How to counteract the lack of donor tissue in cardiac surgery? Initial experiences with a newly established homograft procurement program.

Homograft heart valves may have significant advantages and are preferred for the repair of congenital valve malformations, especially in young women of childbearing age, athletes and in patients with active endocarditis. A growing problem, however, is the mismatch between tissue donation and the increasing demand. The aim of this paper is to describe the initiation process of a homograft procurement program to attenuate the shortage of organs. A comprehensive description of the infrastructure and procedural steps required to initiate a cardiac and vascular tissue donation program combined with a prospective follow-up of all homografts explanted at our institution. Between January 2020 and May 2022, 28 hearts and 12 pulmonary bifurcations were harvested at our institution and delivered to the European homograft bank. Twenty-seven valves (19 pulmonary valves, 8 aortic valves) were processed and allocated for implantation. The reasons for discarding a graft were either contamination (n = 14), or morphology (n = 13) or leaflet damage (n = 2). Five homografts (3 PV, 2 AV) have been cryopreserved and stored while awaiting allocation. One pulmonary homograft with a leaflet cut was retrieved by bicuspidization technique and awaits allocation, as a highly requested small diameter graft. The implementation of a tissue donation program in cooperation with a homograft bank can be achieved with reasonable additional efforts at a transplant center with an in-house cardiac surgery department. Challenging situations with a potential risk of tissue injury during procurement include re-operation, harvesting by a non-specialist surgeon and prior central cannulation for mechanical circulatory support.

Evolution of the visual system in ray-finned fishes.

The vertebrate eye allows to capture an enormous amount of detail about the surrounding world which can only be exploited with sophisticated central information processing. Furthermore, vision is an active process due to head and eye movements that enables the animal to change the gaze and actively select objects to investigate in detail. The entire system requires a coordinated coevolution of its parts to work properly. Ray-finned fishes offer a unique opportunity to study the evolution of the visual system due to the high diversity in all of its parts. Here, we are bringing together information on retinal specializations (fovea), central visual centers (brain morphology studies), and eye movements in a large number of ray-finned fishes in a cladistic framework. The nucleus glomerulosus-inferior lobe system is well developed only in Acanthopterygii. A fovea, independent eye movements, and an enlargement of the nucleus glomerulosus-inferior lobe system coevolved at least five times independently within Acanthopterygii. This suggests that the nucleus glomerulosus-inferior lobe system is involved in advanced object recognition which is especially well developed in association with a fovea and independent eye movements. None of the non-Acanthopterygii have a fovea (except for some deep sea fish) or independent eye movements and they also lack important parts of the glomerulosus-inferior lobe system. This suggests that structures for advanced visual object recognition evolved within ray-finned fishes independent of the ones in tetrapods and non-ray-finned fishes as a result of a coevolution of retinal, central, and oculomotor structures.

Development and clinical implementation of a digital system for risk assessments for radiation therapy.

Before introducing new treatment techniques, an investigation of hazards due to unintentional radiation exposures is a reasonable activity for proactively increasing patient safety. As dedicated software is scarce, we developed a tool for risk assessment to design a quality management program based on best practice methods, i.e., process mapping, failure modes and effects analysis and fault tree analysis. Implemented as a web database application, a single dataset was used to describe the treatment process and its failure modes. The design of the system and dataset allowed failure modes to be represented both visually as fault trees and in a tabular form. Following the commissioning of the software for our department, previously conducted risk assessments were migrated to the new system after being fully re-assessed which revealed a shift in risk priorities. Furthermore, a weighting factor was investigated to bring risk levels of the migrated assessments into perspective. The compensation did not affect high priorities but did re-prioritize in the midrange of the ranking. We conclude that the tool is suitable to conduct multiple risk assessments and concomitantly keep track of the overall quality management activities.

Complication rates of peripherally inserted central catheters vs implanted ports in patients receiving systemic anticancer therapy: A retrospective cohort study.

