Antibodies and complement are key drivers of thrombosis.

Venous thromboembolism (VTE) is a common, deadly disease with an increasing incidence despite preventive efforts. Clinical observations have associated elevated antibody concentrations or antibody-based therapies with thrombotic events. However, how antibodies contribute to thrombosis is unknown. Here, we show that reduced blood flow enabled immunoglobulin M (IgM) to bind to FcµR and the polymeric immunoglobulin receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently, the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent IgG deposition. This leads to classical complement activation, setting in motion a prothrombotic vicious circle. Key elements of this mechanism were present in humans in the setting of venous stasis as well as in the dysregulated immunothrombosis of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically targeting complement. Hence, our results uncover antibodies as previously unrecognized central regulators of thrombosis. These findings carry relevance for therapeutic application of antibodies and open innovative avenues to target thrombosis without compromising hemostasis.

DNA methylation controls stemness of astrocytes in health and ischaemia.

Astrocytes are the most abundant cell type in the mammalian brain and provide structural and metabolic support to neurons, regulate synapses and become reactive after injury and disease. However, a small subset of astrocytes settles in specialized areas of the adult brain where these astrocytes instead actively generate differentiated neuronal and glial progeny and are therefore referred to as neural stem cells1-3. Common parenchymal astrocytes and quiescent neural stem cells share similar transcriptomes despite their very distinct functions4-6. Thus, how stem cell activity is molecularly encoded remains unknown. Here we examine the transcriptome, chromatin accessibility and methylome of neural stem cells and their progeny, and of astrocytes from the striatum and cortex in the healthy and ischaemic adult mouse brain. We identify distinct methylation profiles associated with either astrocyte or stem cell function. Stem cell function is mediated by methylation of astrocyte genes and demethylation of stem cell genes that are expressed later. Ischaemic injury to the brain induces gain of stemness in striatal astrocytes7. We show that this response involves reprogramming the astrocyte methylome to a stem cell methylome and is absent if the de novo methyltransferase DNMT3A is missing. Overall, we unveil DNA methylation as a promising target for regenerative medicine.

Choice of Acromioclavicular Dislocation Treatment Should Not Be Influenced by Risk of Development of Acromioclavicular Osteoarthritis: A Systematic Review With Meta-Analysis.

BACKGROUND: It is currently unknown to what degree surgical or nonoperative treatment of acromioclavicular (AC) dislocation influences the development of osteoarthritis (OA). The aim of this study was to evaluate AC OA after surgical and nonoperative treatment for AC dislocations, compare OA prevalence between treatment options, and compare OA prevalence between the injured and contralateral shoulder. METHODS: Articles reporting on the prevalence of OA after surgical or nonoperative treatment of an AC dislocation with a minimal 2-year follow-up were included. AC OA presence was extracted for the injured and contralateral shoulder. Treatment categories were defined based on anatomical variation in the reattachment of ligaments: AC fixation, coracoclavicular (CC) fixation, AC and CC fixation, Bosworth screw synthetic graft, tendon graft, and conservative. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. RESULTS: Ninety-four articles were included for qualitative analysis, and 7 articles were included for meta-analysis (n = 3,812; follow-up = 2.0-24.2 years; mean age 37.6 ± 10.4 years). A total of 3,483 patients underwent surgical treatment, and 329 patients underwent conservative treatment. OA prevalence ranged from 6.7%-29.3% between 7 pooled treatment categories. Most included studies had a follow-up <10 years (94%) and OA prevalence increased with time, regardless of treatment option. There was no difference in OA prevalence between the injured and contralateral shoulder (p = 0.120). MINORS scores were varied, ranging from poor to very good. CONCLUSION: The pooled AC OA prevalence of the 7 treatment categories ranged from 6.7% for the CC fixation surgical group to 29.3% for the conservative treatment group. However, the included studies were predominantly of low quality and had varying follow-up periods, with most having relatively short follow-up durations. No difference in AC OA prevalence was found between the injured and contralateral shoulder. Based on the available evidence, treatment choice for AC dislocation should not be influenced by the potential development of AC AO. LEVEL OF EVIDENCE: Level IV. See Instructions for Authors for a complete description of levels of evidence.

Determinants of pain intensity and magnitude of incapability more than two years after arthroscopic Bankart repair for anterior shoulder instability.

