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Improved core high-harmonic fast wave (HHFW) heating at longer wavelengths and during start-up and plasma current ramp-up has now been obtained by lowering the edge density with lithium wall conditioning, thereby moving the critical density for perpendicular fast-wave propagation away from the vessel wall. Lithium conditioning allowed significant HHFW core electron heating of deuterium neutral beam injection (NBI) fuelled H-mode plasmas to be observed for the first time. Large edge localized modes were observed immediately after the termination of rf power. Visible and infrared camera images show that fast wave interactions can deposit considerable rf energy on the outboard divertor. HHFW-generated parametric decay instabilities were observed to heat ions in the plasma edge and may be the cause for a measured drag on edge toroidal rotation during HHFW heating. A significant enhancement in neutron rate and fast-ion profile was measured in NBI-fuelled plasmas when HHFW heating was applied. © 2010 American Institute of Physics.

Research on the spherical torus (or spherical tokamak) (ST) is being pursued to explore the scientific benefits of modifying the field line structue fro that in more moderate aspect ratio devices. The ST experiments are being conducted in various US research facilities. The area of power and particle handling is expected to be challenging because of the higher power density expected in the ST relative to that in conventional aspect-ratio tokamaks.

A major research goal of the national spherical torus experiment is establishing long-pulse, high beta, high confinement operation and its physics basis. This research has been enabled by facility capabilities developed during 2001 and 2002, including neutral beam (up to 7 MW) and high harmonic fast wave (HHFW) heating (up to 6 MW), toroidal fields up to 6 kG, plasma currents up to 1.5 MA, flexible shape control, and wall preparation techniques. These capabilities have enabled the generation of plasmas with βT ≡ /(BT02/2μ0) of up to 35%. Normalized beta values often exceed the no-wall limit, and studies suggest that passive wall mode stabilization enables this for H mode plasmas with broad pressure profiles. The viability of long, high bootstrap current fraction operations has been established for ELMing H mode plasmas with toroidal beta values in excess of 15% and sustained for several current relaxation times. Improvements in wall conditioning and fuelling are likely contributing to a reduction in H mode power thresholds. Electron thermal conduction is the dominant thermal loss channel is auxiliary heated plasmas examined thus far. HHFW effectively heats electrons, and its acceleration of fast beam ions has been observed. Evidence for HHFW current drive is obtained by comparison of the loop voltage evolution in plasmas with matched density and temperature profiles but varying phases of launched HHFW waves. Studies of emissions from electron Bernstein waves indicate a density scale length dependence of their transmission across the upper hybrid resonance near the plasma edge that is consistent with theoretical predictions. A peak heat flux to the divertor targets of 10 MW m-2 has been measured in the H mode, with large asymmetries being observed in the power deposition between the inner and outer strike points. Non-inductive plasma startup studies have focused on coaxial helicity injection. With this technique, toroidal currents up to 400 kA have been driven, and studies to assess flux closure and coupling to other current drive techniques have begun.

Objective: To describe the characteristics of research training and scholarly activity during pediatrics residency in Canada and identify facilitators and barriers to resident scholarly activity., Study Design: We conducted a mixed-methods, cross-sectional survey of pediatrics residents in Canada from April to June 2023. Trainees and medical education experts developed the 55-item survey, pilot tested, and distributed electronically to residents in all 17 Canadian residency programs. Responses were complemented with program-level data from pediatrics residency program directors., Results: Of 644 Canadian pediatrics residents, 230 (36%) responded. Resident respondents conducted various types of scholarly projects, including retrospective clinical study (22%), qualitative research (15%), quality improvement (13%), and medical education research (12%). Discordance between the field of career interests and primary scholarly projects was common. Among respondents, 20% had abstracts accepted at national or international conferences, and 12% had manuscripts submitted to peer-reviewed journals. Resident respondents' self-perceived progress in their scholarly projects were discrepant from their actual progress. Key themes related to barriers and facilitators to scholarly activity included protected time for research, mentorship, and research skills training., Conclusions: The research training and scholarly activity of pediatrics residents in Canada is variable. Establishing national standards, implementing progress monitoring mechanisms with tailored support, and offering flexible protected research time are important next steps., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest. Funding for incentives for respondents was provided by the Canadian Paediatric Inpatient Research Network (PIRN). The executive members of the PIRN served as expert reviewers for the survey and reviewed the manuscript for clarity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Orthopaedic surgery has consistently been one of the most competitive specialties in the US residency selection process. This is due in part to the steady upward trend in average applications received per program and average applications submitted per applicant, which is of growing concern. With the implementation of the Preference Signaling Program, the total number of applications has now dropped for the first time in many years, indicating signaling may improve the application process. The hypothesis is that signaling has led to a decrease in applications sent by applicants and a decrease in applications received by programs., Methods: A 7-question survey regarding their interview and match statistics was sent to orthopaedic surgery residency programs that participated in the Electronic Residency Application Service during the 2023-2024 application cycle. A response from the program director/administrator was then recorded., Results: Our program search yielded 159 programs with 106 respondents (66.7%). 82 programs (78.8%) solely interviewed applicants who signaled their program. 92.7% of current interns signaled the program where they matched, and 88 programs (84.6%) matched only applicants who signaled. 95 programs (89.6%) revealed that implementing signaling has improved the application process., Conclusion: Most of the programs only interviewed applicants who also signaled, and nearly all matched orthopaedic surgery applicants from the 2022-2023 cycle signaled their matching program. Orthopaedic surgery applicants should consider only applying to 30 programs and using all 30 available signals. Applicants should also be more confident knowing that beyond the 30 signals they use, there is limited support to say that they will receive an interview outside of these 30 applications. Orthopaedic surgery programs will also now have the ability to allocate more time to applicants most interested in their program, given the reduction of applications., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Latent or subtle syndesmotic instability is defined as an injury to the syndesmosis which is not apparent on static radiographs of the ankle. Syndesmotic injuries have also been referred to as high ankle sprains. Injury to the syndesmosis typically occurs with collision sports and often involves an external rotation force to the ankle. Diagnosis can be delayed because of negative initial imaging studies. Physical examination tests including the external rotation test, proximal squeeze test, and fibular shuck test can assist in the diagnosis. Advanced imaging modalities such as MRI and weight-bearing CT have been studied and can provide prognostic indications for management, although arthroscopic stress evaluation remains the benchmark for diagnosis. Both surgical and nonsurgical management techniques have been described, which can assist patients in returning to their preinjury level of function., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Bacterial synthetic multicellular systems are promising platforms for engineered living materials (ELMs) for medical, biosynthesis, environmental, and smart materials applications. Recent advancements in genetically encoded adhesion toolkits have enabled precise manipulation of cell-cell adhesion and the design and patterning of self-assembled multicellular materials. However, in contrast to gene regulation in synthetic biology, the characterization and control of synthetic adhesins remains limited. Here, we demonstrate the quantitative characterization of a bacterial synthetic adhesion toolbox through various biophysical methods. We determine key parameters, including number of adhesins per cell, in-membrane diffusion constant, production and decay rates, and bond-breaking force between adhesins. With these parameters, we demonstrate the bottom-up prediction and quantitative tuning of macroscopic ELM properties (tensile strength) and, furthermore, that cells inside ELMs are connected only by a small fraction of available adhesins. These results enable the rational engineering, characterization, and modeling of other synthetic and natural adhesins and multicellular consortia., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Background: It is not known how peroneal tendon exploration influences results after modified Broström for lateral ankle instability. We propose peroneal exploration at the time of modified Broström will have similar outcomes as no peroneal exploration., Methods: A retrospective analysis was performed of patients undergoing modified Broström with and without peroneal exploration. Foot and Ankle Outcome scores and data regarding military retention were gathered and compared., Results: Seventeen patients were identified in the modified Broström only cohort and 24 in the peroneal exploration cohort. Patients had mean follow-up of 5 years in both cohorts. The mean FAOS in the modified Broström only cohort was 68 and 72 in the cohort with peroneal exploration (P = .541). When each FAOS subcategory was analyzed, no difference was identified in any subcategory. Eight of 17 patients (47%) in the modified Broström only cohort remained active duty compared with 8 of 24 patients (33%) in the modified Broström with peroneal exploration cohort (P = .518). One patient medically discharged in the modified Broström only cohort versus 6 in peroneal exploration cohort (P = .109). Overall satisfaction with the procedure was 12 of 17 (71%) in the modified Broström only cohort and 19 of 24 (79%) in the peroneal exploration cohort (P = .529)., Conclusions: No significant difference was identified between patients undergoing modified Broström alone or modified Broström with peroneal exploration. There was no significant difference in return to duty, medical discharge or patient satisfaction., Levels of Evidence: Level III: retrospective case-control study with prospectively collected data., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a valuable class of medications for orthopedic surgeons and often play a pivotal role in pain control. However, there are many common stipulations resulting in avoidance of its use in the treatment of musculoskeletal disease. This review summarizes the mechanism of action of NSAIDs as well as provides an overview of commonly used NSAIDs and the differences between them. It provides a concise summary on the osseous effects of NSAIDs with regard to bone healing and heterotopic ossification. Most of all, it serves as a guide or reference for orthopedic providers when counseling patients on the risks and benefits of NSAID use, as it addresses the common stipulations encountered: "It irritates my stomach," "I have a history of bariatric surgery," "I'm already on a blood thinner," "I've had a heart attack," and "I've got kidney problems" and synthesizes both current research and society recommendations regarding safe use and avoidance of NSAIDs., (© 2024 Orthopaedic Research Society.)

