High-threshold and low-overhead fault-tolerant quantum memory.

The accumulation of physical errors1-3 prevents the execution of large-scale algorithms in current quantum computers. Quantum error correction4 promises a solution by encoding k logical qubits onto a larger number n of physical qubits, such that the physical errors are suppressed enough to allow running a desired computation with tolerable fidelity. Quantum error correction becomes practically realizable once the physical error rate is below a threshold value that depends on the choice of quantum code, syndrome measurement circuit and decoding algorithm5. We present an end-to-end quantum error correction protocol that implements fault-tolerant memory on the basis of a family of low-density parity-check codes6. Our approach achieves an error threshold of 0.7% for the standard circuit-based noise model, on par with the surface code7-10 that for 20 years was the leading code in terms of error threshold. The syndrome measurement cycle for a length-n code in our family requires n ancillary qubits and a depth-8 circuit with CNOT gates, qubit initializations and measurements. The required qubit connectivity is a degree-6 graph composed of two edge-disjoint planar subgraphs. In particular, we show that 12 logical qubits can be preserved for nearly 1 million syndrome cycles using 288 physical qubits in total, assuming the physical error rate of 0.1%, whereas the surface code would require nearly 3,000 physical qubits to achieve said performance. Our findings bring demonstrations of a low-overhead fault-tolerant quantum memory within the reach of near-term quantum processors.

Supervised learning with quantum-enhanced feature spaces.

Machine learning and quantum computing are two technologies that each have the potential to alter how computation is performed to address previously untenable problems. Kernel methods for machine learning are ubiquitous in pattern recognition, with support vector machines (SVMs) being the best known method for classification problems. However, there are limitations to the successful solution to such classification problems when the feature space becomes large, and the kernel functions become computationally expensive to estimate. A core element in the computational speed-ups enabled by quantum algorithms is the exploitation of an exponentially large quantum state space through controllable entanglement and interference. Here we propose and experimentally implement two quantum algorithms on a superconducting processor. A key component in both methods is the use of the quantum state space as feature space. The use of a quantum-enhanced feature space that is only efficiently accessible on a quantum computer provides a possible path to quantum advantage. The algorithms solve a problem of supervised learning: the construction of a classifier. One method, the quantum variational classifier, uses a variational quantum circuit1,2 to classify the data in a way similar to the method of conventional SVMs. The other method, a quantum kernel estimator, estimates the kernel function on the quantum computer and optimizes a classical SVM. The two methods provide tools for exploring the applications of noisy intermediate-scale quantum computers3 to machine learning.

Error mitigation extends the computational reach of a noisy quantum processor.

Quantum computation, a paradigm of computing that is completely different from classical methods, benefits from theoretically proved speed-ups for certain problems and can be used to study the properties of quantum systems1. Yet, because of the inherently fragile nature of the physical computing elements (qubits), achieving quantum advantages over classical computation requires extremely low error rates for qubit operations, as well as substantial physical qubits, to realize fault tolerance via quantum error correction2,3. However, recent theoretical work4,5 has shown that the accuracy of computation (based on expectation values of quantum observables) can be enhanced through an extrapolation of results from a collection of experiments of varying noise. Here we demonstrate this error mitigation protocol on a superconducting quantum processor, enhancing its computational capability, with no additional hardware modifications. We apply the protocol to mitigate errors in canonical single- and two-qubit experiments and then extend its application to the variational optimization6-8 of Hamiltonians for quantum chemistry and magnetism9. We effectively demonstrate that the suppression of incoherent errors helps to achieve an otherwise inaccessible level of accuracy in the variational solutions using our noisy processor. These results demonstrate that error mitigation techniques will enable substantial improvements in the capabilities of near-term quantum computing hardware.

HOMA-IR and the Matsuda Index as predictors of progression to type 1 diabetes in autoantibody-positive relatives.

