High-retention membrane bioreactors for sugarcane vinasse treatment: Opportunities for environmental impact reduction and wastewater valorization.

Ethanol production has increased over the years, and Brazil ranking second in the world using sugarcane as the main raw material. However, 10-15 L of vinasse are generated per liter of ethanol produced. Besides large volumes, this wastewater has high polluting potential due to its low pH and high concentrations of organic matter and nutrients. Given the high biodegradability of the organic matter, the treatment of this effluent by anaerobic digestion and membrane separation processes results in the generation of high value-added byproducts such as volatile fatty acids (VFAs), biohydrogen and biogas. Membrane bioreactors have been widely evaluated due to the high efficiency achieved in vinasse treatment. In recent years, high retention membrane bioreactors, in which high retention membranes (nanofiltration, reverse osmosis, forward osmosis and membrane distillation) are combined with biological processes, have gained increasing attention. This paper presents a critical review focused on high retention membrane bioreactors and the challenges associated with the proposed configurations. For nanofiltration membrane bioreactor (NF-MBR), the main drawback is the higher fouling propensity due to the hydraulic driving force. Nonetheless, the development of membranes with high permeability and anti-fouling properties is uprising. Regarding osmotic membrane bioreactor (OMBR), special attention is needed for the selection of a proper draw solution, which desirably should be low cost, have high osmolality, reduce reverse salt flux, and can be easily reconcentrated. Membrane distillation bioreactor (MDBR) also exhibit some shortcomings, with emphasis on energy demand, that can be solved with the use of low-grade and residual heat, or renewable energies. Among the configurations, MDBR seems to be more advantageous for sugarcane vinasse treatment due to the lower energy consumption provided by the use of waste heat from the effluent, and due to the VFAs recovery, which has high added value.

[Self-harming behavior of patients on a closed psychiatric ward]. / Zelfbeschadigend gedrag bij patiënten op een gesloten psychiatrische afdeling.

BACKGROUND: Self-harming behavior is a frequent problem seen in patients admitted to a closed ward in a psychiatric hospital. Little is known about prevalence and characteristics of this behavior as well as the preceding triggering factors. AIM: To gain insights in the self-harming behavior of patients admitted to a closed ward in a psychiatric hospital. METHOD: From September 2019 till January 2021 was gathered information on self-harming incidents and aggressive behavior towards others or objects, of 27 patients admitted to the closed department of the Centre Intensive Treatment (Centrum Intensieve Behandeling). RESULTS: 20 of 27 patients examined (74%) showed 470 incidents of self-harming behavior. Head banging (40.9%) and self-harming using straps/ropes (29.7%) occured most. Tension/stress as triggering factor was mentioned most (19.1%). Self-harming behavior occured more during evenings. Besides self-harm, a high degree of aggressive behavior towards others or objects was registered. CONCLUSION: This study delivers insights in self-harming behavior of patients admitted to closed psychiatric departments that can be used for prevention and treatment.

SPARC-positive macrophages are the superior prognostic factor in the microenvironment of diffuse large B-cell lymphoma and independent of MYC rearrangement and double-/triple-hit status.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with respect to outcome. Features of the tumor microenvironment (TME) are associated with prognosis when assessed by gene expression profiling. However, it is uncertain whether assessment of the microenvironment can add prognostic information to the most relevant and clinically well-established molecular subgroups when analyzed by immunohistochemistry (IHC). PATIENTS AND METHODS: We carried out a histopathologic analysis of biomarkers related to TME in a very large cohort (n = 455) of DLBCL treated in prospective trials and correlated with clinicopathologic and molecular data, including chromosomal rearrangements and gene expression profiles for cell-of-origin and TME. RESULTS: The content of PD1+, FoxP3+ and CD8+, as well as vessel density, was not associated with outcome. However, we found a low content of CD68+ macrophages to be associated with inferior progression-free survival (PFS) and overall survival (OS; P = 0.023 and 0.040, respectively) at both univariable and multivariable analyses, adjusted for the factors of the International Prognostic Index (IPI), MYC break and BCL2/MYC and BCL6/MYC double-hit status. The subgroup of PDL1+ macrophages was not associated with survival. Instead, secreted protein acidic and cysteine rich (SPARC)-positive macrophages were identified as the subtype of macrophages most associated with survival. SPARC-positive macrophages and stromal cells directly correlated with favorable PFS and OS (both, P[log rank] <0.001, P[trend] < 0.001). The association of SPARC with prognosis was independent of the factors of the IPI, MYC double-/triple-hit status, Bcl2/c-myc double expression, cell-of-origin subtype and a recently published gene expression signature [lymphoma-associated macrophage interaction signature (LAMIS)]. CONCLUSIONS: SPARC expression in the TME detected by a single IHC staining with fair-to-good interobserver reproducibility is a powerful prognostic parameter. Thus SPARC expression is a strong candidate for risk assessment in DLBCL in daily practice.