Background: Individuals treated with arthroscopic Bankart repair after anterior shoulder dislocations experience varied discomfort and incapability. The aim of this study was to determine the relative association of mental health and physical health factors with 1) magnitude of capability and 2) pain intensity 2 or more years after surgery. Methods: This cross-sectional study evaluated 80 military patients that experienced one or more traumatic anterior shoulder dislocations a minimum of 2 years after arthroscopic Bankart repair without remplissage. We measured capability (Oxford Shoulder Instability Score), pain intensity using an 11-point ordinal scale, symptoms of anxiety (Generalized Anxiety Disorder-2 questionnaire), symptoms of depression (Patient Health Questionnaire-2), catastrophic thinking (Pain Catastrophizing Scale-4), and kinesiophobia (Tampa scale for kinesiophobia-4). We also identified preoperative presence of a Hill-Sachs lesion on radiographs and postoperative occurrence of subluxation or a dislocation episode. A negative binominal regression analysis sought factors associated with magnitude of incapability and pain intensity. Results: Greater incapability was strongly associated with both greater kinesiophobia (Regression Coefficient [RC] = -0.50; 95% confidence interval [CI] = -0.73 to -0.26; P ≤ .01) and repeat surgery (RC = -0.27; 95% CI = -0.41 to -0.13; P ≤ .01). Greater pain intensity was only strongly associated with greater kinesiophobia (RC = 0.25; 95% CI = 0.039 to 0.46; P = .021). Conclusion: The observation that greater unhelpful thinking is associated with greater pain intensity and greater magnitude of incapability after a Bankart repair for anterior shoulder instability, whereas pathophysiological factors such as glenoid bone loss were not, emphasizes the degree to which mindset is associated with musculoskeletal health.

Type of fixation is not associated with range of motion after operative treatment of proximal radius fractures- a systematic review of 519 patients.

Background: The aims of this study are 1) to assess whether open reduction internal fixation (ORIF) techniques for fractures of the proximal radius are associated with the range of motion (ROM), 2) to determine the incidence of hardware-related complications and removal following plate and screw fixation of the proximal radius, and 3) to evaluate whether the safe-zone definition is described in the literature and its relation to the ROM. Methods: A literature search was performed in the PubMed, Embase, and Cochrane databases. Studies reporting ROM in patients undergoing ORIF for radial head or neck fractures were included. Two treatment groups were defined based on ORIF technique: screws only or plates with and without additional screw placement. Results: A total of 13 articles were included with 519 patients, of which 271 belonged to the screw group and 248 to the plate group. At final follow-up, the screw group reported a mean supination of 79 (95% CI: 74-83), pronation of 76 (95% CI: 69-84), flexion of 131 (95% CI: 124-138), and loss of extension of 4 (95% CI: 1-7). The plate group reported a mean supination of 72 (95% CI: 65-80), pronation of 697 (95% CI: 60-75), flexion of 126 (95% CI: 118-133), and loss of extension of 7 (95% CI: 1-14). Conclusion: Predominantly retrospective studies show that the ROM seems similar for screw and plate osteosynthesis of proximal radius fractures. Complication rates are similar as well. The safe-zone definition is rarely reported.

Patient-Reported Outcome Measures Show No Relevant Change Between 1-year and 2-year Follow-Up Following Treatment for Anterior Shoulder Instability: a Systematic Review.

PURPOSE: The primary aim of this study was to compare patient-reported outcome measures (PROMs) at 1-year and 2-year follow-up following treatment for anterior shoulder instability. METHODS: Randomized controlled trials and prospective studies that evaluated and reported PROMs following a capsulolabral repair (with or without remplissage), bone augmentation or non-operative treatment to treat anterior shoulder instability at both 1-year and 2-year follow-up were included. PROMs were compared between 1-year and 2-year follow-up, forest plots with mean difference were created to compare baseline, 1-year and 2-year follow-up and scatterplots were created to visualize clinical improvement over time. RESULTS: Fourteen studies, comprising 923 patients, with level of evidence I and II were included. Nine PROMs, of which predominantly the Western Ontario Shoulder Instability Index (WOSI; 11 studies; 79%), were evaluated. Minimal to no statistically significant change in WOSI, Oxford Shoulder Instability Score (OSIS), American Shoulder and Elbow Surgeons (ASES), Subjective Shoulder Value (SSV), Simple Shoulder Test (SST), Disabilities of Arm, Shoulder, and Hand (DASH), Quick DASH, Single Assessment Numeric Evaluation (SANE) or Visual Analogue Scale (VAS) was observed between 1-year and 2-year follow-up. Pooling of the WOSI, OSIS, ASES and SANE demonstrated improvement from baseline to 1-year follow-up and minimal to no change between 1-year and 2-year follow-up. Scatterplots of the WOSI and ASES demonstrated the most improvement within 6 months and no clear improvement after 1-year follow-up. Recurrence rates increased with time but varied between studies. CONCLUSION: In contrast to recurrence rates which have been shown to increase with time, minimal to no statistically significant change was observed for any of the included PROMs between 1-year and 2-year follow-up. This finding questions whether it is necessary to evaluate PROMs in long term follow-up of patients following shoulder stabilization treatment. LEVEL OF EVIDENCE: Level II, systematic review of Level I - II studies.