AIM/HYPOTHESIS: We assessed whether HOMA-IR and the Matsuda Index are associated with transitions through stages of type 1 diabetes. METHODS: Autoantibody (AAb)-positive relatives of individuals with type 1 diabetes (n=6256) from the TrialNet Pathway to Prevention were studied. Associations of indicators of insulin resistance (HOMA-IR) and insulin sensitivity (Matsuda Index) with BMI percentile (BMIp) and age were assessed with adjustments for measures of insulin secretion, Index60 and insulinogenic index (IGI). Cox regression was used to determine if tertiles of HOMA-IR and Matsuda Index predicted transitions from Not Staged (<2 AAbs) to Stage 1 (≥2 AAbs and normoglycaemia), from Stage 1 to Stage 2 (≥2 AAbs with dysglycaemia), and progression to Stage 3 (diabetes as defined by WHO/ADA criteria). RESULTS: There were strong associations of HOMA-IR (positive) and Matsuda Index (inverse) with baseline age and BMIp (p<0.0001). After adjustments for Index60, transitioning from Stage 1 to Stage 2 was associated with higher HOMA-IR and lower Matsuda Index (HOMA-IR: HR=1.71, p<0.0001; Matsuda Index, HR=0.40, p<0.0001), as with progressing from Stages 1 or 2 to Stage 3 (HOMA-IR: HR=1.98, p<0.0001; Matsuda Index: HR=0.46, p<0.0001). Without adjustments, associations of progression to Stage 3 were inverse for HOMA-IR and positive for Matsuda Index, opposite in directionality with adjustments. When IGI was used in place of Index60, the findings were similar. CONCLUSIONS/INTERPRETATION: Progression to Stages 2 and 3 of type 1 diabetes increases with HOMA-IR and decreases with the Matsuda Index after adjustments for insulin secretion. Indicators of insulin secretion appear helpful for interpreting associations of progression to type 1 diabetes with HOMA-IR or the Matsuda Index in AAb-positive relatives.

Paternal MTHFR deficiency leads to hypomethylation of young retrotransposons and reproductive decline across two successive generations.

5,10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in the folate metabolic pathway with a key role in generating methyl groups. As MTHFR deficiency impacts male fertility and sperm DNA methylation, there is the potential for epimutations to be passed to the next generation. Here, we assessed whether the impact of MTHFR deficiency on testis morphology and sperm DNA methylation is exacerbated across generations in mouse. Although MTHFR deficiency in F1 fathers has only minor effects on sperm counts and testis weights and histology, F2 generation sons show further deterioration in reproductive parameters. Extensive loss of DNA methylation is observed in both F1 and F2 sperm, with >80% of sites shared between generations, suggestive of regions consistently susceptible to MTHFR deficiency. These regions are generally methylated during late embryonic germ cell development and are enriched in young retrotransposons. As retrotransposons are resistant to reprogramming of DNA methylation in embryonic germ cells, their hypomethylated state in the sperm of F1 males could contribute to the worsening reproductive phenotype observed in F2 MTHFR-deficient males, compatible with the intergenerational passage of epimutations.

The origin of betaine in mouse oocytes and preimplantation embryos†.

Betaine has important roles in preimplantation mouse embryos, including as an organic osmolyte that functions in cell volume regulation in the early preimplantation stages and as a donor to the methyl pool in blastocysts. The origin of betaine in oocytes and embryos was largely unknown. Here, we found that betaine was present from the earliest stage of growing oocytes. Neither growing oocytes nor early preantral follicles could take up betaine, but antral follicles were able to transport betaine and supply the enclosed oocyte. Betaine is synthesized by choline dehydrogenase, and female mice lacking Chdh did not have detectable betaine in their oocytes or early embryos. Supplementing betaine in their drinking water restored betaine in the oocyte only when supplied during the final stages of antral follicle development but not earlier in folliculogenesis. Together with the transport results, this implies that betaine can only be exogenously supplied during the final stages of oocyte growth. Previous work showed that the amount of betaine in the oocyte increases sharply during meiotic maturation due to upregulated activity of choline dehydrogenase within the oocyte. This betaine present in mature eggs was retained after fertilization until the morula stage. There was no apparent role for betaine uptake via the SIT1 (SLC6A20) betaine transporter that is active at the 1- and 2-cell stages. Instead, betaine was apparently retained because its major route of efflux, the volume-sensitive organic osmolyte - anion channel, remained inactive, even though it is expressed and capable of being activated by a cell volume increase.