While implanted port catheters ("PORTs") have historically been the standard device for intravenous systemic anticancer therapy, the use of peripherally inserted central catheters (PICCs) has increased continuously and reliable catheter selection guidelines are lacking. We compare complication rates of PORTs and PICCs in cancer treatment in a retrospective study of 3365 patients with both solid organ (n = 2612) and hematologic (n = 753) malignancies, between 2001 and 2021. 26.4% (n = 890) of all patients were treated via PICCs and 73.6% (2475) via PORTs. 20.7% (578) experienced a major catheter-related complication with a higher rate in PICCs than in PORTs (23.5% vs 14.9%, P < .001). Among major complications, infections and mechanical complications were more common in PICCs than in PORTs (11.9% vs 6.4%, P = .001, 7.3% vs 4.2%, P = .002), whereas the rate of thrombosis was similar (3.4% vs 3.0%, P = .9). While PORTs had a higher rate of periprocedural complications (2.7% vs 1.1%, P < .05), PICCs overall complication rate exceeded PORTs within 3 days from implantation. Median follow-up was 49 (PICC) and 60 weeks (PORT). PORTs are safer and therefore should be preferred in this setting regardless of catheter dwell time.

The Introduction of an MR-Conditional Prototype for Cardiopulmonary Bypass Support: Technical Aspects and System Requirements.

INTRODUCTION: The use of cardiopulmonary bypass (CBP; also known as a heart-lung machine) in newborns with complex congenital heart defects may result in brain damage. Magnetic resonance imaging (MRI) assessments cannot be performed safely because the metal components used to construct CBP devices may elicit adverse effects on patients when they are placed in a magnetic field. Thus, this project aimed to develop a prototype MR-conditional circulatory support system that could be used to perform cerebral perfusion studies in animal models. METHODS: The circulatory support device includes a roller pump with two rollers. The ferromagnetic and most of the metal components of the roller pump were modified or replaced, and the drive was exchanged by an air-pressure motor. All materials used to develop the prototype device were tested in the magnetic field according to the American Society for Testing and Materials (ASTM) Standard F2503-13. The technical performance parameters, including runtime/durability as well as achievable speed and pulsation behavior, were evaluated and compared to standard requirements. The behavior of the prototype device was compared with a commercially available pump. RESULTS: The MRI-conditional pump system produced no image artifacts and could be safely operated in the presence of the magnetic field. The system exhibited minor performance-related differences when compared to a standard CPB pump; feature testing revealed that the prototype meets the requirements (i.e., operability, controllability, and flow range) needed to proceed with the planned animal studies. CONCLUSION: This MR-conditional prototype is suitable to perform an open-heart surgery in an animal model to assess brain perfusion in an MR environment.

The Diversity of the Brains of Ray-Finned Fishes.

Brains are very plastic, both in response to phenotypic diversity and to larger evolutionary trends. Differences between taxa cannot be easily attributed to either factors. Comparative morphological data on higher taxonomic levels are scarce, especially in ray-finned fishes. Here we show the great diversity of brain areas of more than 150 species of ray-finned fishes by volumetric measurements using block-face imaging. We found that differences among families or orders are more likely due to environmental needs than to systematic position. Most notable changes are present in the brain areas processing sensory input (chemosenses and lateral line vs. visual system) between salt- and freshwater species due to fundamental differences in habitat properties. Further, some patterns of brain volumetry are linked to characteristics of body morphology. There is a positive correlation between cerebellum size and body depth, as well as the presence of a swim bladder. Since body morphology is linked to ecotypes and habitat selection, a complex character space of brain and body morphology and ecological factors together could explain better the differentiation of species into their ecological niches and may lead to a better understanding of how animals adapt to their environment.

Sustained effectiveness and safety of subcutaneous tocilizumab over two years in the ARATA observational study.

OBJECTIVES: To investigate long-term effectiveness and safety of subcutaneous tocilizumab (TCZ-SC) in the routine clinical care of patients with rheumatoid arthritis (RA). METHODS: ARATA (ML29087) was a prospective, multicentre, observational study of adult patients with active RA initiating therapy with TCZ-SC. The primary effectiveness outcome was the proportion of patients achieving DAS28-ESR <2.6 at week 104. Additional efficacy outcomes included individual DAS28-dcrit responses (improvement of ≥1.8 from baseline), CDAI remission (≤2.8), and patient-reported outcomes (PROs), including Work Productivity and Activity Impairment scores. Adverse event rates were used to evaluate safety and tolerability. RESULTS: Between May 2014 and July 2018, 114 study centres in Germany enrolled 1,300 patients with RA who received at least one dose of TCZ-SC (mean age 57.3 [SD 12.5] years, mean DAS28-ESR of 4.9 [SD 1.3]). At week 104, 58.7% (365/622) patients achieved DAS28-ESR <2.6, 64.0% had an individual DAS28-dcrit response, and 31.4% (241/767) achieved CDAI remission. PROs, including patient global assessment, pain, and fatigue, showed marked improvements from baseline. Work outcomes, including absenteeism (missed work) and presenteeism (productivity while at work), also improved. Injection reactions were rare and no new safety signals occurred. Patients expressed a high level of satisfaction with treatment. Baseline patient characteristics and outcomes were similar for ARATA and ICHIBAN (an observational study of TCZ-IV in Germany), despite different formulations and time periods. CONCLUSIONS: The safety and effectiveness of TCZ-SC is maintained over 2 years during routine clinical care. TCZ-SC represents a convenient and effective option for RA patients who prefer SC administration.