Gestational diabetes mellitus (GDM) is a metabolic complication that manifests as hyperglycemia during the later stages of pregnancy. In high resource settings, careful management of GDM limits risk to the pregnancy, and hyperglycemia typically resolves after birth. At the same time, previous studies have revealed that the gut microbiome of infants born to mothers who experienced GDM exhibit reduced diversity and reduction in the abundance of several key taxa, including Lactobacillus . What is not known is what the functional consequences of these changes might be. In this case control study, we applied 16S rRNA sequence surveys and metatranscriptomics to profile the gut microbiome of 30 twelve-month-old infants - 16 from mothers with GDM, 14 from mothers without - to examine the impact of GDM during pregnancy. Relative to the mode of delivery and sex of the infant, maternal GDM status had a limited impact on the structure and function of the developing microbiome. While GDM samples were associated with a decrease in alpha diversity, we observed no effect on beta diversity and no differentially abundant taxa. Further, while the mode of delivery and sex of infant affected the expression of multiple bacterial pathways, much of the impact of GDM status on the function of the infant microbiome appears to be lost by twelve months of age. These data may indicate that, while mode of delivery appears to impact function and diversity for longer than anticipated, GDM may not have persistent effects on the function nor composition of the infant gut microbiome.

Competing Interests: JKH has participated in advisory boards for Novo Nordisk.

Spiroplasma is a unique, helical bacterium that lacks a cell wall and swims using propagating helix hand inversions. These deformations are likely driven by a set of cytoskeletal filaments, but how remains perplexing. Here, we probe the underlying mechanism using a model where either twist or bend drive spiroplasma's chirality inversions. We show that Spiroplasma should wrap into plectonemes at different values of the length and external viscosity, depending on the mechanism. Then, by experimentally measuring the bending modulus of Spiroplasma and if and when plectonemes form, we show that Spiroplasma's helix hand inversions are likely driven by bending.

A retrospective review of consecutive patients diagnosed with insertional Achilles tendinopathy (IAT) was performed. Outcomes included Visual Analog Scale (VAS) pain scores, return to run rates, and return to military duty rates. Our data analysis included 113 patients; 58 (55%) patients required surgery. Mean duration of follow-up was 42 months (range, 12-143). Mean age at the time of surgery was 37.2 years (range, 21-54). VAS scores significantly improved from 5.4 at the preoperative visit to 2.9 at 24 months. There was no significant improvement in VAS scores after the 3-month postoperative visit. Mean return to run time was 9 months (range, 4.5-16). At 1 year, 80% (46/58) of patients returned to military duty. Complications requiring return to the operating room were observed in 6 patients (9%). The high rate of return to duty and significant improvement in pain scores demonstrate that the surgical management of IAT is a viable treatment option for patients who could not otherwise remain on active duty. With that said, the complication rate of 27% is high. Patients and providers should consider the risks, benefits, and duration of therapy during their shared decision-making process. Level of Evidence: Level IV.