Resource recovery from sugarcane vinasse by anaerobic digestion - A review.

The increase in biofuel production by 2030, driven by the targets set at the 21st United Nations Framework Convention on Climate Change (COP21), will promote an increase in ethanol production, and consequently more vinasse generation. Sugarcane vinasse, despite having a high polluting potential due to its high concentration of organic matter and nutrients, has the potential to produce value-added resources such as volatile fatty acids (VFA), biohydrogen (bioH2) and biomethane (bioCH4) from anaerobic digestion. The objective of this paper is to present a critical review on the vinasse treatment by anaerobic digestion focusing on the final products. Effects of operational parameters on production and recovery of these resources, such as pH, temperature, retention time and type of inoculum were addressed. Given the importance of treating sugarcane vinasse due to its complex composition and high volume generated in the ethanol production process, this is the first review that evaluates the production of VFAs, bioH2 and bioCH4 in the treatment of this organic residue. Also, the challenges of the simultaneous production of VFA, bioH2 and bioCH4 and resources recovery in the wastewater streams generated in flex-fuel plants, using sugarcane and corn as raw material in ethanol production, are presented. The installation of flex-fuel plants was briefly discussed, with the main impacts on the treatment process of these effluents either jointly or simultaneously, depending on the harvest season.

[The effects of covid-19 on psychiatry training in the Netherlands]. / De invloed van COVID-19 op de opleiding psychiatrie in Nederland.

Background The COVID-19 pandemic changes the training of residents and could offer new opportunities. Aim Gaining insight in the effects of the impact of the COVID-19-pandemic on psychiatry residents. Method A digital questionnaire was designed to evaluate the impact of the COVID-19 pandemic on educational activities. The experience of residents with regards to safety in the workplace, social cohesion with their peers and the involvement of supervisors were examined. Results We approached 34 training institutions. 24 chief residents of the resident group completed the questionnaire. The quality of regional education was considered unchanged by 20% and local education by 33%. Digital communication increased the participation of psychiatrists in the general report and education activities and ensured less travel time. Nevertheless, respondents missed contact with their peers, safety of residents was compromised at five institutions and half of all respondents indicated a lack of personal protective equipment. Conclusions A majority of the psychiatry residents are satisfied with their training during this historic pandemic, but the quality of local and regional education was considered changed, and not being beneficial. The challenge remains for stimulating contact with peers, monitoring the quality of education in general as in psychotherapy and providing personal protective equipment. Tijdschrift voor Psychiatrie 63(2021)1, 16-21.

Transcatheter tricuspid valve repair: early experience in the Netherlands.

BACKGROUND: Symptomatic tricuspid regurgitation (TR) is increasingly prevalent and impairs quality of life and survival, despite medical treatment. Transcatheter tricuspid valve repair (TTVR) has recently become available as a treatment option for patients not eligible for tricuspid valve surgery. In this study we describe the early experience with TTVR in the Netherlands. METHODS: All consecutive patients scheduled for TTVR in two tertiary hospitals were included in the current study. Patients were symptomatic and had severe functional TR. TTVR was performed either with the MitraClip (off-label use) or dedicated TriClip delivery system and device. Procedural success was defined as achievement of clip implantation, TR reduction ≥ 1 grade and no need for re-do surgical or transcatheter intervention. Clinical improvement was evaluated after 4 weeks. RESULTS: Twenty-one patients (median age 78 years, 33% male, 95% New York Heart Association class ≥ 3, 100% history of atrial fibrillation) underwent TTVR. Procedural success was achieved in 16 patients, of whom 15 reported symptomatic improvement (New York Heart Association class 1 or 2). There was no in-hospital mortality and no major complications occurred. Baseline glomerular filtration rate and TR coaptation gap size were associated with procedural success. CONCLUSION: The current study showed that TTVR seems a promising treatment option for patients with severe functional TR deemed high risk for surgery. Successful TR reduction is most likely in patients with limited coaptation gap size and strongly determines clinical benefit. Adequate patient selection and timing of treatment seem essential for an optimal patient outcome.

