International Consensus Research Articles

Developing IBD Outcome Effect Size Thresholds to Inform Research, Guidelines, and Clinical Decisions.

When designing clinical trials, interpreting trial outcomes for guideline development or sharing decisions with patients in clinical practice, the clinical outcomes used and the implicit choices on what constitutes a clinically significant finding can vary greatly. This can lead to diversity or even inequity in care offered to patients with inflammatory bowel disease (IBD). The GRADE approach to guideline development has proposed a process to address this prospectively to solve these issues, but this has never been used in IBD. We aimed to develop the first international consensus set of outcome thresholds to establish their use in Crohn's disease and ulcerative colitis. A Delphi methodology was used to develop a consensus. An online survey was conducted by inviting stakeholders from the British Society of Gastroenterology through a 2-phase process. Participants were asked to select important clinically relevant outcomes and were asked about what magnitude of the effect that they consider large, moderate, small, or trivial for each clinical trial outcome in line with the GRADE guidance. The results were fed back to all participants to ensure consensus agreement. Then, further surveys were sent to Europe and North America to ensure validity and international triangulation of the dataset. Data are presented as mean ± SD. A total of 131 clinical stakeholders participated, including clinicians, IBD nurses, and a small number of patients with IBD. Clinical remission and serious adverse events were considered the most critical outcomes for Crohn's disease, while clinical remission and endoscopic remission were considered the most critical outcomes for ulcerative colitis. The consensus results for thresholds of small, moderate, and large outcome effect sizes were agreed on as follows: clinical remission, 11 ± 6%, 20 ± 8%, and 31 ± 13%; endoscopic remission, 9 ± 5%, 17 ± 9%, and 28 ± 14%; and serious adverse events 6 ± 6%, 11 ± 9%, and 17 ± 12%, respectively. No significant differences were observed for responses for each condition. This is the first study to develop a consensus on magnitude thresholds for outcomes in IBD. These thresholds have been used in the development of the 2024 British Society of Gastroenterology guidelines for the management of IBD but can and should also be used by study designers and, most importantly, by clinicians when discussing evidence with patients as part of shared decision making. Future work to validate these findings globally and with other groups, including patients, is needed.

ESICM-ESPNIC international expert consensus on quantitative lung ultrasound in intensive care.

To provide an international expert consensus on technical aspects and clinical applications of quantitative lung ultrasound in adult, paediatric and neonatal intensive care. The European Society of Intensive Care (ESICM) and the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) endorsed the project. We selected an international panel of 20 adult, paediatric and neonatal intensive care experts with clinical and research expertise in quantitative lung ultrasound, plus two non-voting methodologists. Fourteen clinical questions were proposed by the chairs to the panel, who voted for their priority (1-9 Likert-type scale) and proposed modifications/supplementing (two-round vote). All the questions achieved the predefined threshold (mean score > 5) and 14 groups of 3 mixed adult/paediatric experts were identified to develop the statements for each clinical question; predefined groups of experts in the fields of adult and paediatric/neonatal intensive care voted statements specific for these subgroups. An iterative approach was used to obtain the final consensus statements (two-round vote, 1-9 Likert-type scale); statements were classified as with agreement (range 7-9), uncertainty (4-6), disagreement (1-3) when the median score and ≥ 75% of votes laid within a specific range. A total of 46 statements were produced (4 adults-only, 4 paediatric/neonatal-only, 38 interdisciplinary); all obtained agreement. This result was also achieved by acknowledging in the statements the current limitations of quantitative lung ultrasound. This consensus guides the use of quantitative lung ultrasound in adult, paediatric and neonatal intensive care and helps identify the fields where further research will be needed in the future.

The formal EU-US meniscus rehabilitation 2024 consensus: An ESSKA-AOSSM-AASPT initiative. Part I-Rehabilitation management after meniscus surgery (meniscectomy, repair and reconstruction).