Background: non-alcoholic fatty liver disease (NAFLD) in childhood is an increasing global public health issue with significant long-term consequences. NAFLD management mainly consists of lifestyle modifications, however, adjunct pharmacological therapies are currently lacking. Gut microbiota manipulation via probiotics may alter the course of pediatric NAFLD. The objective of this systematic review was to synthesize all the available literature on the use of probiotics in children and adolescents with NAFLD., Methods: PubMed, EBSCOhost, Scopus, Web of Science, and Cochrane Library were systematically searched for trials on the use of probiotics in pediatric NAFLD. A quantitative DerSimonian Laird random effects meta-analysis was performed when possible; otherwise, a narrative summary of the study outcomes was presented and discussed. A separate search was completed to include all the ongoing registered trials on probiotics use in pediatric NAFLD., Results: five randomized controlled trials met the inclusion criteria. Of these, four trials were included in the final quantitative analysis. Probiotic therapy significantly reduced the levels of alanine aminotransferase (ALT) (mean difference: -10.39 [-19.85, -0.93]), however significant heterogeneity between studies was identified (I2, 93 %)., Conclusions: there is insufficient evidence to support probiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials. Lifestyle modifications focusing on maintaining a normal BMI and regular exercise continue to be the gold standard approach to treating NAFLD in children.

Glenohumeral bone loss is frequently observed in cases of recurrent anterior and posterior shoulder instability and represents a risk factor for failure of nonoperative treatment. Patients with suspected glenoid or humeral bone loss in the setting of recurrent instability should be evaluated with a thorough history and physical examination, as well as advanced imaging including computed tomography (CT) and/or magnetic resonance imaging (MRI). In cases of both anterior and posterior instability, the magnitude and location of bone loss should be determined, as well as the relationship between the glenoid track (GT) and any humeral defects. While the degree and pattern of osseous deficiency help guide treatment, patient-specific risk factors for recurrent instability must also be considered when determining patient management. Treatment options for subcritical anterior bone loss include labral repair and capsular plication, while more severe deficiency should prompt consideration of bony augmentation including coracoid transfer or free bone block procedures. Concomitant humeral lesions are treated according to the degree of engagement with the glenoid rim and may be addressed with soft tissue remplissage or bony augmentation procedures. While critical and subcritical thresholds of glenoid bone loss guide the management of anterior instability, such thresholds are less defined in the setting of posterior instability. Furthermore, current treatment algorithms are limited by a lack of long-term comparative studies. Future high-quality studies as well as possible modifications in indications and surgical technique are required to elucidate the optimal treatment of anterior, posterior, and bipolar glenohumeral bone loss in the setting of recurrent shoulder instability., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoj.amegroups.org/article/view/10.21037/aoj-23-6/coif). The series “Bone Loss in Shoulder Instability and Shoulder Arthroplasty” was commissioned by the editorial office without any funding or sponsorship. JDH served as the unpaid Guest Editor for the series. The authors have no other conflicts of interest to declare., (2023 Annals of Joint. All rights reserved.)