Multiomics analysis identifies oxidative phosphorylation as a cancer vulnerability arising from myristoylation inhibition.

BACKGROUND: In humans, two ubiquitously expressed N-myristoyltransferases, NMT1 and NMT2, catalyze myristate transfer to proteins to facilitate membrane targeting and signaling. We investigated the expression of NMTs in numerous cancers and found that NMT2 levels are dysregulated by epigenetic suppression, particularly so in hematologic malignancies. This suggests that pharmacological inhibition of the remaining NMT1 could allow for the selective killing of these cells, sparing normal cells with both NMTs. METHODS AND RESULTS: Transcriptomic analysis of 1200 NMT inhibitor (NMTI)-treated cancer cell lines revealed that NMTI sensitivity relates not only to NMT2 loss or NMT1 dependency, but also correlates with a myristoylation inhibition sensitivity signature comprising 54 genes (MISS-54) enriched in hematologic cancers as well as testis, brain, lung, ovary, and colon cancers. Because non-myristoylated proteins are degraded by a glycine-specific N-degron, differential proteomics revealed the major impact of abrogating NMT1 genetically using CRISPR/Cas9 in cancer cells was surprisingly to reduce mitochondrial respiratory complex I proteins rather than cell signaling proteins, some of which were also reduced, albeit to a lesser extent. Cancer cell treatments with the first-in-class NMTI PCLX-001 (zelenirstat), which is undergoing human phase 1/2a trials in advanced lymphoma and solid tumors, recapitulated these effects. The most downregulated myristoylated mitochondrial protein was NDUFAF4, a complex I assembly factor. Knockout of NDUFAF4 or in vitro cell treatment with zelenirstat resulted in loss of complex I, oxidative phosphorylation and respiration, which impacted metabolomes. CONCLUSIONS: Targeting of both, oxidative phosphorylation and cell signaling partly explains the lethal effects of zelenirstat in select cancer types. While the prognostic value of the sensitivity score MISS-54 remains to be validated in patients, our findings continue to warrant the clinical development of zelenirstat as cancer treatment.

Estimating Community Disruption from Nighttime Gunshots in 6 U.S. Cities, 2015 to 2021.

BACKGROUND: Gunshots affect those directly involved in an incident and those in the surrounding community. The community-level impact of nighttime gunshots, which may be particularly disruptive to the sleep of nearby community members, is unknown. OBJECTIVE: Our aim is to estimate the number of people potentially affected by nighttime gunshots and the relationship between nighttime gunshots and median household income in the USA. DESIGN: We collected publicly available data on the timing and location of gunshots in six U.S. cities (Baltimore, MD; Boston, MA; Washington, D.C.; New York, NY; Philadelphia, PA; and Portland, OR) from 2015 to 2021. We then analyzed the data by computing rate ratios (RRs) to compare the frequency of gunshots during nighttime hours (6:00 pm to 5:59 am) versus daytime hours (6:00 am to 5:59 pm). Additionally, we used geospatial mapping to create choropleth maps to visualize the variation in nighttime gunshot density across cities. We estimated, using city-wide population, person-nights potentially impacted by the sound of gunshots within areas of 0.2- (low) and 0.5-mile (high) radius. Finally, for five of six cities where data on median household income were available by census tract, we built nonlinear regression models to estimate the relationship between the number of nighttime gunshots and median household income. KEY RESULTS: We analyzed 72,236 gunshots. Gunshots were more common during the nighttime than daytime (overall RR = 2.5). Analyses demonstrated that the low estimates for the mean annual number of person-nights impacted by nighttime gunshots were 0.4 million in Baltimore and Portland, 1.3 million in Philadelphia, 1.6 million in Boston, 2.9 million in New York City, and 5.9 million in Washington. The number of nighttime gunshots was inversely related to median household income. CONCLUSIONS: Nighttime gunshots are prevalent, particularly in low-income neighborhoods, and may have under-recognized effects on the surrounding community.

The lipid flippase ATP8A1 regulates the recruitment of ARF effectors to the trans-Golgi Network.