The aim of part one of this EU-US consensus was to combine literature research and expertise to provide recommendations for the usage of rehabilitation (including physical therapy) of patients undergoing surgical treatment for degenerative meniscus lesions or acute meniscus tears (including meniscectomy, repair, or reconstruction). Prevention programmes, non-operative treatment of acute tears and degenerative lesions, return to sports and patient-reported outcome measures will be presented in a part II article. This consensus followed the European Society for Sports Traumatology and Arthroscopy (ESSKA)'s 'formal consensus' methodology. For this combined ESSKA, American Orthopedic Society for Sports Medicine and American Academy of Sports Physical Therapy initiative, 67 experts (26 in the steering group and 41 in the rating group) from 14 countries (US and 13 European countries), including orthopaedic surgeons, sports medicine doctors and physiotherapists were involved. Steering group members established guiding questions, searched the literature and proposed statements. Rating group members assessed the statements according to a Likert scale and provided grades of recommendations, reaching a final agreement about rehabilitation of the knee after meniscus surgery. Final documents were then assessed by a peer review group to address the geographical adaptability. The overall level of evidence in the literature was low. Of the 19 questions (leading to 29 statements), 1 received a Grade A of recommendation, 2 a Grade B, 9 a Grade C and 17 a Grade D. Nevertheless, the mean median rating of all questions was 8.2/9 (9 being the highest rating on a scale of 1-9). The global mean rating was 8.4 ± 0.2, indicating a high agreement. Rehabilitation depends on the type of lesion, the treatment performed and is the same after medial or lateral meniscus surgery. Rehabilitation after meniscectomy should follow a criterion-based rehabilitation protocol, based on milestones rather than a time-based protocol. After meniscus repair and reconstruction, rehabilitation should be progressed according to both time and criterion-based milestones. Rehabilitation after meniscus surgery is a debated topic that may influence surgical outcomes if not optimally performed. This international formal consensus established clear, updated and structured recommendations for both surgeons and physiotherapists treating patients after meniscus surgery. Level I, consensus.

Treatment strategies of unruptured intracranial aneurysms: A Literature Review

Introduction and purpose Unruptured intracranial aneurysms (UIAs) are often diagnosed incidentally and become a complex clinical dilemma. The main challenge is to choose between invasive treatment and conservative management, considering the low but difficult to predict risk of rupture. The aim of this review is to present current knowledge and approaches regarding UIA management, highlighting both traditional and emerging strategies. Description of state of knowledge Management of UIAs depends on various factors, including aneurysm size, location, morphology, and patient-specific risks. Surgical clipping remains a reasonable method for long-term durability, but more perioperative complications, while endovascular approaches have an advantage due to their less invasive nature, but lower adequate occlusion rate. In selected low-risk patients, conservative monitoring with regular imaging may be appropriate. Advances in computational modeling, artificial intelligence, and hemodynamic analysis are improving our ability to assess rupture risk and tailor treatment plans. However, the lack of universally accepted guidelines continues to complicate decision-making. Conclusion UIA management should be individualized, weighing the risks and benefits of each treatment option. Despite technological progress and improved diagnostic tools, further research and international consensus are needed to establish standardized protocols for clinical practice.

Global research aims for the study of cost and value in health professions education: A Delphi study of international experts

