Anterior Talofibular Ligament Abnormalities on Routine Magnetic Resonance Imaging of the Ankle

Category: Ankle, Sports, Trauma Introduction/Purpose: The anterior talofibular ligament (ATFL) is one of the most commonly injured structures of the lower extremity after an ankle sprain. Evidence of remote injury to this structure is frequently encountered on magnetic resonance imaging (MRI) of the ankle, with uncertain clinical significance. Previous studies in the orthopaedic literature have discussed the prevalence of abnormal MRI findings in asymptomatic patients, most notably with regards to the spine and shoulder. More recently, a study on the prevalence of peroneal tendon abnormalities on routine MRI of the ankle was published. However, to our knowledge, no such study exists for the ATFL. The purpose of this study is to determine the prevalence of abnormal findings of the ATFL on MRI in asymptomatic individuals. Methods: All foot and ankle MRIs performed at our institution over a 4-month period were considered for inclusion in our study. Studies were excluded if performed on patients with documented ankle inversion injuries, ankle sprains, lateral ankle trauma, tenderness over the ATFL, or ankle instability. A total of 320 MRIs were eligible for inclusion. The integrity of the ATFL was noted in addition to the primary pathology. Results: The median age of the patients included in this study was 51 years with 203 females (63%) and 117 males (37%). One hundred eighteen (37%) of the 320 MRIs demonstrated some ATFL pathology. The most commonly encountered ATFL pathologies were thickening (38%), chronic tear (35%), attenuation (25%) and acute tear (2%). Conclusion: The results of this study demonstrate that a sizeable percentage of asymptomatic individuals (37%) will have ATFL abnormalities on magnetic resonance imaging of the foot and ankle. This study can have important clinical implications for patients who present with concerning MRI findings that do not correlate clinically. Based on our results, orthopaedic surgeons or any other physician providing musculoskeletal care can provide counseling and reassurance to patients who present with ATFL pathology on MRI but an absence of clinical findings. Much like MRI of the shoulder or spine, abnormalities must be correlated with the clinical exam

The Association Between Distressed Community Index and Clinical Outcomes Following Surgical Repair of Acute Achilles Tendon Rupture

Category: Ankle; Other Introduction/Purpose: Operative management of acute Achilles tendon ruptures can be associated with a myriad of complications1,2. Demographics and comorbidities have been previously explored in relation to outcomes after operative management of Achilles tendon ruptures3,4. However, the relationship between socioeconomic factors and postoperative outcomes in these patients has not been explored. Distressed community index (DCI) is a score that represents a community’s level of well-being across the United States, with higher scores representing greater distress experienced in the community. Independent socioeconomic deprivation factors have been shown to be associated with suboptimal postoperative outcomes for patients undergoing certain orthopedic surgeries6–9. The purpose of this study is to determine if there is any association between DCI scores and short-term complication rates and functional outcomes following ruptured Achilles tendon repair. Methods: Patients who underwent surgical repair of ruptured Achilles tendon between 2015 and 2019 were identified. Patients’ residence zip codes were obtained and matched to corresponding DCI scores (0-100) based on data provided by the Economic Innovation Group for the same time period (2015-2019). Scores were divided into quintiles. Patient age, race, ethnicity, alcohol and smoking history, need for assistance with activities of daily living, ambulation status unrelated to injury, and access to transportation were also noted. Complications such as re-rupture, superficial or deep infection, wound complications, and deep vein thrombosis within 1-year since date of surgery were noted. Preoperative Foot and Ankle Ability Measure and Visual Analogy Pain scales were compared to postoperative scores at 6 months, 1 year, and 2 years. Analysis of variance (ANOVA) was used to determine the statistical significance of differences in the rate of complications and FAAM-VAS scores between quintiles. Results: Patients in the 2nd DCI quintile experienced the highest rate (9.25%) of total complications while patients in the 5th quintile experienced the lowest rate (3.33%). Difference in complication rates across DCI quintiles was not statistically significant (p=0.925). Out of the 17 patients who experienced complications, 12 (70.6%) patients belonged to the 1st and 2nd quintile while 2 patients (11.7%) belonged to the 4th and 5th quintiles. The differences in FAAM and VAS pain scores were not significantly different at preoperative and at 1-year and 2-year postoperative time points across quintiles. However, patients in the 5th and 4th quintiles experienced the greatest improvement in FAAM Overall scores at 1-year and 2-year postoperative time points, respectively. Conclusion: Patients living in more distressed communities did not experience greater postoperative complication rates or report lower patient-reported outcomes up to 2 years following operative repair of Achilles tendon rupture