First-line treatment with R-CHOP or rituximab-bendamustine in patients with follicular lymphoma grade 3A-results of a retrospective analysis.

Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%, P = 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%, P < 0.01), while there was no significant difference regarding OS or transformation. With the limitations of a retrospective analysis, these results suggest a benefit for R-CHOP over R-B in FL3A or FL1-2-3A. Confirmatory data from prospective clinical trials are needed.

Early mobilisation after transfemoral transcatheter aortic valve implantation: results of the MobiTAVI trial.

BACKGROUND: Immobilisation of patients after transfemoral transcatheter aortic valve implantation (TF-TAVI) is the standard of care, mostly to prevent vascular complications. However, immobilisation may increase post-operative complications such as delirium and infections. In this trial, we determine whether it is feasible and safe to implement early ambulation after TF-TAVI. METHODS: We prospectively included TF-TAVI patients from 2016 to 2018. Patients were assessed for eligibility using our strict safety protocol and were allocated (based on the time at which the procedure ended) to the EARLY or REGULAR group. RESULTS: A total of 150 patients (49%) were deemed eligible for early mobilisation, of which 73 were allocated to the EARLY group and 77 to the REGULAR group. The overall population had a mean age of 80 years, 48% were male with a Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score of 3.8 ± 1.8. Time to mobilisation was 4 h 49 min ± 31 min in the EARLY group versus 20 h 7 min ± 3 h 6 min in the REGULAR group (p < 0.0001). There were no differences regarding the primary endpoint. No major vascular complications occurred and a similar incidence of minor vascular complications was seen in both groups (4/73 [5.5%] vs 6/77 [7.8%], p = 0.570). The incidence of the combined secondary endpoint was lower in the EARLY group (p = 0.034), with a numerically lower incidence for all individual outcomes (delirium, infections, pain and unplanned urinary catheter use). CONCLUSION: Early mobilisation (ambulation 4-6 h post-procedure) of TF-TAVI patients is feasible and safe. Early ambulation decreases the combined incidence of delirium, infections, pain and unplanned urinary catheter use, and its adoption into contemporary TAVI practice may therefore be beneficial.

The Absorb bioresorbable vascular scaffold in real-world practice: long-term follow-up of the AMC Single Centre Real World PCI Registry.

BACKGROUND: Bioresorbable scaffolds have been introduced to overcome the shortcomings of drug-eluting stents. Higher rates of device thrombosis, however, have been reported up to 3 years after implantation of the Absorb bioresorbable vascular scaffold (BVS). In the current article, we therefore report long-term clinical outcomes of the AMC Absorb Registry. METHODS AND RESULTS: In the AMC Absorb Registry, all patients who underwent a percutaneous coronary intervention with Absorb BVS implantation between 30 August 2012 and 5 August 2013 at the Amsterdam University Medical Centre-Academic Medical Centre were included. The composite endpoint of this analysis was target-vessel failure (TVF). The median follow-up of the study cohort of the AMC Absorb Registry was 1534 days. At the time of the cross-sectional data sweep the clinical status at 4 years was known in 124 of 135 patients (91.9%). At long-term follow-up, the composite endpoint of TVF had occurred in 27 patients. The 4­year Kaplan-Meier estimate of TVF was 19.8%. At 4 years cardiac death had occurred in 4 patients (3.2%) and target-vessel myocardial infarction in 9 (6.9%) patients. Definite scaffold thrombosis occurred in 5 (3.8%) patients. We found 1 case of very late scaffold thrombosis that occurred at 911 days after device implantation in a patient who was not on dual anti-platelet therapy. CONCLUSION: In a patient population reflecting routine clinical practice, we found that cases of TVF continued to accrue beyond 2 years after Absorb BVS implantation.