Background Health professions educators constantly make difficult choices about the allocation of finite resources. However, there is limited sound research available to guide their decision-making. The purpose of this study was to address this gap by establishing international consensus on research aims, considering diverse economic and cultural contexts. Methods The authors conducted a three-round Delphi study, engaging an international panel of 73 experts in education research. Panelists were asked to identify (round 1), rank (round 2), and revise (round 3) research aims important for the study of cost and value in medical education. Round 3 results were discussed by an international steering group of nine medical education scientists actively involved in cost and value research, who finalized a list of 20 research aims. Steering group narratives were analyzed to identify additional conceptual insights. Results From 597 research aims suggested in round 1, 20 research aims were identified after steering group discussion. These were clustered into three categories: (1) funding mechanisms for medical education (e.g. financial policies, cost-effectiveness, and equity impacts); (2) cost and outcomes, e.g. how costs in health professions education relate to concrete outcomes; and (3) economic evaluation of teaching, assessment, and training approaches; e.g. designing and applying formal economic evaluation methods. Steering group discussions noted the limited integration of economic theories into medical education research and the need for foundational studies beyond immediate, practical priorities. They further noted lack of consensus on definitions of cost and value, and appropriate methodologies; underutilization of accepted health economics approaches; and infrequent interdisciplinary collaborations. These collectively act as barriers to advancing the field. Conclusion The field of cost and value in health professions education remains theoretically and empirically underdeveloped. The research aims identified herein provide a strategic framework for addressing cost and value comprehensively.

Diagnostic work-up of paediatric adrenocortical tumours - International consensus through a modified Delphi process

Diagnostic work-up of paediatric adrenocortical tumours - International consensus through a modified Delphi process

Stone dust in endourology: a systematic review of its definition, management, and clinical impact.

To evaluate and synthesise the existing literature on stone dust (DUST) in endourology, focusing on its definition, creation methods, and removal techniques. A comprehensive electronic literature search was conducted using the PubMed/Medline, Web Of Science, and Embase databases to identify reports published until October 2024. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed to identify eligible studies. The outcomes assessed included the definition of DUST, the method by which DUST was created, and how it was removed, evaluating both in vitro and in vivo studies. The review also assessed the efficacy of different laser technologies, including holmium-yttrium-aluminium-garnet (Ho:YAG) laser, thulium fibre laser (TFL), and pulsed thulium-YAG laser (p-Tm:YAG) laser, in generating DUST and their clinical relevance in stone management. The systematic review identified 43 eligible studies, revealing significant variability in the definition and evaluation of DUST. Criteria for DUST ranged from sub-millimetre particle sizes to functional properties like floatability and aspiration capability. While Ho:YAG lasers remain widely used for stone dusting, emerging technologies such as TFL and p-Tm:YAG lasers have shown superior efficiency in producing finer particles and reducing retropulsion. No consensus emerged regarding the settings used by surgeons and the pre-settings provided by laser manufacturers. Despite the widespread use of dusting techniques in endourology, a standardised definition of DUST remains lacking, with significant variability in laser settings, particle sizes, and evacuation methods. It must be clarified whether DUST should be defined as a noun-representing a distinct entity with a precise definition-or as the result of the dusting process, in which case clear criteria are needed to characterise it accurately. Establishing standardised definitions and protocols through international consensus is crucial to optimising clinical outcomes and ensuring consistency in future research.

STRIVING TOWARDS A CONSENSUS-BASED PERI-OPERATIVE CARE PROTOCOL FOR PENILE IMPLANTS IN PHALLOPLASTY; A DELPHI APPROACH

STRIVING TOWARDS A CONSENSUS-BASED PERI-OPERATIVE CARE PROTOCOL FOR PENILE IMPLANTS IN PHALLOPLASTY; A DELPHI APPROACH

Comprehensive analysis of culture-negative periprosthetic joint infection with metagenomic next-generation sequencing