The Association Between Distressed Community Index and Clinical Outcomes Following Total Ankle Arthroplasty

Category: Ankle Arthritis; Ankle Introduction/Purpose: Socioeconomic deprivation factors such as income levels, race and ethnicity, low education level, and insurance status have been shown to be associated with suboptimal postoperative outcomes for patients undergoing orthopedic surgeries, including certain foot and ankle procedures1–3. Total ankle arthroplasty (TAA) is a surgical treatment for end-stage ankle joint disease that has seen a significantly increased utilization over the past two decades4. Distressed community index (DCI) is a score that represents a community’s level of well-being across the United States5, with higher scores representing greater distress experienced in the community. The purpose of this study was to determine if there is any association between DCI scores and complications rates along with functional outcomes following primary TAA. Methods: 566 patients who underwent primary TAA between 2015 and 2019 at our institution were identified. Patients’ residence zip codes at the time of surgery were obtained and the corresponding DCI scores (0-100) were determined using DCI data provided by the Economic Innovation Group for the same time period (2015-2019). Scores were divided into quintiles. Patient age, sex, body mass index, race, ethnicity, rheumatic disease status, Osteoporosis status, Charlson comorbidity index, alcohol use, smoking status, length of hospital stay, discharge to rehabilitation facility, depression history, anxiety history, and marital status were obtained. Postoperative FAAM-VAS scores at 6 months, 1-year, and 2-years were compared to their preoperative scores. Revision, infection, steroid injection, loose body or hardware removal, irrigation and debridement, periprosthetic fracture, and tibial/talar exostectomy were noted. Analysis of variance (ANOVA) was used to determine the statistical significance of differences in the rate of subsequent complications and interventions related to index TAA. Results: 88/566 (15.5%) of all patients required at least one operative intervention related to the index TAA. Patients in the 4th DCI quintile experienced the highest rate of subsequent procedures at 18.3% while those in the 5th DCI quintile experienced the lowest rate at 10.6%. The differences in rate of subsequent operative intervention across DCI quintiles was not statistically significant (p=0.775). However, the rates of revision and infection were the highest for patients in the 4th and 5th DCI quintiles, respectively. The differences in improvement of FAAM Overall and VAS Pain scores at 6 months, 1-year, and 2-years from index surgery were not statistically significant. Those in the 5th quintile experienced the least improvement in FAAM Overall at the 1- year and 2-year postoperative time points. Conclusion: DCI score was not associated with increased rates of postoperative complication requiring operative intervention and FAAM-VAS scores in patients undergoing primary TAA. However, patients in the 5th quintile of DCI experienced non-significantly lesser improvement in FAAM-VAS scores up to 2-years from surgery

The Effect of Body Mass Index on Short-Term Complications and Patient-Reported Outcomes in Patients with Surgically-Repaired Achilles Tendon