Acute alterations in glucose homeostasis impact coronary microvascular function in patients presenting with ST-segment elevation myocardial infarction.

BACKGROUND: Microvascular dysfunction in the setting of ST-segment myocardial infarction (STEMI) is thought to be related to stress-related metabolic changes, including acute glucose intolerance. The aim of this study was to assess the relationship between admission glucose levels and microvascular function in non-diabetic STEMI patients. METHODS: 92 consecutive patients with a first anterior-wall STEMI treated with primary percutaneous coronary intervention (PPCI) were enrolled. Blood glucose levels were determined immediately prior to PPCI. After successful PPCI, at 1­week and 6­month follow-up, Doppler flow was measured in culprit and reference coronary arteries to calculate coronary flow velocity reserve (CFVR), baseline (BMR) and hyperaemic (HMR) microvascular resistance. RESULTS: The median admission glucose was 8.3 (7.2-9.6) mmol/l respectively 149.4 mg/dl [129.6-172.8] and was significantly associated with peak troponin T (standardised beta coefficient [std beta] = 0.281; p = 0.043). Multivariate analysis revealed that increasing glucose levels were significantly associated with a decrease in reference vessel CFVR (std beta = -0.313; p = 0.002), dictated by an increase in rest average peak velocity (APV) (std beta = 0.216; p = 0.033), due to a decreasing BMR (std beta = -0.225; p = 0.038) in the acute setting after PPCI. These associations disappeared at follow-up. These associations were not found for the infarct-related artery. CONCLUSION: Elevated admission glucose levels are associated with impaired microvascular function assessed directly after PPCI in first anterior-wall STEMI. This influence of glucose levels is an acute phenomenon and contributes to microvascular dysfunction through alterations in resting flow and baseline microvascular resistance.

Prognostic implications of resting distal coronary-to-aortic pressure ratio compared with fractional flow reserve: a 10-year follow-up study after deferral of revascularisation.

INTRODUCTION: The distal coronary-to-aortic pressure ratio (Pd/Pa) is a non-hyperaemic physiological index to assess the functional severity of coronary stenoses. Studies comparing Pd/Pa with fractional flow reserve (FFR) show superior diagnostic efficiency for myocardial ischaemia. Nevertheless, a direct comparison regarding long-term clinical outcomes is still not available. The present observational study compared the prognostic value of Pd/Pa and FFR for major adverse cardiac events (MACE) during a 10-year follow-up period after deferral of revascularisation. METHODS: Between April 1997 and September 2006, we evaluated 154 coronary stenoses (154 patients) in which revascularisation was deferred with intracoronary pressure and flow measurements during the resting and hyperaemic state. Long-term follow-up (median: 11.8 years) was performed to document the occurrence of MACE, defined as a composite of cardiac death, myocardial infarction and target vessel revascularisation. RESULTS: The study population comprised angiographically intermediate coronary stenoses, with a mean diameter stenosis of 53 ± 8%, and intermediate physiological severity with a median FFR of 0.82 (Q1, Q3: 0.76, 0.88). The association of Pd/Pa with long-term MACE was similar to that of FFR [FFR-standardised hazard ratio (sHR): 0.77, 95% confidence interval (CI): 0.61-0.98; Pd/Pa-sHR: 0.80, 95% CI: 0.67-0.96]. In the presence of disagreement between Pd/Pa and FFR, normal Pd/Pa was generally associated with high coronary flow reserve (CFR) and a favourable clinical outcome, whereas abnormal Pd/Pa was generally associated with CFR around the ischaemic cut-point and an impaired clinical outcome, regardless of the accompanying FFR value. CONCLUSION: The present study suggests that Pd/Pa provides at least equivalent prognostic value compared with FFR. When Pd/Pa disagreed with FFR, the baseline index conferred superior prognostic value in this study population.

