumatology (ILAR). Background: Patients with rheumatoid arthritis (RA) are at a high risk for life-threatening conditions requiring admission to the intensive care unit (ICU), but the data regarding the outcomes of these patients is limited. The present study investigated the clinical characteristics and outcomes of RA patients admitted to an ICU. Methods: This retrospective cohort study included RA patients admitted to the general ICU of the Sheba Medical Center during 2002–2018. The main outcome was 30-day mortality. Using Student’s t test, χ2, and multivariable analyses, we compared the demographic, clinical, and laboratory parameters of the survivors and the non-survivors. Figures with p value < 0.05 were considered statistically significant. Results: Forty-three RA patients were admitted to the ICU during the study period (mean age, 64.0 ± 13.1 years; 74.4% female). The leading causes of ICU admission were infection (72.1%), respiratory failure (72.1%), renal failure (60.5%), and septic shock (55.8%). The 30-day mortality rate was 34.9%, with infection (9/15, 60%) as the most frequent cause. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 19.7 ± 12.5 and 7.0 ± 4.5, respectively. Multivariable analysis showed that heart failure (p = 0.023), liver failure (p = 0.012), SOFA score (p = 0.007), and vasopressor treatment in ICU (p = 0.039) were significantly associated with overall mortality. SOFA score was linked with overall mortality (area under the curve (AUC) = 0.781 ± 0.085, p = 0.003) and mortality from respiratory failure (AUC = 0.861 ± 0.075, p = 0.002), while APACHE II score was only correlated with mortality from infection (AUC = 0.735 ± 0.082, p = 0.032). Conclusions: Our study demonstrated a relatively high mortality rate among RA patients who were admitted to the general ICU. RA patients with risk factors such as heart failure, liver failure, elevated SOFA score, and vasopressor treatment in ICU should be promptly identified and treated accordingly.Key Points• The 30-day mortality rate of patients with RA that were admitted to the general ICU of a tertiary hospital was 34.9%.• The most common causes of ICU admission among patients with RA were infections and respiratory failure. Infections were the most common cause of death among these patients.• Patients with RA that present to the ICU with heart failure, liver failure, elevated SOFA score, and/or require vasopressor treatment in ICU should be promptly identified and treated accordingly.

© 2019 International Hepato-Pancreato-Biliary Association Inc. Background: Laparoscopic liver resection in the posterosuperior segments is technically challenging. This study aimed to compare the perioperative outcomes for laparoscopic and open resection of colorectal liver metastases located in the posterosuperior segments. Methods: This was a subgroup analysis of the OSLO-COMET randomized controlled trial, where 280 patients were randomly assigned to open or laparoscopic parenchyma-sparing liver resections of colorectal metastases. Patients with tumors in the posterosuperior segments were identified, and perioperative outcomes and health related quality of life (HRQoL) were compared. Results: We identified a total of 136 patients, 62 in the laparoscopic and 74 in the open group. The postoperative complication rate was 26% in the laparoscopic and 31% in the open group. The blood loss was less in the open group (500 vs. 250 ml, P = 0.006), but the perioperative transfusion rate was similar. The operative time was similar, while postoperative hospital stay was shorter in the laparoscopic group (2 vs. 4 days, P < 0.001). HRQoL was significantly better after laparoscopy at 1 month. Conclusion: In patients undergoing laparoscopic or open liver resection of colorectal liver metastases in the posterosuperior segments, laparoscopic surgery was associated with shorter hospital stay and comparable perioperative outcomes.

© 2019 The Author(s) A method of 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate synthesis has been developed and the electronic and spatial structure of a new biologically active molecule has been studied both theoretically and experimentally. The title compound was crystallized from acetonitrile and the single crystal X-ray analysis has revealed that it exists in a monoclinic P21/c space group, with one molecule in the asymmetric part of the unit cell. Hirshfeld surface analysis was used to study intermolecular interactions in the crystal. Molecular docking study evaluates the investigated compound as a new potential inhibitor of hepatitis B. Testing for anti-hepatitis B virus activity has shown that this substance demonstrates in vitro nanomolar inhibitory activity against HBV. Organic chemistry; Theoretical chemistry; Pharmaceutical chemistry, Hepatitis B; HBV; Pharmaceutical crystals; 4-Fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate; Benzothiophene; Hydrogen bond; Hirshfeld surface analysis; Molecular docking study