Introduction: A new system was implemented by the Association of American Medical Colleges called the preference signaling program for the 2022 to 2023 orthopaedic surgery residency match. Applicants were able to signal 30 orthopaedic surgery programs to indicate high interest in a specific program. The purpose of this study was to address how important signaling was to an orthopaedic surgery program this 2022 to 2023 application cycle., Methods: A five-question survey was sent to orthopaedic surgery residency programs participating in the Electronic Residency Application Service this application cycle. Contact information was gathered through the Accreditation Council for Graduate Medical Education residency website and program websites., Results: Responses were obtained from 69 of the 151 programs (46%) contacted. The average number of applicants per program was 727 (range, 372 to 1031, SD 155). Thirty-four of 61 respondents (56%) stated that 100% of their interviewees signaled their program. Fifty-five of 61 respondents (90%) indicated that their interviewee pool consisted of 75% or more applicants who signaled. Applicants who signaled had a 24.4% (range, 12.77 to 47.41, SD 8.04) chance of receiving an interview. Applicants who did not signal had just a 0.92% (range, 0 to 13.10, SD 2.08) chance of receiving an interview. Fifty-four of the 63 applicants (86%) answered that signaling played an important role in considering an applicant for an interview., Conclusion: Over half of the responding programs only interviewed applicants who signaled their program, and over 90% of programs' interview lists consisted of at least 75% of signaling applicants. Eighty-six percent of programs indicated that signaling played an important role in considering an applicant for an interview. Applicants who signaled were 26.5 times more likely to receive an interview than those who did not (P < 0.0001). With this information, applicants can narrow down their list of programs to apply to, knowing that their signal to a program will give them a better chance at receiving an interview., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Purpose of Review: The addition of lateral extra-articular tenodesis (LET) to anterior cruciate ligament (ACL) reconstruction (ACLR) has become increasingly popular to address residual rotatory knee instability. The purpose of this article is to review the anatomy and biomechanics of the anterolateral complex (ALC) of the knee, outline different LET techniques, and provide biomechanical and clinical evidence for its use as an augmentation procedure with ACLR., Recent Findings: Rotatory knee instability has been identified as a common contributor to ACL rupture in both the primary and revision settings. Several biomechanical studies have shown that LET reduces strain on the ACL by decreasing excess tibial translation and rotation. Additionally, in vivo studies have demonstrated restoration of side-to-side differences in anterior-posterior knee translation, higher rates of return to play, and overall increased patient satisfaction following combined ACLR and LET. As a result, various LET techniques have been developed to help offload the ACL graft and lateral compartment of the knee. However, conclusions are limited by a lack of concrete indications and contraindications for use of LET in the clinical setting. Recent studies have shown that rotatory knee instability contributes to native ACL and ACL graft rupture and LET may provide further stability to reduce rates of failure. Further investigation is needed to establish concrete indications and contraindications to determine which patients would most benefit from added stability of the ALC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There is a large body of evidence evaluating quality improvement (QI) programmes to improve care for adults living with diabetes. These programmes are often comprised of multiple QI strategies, which may be implemented in various combinations. Decision-makers planning to implement or evaluate a new QI programme, or both, need reliable evidence on the relative effectiveness of different QI strategies (individually and in combination) for different patient populations., Objectives: To update existing systematic reviews of diabetes QI programmes and apply novel meta-analytical techniques to estimate the effectiveness of QI strategies (individually and in combination) on diabetes quality of care., Search Methods: We searched databases (CENTRAL, MEDLINE, Embase and CINAHL) and trials registers (ClinicalTrials.gov and WHO ICTRP) to 4 June 2019. We conducted a top-up search to 23 September 2021; we screened these search results and 42 studies meeting our eligibility criteria are available in the awaiting classification section., Selection Criteria: We included randomised trials that assessed a QI programme to improve care in outpatient settings for people living with diabetes. QI programmes needed to evaluate at least one system- or provider-targeted QI strategy alone or in combination with a patient-targeted strategy. - System-targeted: case management (CM); team changes (TC); electronic patient registry (EPR); facilitated relay of clinical information (FR); continuous quality improvement (CQI). - Provider-targeted: audit and feedback (AF); clinician education (CE); clinician reminders (CR); financial incentives (FI). - Patient-targeted: patient education (PE); promotion of self-management (PSM); patient reminders (PR). Patient-targeted QI strategies needed to occur with a minimum of one provider or system-targeted strategy., Data Collection and Analysis: We dual-screened search results and abstracted data on study design, study population and QI strategies. We assessed the impact of the programmes on 13 measures of diabetes care, including: glycaemic control (e.g. mean glycated haemoglobin (HbA1c)); cardiovascular risk factor management (e.g. mean systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), proportion of people living with diabetes that quit smoking or receiving cardiovascular medications); and screening/prevention of microvascular complications (e.g. proportion of patients receiving retinopathy or foot screening); and harms (e.g. proportion of patients experiencing adverse hypoglycaemia or hyperglycaemia). We modelled the association of each QI strategy with outcomes using a series of hierarchical multivariable meta-regression models in a Bayesian framework. The previous version of this review identified that different strategies were more or less effective depending on baseline levels of outcomes. To explore this further, we extended the main additive model for continuous outcomes (HbA1c, SBP and LDL-C) to include an interaction term between each strategy and average baseline risk for each study (baseline thresholds were based on a data-driven approach; we used the median of all baseline values reported in the trials). Based on model diagnostics, the baseline interaction models for HbA1c, SBP and LDL-C performed better than the main model and are therefore presented as the primary analyses for these outcomes. Based on the model results, we qualitatively ordered each QI strategy within three tiers (Top, Middle, Bottom) based on its magnitude of effect relative to the other QI strategies, where 'Top' indicates that the QI strategy was likely one of the most effective strategies for that specific outcome. Secondary analyses explored the sensitivity of results to choices in model specification and priors.  Additional information about the methods and results of the review are available as Appendices in an online repository. This review will be maintained as a living systematic review; we will update our syntheses as more data become available., Main Results: We identified 553 trials (428 patient-randomised and 125 cluster-randomised trials), including a total of 412,161 participants. Of the included studies, 66% involved people living with type 2 diabetes only. Participants were 50% female and the median age of participants was 58.4 years. The mean duration of follow-up was 12.5 months. HbA1c was the commonest reported outcome; screening outcomes and outcomes related to cardiovascular medications, smoking and harms were reported infrequently. The most frequently evaluated QI strategies across all study arms were PE, PSM and CM, while the least frequently evaluated QI strategies included AF, FI and CQI. Our confidence in the evidence is limited due to a lack of information on how studies were conducted.  Four QI strategies (CM, TC, PE, PSM) were consistently identified as 'Top' across the majority of outcomes. All QI strategies were ranked as 'Top' for at least one key outcome. The majority of effects of individual QI strategies were modest, but when used in combination could result in meaningful population-level improvements across the majority of outcomes. The median number of QI strategies in multicomponent QI programmes was three.  Combinations of the three most effective QI strategies were estimated to lead to the below effects:  - PR + PSM + CE: decrease in HbA1c by 0.41% (credibility interval (CrI) -0.61 to -0.22) when baseline HbA1c < 8.3%; - CM + PE + EPR: decrease in HbA1c by 0.62% (CrI -0.84 to -0.39) when baseline HbA1c > 8.3%;  - PE + TC + PSM: reduction in SBP by 2.14 mmHg (CrI -3.80 to -0.52) when baseline SBP < 136 mmHg; - CM + TC + PSM: reduction in SBP by 4.39 mmHg (CrI -6.20 to -2.56) when baseline SBP > 136 mmHg;  - TC + PE + CM: LDL-C lowering of 5.73 mg/dL (CrI -7.93 to -3.61) when baseline LDL < 107 mg/dL; - TC + CM + CR: LDL-C lowering by 5.52 mg/dL (CrI -9.24 to -1.89) when baseline LDL > 107 mg/dL. Assuming a baseline screening rate of 50%, the three most effective QI strategies were estimated to lead to an absolute improvement of 33% in retinopathy screening (PE + PR + TC) and 38% absolute increase in foot screening (PE + TC + Other)., Authors' Conclusions: There is a significant body of evidence about QI programmes to improve the management of diabetes. Multicomponent QI programmes for diabetes care (comprised of effective QI strategies) may achieve meaningful population-level improvements across the majority of outcomes. For health system decision-makers, the evidence summarised in this review can be used to identify strategies to include in QI programmes. For researchers, this synthesis identifies higher-priority QI strategies to examine in further research regarding how to optimise their evaluation and effects. We will maintain this as a living systematic review., (Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: Surgical fixation of midshaft clavicle fractures with a single 3.5 mm superior clavicular plate has been associated with a high rate of hardware removal due to symptomatic hardware. Because of this, dual-plating techniques with lower-profile implants have been proposed. However, dual-plating systems have disadvantages, including increased cost and increased surgical morbidity. The aim of this study was to define the rate of symptomatic hardware removal for all midshaft clavicle fractures., Methods: We retrospectively reviewed information on all patients from 2014 to 2018 at a single level 1 trauma institution with surgeries performed by two fellowship-trained orthopedic trauma surgeons. Documented removal of hardware and the reason for removal were recorded. We then contacted all patients at their listed telephone number to confirm the hardware was still in place and to administer patient outcome questionnaires. If patients did not answer, attempts were made to contact them multiple times on multiple days. Those who were not reached but had documented hardware removal were included in the total number of patients with hardware removal., Results: The search revealed 158 patients, of whom 89 (61.8%) were included in the study. Average follow up was 4.09 years (range 2.02-6.50 years). Five patients (5.56%) underwent hardware removal. Removal was for symptomatic or irritating hardware in two of these patients (2.22%). Average abbreviated Disability of Arm, Shoulder, and Hand score was 6.27, and average American Society of Shoulder and Elbow Surgeons shoulder score was 93.6., Conclusion: In our series, the rate of symptomatic hardware removal was 2.22%, well below reported removal rates. Hardware removal rates for prominent symptomatic superior clavicular plates may be significantly lower than previously reported, and these fractures may be adequately treated with a single, superior plate., Competing Interests: The authors report no funding or conflicts of interest., (Copyright © 2023 Baylor University Medical Center.)