DISEMM: a tool for the investigation of elasto-plastic behaviour on polycrystalline samples using X-ray and neutron diffraction.

The software DISEMM is designed to analyse diffraction data from in situ loading experiments on polycrystalline samples for the determination of single-crystal elastic constants (SECs) and elasto-plastic self-consistent (EPSC) modelling of lattice strains. The SECs can be obtained from powder-diffraction elastic constants using a variety of grain-to-grain interaction models, namely Voigt, Reuss, Hill, Kröner, de Wit and Matthies approaches. The texture of the polycrystalline sample can be taken into account using the orientation distribution function of the grains. For the analysis of two-phase materials, an approach was implemented to calculate the stress transfer between the phases and its impact on the apparent elastic properties. The calculated SECs can then be used as input into the EPSC model, which allows the user to predict the elasto-plastic behaviour for comparison with experimental lattice strain data and to investigate the activation of individual slip systems. For this purpose, critical resolved shear stresses and hardening parameters are adapted iteratively.

In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications.

Several locally acting colon-targeted products to treat colonic diseases have been recently developed and marketed, taking advantage of gastrointestinal physiology to target delivery. Main mechanisms involve pH-dependent, time-controlled and/or enzymatic-triggered release. With site of action located before systemic circulation and troublesome colonic sampling, there is room for the introduction of meaningful in vitro methods for development, quality control (QC) and regulatory applications of these formulations. A one-size-fits-all method seems unrealistic, as the selection of experimental conditions should resemble the physiological features exploited to trigger the release. This article reviews the state of the art for bio-predictive dissolution testing of colon-targeted products. Compendial methods overlook physiological aspects, such as buffer molarity and fluid composition. These are critical for pH-dependent products and time-controlled systems containing ionizable drugs. Moreover, meaningful methods for enzymatic-triggered products including either bacteria or enzymes are completely ignored by pharmacopeias. Bio-predictive testing may accelerate the development of successful products, although this may require complex methodologies. However, for high-throughput routine testing (e.g., QC), simplified methods can be used where balance is struck between simplicity, robustness and transferability on one side and bio-predictivity on the other. Ultimately, bio-predictive methods can occupy a special niche in terms of supplementing plasma concentration data for regulatory approval.

Early and Mid-Term Outcomes of Open versus Endovascular Left Subclavian Artery Debranching for Thoracic Aortic Diseases.

PURPOSE: To compare open versus endovascular left subclavian artery debranching for thoracic endovascular aortic repair of thoracic aortic pathologies. METHODS: This is a retrospective study of patients receiving left subclavian artery debranching in our institution from October 2009 to January 2020. The primary outcome was freedom from aortic reintervention. Secondary outcomes were type I endoleaks, left subclavian artery (LSA) debranching failure, stroke, technical or clinical success, procedure-related reintervention, as well as 30-day or overall all-cause and aorta-related mortality. RESULTS: Forty-eight patients received parallel graft-based (n = 24, ENDO; median age 75 years [70-80 years]) or open (n = 24, OPEN; median age 71 years [59-75 years]) debranching for type B aortic dissection (n = 25), degenerative aneurysm (n = 12), type IA endoleak (n = 6), suture-associated (n = 3) or ostial LSA aneurysm (n = 1), or penetrating aortic ulcer (n = 1). The median follow-up was 36 months (13-61 months). After 16 months, aortic reintervention-free survival in groups OPEN and ENDO was 91% (95% confidence interval [CI]: 79 to 100%) and 86% (73 to 100%) (p = 0.71), respectively. After 36 months, all-cause survival in groups OPEN and ENDO was 74% (95% CI: 55 to 99%) and 79% (95% CI: 64 to 97%) (p = 0.74), respectively; freedom from aorta-related mortality was 81% (95% CI: 62 to 100%) and 91% (95% CI: 80 to 100%) (p = 0.78), respectively. Group OPEN presented less type I endoleaks (OPEN/ENDO = 3/19, p <0.001) and higher technical (OPEN/ENDO = 81/36%, p = 0.003) and clinical success rates (OPEN/ENDO = 67/36%, p = 0.047). No statistical differences were found for other outcomes. CONCLUSION: Both strategies achieved comparable reintervention and mortality rates, but open debranching should be preferred due to its higher technical and clinical success and less type I endoleaks.