Spectrum of cutaneous lupus erythematosus in South Africans with systemic lupus erythematosus.

BACKGROUND: Cutaneous involvement is very common in systemic lupus erythematosus. We describe the prevalence and spectrum of lupus-specific (cutaneous lupus erythematosus) and non-specific cutaneous features amongst mostly black South Africans with systemic lupus erythematosus. PATIENTS AND METHODS: A retrospective record review of 298 South Africans (262 blacks and 36 non-blacks) with systemic lupus erythematosus was carried out. Cutaneous features were classified according to the Gilliam and Sontheimer classification of cutaneous lupus. RESULTS: Most (81.5%) patients were black African females. The mean (SD) age at diagnosis and follow-up duration were 35.0 (11.8) and 8.0 (5.9) years, respectively. Cutaneous lupus erythematosus was seen in 76.1% of patients, mainly chronic cutaneous lupus erythematosus with the discoid lupus erythematosus subtype seen in 52.1% of patients. Acute cutaneous lupus erythematosus was seen in 30.2% of patients and was more common in non-blacks than blacks (odds ratio = 3.8 (1.9-7.9)); localized acute cutaneous lupus erythematosus was more common than generalized acute cutaneous lupus erythematosus (odds ratio = 2.6 (1.6-4.4)). Non-specific cutaneous features occurred in 77.2%, with oral/nasal ulcers and Raynaud's phenomenon each occurring in approximately 40% of patients. Diffuse melanonychia at initial diagnosis was present in 37.4% of patients and was more common in blacks than non-blacks (odds ratio = 3.1 (1.3-7.3)). Acute cutaneous lupus erythematosus was associated with renal disease (odds ratio = 2.8 (1.6-4.7)) and chronic cutaneous lupus erythematosus with arthritis (odds ratio = 2.02 (1.24-3.29)). Diffuse melanonychia was associated with less renal disease and anti-dsDNA antibody positivity (odds ratio = 0.4 (0.3-0.7) and 0.4 (0.2-0.6), respectively) and significantly lower lupus severity index scores (mean (SD) = 5.99 (1.11) vs 6.56 (1.36) in patients with no melanonychia, p < 0.05)). CONCLUSION: In this study of South Africans with systemic lupus erythematosus, the skin was the most commonly affected organ. In general, cutaneous lupus erythematosus was associated with less severe systemic disease. Acute cutaneous lupus erythematosus was less common in blacks, whereas discoid lupus erythematosus was more common than reported in Caucasians. Diffuse melanonychia was a distinctive finding and was associated with milder systemic disease.

Transcatheter aortic valve replacement alters ascending aortic blood flow and wall shear stress patterns: A 4D flow MRI comparison with age-matched, elderly controls.

BACKGROUND: With the implementation of transcatheter aortic valve replacement (TAVR) in lower-risk patients, evaluation of blood flow characteristics and the effect of TAVR on aortic dilatation becomes of considerable interest. We employed 4D flow MRI in the ascending aorta of patients after TAVR to assess wall shear stress (WSS) and compare blood flow patterns with surgical aortic valve replacement (SAVR) and age- and gender-matched controls. METHODS: Fourteen post-TAVR patients and ten age- and gender-matched controls underwent kt-PCA accelerated 4D flow MRI of the thoracic aorta at 3.0 Tesla. Velocity and wall shear stress was compared between the two groups. In addition, aortic flow eccentricity and displacement was assessed and compared between TAVR patients, controls and 14 SAVR patients recruited as part of an earlier study. RESULTS: Compared to controls, abnormally elevated WSS was present in 30±10% of the ascending aortic wall in TAVR patients. Increased WSS was present along the posterior mid-ascending aorta and the anterior distal-ascending aorta in all TAVR patients. TAVR results in eccentric and displaced flow in the mid- and distal-ascending aorta, whereas blood flow displacement in SAVR patients occurs only in the distal-ascending aorta. CONCLUSION: This study shows that TAVR results in increased blood flow velocity and WSS in the ascending aorta compared to age- and gender-matched elderly controls. This finding warrants longitudinal assessment of aortic dilatation after TAVR in the era of potential TAVR in lower-risk patients. Additionally, TAVR results in altered blood flow eccentricity and displacement in the mid- and distal-ascending aorta, whereas SAVR only results in altered blood flow eccentricity and displacement in the distal-ascending aorta. KEY POINTS: • TAVR results in increased blood flow velocity and WSS in the ascending aorta. • Longitudinal assessment of aortic dilatation after TAVR is warranted in the era of potential TAVR in lower-risk patients. • Both TAVR and SAVR result in altered blood flow patterns in the ascending aorta when compared to age-matched controls.