ObjectiveThis study aimed to identify the risk factors and microbial profiles of patients with culture-negative periprosthetic joint infection (PJI) using metagenomic next generation sequencing (mNGS) and to compare the clinical characteristics and treatment outcomes of culture-negative PJI (CN PJI) with culture-positive PJI (CP PJI).MethodsA retrospective analysis was conducted on 223 patients who met the International Consensus Meeting criteria for PJI and underwent surgical treatment at our hospital between February 2013 and January 2023. Clinical and follow-up data, including microbiological culture results and mNGS findings, were collected. Based on culture results, patients were divided into the CP PJI and CN PJI groups. Risk factors and microbial profiles of CN PJI patients were summarized with the aid of mNGS results. Differences in clinical characteristics and treatment outcomes between the two groups were also analyzed.ResultsAmong the 223 patients, 168 were in the CP PJI group, and 55 were in the CN PJI group. Risk factors for negative cultures included polymicrobial infections, infections caused by rare pathogens, and prolonged antibiotic use prior to sampling. In the CN PJI group, over a quarter of cases involved polymicrobial infections (25.5%) or rare pathogen infections (38.2%), with Mycoplasma sp. being the most frequently identified rare pathogen (7.2%). Compared to the CP PJI group, the CN PJI group exhibited distinctly longer hospital stays (P<0.001), extended antibiotic use (P=0.02), and a higher rate of antibiotic-related complications (P=0.026). However, no significant difference was noted in reinfection rates between the two groups (P=0.412).ConclusionCN PJI presents a unique microbial spectrum and distinct clinical therapeutic characteristics. mNGS offers a more comprehensive understanding of infecting microorganisms, particularly those often missed by conventional culture techniques. With advancements in sample collection, optimized culture methods, molecular diagnostic tools, and early targeted therapies, CN PJI may achieve clinical outcomes comparable to CP PJI.

Dose-Escalated Stereotactic Versus Conventional Radiotherapy for Painful Bone Metastases (ROBOMET): A Multicenter, Patient-Blinded Randomized Clinical Trial.

To test whether dose-escalated single fraction (SF) stereotactic body radiotherapy (SBRT) of 20 Gy to painful bone metastases is superior to conventional SF three-dimensional (3D) conformal radiotherapy (RT) to a standard dose of 8 Gy in achieving complete pain response (CR). A single-blind, randomized, controlled, phase III trial (ROBOMET) included 126 patients with up to three painful bone metastases, randomly assigned between April 2019 and October 2022 at multiple centers in Belgium. Inclusion criteria were uncomplicated painful bone metastases (worst pain score ≥2 on a 0-10 pain scale) arising from a solid tumor. Treatment consisted of either a single SBRT fraction of 20 Gy or a single conventional RT fraction of 8 Gy. The primary end point was the proportion of patients with a CR 1 month after RT scored according to the International Consensus on Palliative Radiotherapy Endpoints analyzed as per an intention-to-treat principle. After 1 month, 16 of 63 (25% [95% CI, 15 to 38]) patients treated with conventional RT achieved CR versus 23 of 63 (37% [95% CI, 25 to 50]) treated with SBRT (P = .25). After 3 months, 15 of 63 (24% [95% CI, 14 to 36]) patients achieved CR after conventional RT versus 21 of 63 (33% [95% CI, 22 to 46]) after SBRT (P = .32). Among patients evaluable after 3 months and treated per protocol, the SBRT group had more complete responders (21/39, 54% [95% CI, 37 to 70]) than the conventional RT group (15/48, 31% [95% CI, 19 to 46]; P = .048). SBRT failed to demonstrate improved CR rates after 1 month.

International Consensus on Reporting Anastomotic Leaks After Colorectal Cancer Surgery: The CoReAL Reporting Framework.