Background and Purpose- Ischemic stroke is one of the leading causes of disability and death. The principal goal of acute stroke treatment is the recanalization of the occluded cerebral arteries, which is, however, only effective in a very narrow time window. Therefore, neuroprotective treatments that can be combined with recanalization strategies are needed. Calcium overload is one of the major triggers of neuronal cell death. We have previously shown that capacitative Ca2+ entry, which is triggered by the depletion of intracellular calcium stores, contributes to ischemia-induced calcium influx in neurons, but the responsible Ca2+ channel is not known. Methods- Here, we have generated mice lacking the calcium channel subunit Orai2 and analyzed them in experimental stroke. Results- Orai2-deficient mice were protected from ischemic neuronal death both during acute ischemia under vessel occlusion and during ischemia/reperfusion upon successful recanalization. Calcium signals induced by calcium store depletion or oxygen/glucose deprivation were significantly diminished in Orai2-deficient neurons demonstrating that Orai2 is a central mediator of neuronal capacitative Ca2+ entry and is involved in calcium overload during ischemia. Conclusions- Our experimental data identify Orai2 as an attractive target for pharmaceutical intervention in acute stroke.

© 2019 The Authors Background: The aim was to estimate the prevalence of harmful alcohol use in relation to socio-demographic characteristics among acutely ill medical patients, and examine identification measures of alcohol use, including the alcohol biomarker phosphatidylethanol 16:0/18:1 (PEth). Methods: A cross-sectional study, lasting one year at one hospital in Oslo, Norway and one in Moscow, Russia recruiting acute medically ill patients (≥ 18 years), able to give informed consent. Self-reported data on socio-demographics, mental distress (Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4 (AUDIT-4) and alcohol consumption past 24 h were collected. PEth and alcohol concentration were measured in whole blood. Results: Of 5883 participating patients, 19.2% in Moscow and 21.1% in Oslo were harmful alcohol users, measured by AUDIT-4, while the prevalence of PEth-positive patients was lower: 11.4% in Oslo, 14.3% in Moscow. Men in Moscow were more likely to be harmful users by AUDIT-4 and PEth compared to men in Oslo, except of those being ≥ 71 years. Women in Oslo were more likely to be harmful users compared to those in Moscow by AUDIT-4, but not by PEth for those aged < 61 years. Conclusions: The prevalence of harmful alcohol use was high at both study sites. The prevalence of harmful alcohol use was lower when assessed by PEth compared to AUDIT-4. Thus, self-reporting was the most sensitive measure in revealing harmful alcohol use among all groups except for women in Moscow. Hence, screening and identification with objective biomarkers and self-reporting might be a method for early intervention.

© 2019, Springer Nature B.V. Mitochondria-targeted antioxidants (also known as ‘Skulachev Ions’ electrophoretically accumulated by mitochondria) exert anti-ageing and ROS-protecting effects well documented in animal and human cells. However, their effects on chloroplast in photosynthetic cells and corresponding mechanisms are scarcely known. For the first time, we describe a dramatic quenching effect of (10-(6-plastoquinonyl)decyl triphenylphosphonium (SkQ1) on chlorophyll fluorescence, apparently mediated by redox interaction of SkQ1 with Mn cluster in Photosystem II (PSII) of chlorophyte microalga Chlorella vulgaris and disabling the oxygen-evolving complex (OEC). Microalgal cells displayed a vigorous uptake of SkQ1 which internal concentration built up to a very high level. Using optical and EPR spectroscopy, as well as electron donors and in silico molecular simulation techniques, we found that SkQ1 molecule can interact with Mn atoms of the OEC in PSII. This stops water splitting giving rise to potent quencher(s), e.g. oxidized reaction centre of PSII. Other components of the photosynthetic apparatus proved to be mostly intact. This effect of the Skulachev ions might help to develop in vivo models of photosynthetic cells with impaired OEC function but essentially intact otherwise. The observed phenomenon suggests that SkQ1 can be applied to study stress-induced damages to OEC in photosynthetic organisms.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was to assess the levels of Se, as well as other essential and toxic trace elements in wheat grains and traditional Roti-bread from whole-grain flour in a seleniferous area of Punjab (India) using inductively-coupled plasma mass-spectrometry. Wheat grain and bread selenium levels originating from seleniferous areas exceeded the control values by a factor of more than 488 and 179, respectively. Se-rich wheat was also characterized by significantly increased Cu and Mn levels. Se-rich bread also contained significantly higher levels of Cr, Cu, I, Mn, and V. The level of Li and Sr was reduced in both Se-enriched wheat and bread samples. Roti bread from Se-enriched wheat was also characterized by elevated Al, Cd, and Ni, as well as reduced As and Hg content as compared to the respective control values. Se intake with Se-rich bread was estimated as more than 13,600% of RDA. Daily intake of Mn with both Se-unfortified and Se-fortified bread was 133% and 190% of RDA. Therefore, Se-rich bread from wheat cultivated on a seleniferous area of Punjab (India) may be considered as a potent source of selenium, although Se status should be monitored throughout dietary intervention.