The safety and effectiveness of tocilizumab in elderly patients with rheumatoid arthritis and in patients with comorbidities associated with age.

OBJECTIVES: To examine the safety and effectiveness of long-term tocilizumab treatment in elderly patients with rheumatoid arthritis (RA) and patients with age-associated comorbidities. METHODS: ICHIBAN (NCT01194401) was a prospective, non-interventional study that observed adult patients with active moderate-to-severe RA in German rheumatology clinics and practices for up to two years. Patients were to be treated according to the tocilizumab label. Here, we present safety and effectiveness data analysed according to patient age. RESULTS: Of the 3,164 patients treated with at least one dose of tocilizumab, 924 patients were <50 years old, 1496 patients were 50-65 years old, and 744 patients were >65 years old at baseline. Patients >65 years had the highest baseline DAS28-ESR, CDAI, and HAQ-DI scores, along with the highest burden of comorbidities, such as diabetes, coronary heart disease, anaemia, and renal insufficiency. Under treatment with tocilizumab, patients >65 years had similar improvements in DAS28-ESR, CDAI and patient-reported outcomes (fatigue, pain, sleeplessness) with similar glucocorticoid savings compared to patient groups <65 years. Patients >65 years with late-onset RA achieved similar reductions in disease activity compared to early-onset patients. Despite numerically higher rates of adverse events (AEs), serious AEs and serious infections in patients >65 years, there were similar rates of AEs leading to withdrawal. CONCLUSIONS: Elderly patients in ICHIBAN experienced improvements similar to younger patients in most effectiveness endpoints with only slightly higher rates of AEs, indicating an overall net-positive risk-benefit ratio of tocilizumab treatment regardless of patient age.

Complex Multi-Stage Total Aortic and Subclavian Artery Replacement in a 9-year old boy with Loeys-Dietz-Syndrome.

BACKGROUND: Loeys-Dietz Syndrome is a rare connective tissue disorder that is associated with arterial pathologies such as aortic dissections, tortuosity and aneurysms.We present a child with Loeys-Dietz Syndrome type 2 that received total aortic and bilateral subclavian artery replacement. CASE REPORT: A 9-year old boy with Loeys-Dietz Syndrome type 2 and acute type B aortic dissection received an urgent complete thoracic and thoraco-abdominal aortic repair within three days. First, the ascending aorta and aortic root were replaced in a Tirone David and Frozen Elephant Trunk procedure. Then, the descending and supramesenteric aorta was replaced by a Dacron interposition graft with direct implantation of the celiac trunk. During the 15 months follow-up, the patient required three more surgical interventions for rapid expanding aneurysms of both subclavian arteries and the infrarenal aorta. No major adverse event nor secondary interventions occurred. Ultrasonographic and magnetic resonance imaging follow-up is continued at 6-months intervals. CONCLUSION: Children with Loeys-Dietz Syndrome may require extensive aortic repair for aortic dissection and show rapidly expanding aneurysms. Referral to a center with pediatric vascular expertise and long-term follow-up examinations are crucial.

Characterisation of depressive symptoms in rheumatoid arthritis patients treated with tocilizumab during routine daily care.

OBJECTIVES: To assess whether tocilizumab treatment is associated with changes in depression symptoms in patients with rheumatoid arthritis (RA) during routine daily care. METHODS: We retrospectively analysed data from a German non-interventional study (ARATA) of adult, tocilizumab-naïve RA patients who initiated subcutaneous tocilizumab and were followed for 52 weeks. The Beck Depression Inventory II (BDI-II) was used to assess symptoms of depression and create baseline subgroups of no (BDI-II<14), mild (14-19), moderate (20-28), and severe (≥29) depression. Other key outcomes included Disease Activity Score-28 joints (DAS28), patient-reported outcomes (PROs), and adverse events. Mixed model repeated measures (MMRM) assessed the impact of DAS28 on BDI-II over time, and Pearson correlation analyses evaluated associations between changes from baseline. RESULTS: Of 474/1155 ARATA patients who completed the BDI-II at baseline, 47.7% had evidence of depression: 18.4% mild, 17.7% moderate, and 11.6% severe. 229 patients (48.3%) completed the BDI-II at both baseline and week 52. Two-thirds of patients with moderate or severe depression at baseline improved to a milder or no depression subgroup at week 52 (44/65 [67.7%]). Improvements in disease activity and PROs were observed in all subgroups, but patients with depression had lower response and higher adverse events rates. We observed an association between DAS28 and BDI-II over time in MMRM analyses, but the Pearson correlation for change from baseline was weak (r=0.10). CONCLUSIONS: Depression is common in patients receiving routine care for RA. Improvements in depressive symptoms in RA during tocilizumab therapy appear to be distinct from changes in disease activity.