Category: Ankle; Other Introduction/Purpose: Obesity has shown to be associated with postoperative wound complications, infection, VTE, and wound dehiscence in patients undergoing surgical repair of the Achilles tendon1–3. Obesity is often defined as body mass index (BMI) greater than 30kg/m 2 . The Center for Disease Control defines adult BMI ranges as follows: underweight ( 35kg/m 2 (Group 4;n=22). Analysis of Variance Testing or Kruskal-Wallis Testing was used to calculate p-values for continuous data and Chi-Square testing was used to calculate p-values for categorical data. Pairwise testing was also conducted when appropriate. Results: The difference in rates of infection resulting in wound dehiscence or abscess drainage was not statistically significant across groups (p=0.362). No patient experienced re-rupture of the ipsilateral Achilles tendon. Group 4 patients reported the highest preoperative FAAM Overall, FAAM-ADL, and VAS scores. Their postoperative FAAM-Overall and FAAM-ADL scores were the lowest at all postoperative time points. Compared to patients in Group 2, patients in Group 4 demonstrated significantly less improvement in FAAM Overall score at 6 months (p= 0.029), 1-year (p=0.006), and 2-years (p=0.039) from surgery. The improvement in FAAM-ADL and VAS pain scores were not significantly different across BMI groups. However, the magnitude of improvement in FAAM-ADL was the lowest for patients in Group 4 at all postoperative time points. Conclusion: BMI was not significantly correlated with postoperative wound complication, infection, or re-rupture rates, but patients with BMI >35kg/m 2 reported significantly less improvement in FAAM Overall scores at the 6-month, 1-year, and 2-year postoperative periods compared to those with BMI between 25 and 30kg/m 2

Midterm Outcomes of the Salto Talaris Total Ankle Arthroplasty

Category: Ankle Arthritis; Ankle Introduction/Purpose: Total ankle arthroplasty (TAA) has become an accepted alternative to ankle arthrodesis for end-stage ankle arthritis and has seen significantly increased utilization in the past decade1. The Salto Talaris total ankle prosthesis has shown excellent short-term and mid-term survivorship results since its FDA approval in the U.S. in 20062,3. At a minimum of five-year follow-up, the currently reported midterm survivorship has ranged from 93.3% to 100% with equally satisfactory clinical outcomes as evidenced in short-term outcome studies4–8. The purpose of this study is to report the outcomes of one of the largest cohort of patients who underwent a Salto Talaris total ankle arthroplasty with a minimum of five-year follow-up. Methods: 103 Salto Talaris TAA patients with 5-view weight-bearing series of radiographs and minimum follow-up time of 5 years since index surgery were included. Age at time of surgery, gender, body mass index, diagnosis, diabetes status, and tobacco use were collected through chart review. Radiographic imaging was assessed at the most recent follow-up for evidence of radiolucency and osteolysis as previously described9. Range of motion was assessed on plantarflexion and dorsiflexion views on sagittal radiographs as previously described10. The Foot and Ankle Ability Measure (FAAM) and Visual Analog Scale for pain (VAS) scores were obtained at the most recent follow up visit and compared with preoperative scores. Baseline characteristics were compared between groups using Wilcoxon rank-sum test for continuous data or Fisher exact test for discrete data. Survivorship probability was calculated using a Kaplan-Meier analysis for revisions and reoperations. Revisions were defined as exchange or removal of metal component. Results: The survivorship for revision surgery was 93.2% (95% CI [89.8,98.8]). 5 out of the 7 patients requiring revision surgery experienced talar subsidence, 1 patient experienced an infection, and 1 patient experienced lateral impingement. The survivorship for reoperation was 90.2% (95% CI [83.4-95.4]). 5 out of the 10 patients requiring reoperation experienced pain from impingement, 2 experienced periprosthetic fractures, 1 experienced infection, and 2 experienced osteolytic cysts. At last follow- up, the FAAM-ADL, FAAM-Sport, and VAS pain scores were improved from preoperatively. The average range of motion at last follow-up was 31.6 degrees. On the AP view, radiolucency and osteolysis were most frequently detected in zones 3 and 4, while on the lateral view they were most frequently seen in zones 2 and 6. Conclusion: Patients undergoing Salto Talaris prosthesis showed improvements in patient-reported outcomes with satisfactory survival rates

Comparison of Bone Healing and Delayed or Nonunion Rates Between Operatively and Non- operatively Treated Displaced Zone 1 Fifth Metatarsal Fractures