Objective: This study was aimed to establish a reference interval for high-sensitivity cardiac troponin I (hs-cTnI) in umbilical cord blood of infants and to assess its association with the risk of predetermined early neonatal outcomes in a high-acuity tertiary care hospital., Study Design: Umbilical cord-blood samples were collected and hs-cTnI was measured in all infants born between August 2015 and September 2015 at McMaster Children's Hospital ( n =  256). Gestational age, birth weight, Apgar's scores, age in days at which feeding was established, neonatal intensive care unit (NICU) admission, and discharge in days after birth were recorded., Results: The 90th, 95th, and 99th percentiles for the term infant subcohort were 19.75, 41.45, and 166.30 ng/L, respectively. We observed decreased mean gestational ages and birth weights in both the 90th (37.7 weeks; 2,961.4 g) and 95th percentiles (37.1 weeks; 2,709.9 g) when compared with the remaining infants. Moreover, levels of hs-cTnI were significantly higher in infants with respiratory distress requiring intervention ( p  < 0.05), low birth weight infants ( p  < 0.01), preterm infants ( p  < 0.001), and those requiring NICU admission ( p  < 0.01). Multiple linear regression of the recorded demographic factors revealed prematurity (gestational age <35 weeks: coefficient 0.346 ± 0.160, p  < 0.05; gestational age <37 weeks: coefficient 0.253 ± 0.105, p  < 0.05) and male sex (coefficient 0.138 ± 0.047; p  < 0.01) to be most predictive of log-hs-cTnI levels., Conclusion: This study establishes the reference values for cord-blood hs-cTnI in infants at a tertiary care center. Premature and sick infants requiring NICU admission had significantly higher levels of hs-cTnI., Key Points: · Established the 90th, 95th, and 99th percentiles of neonatal cord-blood hs-cTnI in term infants as 19.75, 41.45, and 166.30 ng/L, respectively.. · Infants with hs-cTnI levels exceeding the 90th percentile had lower gestational ages and birth weights with higher rates of NICU admissions.. · Infants with respiratory distress or requiring NICU admission were found to have higher levels of hs-cTnI.., Competing Interests: None declared., (Thieme. All rights reserved.)

This review aims to describe and compare porcine models of metabolic syndrome. This syndrome and its associated secondary comorbidities are set to become the greatest challenge to healthcare providers and policy makers in the coming century. However, an incomplete understanding of the pathogenesis has left significant knowledge gaps in terms of efficacious therapeutics. To further our comprehension and, in turn, management of metabolic syndrome, appropriate high-fidelity models of the disease complex are of great importance. In this context, our review aims to assess the most promising porcine models of metabolic syndrome currently available for their similarity to the human phenotype. In addition, we aim to highlight the strengths and shortcomings of each model in an attempt to identify the most appropriate application of each. Although no porcine model perfectly recapitulates the human metabolic syndrome, several pose satisfactory approximations. The Ossabaw miniature swine in particular represents a highly translatable model that develops each of the core parameters of the syndrome with many of the associated secondary comorbidities. Future high-fidelity porcine models of metabolic syndrome need to focus on secondary sequelae replication, which may require extended induction period to reveal.

Background: The triglyceride glucose (TyG) index is a novel surrogate marker of insulin resistance and increases cardiovascular disease risk. We sought to explore sex differences in the relationship between TyG and cardiovascular (CV) risk factors in metabolically obese normal weight (MONW) phenotype., Method: We analyzed data of 1208 healthy men and nonpregnant women enrolled in a population-based longitudinal study from January 2017-June 2020. MONW phenotype was defined by normal body mass index (BMI: 18-<25 kg/m 2 ) with at least one of the following metabolic disorders (MONW phenotype): elevated blood pressure (BP), hypertriglyceridemia, hyperglycemia, and low HDL cholesterol. Multiple logistic regression analysis was performed to assess the association between elevated TyG index and the CV risk factors in women and men and was presented in odds ratio (OR) with 95% confidence interval (CI)., Results: Of 1208 subjects, 350 (29%) were MONW phenotype (mean age (years): male: 43.5 ± 12.4 and female: 43.1 ± 12.7) and 858 were metabolically healthy normal weight (MHNW; n  = 858 (71%)). MONW women had higher mean values of the TyG index (8.03 ± 5.07) than men (7.47 ± 4.68). Multivariate analysis revealed that the elevated TyG index is significantly associated with MONW phenotype in women (adjusted OR: 8.73, 95% CI: 5.62-13.57) and men (aOR: 5.90, 95% CI: 4.23-8.23). TyG was found to be an excellent predictor of MONW status in both women (receiver operating characteristic (ROC) area under the curve (AUC): 0.979, 95% CI: 0.969-0.988) and men (ROC-AUC: 0.968, 95% CI: 0.952-0.983)., Conclusion: Our study revealed that the TyG index may represent a cost-effective and informative screening tool for the high-risk MONW phenotype., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Xiaoyang Xu et al.)

Objective: Inconsistent results regarding the association between the Body Mass Index (BMI) and brain disorders have been reported. We performed this study to investigate the association between BMI and risk of Parkinson, Alzheimer, Dementia and Dementia-mortality. Methods: A systematic search was conducted up to April 2019 in MEDLINE/PubMed, SCOPUS, and Cochrane Library. Results pooled with random-effects model. Results: Totally, 29 articles which were included in this study with4,978,621 participants. The pooled HR for Parkinson's in the underweight person was 1.20 (95%CI1.10-1.30). The pooled HR for dementia in underweight and overweight category was 1.23 (95%CI = 1.05-1.45) and 0.88 (95%CI = 0.83-0.94), respectively. There is not any significant relation between each categories of BMI and Alzheimer disease. The pooled HR for dementia in underweight and overweight category was 1.36 (95%CI = 1.14-1.63) and 0.81 (95%CI = 0.49-1.33), respectively. The non-linear association between BMI and risk of Dementia-mortality was significant ( p  = 0.001,Coeff = 0.003). Conclusion: This study highlights underweight related to increase incidence of Parkinson, Dementia, and Dementia mortality but no on Alzheimer disease.