Depletion of Numb and Numblike in Murine Lung Epithelial Cells Ameliorates Bleomycin-Induced Lung Fibrosis by Inhibiting the ß-Catenin Signaling Pathway.

Idiopathic pulmonary fibrosis (IPF) represents the most aggressive form of pulmonary fibrosis (PF) and is a highly debilitating disorder with a poorly understood etiology. The lung epithelium seems to play a critical role in the initiation and progression of the disease. A repeated injury of lung epithelial cells prompts type II alveolar cells to secrete pro-fibrotic cytokines, which induces differentiation of resident mesenchymal stem cells into myofibroblasts, thus promoting aberrant deposition of extracellular matrix (ECM) and formation of fibrotic lesions. Reactivation of developmental pathways such as the Wnt-ß-catenin signaling cascade in lung epithelial cells plays a critical role in this process, but the underlying mechanisms are still enigmatic. Here, we demonstrate that the membrane-associated protein NUMB is required for pathological activation of ß-catenin signaling in lung epithelial cells following bleomycin-induced injury. Importantly, depletion of Numb and Numblike reduces accumulation of fibrotic lesions, preserves lung functions, and increases survival rates after bleomycin treatment of mice. Mechanistically, we demonstrate that NUMB interacts with casein kinase 2 (CK2) and relies on CK2 to activate ß-catenin signaling. We propose that pharmacological inhibition of NUMB signaling may represent an effective strategy for the development of novel therapeutic approaches against PF.

Neutron and X-ray Diffraction Analysis of Macro and Phase-Specific Micro Residual Stresses in Deep Rolled Duplex Stainless Steels.

Experimental analyses of depth distributions of phase-specific residual stresses after deep rolling were carried out by means of laboratory X-ray diffraction and neutron diffraction for the two duplex steels X2CrNiMoN22-5-3 and X3CrNiMoN27-5-2, which differ significantly in their ferrite to austenite ratios. The aim of the investigation was to elucidate to which extent comparable results can be achieved with the destructive and the non-destructive approach and how the process induced phase-specific micro residual stresses influence the determination of the phase- and {hkl}-specific reference value d0, required for evaluation of neutron strain scanning experiments. A further focus of the work was the applicability of correction approaches that were developed originally for single-phase materials for accounting for spurious strains during through surface neutron scanning experiments on coarse two-phase materials. The depth distributions of macro residual stresses were separated from the phase-specific micro residual stresses. In this regard, complementary residual stress analysis was carried out by means of incremental hole drilling. The results indicate that meaningful macro residual stress depth distributions can be determined non-destructively by means of neutron diffraction for depths starting at about 150-200 µm. Furthermore, it was shown that the correction of the instrumental surface effects, which are intrinsic for surface neutron strain scanning, through neutron ray-tracing simulation is applicable to multiphase materials and yields reliable results. However, phase-specific micro residual stresses determined by means of neutron diffraction show significant deviations to data determined by means of lab X-ray stress analysis according to the well-known sin2ψ-method.

On the determination of residual stresses in additively manufactured lattice structures.

The determination of residual stresses becomes more complicated with increasing complexity of the structures investigated. Additive manufacturing techniques generally allow the production of 'lattice structures' without any additional manufacturing step. These lattice structures consist of thin struts and are thus susceptible to internal stress-induced distortion and even cracks. In most cases, internal stresses remain locked in the structures as residual stress. The determination of the residual stress in lattice structures through nondestructive neutron diffraction is described in this work. It is shown how two difficulties can be overcome: (a) the correct alignment of the lattice structures within the neutron beam and (b) the correct determination of the residual stress field in a representative part of the structure. The magnitude and the direction of residual stress are discussed. The residual stress in the strut was found to be uniaxial and to follow the orientation of the strut, while the residual stress in the knots was more hydro-static. Additionally, it is shown that strain measurements in at least seven independent directions are necessary for the estimation of the principal stress directions. The measurement directions should be chosen according to the sample geometry and an informed choice on the possible strain field. If the most prominent direction is not measured, the error in the calculated stress magnitude increases considerably.