Formation of transport vesicles requires the coordinate activity of the coating machinery that selects cargo into the nascent vesicle and the membrane bending machinery that imparts curvature to the forming bud. Vesicle coating at the trans-Golgi Network (TGN) involves AP1, GGA2 and clathrin, which are recruited to membranes by activated ARF GTPases. The ARF activation at the TGN is mediated by the BIG1 and BIG2 guanine nucleotide exchange factors (GEFs). Membrane deformation at the TGN has been shown to be mediated by lipid flippases, including ATP8A1, that moves phospholipids from the inner to the outer leaflet of the TGN membrane. We probed a possible coupling between the coating and deformation machineries by testing for an interaction between BIG1, BIG2 and ATP8A1, and by assessing whether such an interaction may influence coating efficiency. Herein, we document that BIG1 and BIG2 co-localize with ATP8A1 in both, static and highly mobile TGN elements, and that BIG1 and BIG2 bind ATP8A1. We show that the interaction involves the catalytic Sec7 domain of the GEFs and the cytosolic C-terminal tail of ATP8A1. Moreover, we report that the expression of ATP8A1, but not ATP8A1 lacking the GEF-binding cytosolic tail, increases the generation of activated ARFs at the TGN and increases the selective recruitment of AP1, GGA2 and clathrin to TGN membranes. This occurs without increasing BIG1 or BIG2 levels at the TGN, suggesting that the binding of the ATP8A1 flippase tail to the Sec7 domain of BIG1/BIG2 increases their catalytic activity. Our results support a model in which a flippase component of the deformation machinery impacts the activity of the GEF component of the coating machinery.

Inflammasomes: emerging therapeutic targets in hidradenitis suppurativa?

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterised by recurrent inflammatory lesions, which affect skin and hair follicles in intertriginous areas. HS has a multifactorial aetiology resulting in barrier dysfunction associated with aberrant immune activation. There is increased evidence for the role of inflammasomes in the pathophysiology of inflammatory skin diseases, including HS. Inflammasomes are multiprotein complexes activated following exposure to danger signals including microbial ligands and components of damaged host cells. Inflammasome activation induces many signalling cascades and subsequent cleavage of pro-inflammatory cytokines, most notably interleukin (IL)-1ß, which have a role in HS pathogenesis. Limited immunotherapies are approved for treating moderate-to-severe HS, with variable response rates influenced by disease heterogeneity. Inflammasomes represent attractive targets to suppress multiple inflammatory pathways in HS including IL-1ß and IL-17. This review aims to summarise the role of inflammasomes in HS and to evaluate evidence for inflammasomes as therapeutic targets for HS treatment.

Considering the cellular landscape in marrow stimulation techniques for cartilage repair.

BACKGROUND: Marrow stimulation is a common reparative approach to treat injuries to cartilage and other soft tissues (e.g., rotator cuff). It involves the recruitment of bone marrow elements and mesenchymal stem cells (MSCs) into the defect, theoretically initiating a regenerative process. However, the resulting repair tissue is often weak and susceptible to deterioration with time. The populations of cells at the marrow stimulation site (beyond MSCs), and their contribution to inflammation, vascularity, and fibrosis, may play a role in quality of the repair tissue. SUMMARY: In this review, we accomplish three goals: 1) systematically review clinical trials on the augmentation of marrow stimulation and evaluate their assumptions on the biological elements recruited; 2) detail the cellular populations in bone marrow and their impact on healing; and 3) highlight emerging technologies and approaches that could better guide these specific cell populations towards enhanced cartilage or soft tissue formation. KEY MESSAGES: We found that most clinical trials do not account for cell heterogeneity, nor do they specify the regenerative element recruited, and those that do typically utilize descriptions such as "clots", "elements", and "blood". Furthermore, our review of bone marrow cell populations demonstrates a dramatically heterogenous cell population, including hematopoietic cells, immune cells, fibroblasts, macrophages, and only a small population of MSCs. Finally, the field has developed numerous innovative techniques to enhance the chondrogenic potential (and reduce the anti-regenerative impacts) of these various cell types. We hope this review will guide approaches that account for cellular heterogeneity and improve marrow stimulation techniques to treat chondral defects.

Creative Arts Therapies in Rehabilitation.