Background: The prevalence and severity of COVID-19 are greatly reduced in children, yet some pediatric patients develop a syndrome resembling Kawasaki Disease (KD), termed Multisystem Inflammatory Syndrome in Children (MIS-C). With an estimated incidence of 2/100,000 children, MIS-C is relatively rare but can be fatal. Clinical features can include fever, hyperinflammatory state, gastrointestinal symptoms, myocardial dysfunction, and shock. The pathogenesis of MIS-C, although yet to be completely elucidated, appears to be distinct from KD in terms of epidemiology, severity, and biochemical signature., Aim of Review: Although efficacy of treatments for MIS-C have largely not yet been investigated, we aim to conduct a comprehensive literature search of numerous medical databases (AMED, EBM Reviews, Embase, Healthstar, MEDLINE, ERIC, and Cochrane) to highlight treatments used around the world, their rationale, and outcomes to better inform guidelines in the future. Using the findings, an approach to MIS-C management will be outlined., Key Scientific Concepts of Review: •MIS-C appears to be a SARS-CoV-2 related post-infection phenomenon that is distinct from Kawasaki disease.•Although outcomes are largely favorable, there is significant variation in MIS-C treatment. Most management regimens reported to date mirror that of KD; however, targeted therapy based on specific MIS-C phenotypes may have the potential to improve outcomes.•We recommend close monitoring by a multidisciplinary team, symptomatic treatment (e.g., intravenous immunoglobulin for KD-like symptoms, steroids/immunotherapy for multisystem inflammation), and long-term follow-up.•Further research is required to evaluate the effectiveness of current MIS-C treatments and to determine more refined therapies., Competing Interests: The authors have no duality of interest to declare., (© 2021 Elsevier B.V. All rights reserved.)

Background: Hallux valgus affects 23-36% in general populations. The purpose of this study was to evaluate return to run following either a modified Lapidus procedure or a metatarsal osteotomy. We hypothesized that there would be no difference in the ability to return to running., Methods: A Retrospective review of a consecutive series of patients at a single institution with surgical correction was performed. 51 patients were identified. 35 were treated with a metatarsal shaft osteotomy and 16 with a modified Lapidus., Results: No difference was found between the cohorts in terms of age, sex, or preoperative hallux valgus angle (HVA). 27/35 (77%) with metatarsal shaft osteotomy were able to return to running versus 13/16 (81%) with modified Lapidus. There was no significant difference in the ability to return to running between cohorts (p =1.00)., Conclusion: Our study showed no statistical difference for the modified Lapidus versus metatarsal osteotomies relative to return to running., (Published by Elsevier Ltd.)

Background: Patient-reported outcomes (PROs) measure progression and quality of care. While legacy PROs such as the International Knee Documentation Committee (IKDC) survey are well-validated, a lengthy PRO creates a time burden on patients, decreasing adherence. In recent years, PROs such as the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function and Pain Interference surveys were developed as computer adaptive tests, reducing time to completion. Previous studies have examined correlation between legacy PROs and PROMIS; however, no studies have developed effective prediction models utilizing PROMIS to create an IKDC index. While the IKDC is the standard knee PRO, computer adaptive PROs offer numerous practical advantages., Purpose: To develop a nonlinear predictive model utilizing PROMIS Physical Function and Pain Interference to estimate IKDC survey scores and examine algorithm sensitivity and validity., Study Design: Cohort study (diagnosis); Level of evidence, 3., Methods: The MOTION (Military Orthopaedics Tracking Injuries and Outcomes Network) database is a prospectively collected repository of PROs and intraoperative variables. Patients undergoing knee surgery completed the IKDC and PROMIS surveys at varying time points. Nonlinear multivariable predictive models using Gaussian and beta distributions were created to establish an IKDC index score, which was then validated using leave-one-out techniques and minimal clinically important difference analysis., Results: A total of 1011 patients completed the IKDC and PROMIS Physical Function and Pain Interference, providing 1618 complete observations. The algorithms for the Gaussian and beta distribution were validated to predict the IKDC (Pearson = 0.84-0.86; R 2 = 0.71-0.74; root mean square error = 9.3-10.0)., Conclusion: The publicly available predictive models can approximate the IKDC score. The results can be used to compare PROMIS Physical Function and Pain Interference against historical IKDC scores by creating an IKDC index score. Serial use of the IKDC index allows for a lower minimal clinically important difference than the conventional IKDC. PROMIS can be substituted to reduce patient burden, increase completion rates, and produce orthopaedic-specific survey analogs.