Initiation of an inter-hospital extracorporeal membrane oxygenation transfer programme for critically ill patients with coronavirus disease 2019: bringing extracorporeal membrane oxygenation support to peripheral hospitals.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is a resource-intensive, highly specialized and expensive therapy that is often reserved for high-volume centres. In recent years, we established an inter-hospital ECMO transfer programme that enables ECMO implants in peripheral hospitals. During the pandemic, the programme was expanded to include ECMO support in selected critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective single-centre study reports the technical details and challenges encountered during our initial experience with ECMO implants in peripheral hospitals for patients with COVID-19. RESULTS: During March and April 2020, our team at the University Hospital of Zurich performed 3 out-of-centre ECMO implants at different peripheral hospitals. The implants were performed without any complications. The patients were transported by ambulance or helicopter. Good preparation and selection of the required supplies are the keys to success. The implant should be performed by a well-trained, seasoned ECMO team, because options are limited in most peripheral hospitals. CONCLUSIONS: Out-of-centre ECMO implants in well-selected patients with COVID-19 is feasible and safe if a well-established organization is available and if the implantation is done by an experienced and regularly trained team.

Stimulus-evoked phase-locked activity along the human auditory pathway strongly varies across individuals.

Phase-locking to the temporal envelope of speech is associated with envelope processing and speech perception. The phase-locked activity of the auditory pathway, across modulation frequencies, is generally assessed at group level and shows a decrease in response magnitude with increasing modulation frequency. With the exception of increased activity around 40 and 80 to 100 Hz. Furthermore, little is known about the phase-locked response patterns to modulation frequencies ≤ 20 Hz, which are modulations predominately present in the speech envelope. In the present study we assess the temporal modulation transfer function (TMTFASSR) of the phase-locked activity of the auditory pathway, from 0.5 to 100 Hz at a high-resolution and by means of auditory steady-state responses. Although the group-averaged TMTFASSR corresponds well with those reported in the literature, the individual TMTFASSR shows a remarkable intersubject variability. This intersubject variability is especially present for ASSRs that originate from the cortex and are evoked with modulation frequencies ≤ 20 Hz. Moreover, we found that these cortical phase-locked activity patterns are robust over time. These results show the importance of the individual TMTFASSR when assessing phase-locked activity to envelope fluctuations, which can potentially be used as a marker for auditory processing.

ICHIBAN, a non-interventional study evaluating tocilizumab long-term effectiveness and safety in patients with active rheumatoid arthritis.

OBJECTIVES: We aimed to measure long-term effectiveness and safety of tocilizumab in patients with rheumatoid arthritis in daily German practice. METHODS: ICHIBAN was a prospective, multi-centre, non-interventional study (ML22928) that enrolled adult patients with active moderate to severe rheumatoid arthritis. Patients were to be treated according to tocilizumab label and observed for up to two years. Effectiveness outcomes included DAS28-ESR remission, EULAR response, CDAI and HAQ. RESULTS: Overall, 3164 patients received at least one dose of tocilizumab. Patient mean age was 55.5±13.1 years (74.8% female). At baseline, 72.1% of patients had at least one comorbidity. Approximately 50.9% of patients received concomitant csDMARDs, mostly methotrexate, and 80.7% received concomitant glucocorticoids (GCs). In patients receiving GCs at baseline, the mean dose decreased from 9.32±16.36 mg/d to 4.60±4.48 mg/d at week 104. In the effectiveness population with no prior TCZ (n=2902), 61.4% of patients achieved the primary outcome, DAS28-ESR remission. Improvements were seen as early as week 4. At week 104, 77.9% of patients had DAS28-ESR low disease activity, 89.6% achieved good or moderate EULAR response, and 29.5% achieved a CDAI-based remission. Effectiveness outcomes were similar in all previous therapy subgroups. The incidence of serious infections was similar to the rates in former studies involving tocilizumab. Patients receiving GC at baseline experienced slightly higher rates of treatment-related serious adverse events, mainly infections. No new safety signals were observed. CONCLUSIONS: Long-term effectiveness and safety in ICHIBAN were in line with previously reported tocilizumab efficacy and safety studies.