© 2019 Elsevier Ltd Hexavalent chromium raises high concern because of its wide industrial applications and reported toxicity. Long-term (135 days) oral exposure of Wistar rats to chromium in the form of K2Cr2O7 (exposed group~20 mg/kg/day) led to a decrease in thymus mass and thymocytes' number and caused structural and functional changes in the lymph nodes and spleen, namely lymphoreticular hyperplasia and plasmocytic macrophage transformation. Programmed cell death was increased in both thymocytes and splenocytes and decreased in lymphocytes in the T-zones of spleen and lymph nodes. Moreover, Cr (VI) administration decreased myeloid cells' and neutrophils' number, while it increased lymphoid and erythroid cells' number in bone marrow. Cr (VI) immune system effects seem to be related to oxidative stress induction, as depicted by the increased levels of diene conjugates and malondialdehyde in the spleen and liver and by the decreased activity of catalase and superoxide dismutase in rats’ erythrocytes. In addition, exposure to Cr (VI) decreased copper, nickel and iron concentrations in blood and liver, while Cr levels in blood, spleen and liver were increased, as expected. The observed changes in the series of immunological parameters studied contribute to the development of new approaches for the prevention of low level Cr exposure toxicity.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Background: Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the major cause of viral persistence in patients with chronic HBV infection. Understanding the mechanisms underlying stability and persistence of HBV cccDNA in hepatocytes is critical for developing novel therapeutics and managing chronic hepatitis B. In this study, we observed an unexpected increase in HBV cccDNA levels upon suppression of transcription by de novo DNA methyltransferase DNMT3A and uncovered additional mechanisms potentially involved in HBV cccDNA maintenance. Methods: HBV-expressing cell lines were transfected with a DNMT3A-expressing plasmid. Real-time PCR and HBsAg assays were used to assess the HBV replication rate. Cell cycling was analyzed by fluorescent cell sorting. CRISPR/Cas9 was utilized to abrogate expression of APOBEC3A and APOBEC3B. Alterations in the expression of target genes were measured by real-time PCR. Results: Similar to previous studies, HBV replication induced DNMT3A expression, which in turn, led to reduced HBV transcription but elevated HBV cccDNA levels (4-to 6-fold increase). Increased levels of HBV cccDNA were not related to cell cycling, as DNMT3A accelerated proliferation of infected cells and could not contribute to HBV cccDNA expansion by arresting cells in a quiescent state. At the same time, DNMT3A suppressed transcription of innate immunity factors including cytidine deaminases APOBEC3A and APOBEC3B. CRISPR/Cas9-mediated silencing of APOBEC3A and APOBEC3B transcription had minor effects on HBV transcription, but significantly increased HBV cccDNA levels, similar to DNMT3A. In an attempt to further analyze the detrimental effects of HBV and DNMT3A on infected cells, we visualized γ-H2AX foci and demonstrated that HBV inflicts and DNMT3A aggravates DNA damage, possibly by downregulating DNA damage response factors. Additionally, suppression of HBV replication by DNMT3A may be related to reduced ATM/ATR expression. Conclusion: Formation and maintenance of HBV cccDNA pools may be partially suppressed by the baseline expression of host inhibitory factors including APOBEC3A and APOBEC3B. HBV inflicts DNA damage both directly and by inducing DNMT3A expression.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The relative age effect (RAE) has been well studied in adolescent and adult soccer players; however, less information has been available about children engaged in regular soccer training and the role of performance. Thus, the aim of the present study was to examine the prevalence of RAE in children and adolescent soccer players, as well as the role of age and performance. Russian soccer players (n = 10,446) of various ages, playing positions and performance levels were examined for their date of birth. It was observed that RAE was widespread in Russian soccer teams of all age groups. RAE was most pronounced in children teams of the top tier Russian soccer academies and junior Russia national teams, where the proportions of soccer players born in the first quarter were 43.9% and 39.8%, respectively, whereas those born in the fourth quarter of the year were 7.7% and 6.3%, respectively. In top tier soccer academies, RAE did not vary by age group. In the middle tier soccer academies, RAE was less pronounced. It was still prevalent in the junior teams of the top tier clubs of the Russian Premier League, where 14.3% of the soccer players were born in the fourth quarter of the year compared to 42.9% born in the first quarter of the year. RAE can be observed in the top tier Russian adult teams as well, although it is less pronounced there. In summary, RAE is highly prevalent in Russian children and junior soccer and is associated with the level of competitiveness. At the same time, the proportion of players born in the fourth quarter of the year is higher in adult teams than in junior and youth teams, which is most likely due to the wider selection of players, not limited by their age and place of residence. In junior teams, RAE results in a bias towards selection of players who are more physically mature, whereas children who may be more talented but are less developed due to their younger chronological age tend to be overlooked.