Parvimonas micra is an anaerobic, fastidious, gram positive organism commonly found in the oral cavity and gastrointestinal tract. It has been increasingly reported as the cause of septic arthritis of native joints, often times with delayed diagnosis leading to increased morbidity. Risk factors include immunosuppression, inflammation of the joint, and recent dental procedures or infections. It has been a historically difficult organism to culture. However, the development of and increasing use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has led to increased identification of P. micra. Common antibiotic susceptibilities, as well as data regarding susceptibilities in specific situations, have been reported, but susceptibility testing is required in all cases. Common treatments include clindamycin, penicillin, and metronidazole for six to ten weeks., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Stress radiographs have demonstrated superior efficacy in the evaluation of ankle instability., Aim: To determine if there is a degree of instability evidenced by stress radiographs that is associated with pathology concomitant with ankle ligamentous instability., Methods: A retrospective review of 87 consecutive patients aged 18-74 who had stress radiographs performed at a single institution between 2014 and 2020 was performed. These manual radiographic stress views were then correlated with magnetic resonance imaging and operative findings., Results: A statistically significant association was determined for the mean and median stress radiographic values and the presence of peroneal pathology ( P = 0.008 for tendonitis and P = 0.020 for peroneal tendon tears). A significant inverse relationship was found between the presence of an osteochondral defect and increasing degrees of instability ( P = 0.043)., Conclusion: Although valuable in the clinical evaluation of ankle instability, stress radiographs are not an independent predictor of conditions associated with ankle instability., Competing Interests: Conflict-of-interest statement: None of the authors have a conflict of interest with the submitted study., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: To determine the weight, body mass index (BMI), cardiometabolic, and gastrointestinal effects of glucagon-like peptide-1 (GLP-1) receptor agonists in children with obesity., Study Design: Web of Science, PubMed/MEDLINE, and Scopus databases from 01/01/1994-01/01/2021 for randomized control trials examining the weight, BMI, cardiometabolic, or gastrointestinal effects of GLP-1 receptor agonists in children and adolescents with obesity. Data were extracted by 2 independent surveyors and a random effects model was applied to meta-analyze generic inverse variance outcomes. Primary outcomes were related to weight and cardiometabolic profile, and secondary outcomes of interest were gastrointestinal-related treatment-emergent adverse events., Results: Nine studies involving 574 participants were identified, of which 3 involved exenatide and 6 involved liraglutide. GLP-1 receptor agonists use caused a modest reduction in body weight (mean difference [MD] -1.50 [-2.50,-0.50] kg, I 2 64%), BMI (MD -1.24 [-1.71,-0.77] kg/m 2 , I 2 0%), and BMI z score (MD -0.14 [-0.23,-0.06], I 2 43%). Glycemic control was improved in children with proven insulin resistance (glycated hemoglobin A1c MD -1.05 [-1.93,-0.18] %, I 2 76%). Although no lipid profile improvements were noted, a modest decrease in systolic blood pressure was detected (MD -2.30 [-4.11,-0.49] mm Hg; I 2 0%). Finally, analysis of gastrointestinal-related treatment-emergent adverse events revealed an increased risk of nausea (risk ratio 2.11 [1.44, 3.09]; I 2 0%), without significant increases in other gastrointestinal symptoms., Conclusions: This meta-analysis indicates that GLP-1 receptor agonists are safe and effective in modestly reducing weight, BMI, glycated hemoglobin A1c, and systolic blood pressure in children and adolescents with obesity in a clinical setting, albeit with increased rates of nausea., Prospero Id: CRD42020195869., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Senior individuals can suffer from immunosenescence and novel strategies to bolster the immune response could contribute to healthy ageing. In this double-blind, randomised, controlled pilot trial, we investigated the ability of non-digestible polysaccharide (NPS) preparations to enhance the immune response in a human vaccination model. In total, 239 subjects (aged 50-79 years) were randomised to consume one of five different NPS (yeast β-glucan (YBG), shiitake β-glucan (SBG), oat β-glucan (OBG), arabinoxylan (AX), bacterial exopolysaccharide (EPS)) or control (CTRL) product daily for five weeks. After two weeks of intervention, subjects were vaccinated with seasonal influenza vaccine. The post-vaccination increases in haemagglutination inhibition antibody titres and seroprotection rate against the influenza strains were non-significantly enhanced in the NPS intervention groups compared to CTRL. Specifically, a trend towards a higher mean log 2 fold increase was observed in the AX group (uncorrected p = 0.074) combined with a trend for an increased seroprotection rate, AX group (48.7%) compared to CTRL (25.6%) (uncorrected p = 0.057), for the influenza A H1N1 strain. Subjects consuming AX also had a reduced incidence of common colds compared to CTRL (1 vs. 8; p = 0.029 in Fisher exact test). No adverse effects of NPS consumption were reported. The findings of this pilot study warrant further research to study AX as an oral adjuvant to support vaccine efficacy.

Background: COVID-19 has resulted in the death of over 1 million people to date. Following government-implemented regulations, there has been concern over the apparent decline in emergency department (ED) attendances and the resultant health legacy. Therefore, we aimed to characterise the attendances to an Irish tertiary hospital ED following the implementation of these regulations during the COVID-19 pandemic., Methods: This retrospective observational study investigated all attendances to the Cork University Hospital ED from 15 February to 11 April in 2020 and 2017-2019. Attendances were stratified into four periods: Before COVID (BC) (15 February to 5 March), After COVID (AC) (6 March to 12 March), Educational Closure (EC) (13 March to 27 March) and Stay Home (SH) (28 March to 11 April), as per government regulations. Triage presentations of abdominal pain, shortness of breath, chest pain, headache and trauma were examined. Data were analysed by independent t-tests and χ 2 analysis., Results: There were 8261 attendances to the ED in the 2020 time period compared with a mean of 10 389 attendances during the corresponding periods in 2017-2019. There was a significant decrease in daily attendances in 2020 compared with 2017-2019 in the AC (142 vs 188, p=0.02), EC (122 vs 184, p<0.001) and SH (121 vs 181, p<0.001) periods, including significant decreases in abdominal pain (AC: 9 vs 22, EC: 10 vs 19, SH: 11 vs 18, p<0.001), chest pain (AC: 9 vs 15, EC: 8 vs 15, SH: 9 vs 15, p<0.01), headache (AC: 5 vs 11, EC: 4 vs 9, SH: 4 vs 9, p<0.01) and trauma (AC: 3 vs 5, EC: 2 vs 6, SH: 3 vs 5, p<0.01 ) ., Conclusion: Our findings suggest that the combination of government-imposed restrictions and perceived risk of attending an ED during a pandemic may contribute to reduced attendances. Public confidence in EDs is necessary to reduce collateral damage caused by failure to seek medical attention during a pandemic; adequate infrastructure to allow social distancing and isolation capacity in EDs is a necessity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The preferred patient-reported outcome measure for the assessment of shoulder conditions continues to evolve. Previous studies correlating the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests (CATs) to the American Shoulder and Elbow Surgeons (ASES) score have focused on a singular domain (pain or physical function) but have not evaluated the combined domains of pain and physical function that compose the ASES score. Additionally, previous studies have not provided a multivariable prediction tool to convert PROMIS scores to more familiar legacy scores., Purpose: To establish a valid predictive model of ASES scores using a nonlinear combination of PROMIS domains for physical function and pain., Study Design: Cohort study (Diagnosis); Level of evidence, 3., Methods: The Military Orthopaedics Tracking Injuries and Outcomes Network (MOTION) database is a prospectively collected repository of patient-reported outcomes and intraoperative variables. Patients in MOTION research who underwent shoulder surgery and completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at varying time points were included in the present analysis. Nonlinear multivariable predictive models were created to establish an ASES index score and then validated using "leave 1 out" techniques and minimal clinically important difference /substantial clinical benefit (MCID/SCB) analysis., Results: A total of 909 patients completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at presurgery, 6 weeks, 6 months, and 1 year after surgery, providing 1502 complete observations. The PROMIS CAT predictive model was strongly validated to predict the ASES (Pearson coefficient = 0.76-0.78; R 2 = 0.57-0.62; root mean square error = 13.3-14.1). The MCID/SCB for the ASES was 21.7, and the best ASES index MCID/SCB was 19.4, suggesting that the derived ASES index is effective and can reliably re-create ASES scores., Conclusion: The PROMIS CAT predictive models are able to approximate the ASES score within 13 to 14 points, which is 7 points more accurate than the ASES MCID/SCB derived from the sample. Our ASES index algorithm, which is freely available online (https://osf.io/ctmnd/), has a lower MCID/SCB than the ASES itself. This algorithm can be used to decrease patient survey burden by 11 questions and provide a reliable ASES analog to clinicians.