[Hematological neoplasias as differential diagnoses of soft tissue tumors]. / Hämatologische Neoplasien als Differenzialdiagnosen von Weichgewebstumoren.

BACKGROUND: Several hematological malignancies might morphologically present as differential diagnoses of sarcomas. OBJECTIVES: To illustrate entities of hematological malignancies that might cause difficulties in differentiation from sarcomas and to introduce immunohistochemical and molecular tests that facilitate the diagnosis. MATERIAL AND METHODS: Selective literature research ( http://www.ncbi.nlm.nih.gov ) was combined with the clinico-pathological experience of the authors. RESULTS: In particular, hematologic malignancies with small blue round cell cytology, as well as lymphomas with anaplastic or spindle cell morphology, may mimic sarcomas. Identification of the correct diagnosis is usually possible by applying immunohistochemical and molecular analyses. Lymphomas without expression of CD45 and hematological neoplasias with expression of markers characteristic of sarcomas may cause difficulties in differential diagnosis. CONCLUSION: Hematological malignancies should be kept in mind as differential diagnoses of sarcomas and should be excluded by immunohistochemical and molecular analyses according to morphology and the clinical picture.

[Importance of interdisciplinary collaboration for optimal treatment of orbital tumors]. / Bedeutung der interdisziplinären Zusammenarbeit für eine optimale Behandlung orbitaler Tumoren.

Optimal treatment of tumors with orbital invasion may exceed the competences of an individual medical specialty and require interdisciplinary cooperation. The aim of this article is to present an interdisciplinary treatment concept based on the examples of intraorbital hemangioma and squamous cell carcinoma of the paranasal sinuses infiltrating the orbit. In addition to a detailed medical history and a complete ophthalmological examination, a detailed imaging technique with standardized echography and tomography methods such as orbital thin-slice CT and/or in many cases MRI is essential for the primary classification of an intraorbital pathology. Depending on the type of pathology, a purely surgical procedure involving various disciplines such as ophthalmology, otorhinolaryngology, maxillofacial surgery, neurosurgery, and pathology, or an interdisciplinary treatment regimen including (neo)adjuvant radiotherapy or chemotherapy is necessary. Orbital tumors have a wide range of potential pathologies, requiring complex surgical procedures and multimodal therapies. In case of infiltration of the paranasal sinuses or intracranial structures, an interdisciplinary team including neuroradiologists, oral-maxillofacial surgeons, otorhinolaryngologists, neurosurgeons, radiation therapists, ophthalmologists, pathologists, oncologists, and psycho-oncologists is essential for successful treatment.

Cardiology fellows-in-training are exposed to relatively high levels of radiation in the cath lab compared with staff interventional cardiologists-insights from the RECAP trial.

BACKGROUND: Interventional cardiologists are inevitably exposed to low-dose radiation, and consequently are at risk for radiation induced diseases like cataract and left-sided brain tumours. Operator behaviour may possibly be the largest influencer on radiation exposure. We hypothesised that awareness regarding radiation exposure grows as skill and the general experience in the catheterization laboratory increase. OBJECTIVES: In this study we determined the difference in the relative radiation exposure of staff interventional cardiologists compared with cardiology fellows-in-training. METHODS: During this prospective trial the operator's radiation exposure (E in µSv) was measured at chest height during 766 diagnostic catheterisations and percutaneous coronary interventions. Also, the patient exposure (DAP in mGy·cm2), representing the amount of radiation administered by the operator per procedure, was collected. The primary outcome of this study was the difference in relative exposure between staff interventional cardiologists versus cardiology fellows-in-training (E/DAP). RESULTS: From January to May 2017, staff interventional cardiologists performed 637 procedures and cardiology fellows-in-training 129 procedures. The performance of relatively complex procedures by staff interventional cardiologists resulted in a 74% higher use of radiation compared with fellows-in-training. Consequently, staff interventional cardiologists were exposed to 50% higher levels of actual radiation exposure. However, when correcting for the complexity of the procedure, by comparing the relative operator exposure (E/DAP), fellows-in-training were exposed to a 34% higher relative exposure compared with staff interventional cardiologists (p = 0.025). CONCLUSIONS: In the current study, when corrected for complexity, cardiology fellows-in-training were exposed to significantly higher radiation levels than staff interventional cardiologists during catheterisation procedures.