Anastomotic leak frequently complicates colorectal anastomoses with high morbidity and mortality. The substantial variability in published leak rates reflects the lack of consistency in reporting variables that may impact the occurrence, management, short and long-term outcomes of patients. The Consensus for Reporting of colorectal Anastomotic Leaks is an international collaborative that developed a standardized evidence-based framework for reporting key variables related to the entire episode of colorectal anastomotic leak in cancer patients. Along the preoperative, intraoperative, short- and long-term postoperative phases of a left-sided colorectal anastomotic leak, key questions regarding all potentially relevant variables were formulated. A literature review was conducted to generate evidence-based statements in response to these questions. Statements that reached consensus, together with input from patients' experience and experts' opinion, were incorporated into the framework as reporting elements. Modified Delphi methodology, including online voting and an in-person consensus meeting, was used to generate consensus statements based on the literature review, and to develop the reporting framework. An international panel of 32 colorectal surgeons with expertise in the field of colorectal anastomotic leaks, representing 6 surgical societies, along with radiologists, research collaborators, patients, healthcare economists and surgical trial methodologists. Evidence-based statements and reporting elements with >70% agreement were included. Consensus among experts was achieved on 33 evidence-based statements and 43 reporting elements for the CoReAL framework. The reporting elements encompassed evidence-based statements (27), patient perspectives (7), as well as expert opinion (9). Sampling did not represent all regions in the world. Because of the paucity of evidence for some topics, evidence-based statements were primarily based on moderate to low level of evidence. This international consensus provides an evidence-based standardized framework for reporting of key variables related to a colorectal anastomotic leak following oncologic resection. See Video Abstract.

Detection of antinuclear antibodies: a survey done by the European Organsation for External Quality Assurance Providers in Laboratory Medicine.

A questionnaire was sent to immunology laboratories worldwide by the European Organisation for External Quality Assurance Providers in Laboratory Medicine to evaluate current practice with regard to how antinuclear antibodies (ANAs) are routinely tested in clinical laboratories. In total, 494 questionnaires were returned from 44 countries. Of these, 379 provided sufficient information to be included in the analysis. Indirect immunofluorescence on HEp-2 cells is still the most common method to test ANAs and is used by 330 of our 379 respondents. The most common (60%) screening dilution is 1:80, followed by 1:160 (15%) and, in equal amounts, 1:40 and 1:100 (8% each). In most laboratories, ANA-positive samples are further diluted to an end titer of 1:1280 (40%), 1:2560 (21%), 1:5120 (16%), or 1:640 (19%). An increasing number of laboratories (178/330) use the International Consensus on ANA Patterns (ICAP) nomenclature to describe the immunofluorescence pattern on HEp-2 cells. In countries with the most respondents, the percentage of laboratories accredited to EN International Organization for Standardization (ISO) 15189 (in Britain, BS EN ISO 15189, which is a British standard as well as a European standard as well as an ISO standard with identical content) is between 8% (Belgium) and 60% (France). There was no difference in the portion of accredited laboratories between university hospitals, nonuniversity hospitals, and private laboratories. Indirect immunofluorescence continues to be the most frequently used technique for ANA testing in laboratories. The increasing number of laboratories using the ICAP classification reflects an ongoing harmonization of describing ANA patterns on HEp-2 cell substrates.

Current Concepts in Histiocytic Neoplasms.

Histiocytic neoplasms are a diverse group of disorders arising from macrophages, dendritic cells, and monocytes of the mononuclear phagocyte system. These neoplasms encompass a clinical spectrum from indolent, self-limited, and localized conditions to highly aggressive malignancies. Since the publication of the Revised Fourth Edition of the World Health Organization (WHO) classification, advances in molecular diagnostics have improved our understanding of the pathogenesis and classification of these disorders. In contrast to the Revised Fourth Edition, the International Consensus Classification (ICC) now recognizes Rosai-Dorfman-Destombes disease as a neoplastic disorder and introduces ALK-positive histiocytosis as a distinct entity. This manuscript reviews the current concepts regarding histiocytic neoplasms, focusing on the diagnostic criteria recommended by the ICC based on histopathology, immunophenotype, molecular alterations, as well as clinical and imaging characteristics.