Aim: To establish the incidence and characteristics of paediatric thrombosis (PT) in a Canadian tertiary care centre during the era of low molecular weight heparin (LMWH)., Methods: A retrospective observational case study of all patients <18 years of age evaluated for arterial and venous thrombosis from May 2008 to July 2018 at McMaster Children's Hospital was conducted through the electronic medical record., Results: The incidence of PT was 52.2 per 10 000 hospital admissions (n = 477/91 462). Provoked thrombosis was more prevalent (88.9%, n = 424/477) than unprovoked (2.9%, n = 14/477) or idiopathic thrombosis (4%, n = 19/477). Half of PT were in children <2 years (51.2%, n = 244/477). Central vascular catheterisation was a contributory factor in more than half of thrombotic events (56.2%, n = 268/477), while trauma (1.1%, n = 5/477), oral contraceptives (4%, n = 19/477), infection (4%, n = 19/477), surgery (6.9%, n = 33/477) and malignancy (8.4%, n = 40/477) were also risk factors. Arterial ischaemic stroke was diagnosed in 11.1% of cases (n = 53/477), while pulmonary embolism was identified in 7.1% (n = 34/477) and 1.7% of cases were fatal (n = 8/477). LMWH was the first-line therapeutic of choice (47.8%, n = 228/477), with 28.1% (n = 134/477) requiring no intervention., Conclusion: These data reiterate the elevated thrombosis risk to which infants and children with central vascular access are exposed., (©2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

In order to best treat a patient, the carer must be able to clearly see their point of view. In the case of the complexities of insulin pump therapy, physicians may not fully understand the common challenges that drive patients to non-adherence. The author undertook a three-day simulation using wearable technology to explore this experience. This form of simulation represents a simple yet effective means by which to foster cognitive empathy in undergraduate and postgraduate medical education settings alike., Competing Interests: Conflicts of Interest: The author reports no conflicts of interest., (© 2021 Ryan; licensee Synergies Partners.)

Purpose: Tenofovir (TDF) and entecavir (ETV) are both equally recommended as first-line treatments for patients with chronic hepatitis B (CHB). They have comparable efficacy in virologic response, but their effect on the development of hepatocellular carcinoma (HCC) in CHB is controversial. Therefore, we aimed to compare TDF and ETV evaluating the risk of HCC development in CHB patients., Methods: A systematic literature search was conducted up to November 2019 in MEDLINE/PubMed, SCOPUS, and Web of Science databases without language and time restrictions. DerSimonian and Laird random-effects models were used to estimate combined hazard ratios (HRs) and 95% CIs., Results: Seven studies containing 35,785 participants were included in this systematic review and meta-analysis. The pooled HR (95% CI) of HCC in the patients who used TDF versus patients who used ETV was 0.75 (0.56-0.96). There was no significant heterogeneity detected among the included studies results ( I 2 = 47.5%). There was no significant publication bias detected among the included studies (Begg's p = 0.88 and Egger's regression test p = 0.96)., Conclusions: Evidence to date suggests that TDF treatment is associated with significantly fewer cases of HCC when compared to ETV., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by S. Karger AG, Basel.)

Fibroblast growth factor-19 (FGF-19) is a gut hormone which interacts with metabolism and is depleted in obesity. There is some indication that the hormone undergoes a resurgence following bariatric surgery (BS), an effect which may contribute to the beneficial outcomes of such procedures. This systematic review and meta-analysis aims to synthesize the available literature on FGF-19 levels before and after BS. MEDLINE, Scopus and Web of Science databases were searched, and the effect of different surgical procedures and degrees of body mass index (BMI) reduction on FGF-19 levels was assessed by DerSimonian and Laird random-effects model in meta-analysis and dose-response analyses. This meta-analysis, which included 474 patients from 25 arms undergoing one of five BS procedures, revealed a significant increase in the levels of circulating FGF-19 following all-type BS. Vertical sleeve gastrectomy, duodenal-jejunal bypass liner and Roux-en-Y gastric bypass all significantly increased circulating FGF-19 levels from baseline. However, gastric banding failed to achieve the same, and in fact, biliopancreatic diversion was associated with decreased circulating FGF-19. Finally, an inverse association between FGF-19 and the degree of BMI-reduction post-operatively was noted. FGF-19 is increased by BS and may represent a pharmaceutical target in efforts to reproduce the beneficial effects of BS in a medical setting., (© 2020 World Obesity Federation.)

Background: The relationship between body mass index (BMI) and risk of venous thromboembolism (VTE) and pulmonary embolism (PE) is a controversial issue. This dose-response meta-analysis was performed to investigate the association between BMI and risk of VTE and PE incidence based on cohort studies., Method: A comprehensive systematic search was conducted up to August 2019 in MEDLINE/PubMed, SCOPUS, and Cochrane. DerSimonian and Laird random-effects models were run to estimate combined hazard ratios (HRs) with 95% confidence intervals (CIs). Dose-response analysis was also carried out based on BMI values., Results: Eleven articles with 16 arms and 3,910,747 participants were eligible for inclusion in this systematic review and meta-analysis. Pooled results showed a positive association between BMI and risk of VTE in the obese participants compared to participants classified in the normal BMI category (HR: 1.62, 95% CI: 1.29-2.04, I 2  = 95%). Furthermore, results showed a significant association between lower BMI (underweight versus normal BMI category) and reduced risk of PE (HR: 0.80, 95% CI: 0.70-0.92, I 2  = 9%) and higher risk of PE in obese versus normal BMI participants (HR: 2.24, 95% CI: 1.93-2.60, I 2  = 0%). There was a significant linear relationship between BMI and risk of VTE (p < 0.001) and PE (p < 0.001)., Conclusions: This systematic review and dose-response meta-analysis with 3,910,747 participants highlights obesity as a significant risk factor related to the incidence of VTE and PE., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Coronavirus disease 2019 (COVID-19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcomes include advanced age, male sex, preexisting cardiovascular disease, and risk factors including hypertension, diabetes, and, more recently, obesity. This article posits new obesity-driven predictors of poor COVID-19 outcomes, over and above the more obvious extant risks associated with obesity, including cardiometabolic disease and hypoventilation syndrome in intensive care patients. This article also outlines a theoretical mechanistic framework whereby adipose tissue in individuals with obesity may act as a reservoir for more extensive viral spread, with increased shedding, immune activation, and cytokine amplification. This paper proposes studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in individuals with obesity and COVID-19. Finally, this paper underscores emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal., (© 2020 The Obesity Society.)