Five-year clinical follow-up of the STENTYS self-apposing stent in complex coronary anatomy: a single-centre experience with report of specific angiographic indications.

OBJECTIVES: We sought to investigate angiographic indications for the use of the STENTYS technique and evaluated the long-term safety and clinical efficacy of the stent. BACKGROUND: Coronary lesions involving complex anatomy, including aneurysmatic, ectatic, or tapered vessel segments often carry a substantial risk of stent malapposition. The self-apposing stent technique may reduce the risk of stent malapposition and therefore improve clinical outcomes. METHODS: A total of 120 consecutive patients treated with the STENTYS stent were included (drug-eluting stent (DES) n = 101, bare-metal stent (BMS) n = 19). All lesions were scored for angiographic indications for the STENTYS stent, including aneurysms, ectasias, tapering, absolute diameters, bifurcation lesions, and saphenous vein grafts. Off-line quantitative coronary angiography analyses were performed pre-procedure and post-procedure. Five years follow-up was obtained including cardiac death, target vessel myocardial infarction (TV-MI), target vessel revascularisation, stent thrombosis, and the composite endpoint target vessel failure (cardiac death, TV-MI and target vessel revascularisation). RESULTS: Angiographic indications for STENTYS use were aneurysm (30%), ectasia (19%), tapering (27%), bifurcation lesions (8%), and saphenous vein graft lesions (16%) and absolute diameters (22%). Mean maximal diameter was 4.51 ± 0.99 mm. At 5­year follow-up target vessel failure rates were 24.1% in the total cohort (DES 22.8% vs. BMS 33%, p = 0.26). Definite stent thrombosis rate was 3.8% at 5­year follow-up in this cohort with complex and high-risk lesions (DES 4.5% vs. BMS 0%, p = 0.39). CONCLUSIONS: Angiographic indications for the use of the self-apposing stent were complex lesions with atypical coronary anatomy. Our data showed reasonable stent thrombosis rates at 5­year follow-up, considering the high-risk lesion characteristics.

Trends in patient characteristics and clinical outcome over 8 years of transcatheter aortic valve implantation.

AIM: In the evolving field of transcatheter aortic valve implantations (TAVI) we aimed to gain insight into trends in patient and procedural characteristics as well as clinical outcome over an 8­year period in a real-world TAVI population. METHODS: We performed a single-centre retrospective analysis of 1,011 consecutive patients in a prospectively acquired database. We divided the cohort into tertiles of 337 patients; first interval: January 2009-March 2013, second interval: March 2013-March 2015, third interval: March 2015-October 2016. RESULTS: Over time, a clear shift in patient selection was noticeable towards lower surgical risks including Society of Thoracic Surgeons predicted risk of mortality score and comorbidity. The frequency of transfemoral TAVI increased (from 66.5 to 77.4%, p = 0.0015). Device success improved (from 62.0 to 91.5%, p < 0.0001) as did the frequency of symptomatic relief (≥1 New York Heart Association class difference) (from 73.8 to 87.1%, p = 0.00025). Complication rates decreased, including in-hospital stroke (from 5.0 to 2.1%, p = 0.033) and pacemaker implantations (from 10.1 to 5.9%, p = 0.033). Thirty-day mortality decreased (from 11.0 to 2.4%, p < 0.0001); after adjustment for patient characteristics, a mortality-risk reduction of 72% was observed (adjusted hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.13-0.62). One-year mortality rates decreased (from 23.4 to 11.4%), but this was no longer significant after a landmark point was set at 30 days (mortality from 31 days until 1 year) (adjusted HR: 0.69, 95% CI: 0.41-1.16, p = 0.16). CONCLUSION: A clear shift towards a lower-risk TAVI population and improved clinical outcome was observed over an 8­year period. Survival after TAVI improved impressively, mainly as a consequence of decreased 30-day mortality.