Appreciation for the utility of creative arts therapy in rehabilitation is on the rise. The limitations of conventional approaches to address posttraumatic stress disorder and co-occurring traumatic brain injury is spurring the development and increased use of creative arts therapies, especially in US military health care systems. However, emerging applications of creative arts therapies in rehabilitation extend well beyond posttraumatic stress disorder/traumatic brain injury and military populations to span the continuum of care, from the intensive care unit, postoperative recovery unit, acute inpatient medical and surgical wards, outpatient clinics, and home health, as well as in traditional long-term care and psychiatric settings. Critical steps to more fully integrating creative arts therapies in rehabilitation include the following: (1) incorporation of education about creative arts therapies into the curricula across rehabilitation disciplines; (2) alteration of national and state policies to promote greater inclusion of creative arts therapies as reimbursable treatments for a wide array of clinical diagnoses and conditions; and (3) significant expansion of creative arts therapies' evidence base. This can be achieved by increasing funding levels to encourage rigorously designed and controlled studies to determine the efficacy, populations, diagnoses and conditions, cofactors, and the mechanisms of action of creative arts therapies. The time has come for a concentrated effort from the community of rehabilitation professional associations, advocacy organizations, and practitioners to promote the advancement and inclusion of creative arts therapies into appropriate clinical settings to optimize outcomes for patients.

Radiofrequency ablation for the treatment of uterine fibroids: A systematic review and meta-analysis by the AAGL Practice Committee.

OBJECTIVE: To systematically review clinical and patient-reported outcomes after radiofrequency ablation (RFA) for the treatment of uterine fibroids. DATA SOURCES: We searched Medline, EMBASE, Cochrane Registry of Controlled Trials (CENTRAL) on September 8, 2023, and requested additional data from industry sources. We included published, peer-reviewed studies of patient-centered outcomes of RFA when used for symptomatic fibroids. Abstracts and potentially relevant full-text articles were screened and data were extracted regarding study characteristics, arms, outcomes, and results, together with risk of bias assessment. METHODS OF STUDY SELECTION: We included 30 studies published in 49 articles (3 randomized controlled trials, 1 nonrandomized comparative study, and 26 single-group studies, as well as 4 publications from the TRUST Study) with variable risks of bias. TABULATION, INTEGRATION, AND RESULTS: The study populations were demographically diverse and clinically heterogeneous. Across studies, RFA treatment was associated with fibroid volume reduction of 46.0% (95% confidence interval [CI] 52.1, 40.0; 11 studies) at 3 months and 65.4% (95% CI 74.7, 56.1; 10 studies) at 12 months. All studies reported a decrease in proportion of patients experiencing abnormal, heavy, or prolonged menstrual bleeding, with the most substantial improvement within the first 3 months. Meta-analyses of health-related quality of life (HRQOL) scores demonstrated significant improvements in scores from baseline for Uterine Fibroid Symptoms and Quality of Life [UFS-QOL] (53.4, 95% CI 48.2, 58.5; 19 studies), EuroQol 5 Dimension [EQ-5D] (71.6, 95% CI 65.0, 78.1; 4 studies), and Symptom Severity Score [SSS] (52.2, 95% CI 46.4, 58.1; 17 studies), with a peak at 6 months on the UFS-QOL scale (88.0, 95% CI 83.0, 92.9; 11 studies), a peak at 24 months on the EuroQol-5D scale (88.3, 95% CI 86.0, 90.6; 2 studies), and a trough at 12 months for SSS (12.8, 95% CI 7.0, 18.6; 11 studies). Studies mostly demonstrated return to work and normal activities within 2 weeks. Reported unplanned hospitalizations were infrequent, and durations of hospital stay were generally short. Post-procedure complications were inconsistently reported, but assessed overall to be infrequent. Long-term need for medical and surgical re-intervention varied. Post-RFA hysterectomy rates ranged from 2/205 (1.0%) to 15/62 (24.1%) with variable follow-up periods ranging from 45 days to 74 months. Most studies did not include patients who desired to maintain fertility; thus, reproductive data are insufficient for interpretation. CONCLUSION: There is a paucity of comparative studies, and the small number of RCTs are limited by lack of blinding. Few studies had the long-term follow-up time required to draw definitive conclusions regarding the durability of symptom relief. However, despite these limitations, there is overall agreement on several important clinical measures following RFA, such as decreased fibroid volume, improved uterine bleeding and improved quality of life. Future high quality randomized controlled trials with standardized outcomes measures are required to better characterize the use of RFA among fibroid patients.