Reference ranges of peripheral-muscle oxygenation in term neonates delivered by Caesarean section during immediate transition after birth.

AIM: To establish reference ranges of peripheral-muscle regional oxygen saturation (prSO2) and peripheral fractional tissue oxygen extraction (pFTOE) during the first 15 min after birth in stable term neonates. METHODS: Secondary outcome parameters of prospective observational studies in healthy term neonates delivered by Caesarean section were analysed. prSO2 was measured on the right forearm using the INVOS 5100C monitor. pFTOE was calculated out of prSO2 and arterial oxygen saturation (SpO2). Centile charts (10th-90th) of prSO2 and pFTOE were defined during the first 15 min after birth. RESULTS: Three-hundred-five term neonates with a mean gestational age and birth weight of 39.0 ± 0.9 weeks and 3321 ± 454 g, respectively, were included. The 50th centiles of prSO2 were 39% (minute two), 52% (minute five), 71% (minute 10), and 73% (minute 15). The 50th centiles of pFTOE were 0.529 (minute two), 0.378 (minute five), 0.237 (minute 10), and 0.231 (minute 15). CONCLUSION: Reference ranges of prSO2 and pFTOE were established for term neonates delivered by Caesarean section during the immediate transition after birth. These reference ranges increase knowledge of physiological processes taking place immediately after birth and are necessary for possible future clinical applications.

Substantial variability in what is considered important in the radiological report for anterior shoulder instability: a Delphi study with Dutch musculoskeletal radiologists and orthopedic surgeons.

Background: Standardized consensus-based radiological reports for shoulder instability may improve clinical quality, reduce heterogeneity, and reduce workload. Therefore, the aim of this study was to determine important elements for the x-ray, magnetic resonance imaging (MRI) arthrography (MRA), and computed tomography (CT) report, the extent of variability, and important MRI views and settings. Methods: An expert panel of musculoskeletal radiologists and orthopedic surgeons was recruited in a three-round Delphi design. Important elements were identified for the x-ray, MRA, and CT report and important MRI views and setting. These were rated on a 0-9 Likert scale. High variability was defined as at least one score between 1-3 and 7-9. Consensus was reached when ≥80% scored an element 1-3 or 7-9. Results: The expert panel consisted of 21 musculoskeletal radiologists and 15 orthopedic surgeons. The number of elements identified in the first round was seventeen for the x-ray report, 52 for MRA, 21 for CT, and 23 for the MRI protocol. The number of elements that reached consensus was five for x-ray, twenty for MRA, nine for CT, and two for the MRI protocol. High variability was observed in 76.5% (n = 13) x-ray elements, 85.0% (n = 45) MRA, 76.2% (n = 16) CT, and 85.7% (n = 18) MRI protocol. Conclusion: Substantial variability was observed in the scoring of important elements in the radiological for the evaluation of anterior shoulder instability, regardless of modality. Consensus was reached for five elements in the x-ray report, twenty in the MRA report, and nine in the CT report. Finally, consensus was reached on two elements regarding MRA views and settings.

Peripheral arterial catheters in extremely preterm infants born at less than 28 weeks of gestation-a single-center experience.