Validation of the 5th edition of the World Health Organization and International Consensus Classification guidelines for TP53-mutated myeloid neoplasm in an independent international cohort

The World Health Organization (WHO-5) and International Consensus Classification (ICC) acknowledge the poor prognosis of TP53-mutated (TP53mut) myeloid neoplasm (MN). However, there are substantial differences between the two classifications that may lead to under- or overestimation of the prognostic risk. We retrospectively applied WHO-5 and ICC to 603 MN cases harboring TP53mut (variant allele frequency, VAF ≥ 2%). WHO-5 and ICC would not classify 64% and 20% of these cases as TP53mut MN, respectively. Moreover, of those classified, 67.5% would be classified discrepantly. Primary drivers of discrepancies included: (i) prognostic importance of TP53mut acute myeloid leukemia (AML), (ii) interaction of the blast percentage and allelic status, (iii) 17p.13.1 deletion detected by cytogenetics, (iv) complex karyotype (CK) as multi-hit equivalent, and (v) TP53mut VAF threshold, we analyzed survival outcomes of each of these groups with an aim to provide clarity. TP53mut AML was associated with significantly poor survival compared to TP53-wild type TP53wt AML, myelodysplasia-related (AML, MR 4.7 vs. 18.3 months; P < 0.0001), supporting its inclusion within TP53mut MN as a distinct subentity. Secondly, the survival of TP53mut with blast 10–19% was poor regardless of the allelic status. Thirdly, for cases with a single TP53mut with VAF < 50%, 17p13.1 del or CK serve as practical surrogates of biallelic inactivation, obviating the need for an additional copy number analysis. Finally, TP53mut AML, MDS multi-hit/multi-hit equivalent with VAF < 10% had significantly poorer survival compared to TP53mut MDS VAF < 10% without CK and 17p del, and were comparable to those with VAF ≥ 10% (14.1 vs. 48.8 vs.7.8 months, P < 0.0001). Collectively, these findings address key areas of contention and provide valuable insights that will guide future revisions of the WHO and ICC classifications.

Prevalence and Development of Cachexia Before and After Diagnosis of Non-small Cell Lung Cancer.

Cachexia is commonly defined based on weight loss at the time of cancer diagnosis. However, regular weight measurements before cancer diagnosis are often lacking and may be subject to recall bias if retrospectively self-reported by patients. To analyze the development and progression of cachexia, we employ body weight trajectories from 1 year before and after diagnosis of non-small cell lung cancer (NSCLC). We hypothesized that cachexia could be detected as early as 1 year before NSCLC diagnosis and that cachexia prevalence would increase in the year following diagnosis. This retrospective study included consecutive patients with NSCLC treated at UTSW between 2005 and 2019 who had body weight measurements before and after NSCLC diagnosis recorded in their electronic health records. Weights were binned in 3-month intervals. Cachexia was defined per the International Consensus Definition of cachexia, that is, loss of >5% body weight 12 months preceding cancer diagnosis for patients with BMI ≥20kg/m2 or weight loss of >2% for patients with a BMI <20kg/m2. The association of disease stage and primary treatment with weight changes was investigated. Among 4294 patients screened, 661 patients were included in the final analysis. Patients had a mean age of 69.3 (SD: 10.6) years, and a majority were current/former smokers (83%), identified as white (76%), and were diagnosed with either stage I (47%) or stage IV (28%) nonsquamous NSCLC (78%). At cancer diagnosis, 28% (n=183) presented with cachexia, having incurred a mean loss of 8.6 (SEM: 0.4%) (P<0.0001) of body weight within the year before cancer diagnosis. Weight loss after cancer diagnosis was comparable in patients with and without cachexia at cancer diagnosis (P=0.05). By 12 months postcancer diagnosis, 58% of patients (n=383) met the criteria for cachexia based on weight loss. Weight loss consistent with cachexia occurred over a median period of 220 (IQR: 265) days. Weight loss in patients with cachexia at NSCLC diagnosis may commence as early as 12 months before cancer diagnosis. Within a year after a cancer diagnosis, more than half of patients develop cachexia, particularly those with advanced disease. These findings support the integration of early nutritional and pharmacological interventions in patients with NSCLC.

Pregnancy After Bariatric Surgery: A Comparison of Antenatal Care Practices With the 2019 International Consensus Recommendations in Queensland, Australia.