Category: Midfoot/Forefoot; Other Introduction/Purpose: Acute fractures of the proximal fifth metatarsal are one of the most common injuries to the foot, occurring in up to 70% of all metatarsal fractures1. Displaced zone 1 fractures of the fifth metatarsal with greater than 2 mm fracture gap or those comprising greater than 30% of the cubometatarsal joint warrant operative treatment with open reduction internal fixation (ORIF)2,7, as satisfactory bone healing and patient-reported outcomes have been reported previously8–13. More recently, a few studies have demonstrated good functional outcomes after conservative treatment of zone 1 fractures with initial displacement greater than 2 mm7,13. Nevertheless, the lack of comparative studies and conflicting available evidence of outcomes warrant further investigation on this topic. Methods: A chart review was conducted to identify patients with displaced zone 1 fractures of the fifth metatarsal. Age at time of injury, gender, smoking and diabetes history, were collected. Degree of fracture displacement were measured (mm) on AP, lateral, and oblique view radiographs obtained at the initial encounter. Non-operatively treated patients were instructed to weightbear as tolerated in a Controlled Ankle Motion (CAM) boot for 6 weeks. Surgically-treated patients were placed in a short-leg splint for 2 weeks, and remained non-weightbearing in a CAM boot until 6 week period. They transitioned to normal shoe wear at the 8 week postoperative period. Chart notes were reviewed to identify the time to complete healing and incidences of delayed or nonunion. Means were compared using a one-way ANOVA or Kruskal Wallis test depending on normality, and categorical variables were compared using Chi-square or Fisher’s exact test. Results: The average time to complete healing was greater in non-operatively treated patients by 3 weeks (17.1 vs. 14.1, p=0.282). 4/37 (10.8%) non-operatively treated patients experienced delayed or non-union whereas 4/38 (13.2%) operatively-treated patients experienced delayed or non-union. This difference was statistically non-significant. The average fracture displacement (mm) on the oblique view was significantly greater in operatively-treated patients (2.68 vs. 5.40, p< 0.001). For patients with fracture gaps greater than 2 mm on the oblique view, non-operatively treated patients took 20.9 weeks whereas operatively- treated patients took 11.8 weeks to reach complete healing (p < 0.01). Conclusion: Patients who were treated non-operatively for displaced zone 1 fractures of the fifth metatarsal took on average 3 weeks longer to reach complete healing than operatively-treated patients. For patients with fracture gap greater than 2 mm on the oblique view, operative treatment was associated with significantly reduced time to complete healing

Comparison between Listeria sensu stricto and Listeria sensu lato strains identifies novel determinants involved in infection

Abstract The human pathogen L. monocytogenes and the animal pathogen L. ivanovii, together with four other species isolated from symptom-free animals, form the “Listeria sensu stricto” clade. The members of the second clade, “Listeria sensu lato”, are believed to be solely environmental bacteria without the ability to colonize mammalian hosts. To identify novel determinants that contribute to infection by L. monocytogenes, the causative agent of the foodborne disease listeriosis, we performed a genome comparison of the two clades and found 151 candidate genes that are conserved in the Listeria sensu stricto species. Two factors were investigated further in vitro and in vivo. A mutant lacking an ATP-binding cassette transporter exhibited defective adhesion and invasion of human Caco-2 cells. Using a mouse model of foodborne L. monocytogenes infection, a reduced number of the mutant strain compared to the parental strain was observed in the small intestine and the liver. Another mutant with a defective 1,2-propanediol degradation pathway showed reduced persistence in the stool of infected mice, suggesting a role of 1,2-propanediol as a carbon and energy source of listeriae during infection. These findings reveal the relevance of novel factors for the colonization process of L. monocytogenes

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)

Search for the Standard Model Higgs Boson in the Diphoton Decay Channel with 4.9 fb(-1) of pp Collision Data at root s=7 TeV with ATLAS

A search for the Standard Model Higgs boson is performed in the diphoton decay channel. The data used corresponds to an integrated luminosity of 4.9 fb-1 collected with the ATLAS detector at the Large Hadron Collider in proton-proton collisions at a center-of-mass energy of sqrt(s) = 7 TeV. In the diphoton mass range 110-150 GeV, the largest excess with respect to the background-only hypothesis is observed at 126.5 GeV, with a local significance of 2.8 standard deviations. Taking the look-elsewhere effect into account in the range 110-150 GeV, this significance becomes 1.5 standard deviations. The Standard Model Higgs boson is excluded at 95% confidence level in the mass ranges of 113-115 GeV and 134.5-136 GeV