The aim of this study was to perform a retrospective data analysis of established peripheral artery catheters (pAC) in extremely preterm infants. The primary outcome was the pAC life span and its correlation to gestational age, birth weight, localizations, and pAC removal. Retrospective data analysis of electronic patient records of all extremely preterm infants (born less than 28 weeks gestation) admitted to the neonatal intensive care unit in Graz (Austria) between January 2014 and December 2020. A total of 196 preterm infants with a median (IQR) gestational age of 25.7 (24.6-26.6) weeks and a birth weight of 730 (614-898) g were included. In 155 (79%) of these preterm infants, 286 pAC and six umbilical artery catheters were inserted successfully. The first pAC was inserted 2.5 (1.4-7.4) h after birth, and the median pAC life span was 57.5 (22.-107.2) h. Gestational age, birth weight, and catheter localization did not correlate with the pAC life span. The pAC localizations were the radial artery (63%), tibial posterior artery (21%), ulnar artery (6%), dorsal artery of the foot (6%), others (1%), and not documented (3%). Adverse reactions including temporarily impaired peripheral perfusion, local inflammation, extravasation, or bleeding were reported in 13% of all pAC, but none of these resulted in long-term sequelae. A median (IQR) of 9 (5-18) arterial blood samples were drawn via pAC, resulting in a notable reduction of pain stimuli.Conclusion: The use of pAC in extremely preterm infants is feasible and safe. Neither gestational age, birth weight nor localization did affect the life span of pAC. No long-term sequelae were observed, and pain events were reduced by using pAC for blood drawing. What is Known: • Peripheral artery catheters can be used for continuous blood pressure measurement and blood draw even in extremely preterm infants. • (Severe) adverse reactions such as bleeding, necrosis, or amputation occur between 1 and 4%. • What is New: • The median peripheral arty catheter life span is 58 h and is not affected by gestational age, birth weight, nor localization. • A median of nine blood samples can be taken per each single pAC and, therefore, prevent pain events in extremely preterm infants.

Analyzing single-cell bisulfite sequencing data with MethSCAn.

Single-cell bisulfite sequencing (scBS) is a technique that enables the assessment of DNA methylation at single-base pair and single-cell resolution. The analysis of large datasets obtained from scBS requires preprocessing to reduce the data size, improve the signal-to-noise ratio and provide interpretability. Typically, this is achieved by dividing the genome into large tiles and averaging the methylation signals within each tile. Here we demonstrate that this coarse-graining approach can lead to signal dilution. We propose improved strategies to identify more informative regions for methylation quantification and a more accurate quantitation method than simple averaging. Our approach enables better discrimination of cell types and other features of interest and reduces the need for large numbers of cells. We also present an approach to detect differentially methylated regions between groups of cells and demonstrate its ability to identify biologically meaningful regions that are associated with genes involved in the core functions of specific cell types. Finally, we present the software tool MethSCAn for scBS data analysis ( https://anders-biostat.github.io/MethSCAn ).

Post-transplant-cyclophosphamide and short-term Everolimus as graft-versus-host-prophylaxis in patients with relapsed/refractory lymphoma and myeloma-Final results of the phase II OCTET-EVER trial.

BACKGROUND: Conditioning regimens and the choice of immunosuppression have substantial impact on immune reconstitution after allogeneic hematopoietic stem cell transplantation (aHSCT). The pivotal mechanism to maintain remission is the induction of the graft-versus-tumor effect. Relapse as well as graft versus host disease remain common. Classic immunosuppressive strategies implementing calcineurin inhibitors (CNI) have significant toxicities, hamper the immune recovery, and reduce the anti-cancer immune response. METHODS: We designed a phase II clinical trial for patients with relapsed and refractory lymphoid malignancies undergoing aHSCT using a CNI-free approach consisting of post-transplant cyclophosphamide (PTCy) and short-term Everolimus after reduced-intensity conditioning and matched peripheral blood stem cell transplantation. The results of the 19 planned patients are presented. Primary endpoint is the cumulative incidence and severity of acute GvHD. RESULTS: Overall incidence of acute GvHD was 53% with no grade III or IV. Cumulative incidence of NRM at 1, 2, and 4 years was 11%, 11%, and 16%, respectively, with a median follow-up of 43 months. Cumulative incidence of relapse was 32%, 32%, and 42% at 1, 2, and 4 years after transplant, respectively. Four out of six early relapses were multiple myeloma patients. Overall survival was 79%, 74%, and 62% at 1, 2, and 4 years. GvHD-relapse-free-survival was 47% after 3 years. CONCLUSIONS: Using PTCy and short-term Everolimus is safe with low rates of aGvHD and no severe aGvHD or cGvHD translating into a low rate of non-relapse mortality. Our results in this difficult to treat patient population are encouraging and warrant further studies.

Statistical shape models that predict native glenoid width based on glenoid height are inaccurate in their current form: a cross-sectional study.