Clinical practice guidelines recommend additional monitoring in pregnancy for women post-bariatric surgery, to reduce the risk of maternal and infant complications. To examine if pregnancy care post-bariatric surgery at an Australian quaternary public hospital is consistent with guidelines and to report on perinatal outcomes. A retrospective audit of medical records and perinatal outcomes from post-bariatric surgery pregnancies from June 2016 to February 2021 was completed. Micronutrient monitoring and supplementation practices, gestational diabetes mellitus (GDM) screening, gestational weight gain (GWG) and fetal growth (FG) monitoring were compared with guidelines. Perinatal outcomes were compared with Queensland and Australian population data. Eighty-three women meeting the inclusion criteria delivered 86 infants. Twenty percent (n = 16) had recommended GDM screening, 86% (n = 71) recommended FG monitoring at 12-weeks and 98% (n = 81) at 20-weeks, but only 24% (n = 20) had monthly monitoring from viability. GWG monitoring was 95% (n = 79) in the second trimester and 94% (n = 78) in the third trimester. Monitoring rates were highest for iron, and lowest for copper and selenium. Adverse infant outcomes for length of stay, neonatal intensive and special care admissions and caesarean section were significantly higher than the Queensland and Australian populations (all p < 0.05). Adherence with consensus recommendations aligning to standard antenatal monitoring for the general population was high, but additional monitoring for post-bariatric surgery specific care was lower. The evidence suggesting increased rates of adverse perinatal outcomes highlights the importance of consistency and adherence with post-bariatric surgery specific care for this group during pregnancy.

The acyl glucuronide of 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid: Synthesis, structural assignment, occurrence as a human phase II metabolite of Uvinul® A Plus and acute aquatic toxicity.

The acyl glucuronide of 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid: Synthesis, structural assignment, occurrence as a human phase II metabolite of Uvinul® A Plus and acute aquatic toxicity.

Safety of Janus kinase inhibitors in immune-mediated inflammatory diseases - a systematic literature review informing the 2024 update of an international expert consensus statement.

This systematic literature review (SLR) on safety outcomes was performed to inform the 2024 update of the expert consensus statement on the treatment of immune-mediated inflammatory diseases (IMIDs) with Janus kinase inhibitors (JAKi). An update of the 2019 SLR was performed in MEDLINE, Embase, and the Cochrane Library. For safety, randomised, placebo-controlled or active-controlled trials on all JAKi investigated in IMIDs, long-term extension (LTE) studies, pooled trial data analyses, and cohort and claims studies were included. We screened 13,905 records, of which 209 were finally included. Three safety trials and 13 post hoc analyses, 83 efficacy randomised controlled trials (RCTs) with adequate safety reporting, 56 integrated safety analyses and LTE of RCTs, 20 additional conference abstracts on RCT data, as well as 37 real-world cohort studies were presented to the task force. Safety profiles of JAKi were overall consistent across compounds and indications, but impacts of patient profiles, treatment dosing, and other cofactors like background medications on drug safety could be observed. Furthermore, differential effects of variously selective JAKi on distinct adverse events of special interest (AESI) and laboratory outcomes were discerned. A substantial amount of literature was published on JAKi safety since 2019. A comprehensive overview of these data supports the optimal use of JAKi in patients with IMIDs, by consideration and balance of their benefits as well as risks in every patient.

THU-275 Terminology, diagnosis and management of primary biliary cholangitis-autoimmune hepatitis variant syndrome (PBC-AIH): results from an international Delphi consensus process

THU-275 Terminology, diagnosis and management of primary biliary cholangitis-autoimmune hepatitis variant syndrome (PBC-AIH): results from an international Delphi consensus process

Status update of NASAs assessment of the biological contamination threat of crewed mars surface missions.

Status update of NASAs assessment of the biological contamination threat of crewed mars surface missions.