© 2019 Nordic Federation of Societies of Obstetrics and Gynecology Introduction: The aim of this systematic review was to explore the outcome of fetuses with a prenatal diagnosis of isolated talipes. Material and methods: Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched. The outcomes explored were: associated anomalies detected at follow-up ultrasound examination; fetal magnetic resonance imaging (MRI) and birth; chromosomal abnormalities detected with standard and chromosomal microarray analysis, intrauterine, neonatal, and perinatal death, and termination of pregnancy; rate of surgical and nonsurgical treatment; neurodevelopmental outcome; and false-positive rate of prenatal diagnosis. Meta-analyses of proportions were used to combine data. Results: Twenty-five studies (1567 fetuses) were included. Associated anomalies were detected in 7.8% (95% CI 0.1%-29.3%) of cases at follow-up ultrasound, and in 4.0% (95% CI 0.1%-13.2%) of cases, fetal MRI identified anomalies not detected at ultrasound assessment. Similarly, 7.0% (95% CI 3.4%-11.7%) of cases labeled as isolated talipes on prenatal imaging were found to have associated anomalies at birth. Abnormal karyotype was present in 3.6% (95% CI 1.7%-6.2%) of fetuses, whereas no anomaly was found at chromosomal microarray analysis, although this outcome was reported by only 1 study. Intrauterine death occurred in 0.99% (95% CI 0.4%-1.9%) of fetuses, whereas the corresponding figures for neonatal death and termination of pregnancy were 1.5% (95% CI 0.6%-2.6%) and 2.2% (95% CI 1.2%-3.4%), respectively. Surgical management of anomalies after birth was found in 41.7% (95% CI 27.0%-57.2%) of fetuses with isolated talipes, and 54.8% (95% CI 31.5%-77.0%) had nonsurgical management of the anomalies after birth. Abnormal neurodevelopmental outcome was reported in 7.6% (95% CI 1.0%-19.4%) of children, although this analysis was affected by the small number of included cases and short time of follow up. Conclusions: Isolated talipes detected on prenatal ultrasound carries a generally good prognosis. The incidence of additional abnormalities detected on fetal MRI, aneuploidy, or neurodevelopmental disability is relatively low. However, longitudinal ultrasound assessment during pregnancy and a thorough postnatal evaluation are recommended to rule out associated anomalies that may significantly impact short- and long-term prognosis.