BACKGROUND: The extent of measurement errors of statistical shape models that predict native glenoid width based on glenoid height to subsequently determine the amount of anterior glenoid bone loss is unclear. Therefore, the aim of this study was to (1) create a statistical shape model based on glenoid height and width measured on 3-dimensional computed tomography (3D-CT) and determine the accuracy through measurement errors and (2) determine measurement errors of existing 3D-CT statistical shape models. MATERIALS AND METHODS: A retrospective cross-sectional study included all consecutive patients who underwent CT imaging before undergoing primary surgical treatment of traumatic anterior shoulder dislocation between 2007 and 2022 at the Tohoku University Hospital and affiliated hospitals. Patients were included when instability was unilateral and CT scans of both the injured and contralateral uninjured shoulder were available. 3D segmentations were created and glenoid height and width of the injured and contralateral uninjured side (gold standard) were measured. Accuracy was determined through measurement errors, which were defined as a percentage error deviation from native glenoid width (contralateral uninjured glenoid), calculated as follows: measurement error = [(estimated glenoid width with a statistical shape model - native glenoid width) / native glenoid width] × 100%. A linear regression analysis was performed to create a statistical shape model based on glenoid height according to the formula: native glenoid width = a × glenoid height + b. RESULTS: The diagnosis and procedure codes identified 105 patients, of which 69 (66%) were eligible for inclusion. Glenoid height demonstrated a very strong correlation (r = 0.80) with native glenoid width. The linear regression formula based on this cohort was as follows: native glenoid width = 0.75 × glenoid height - 0.61, and it demonstrated an absolute average measurement error of 5% ± 4%. The formulas by Giles et al, Chen et al and Rayes et al demonstrated absolute average measurement errors of 10% ± 7%, 6% ± 5%, and 9% ± 6%, respectively. CONCLUSION: Statistical shape models that estimate native glenoid width based on glenoid height demonstrate unacceptable measurement errors, despite a high correlation. Therefore, great caution is advised when using these models to determine glenoid bone loss percentage. To minimize errors caused by morphologic differences, preference goes to methods that use the contralateral side as reference.

Disequilibrium reaction pathways and the twin-mediated growth of tabular forsterite during contact metamorphism of quartz-bearing dolomite.

The forsterite zone of the Ubehebe Peak contact aureole, Death Valley, USA consists of an outer zone of tabular/jack-straw olivine and an inner zone of subequant polyhedral olivine. Subequant polyhedral forsterite crystals close to the intrusion are small and tabular forsterite crystals farther away are larger. To investigate the formation of the two morphologies, forsterite growth experiments were conducted in cold seal pressure vessels in the CaO-MgO-SiO2-CO2-H2O system. Forsterite precipitation follows a disequilibrium reaction pathway made of three reactions: [1] tabular forsterite growth from quartz and dolomite, [2] forsterite growth from tremolite dissolution, and [3] subequant polyhedral forsterite growth from tabular forsterite dissolution. Initially, quartz reacts with dolomite to simultaneously form twinned tabular forsterite and tremolite. As quartz reacts away, forsterite precipitation continues at a slower rate through tremolite dissolution. A second generation of forsterite then precipitates on top of some tabular forsterite but has different habit and tracht. Once all the tremolite reacts away, subequant polyhedral forsterite precipitation continues at an even slower rate through dissolution of tabular forsterite. The tabular morphology of jack-straw olivine is a consequence of twin-mediated unidirectional growth; the abundance of twins being due to rapid nucleation and growth at initially high reaction affinities. Twin junctions are preferential nucleation centers for steps, so faceted growth is enhanced on {100}. This phenomenon is the twin plane re-entrant effect. Subequant polyhedral forsterite in the Ubehebe Peak inner contact aureole recrystallized and ripened from tabular forsterite. In the outer contact aureole, conditions were not conducive to recrystallization and ripening so well-developed tabular forsterite persists.

Triggered contraction of self-assembled micron-scale DNA nanotube rings.

Contractile rings are formed from cytoskeletal filaments during cell division. Ring formation is induced by specific crosslinkers, while contraction is typically associated with motor protein activity. Here, we engineer DNA nanotubes and peptide-functionalized starPEG constructs as synthetic crosslinkers to mimic this process. The crosslinker induces bundling of ten to hundred DNA nanotubes into closed micron-scale rings in a one-pot self-assembly process yielding several thousand rings per microliter. Molecular dynamics simulations reproduce the detailed architectural properties of the DNA rings observed in electron microscopy. Theory and simulations predict DNA ring contraction - without motor proteins - providing mechanistic insights into the parameter space relevant for efficient nanotube sliding. In agreement between simulation and experiment, we obtain ring contraction to less than half of the initial ring diameter. DNA-based contractile rings hold promise for an artificial division machinery or contractile muscle-like materials.