Generating tumor-selective conditionally active biologic anti-CTLA4 antibodies via protein-associated chemical switches.

Anticytotoxic T lymphocyte-associated protein 4 (CTLA4) antibodies have shown potent antitumor activity, but systemic immune activation leads to severe immune-related adverse events, limiting clinical usage. We developed novel, conditionally active biologic (CAB) anti-CTLA4 antibodies that are active only in the acidic tumor microenvironment. In healthy tissue, this binding is reversibly inhibited by a novel mechanism using physiological chemicals as protein-associated chemical switches (PaCS). No enzymes or potentially immunogenic covalent modifications to the antibody are required for activation in the tumor. The novel anti-CTLA4 antibodies show similar efficacy in animal models compared to an analog of a marketed anti-CTLA4 biologic, but have markedly reduced toxicity in nonhuman primates (in combination with an anti-PD1 checkpoint inhibitor), indicating a widened therapeutic index (TI). The PaCS encompass mechanisms that are applicable to a wide array of antibody formats (e.g., ADC, bispecifics) and antigens. Examples shown here include antibodies to EpCAM, Her2, Nectin4, CD73, and CD3. Existing antibodies can be engineered readily to be made sensitive to PaCS, and the inhibitory activity can be optimized for each antigen's varying expression level and tissue distribution. PaCS can modulate diverse physiological molecular interactions and are applicable to various pathologic conditions, enabling differential CAB antibody activities in normal versus disease microenvironments.

Treatment Adherence in Pediatric Atopic Dermatitis: A Systematic Review.

INTRODUCTION: Adherence to pediatric atopic dermatitis (AD) treatment regimens can be complex and a major challenge to optimizing treatment outcome. We aimed to review factors associated with nonadherence in pediatric AD and propose interventions to improve adherence. METHODS: PubMed and EMBASE databases were systematically searched for articles from 2000 to February 2023 related to AD and adherence, with an additional update in December 2023. Non-human studies, reviews, commentaries, and meta-analyses were excluded. Articles were sorted into pediatric versus adult study population based on volume. Herein, we examine the results of papers discussing adherence factors related to pediatric patients. RESULTS: A total of 62 studies met inclusion criteria. Thirty-six studies surveyed patients and caregivers (N = 10,268) to identify barriers to treatment adherence. None of the included studies were specific to systemic medications. Barriers included poor caregiver quality of life, inadequate AD-related education, topical corticosteroid (TCS) phobia, unclear therapy-related instructions, and dissatisfaction with physician interaction. Five studies solely measured adherence using medication electronic monitoring systems, Morisky medication adherence scale, or self-reported adherence to measure adherence to topical medications. Twenty-one studies described interventions involving nurse-led or web-based education programs, text message or email reminders, and TCS education. Adherence was improved with caregiver education programs, daily text-message reminders, eczema action plans, TCS potency "traffic light" color system, and frequent follow-up visits. CONCLUSION: Adherence to pediatric AD treatment poses a multifactorial challenge for caregivers and patients. This study provides an index of strategies to optimize adherence, as it is essential for prevention of long-term sequela associated with AD in children. As the AD treatment landscape rapidly expands, further studies are vital to assess pediatric adherence to new topical, oral, and injectable medications. TRIAL REGISTRATION: PROSPERO: CRD42023488557.

Corymbiform cutaneous disorders in pediatric dermatology: Exploring this pattern of presentation beyond secondary syphilis.

"Corymbiform" is a term found in medical literature as early as 1876 to describe a central larger lesion with smaller surrounding lesions, leading to the appearance of an irregular border. While the term in current medical literature most often describes a possible morphology of secondary syphilis, the authors have noted this pattern presenting in other cutaneous conditions. We present a commentary on the corymbiform pattern in dermatology including a series of photographs of cutaneous disorders presenting in a corymbiform morphology in pediatric patients. While the term corymbiform is not commonly used in the present-day dermatologic literature, increased recognition and use of this term may aid in the recognition of various dermatologic diagnoses presenting in a less common morphology and may also lend to increased fluidity of dermatologic descriptions in the literature.