CBF1 is clinically prognostic and serves as a target to block cellular invasion and chemoresistance of EMT-like glioblastoma cells.

BACKGROUND: Glioblastoma is the most common and most lethal primary brain cancer. CBF1 (also known as Recombination signal Binding Protein for immunoglobulin kappa J, RBPJ) is the cardinal transcriptional regulator of the Notch signalling network and has been shown to promote cancer stem-like cells (CSCs) in glioblastoma. Recent studies suggest that some of the malignant properties of CSCs are mediated through the activation of pro-invasive programme of epithelial-to-mesenchymal transition (EMT). Little is known whether CBF1 is involved in the EMT-like phenotype of glioma cells. METHODS: In a collection of GBM neurosphere lines, we genetically inhibited CBF1 and investigated the consequences on EMT-related properties, including in vitro invasiveness by Boyden chambers assay, chemoresistance using a clinical drug library screen and glycolytic metabolism assessing live-cell extracellular acidification rate. We also compared CBF1 expression in cells exposed to low and high oxygen tension. In silico analysis in large-scale Western and Eastern patient cohorts investigated the clinical prognostic value of CBF1 expression in low- and high-grade glioma as well as medulloblastoma. RESULTS: Mean CBF1 expression is significantly increased in isocitrate dehydrogenase 1 (IDH1) R132H mutant glioblastoma and serves as prognostic marker for prolonged overall survival in brain tumours, particularly after therapy with temozolomide. Hypoxic regions of glioblastoma have higher CBF1 activation and exposure to low oxygen can induce its expression in glioma cells in vitro. CBF1 inhibition blocks EMT activators such as zinc finger E-box-binding homeobox 1 (ZEB1) and significantly reduces cellular invasion and resistance to clinically approved anticancer drugs. Moreover, we indicate that CBF1 inhibition can impede cellular glycolysis. CONCLUSIONS: Mean CBF1 activation in bulk tumour samples serves as a clinical predictive biomarker in brain cancers but its intratumoral and intertumoral expression is highly heterogeneous. Microenvironmental changes such as hypoxia can stimulate the activation of CBF1 in glioblastoma. CBF1 blockade can suppress glioblastoma invasion in vitro in particular in cells undergone EMT such as those found in the hypoxic niche. Targeting CBF1 can be an effective anti-EMT therapy to impede invasive properties and chemosensitivity in those cells.

Hypogyrification in obsessive-compulsive disorder.

BACKGROUND: Previous studies hypothesized that neurodevelopmental risk factors may play a role in the pathogenesis of obsessive-compulsive disorder (OCD). Cortical folding has been shown to be a reliable indicator for normal and altered neurodevelopment, but in OCD it has barely been investigated up to now. The present study investigates whether alterations in gyrification are detectable in OCD and, if so, how these are associated with clinical characteristics. METHOD: We compared the local Gyrification Index (lGI) between 75 OCD patients and 75 matched healthy subjects across the whole brain. In addition, for those regions exhibiting an altered lGI in patients we explored a potential relationship to symptom severity, age of onset, and influence of medication. RESULTS: OCD patients had a significantly decreased lGI in right parietal, precentral but also insula, temporal, pars triangularis and rostral middle frontal regions compared to healthy subjects. A positive association with age of onset was found but no association with symptom severity. There was no effect of co-morbidity or medication. CONCLUSIONS: The reduced gyrification found in OCD confirms previous findings in other psychiatric disorders and suggests that alterations may already occur during early stages of brain development. Our findings support the idea that altered cortical folding might represent a trait characteristic of the disorder although longitudinal studies are needed to clarify the trajectory of this morphological measure in OCD.