© 2019 Chinese Society of Rare Earths In this paper, we report on the crystal structure and magnetic properties of the nanostructured Ba-ordered phases of rare-earth manganites obtained from the optimally doped solid solutions Ln0.70Ba0.30MnO3 (Ln = Pr, Nd). The materials were studied by X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy and SQUID-magnetometry techniques. It is found that states with different degrees of cation ordering in the A-sublattice of the ABO3 perovskite can be obtained by employing special conditions of chemical treatment. In particular, reduction of the parent compounds results in the formation of a nanocomposite containing ferrimagnetic anion-deficient ordered phase LnBaMn2O5. Oxidation of the composite does not change an average size of the nanocrystallites, but drastically alters their phase composition to stabilize ferromagnetic stoichiometric ordered phase LnBaMn2O6 and ferromagnetic superstoichiometric disordered phase Ln0.90Ba0.10MnO3+δ. It is shown that the magnetic properties of the materials are determined by the joint action of chemical (cation ordering) and external (surface tension) pressures.

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Background: Epidemiologic studies that investigated alcohol consumption in relation to the risk of bladder cancer (BCa) have demonstrated inconsistent results. We conducted a systematic review and meta-analysis of the literature to investigate the association of alcohol including different types of alcoholic beverages consumption with the risk of BCa. Materials and methods: A systematic search of Web of Science, Medline/PubMed and Cochrane library was performed in May 2018. Studies were considered eligible if they assessed the risk of BCa due to alcohol consumption (moderate or heavy dose) and different types of alcoholic beverages (moderate or heavy dose) in multivariable analysis in the general population (all genders, males or females) or compared with a control group of individuals without BCa. Study design: observational cohorts or case–control. Results: Sixteen studies were included in this meta-analysis. Moderate and heavy alcohol consumption did not increase the risk of BCa in the entire population. Sub-group and sensitivity analyses revealed that heavy alcohol consumption increased significantly the risk of BCa in the Japanese population, RR 1.31 (95% CI 1.08–1.58, P < 0.01) in the multivariable analysis, and in males RR of 1.50 (95% CI 1.18–1.92, P < 0.01), with no significant statistical heterogeneity. Moreover, heavy consumption of spirits drinks increased the risk of BCa in males, RR 1.42 (95% CI 1.15–1.75, P < 0.01). Conclusion: In this meta-analysis, moderate and heavy alcohol consumption did not increase the risk of bladder cancer significantly. However, heavy consumption of alcohol might increase the risk of BCa in males and in some specific populations.

© 2019 John Wiley  &  Sons Ltd Background: Understanding consumer perceptions is crucial if effective food safety policy and risk communication are to be developed and implemented. We sought to understand how those living with food allergy assess risk with precautionary allergen labelling (PAL) and their preference in how risks are communicated within a quantitative risk assessment (QRA) framework. Methods: The Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) labelling online survey was developed for adults and parents of children with food allergy and distributed across Germany, Ireland, Netherlands, Spain and UK via patient support groups. Results: There were 1560 complete responses. ‘This product is not suitable for’ was selected as first choice for PAL by 46% overall and ‘May contain’ was selected as the first choice by 44%. Seventy-three percent reported that it would improve their trust in a product if a QRA process had been used to make a decision about whether to include ‘may contain’. Overall, 66% reported that a ‘statement + symbol’ on the label indicating a QRA, would help them to understand the risk assessment process that had been used by the food manufacturer. Conclusions: Consumers want to know what process has actually taken place for the placing of a PAL and/or risk assessment statement on a particular food product. Our findings provide a basis for the development of more informative communication around food allergen risk and safety and support evidence-based policy-making in the context of the legislative requirements of the European Union's Food Information for Consumers Regulation.