High Variability in Standardized Outcome Thresholds of Clinically Important Changes in Shoulder Instability Surgery: A Systematic Review.

PURPOSE: To examine reported minimal clinically important difference (MCID) and patient-acceptable satisfactory state (PASS) values for patient-reported outcome measures (PROMs) after shoulder instability surgery and assess variability in published values depending on the surgery performed. Our secondary aims were to describe the methods used to derive MCID and PASS values in the published literature, including anchor-based, distribution-based, or other approaches, and to assess the frequency of MCID and PASS use in studies on shoulder instability surgery. METHODS: A systematic review of MCID and PASS values after Bankart, Latarjet, and Remplissage procedures was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were queried from 1985 to 2023. Inclusion criteria included studies written in English and studies reporting use of MCID or PASS for patient-reported outcome measures (PROMS) after Latarjet, Bankart, and Remplissage approaches for shoulder instability surgery. Extracted data included study population characteristics, intervention characteristics, and outcomes of interest. Continuous data were described using medians and ranges. Categorical variables, including PROMs and MCID/PASS methods, were described using percentages. Because MCID is a patient-level rather than a group-level metric, the authors confirmed that all included studies reported proportions (%) of subjects who met or exceeded the MCID. RESULTS: A total of 174 records were screened, and 8 studies were included in this review. MCID was the most widely used outcome threshold and was reported in all 8 studies, with only 2 studies reporting both the MCID and the PASS. The most widely studied PROMs were the American Shoulder and Elbow Surgeons (range 5.65-9.6 for distribution MCID, 8.5 anchor MCID, 86 anchor PASS); Single Assessment Numeric Evaluation (range 11.4-12.4 distribution MCID, 82.5-87.5 anchor PASS); visual analog scale (VAS) (range 1.1-1.7 distribution MCID, 1.5-2.5 PASS); Western Ontario Shoulder Instability Index (range 60.7-254.9 distribution MCID, 126.43 anchor MCID, 571-619.5 anchor PASS); and Rowe scores (range 5.6-8.4 distribution MCID, 9.7 anchor MCID). Notably, no studies reported on substantial clinical benefit or maximal outcome improvement. CONCLUSIONS: Despite the wide array of available PROMs for assessing shoulder instability surgery outcomes, the availability of clinically significant outcome thresholds such as MCID and PASS remains relatively limited. Although MCID has been the most frequently reported metric, there is considerable interstudy variability observed in their values. CLINICAL RELEVANCE: Knowing the outcome thresholds such as MCID and PASS of the PROMs frequently used to evaluate the results of glenohumeral stabilization surgery is fundamental because they allow us to know what is a clinically significant improvement for the patient.

Posterior Shoulder Instability, Part I-Diagnosis, Nonoperative Management, and Labral Repair for Posterior Shoulder Instability-An International Expert Delphi Consensus Statement.

PURPOSE: To establish consensus statements on the diagnosis, nonoperative management, and labral repair for posterior shoulder instability. METHODS: A consensus process on the treatment of posterior shoulder instability was conducted, with 71 shoulder/sports surgeons from 12 countries participating on the basis of their level of expertise in the field. Experts were assigned to 1 of 6 working groups defined by specific subtopics within posterior shoulder instability. Consensus was defined as achieving 80% to 89% agreement, whereas strong consensus was defined as 90% to 99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: Unanimous agreement was reached on the indications for nonoperative management and labral repair, which include whether patients had primary or recurrent instability, with symptoms/functional limitations, and whether there was other underlying pathology, or patient's preference to avoid or delay surgery. In addition, there was unanimous agreement that recurrence rates can be diminished by attention to detail, appropriate indication and assessment of risk factors, recognition of abnormalities in glenohumeral morphology, careful capsulolabral debridement and reattachment, small anchors with inferior placement and multiple fixation points that create a bumper with the labrum, treatment of concomitant pathologies, and a well-defined rehabilitation protocol with strict postoperative immobilization. CONCLUSIONS: The study group achieved strong or unanimous consensus on 63% of statements related to the diagnosis, nonoperative treatment, and labrum repair for posterior shoulder instability. The statements that achieved unanimous consensus were the relative indications for nonoperative management, and the relative indications for labral repair, as well as the steps to minimize complications for labral repair. There was no consensus on whether an arthrogram is needed when performing advanced imaging, the role of corticosteroids/orthobiologics in nonoperative management, whether a posteroinferior portal is required. LEVEL OF EVIDENCE: Level V, expert opinion.