Minimal but potentially clinically relevant anteroinferior position of the humeral head following traumatic anterior shoulder dislocations: A 3D-CT analysis.

In unstable shoulders, excessive anteroinferior position of the humeral head relative to the glenoid can lead to a dislocation. Measuring humeral head position could therefore be valuable in quantifying shoulder laxity. The aim of this study was to measure (1) position of the humeral head relative to the glenoid and (2) joint space thickness during passive motion in unstable shoulders caused by traumatic anterior dislocations and in contralateral uninjured shoulders. A prospective cross-sectional CT-study was performed in patients with unilateral anterior shoulder instability. Patients underwent CT scanning of both injured and uninjured side in supine position (0° abduction and 0° external rotation) and in 60°, 90°, and 120° of abduction with 90° of external rotation without an external load. Subsequently, 3D virtual models were created of the humerus and the scapula to create a glenoid coordinate system to identify poster-anterior, inferior-superior, and lateral-medial position of the humeral head relative to the glenoid. Joint space thickness was defined as the average distance between the subchondral bone surfaces of the humeral head and glenoid. Fifteen consecutive patients were included. In supine position, the humeral head was positioned more anteriorly (p = 0.004), inferiorly (p = 0.019), and laterally (p = 0.021) in the injured compared to the uninjured shoulder. No differences were observed in any of the other positions. A joint-space thickness map, showing the bone-to-bone distances, identified the Hill-Sachs lesion footprint on the glenoid surface in external rotation and abduction, but no differences on average joint space thickness were observed in any position.

High variability in what is considered important to report following instability surgery: a Delphi study among Dutch shoulder specialists.

Background: Standardized reporting leads to high-quality data and can reduce administration time. The aim of this study was to (1) get an insight into the variability of what is considered important to report in the surgical report following shoulder instability surgery and (2) determine which elements should be included in the surgical report following shoulder instability surgery according to Dutch surgeons using a Delphi method. Methods: Dutch orthopedic shoulder surgeons were included in a panel for a Delphi study consisting of 3 rounds. Importance of the elements was rated on a 9-point Likert scale. High variability was defined as an element that received at least 1 score between 1 and 3 and 1 score between 7 and 9 in round 3. Consensus was defined as ≥80% of the panel giving a score of 7 or more. Results: Seventeen shoulder specialists completed all 3 rounds and identified a total of 82 elements for the arthroscopic Bankart repair and 60 for the open Latarjet. High variability was observed in 57 (70%) and 52 (87%) of the elements, respectively. After round 3, the panel reached consensus on 27 and 11 elements that should be mentioned in the surgical report following arthroscopic Bankart repair and open Latarjet. Conclusion: There is high variability in what shoulder specialists regard essential to report. Consensus was reached on 27 and 11 elements to be reported following arthroscopic Bankart repair and open Latarjet, respectively. Future studies on an international scale can further improve data collection and communication between specialists.

A modified Delphi study to identify which items should be evaluated in shoulder instability research: a first step in developing a core outcome set.

Background: The aim of this study was to identify items that healthcare providers and/or patients consider important to include in a questionnaire for clinical trials and cohort studies in shoulder instability research. This could serve as a basis to develop a core outcome set for shoulder instability research. Methods: Healthcare providers and patients were included in a panel for a modified Delphi consensus study. The study consisted of three rounds, comprising (1) identifying items, (2) rating the importance of the items, and (3) rating the importance again after seeing a summary of the results of round two. Importance was rated on a 9-point Likert scale. Consensus was defined as ≥ 80% of the panel giving a score of 7 or higher. Results: In total, 44 healthcare providers and 30 patients completed all three rounds. Round one identified 54 items. After round three, the panel reached a consensus on 11 items that should be included in a questionnaire, comprising re-dislocation (99%), instable feeling of the shoulder (96%), limitations during sport (93%), patient satisfaction with the shoulder (93%), fear/anxiety for re-dislocation (91%), range of motion (88%), return to old level of functioning (85%), performing daily activities (85%), return to sport (82%), return to work (82%), and trusting the shoulder (81%). Conclusion: Healthcare providers and patients reached a consensus on 11 items that should be included in a questionnaire for shoulder instability research. These items can facilitate design and development of future clinical trials and form the basis for the development of a core outcome set.