© 2019 Context: This overview presents the updated European Association of Urology (EAU) guidelines for non–muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ (CIS). Objective: To provide practical recommendations on the clinical management of NMIBC with a focus on clinical presentation and recommendations. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines has been performed annually since the last published version in 2017. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1, and/or CIS are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of the tissue obtained by transurethral resection (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a T1 tumour is detected, a second TURB should be performed within 2–6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system. Stratification of patients into low-, intermediate-, and high-risk groups is pivotal to the recommendation of adjuvant treatment. In patients with tumours presumed to be at a low risk and in those presumed to be at an intermediate risk with a low previous recurrence rate and an expected EORTC recurrence score of <5, one immediate chemotherapy instillation is recommended. Patients with intermediate-risk tumours should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1–3 yr is indicated. In patients at the highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-unresponsive tumours. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/. Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Patient summary: The European Association of Urology Non–muscle-invasive Bladder Cancer (NMIBC) Panel has released an updated version of their guidelines, which contains information on classification, risk factors, diagnosis, prognostic factors, and treatment of NMIBC. The recommendations are based on the current literature (until the end of 2018), with emphasis on high-level data from randomised clinical trials and meta-analyses. Stratification of patients into low-, intermediate-, and high-risk groups is essential for deciding appropriate use of adjuvant intravesical chemotherapy or bacillus Calmette-Guérin (BCG) instillations. Surgical removal of the bladder should be considered in case of BCG-unresponsive tumours or in NMIBCs with the highest risk of progression.

© 2019 American Medical Association. All rights reserved. Importance: Patients with atrial fibrillation (AF) who use a direct oral anticoagulant (DOAC) and request elective surgery or procedure present a common clinical situation yet perioperative management is uncertain. Objective: To investigate the safety of a standardized perioperative DOAC management strategy. Design, Setting, and Participants: The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) cohort study conducted at 23 clinical centers in Canada, the United States, and Europe enrolled and screened patients from August 1, 2014, through July 31, 2018. Participants (n = 3007) had AF; were 18 years of age or older; were long-term users of apixaban, dabigatran etexilate, or rivaroxaban; were scheduled for an elective surgery or procedure; and could adhere to the DOAC therapy interruption protocol. Interventions: A simple standardized perioperative DOAC therapy interruption and resumption strategy based on DOAC pharmacokinetic properties, procedure-associated bleeding risk, and creatinine clearance levels. The DOAC regimens were omitted for 1 day before a low-bleeding-risk procedure and 2 days before a high-bleeding-risk procedure. The DOAC regimens were resumed 1 day after a low-bleeding-risk procedure and 2 to 3 days after a high-bleeding-risk procedure. Follow-up of patients occurred for 30 days after the operation. Main Outcomes and Measures: Major bleeding and arterial thromboembolism (ischemic stroke, systemic embolism, and transient ischemic attack) and the proportion of patients with an undetectable or minimal residual anticoagulant level (<50 ng/mL) at the time of the procedure. Results: The 3007 patients with AF (mean [SD] age of 72.5 [9.39] years; 1988 men [66.1%]) comprised 1257 (41.8%) in the apixaban cohort, 668 (22.2%) in the dabigatran cohort, and 1082 (36.0%) in the rivaroxaban cohort; 1007 patients (33.5%) had a high-bleeding-risk procedure. The 30-day postoperative rate of major bleeding was 1.35% (95% CI, 0%-2.00%) in the apixaban cohort, 0.90% (95% CI, 0%-1.73%) in the dabigatran cohort, and 1.85% (95% CI, 0%-2.65%) in the rivaroxaban cohort. The rate of arterial thromboembolism was 0.16% (95% CI, 0%-0.48%) in the apixaban cohort, 0.60% (95% CI, 0%-1.33%) in the dabigatran cohort, and 0.37% (95% CI, 0%-0.82%) in the rivaroxaban cohort. In patients with a high-bleeding-risk procedure, the rates of major bleeding were 2.96% (95% CI, 0%-4.68%) in the apixaban cohort and 2.95% (95% CI, 0%-4.76%) in the rivaroxaban cohort. Conclusions and Relevance: In this study, patients with AF who had DOAC therapy interruption for elective surgery or procedure, a perioperative management strategy without heparin bridging or coagulation function testing was associated with low rates of major bleeding and arterial thromboembolism.

© Author(s) (or their employer(s)) 2019. Objectives To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc). Methods 601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed. Results During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05). Conclusions The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.

© 2019, The Author(s). Abstract: In 2014 the International Endohernia Society (IEHS) published the first international “Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias”. Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. Methods: For the development of the original guidelines all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based-Medicine. For the present update all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne) the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. Results: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques—minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite still insufficient evidence with respect to these new techniques it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. Conclusion: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initially guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.