Posterior Shoulder Instability, Part II-Glenoid Bone Grafting, Glenoid Osteotomy, and Rehabilitation/Return to Play-An International Expert Delphi Consensus Statement.

PURPOSE: To establish consensus statements on glenoid bone grafting, glenoid osteotomy, rehabilitation, return to play, and follow-up for posterior shoulder instability. METHODS: A consensus process on the treatment of posterior shoulder instability was conducted, with 71 shoulder/sports surgeons from 12 countries participating on the basis of their level of expertise in the field. Experts were assigned to 1 of 6 working groups defined by specific subtopics within posterior shoulder instability. Consensus was defined as achieving 80% to 89% agreement, whereas strong consensus was defined as 90% to 99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: All of the statements relating to rehabilitation, return to play, and follow-up achieved consensus. There was unanimous consensus that the following criteria should be considered: restoration of strength, range of motion, proprioception, and sport-specific skills, with a lack of symptoms. There is no minimum time point required to return to play. Collision athletes and military athletes may take longer to return because of their greater risk for recurrent instability, and more caution should be exercised in clearing them to return to play, with elite athletes potentially having different considerations in returning to play. The relative indications for revision surgery are symptomatic apprehension, multiple recurrent instability episodes, further intra-articular pathologies, hardware failure, and pain. CONCLUSIONS: The study group achieved strong or unanimous consensus on 59% of statements. Unanimous consensus was reached regarding the criteria for return to play, collision/elite athletes having different considerations in return to play, indications for revision surgery, and imaging only required as routine for those with glenoid bone grafting/osteotomies at subsequent follow-ups. There was no consensus on optimal fixation method for a glenoid bone block, the relative indications for glenoid osteotomy, whether fluoroscopy is required or if the labrum should be concomitantly repaired. LEVEL OF EVIDENCE: Level V, expert opinion.

Glenohumeral morphological predictors of recurrent shoulder instability following arthroscopic Bankart repair.

PURPOSE: The purpose of this study was to evaluate glenohumeral morphological features on a magnetic resonance arthrogram (MRA) to determine risk factors for recurrence of anterior shoulder instability following arthroscopic Bankart repair (ABR). METHODS: A retrospective review of patients who underwent ABR between 2012 and 2017 was performed to identify patients who had recurrence of instability following stabilisation (Group 1). These were pair-matched in a 2:1 ratio for age, gender and sport with a control (Group 2) who underwent ABR without recurrence. Preoperative MRAs were evaluated for risk factors for recurrence, with glenoid bone loss and Hill-Sachs lesions also measured. Multilinear and multilogistic regression models were used to evaluate factors affecting recurrence. RESULTS: Overall, 72 patients were included in this study, including 48 patients without recurrence and 24 patients with recurrent instability. There was a significant difference between the two groups in mean glenoid bone loss (Group 1: 7.3% vs. Group 2: 5.7%, p < 0.0001) and the rate of off-track Hill-Sachs lesions (Group 1: 20.8% vs. Group 2: 0%, p = 0.0003). Of the variables analysed in logistic regression, increased glenoid anteversion (p = 0.02), acromioclavicular (AC) degeneration (p = 0.03) and increased Hill-Sachs width were associated with increased risk of failure. Increased chondral version (p = 0.01) and humeral head diameter in the anteriorposterior view were found to be protective and associated with a greater likelihood of success. CONCLUSION: Glenoid anteversion was a risk factor for recurrent instability, whereas increased chondral version and humeral head diameter were associated with higher rates of success following ABR. Glenoid bone loss, presence of an off-track Hill-Sachs lesion, increased Hill-Sachs width and AC degeneration were also associated with failure. These findings should be used by surgeons to stratify risk for recurrence following ABR. LEVEL OF EVIDENCE: Level III.