Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension.

Matrix Metalloproteinases (MMPs) are drivers of many diseases including cancer and are established targets for drug development. Tissue inhibitors of metalloproteinases (TIMPs) are human proteins that inhibit MMPs and are being pursued for the development of anti-MMP therapeutics. TIMPs possess many attractive properties of a drug candidate, such as complete MMP inhibition, low toxicity and immunogenicity, high tissue permeability and others. A major challenge with TIMPs, however, is their formulation and delivery, as these proteins are quickly cleared from the bloodstream due to their small size. In this study, we explore a new method for plasma half-life extension for the N-terminal domain of TIMP2 (N-TIMP2) through appending it with a long intrinsically unfolded tail containing a random combination of Pro, Ala, and Thr (PATylation). We design, produce and explore two PATylated N-TIMP2 constructs with a tail length of 100- and 200-amino acids (N-TIMP2-PAT100 and N-TIMP2-PAT200, respectively). We demonstrate that both PATylated N-TIMP2 constructs possess apparent higher molecular weights compared to the wild-type protein and retain high inhibitory activity against MMP-9. Furthermore, when injected into mice, N-TIMP2-PAT200 exhibited a significant increase in plasma half-life compared to the non-PATylated variant, enhancing the therapeutic potential of the protein. Thus, we establish that PATylation could be successfully applied to TIMP-based therapeutics and offers distinct advantages as an approach for half-life extension, such as fully genetic encoding of the gene construct, mono-dispersion, and biodegradability. Furthermore, PATylation could be easily applied to N-TIMP2 variants engineered to possess high affinity and selectivity toward individual MMP family members, thus creating attractive candidates for drug development against MMP-related diseases.

Defining accurate terminology for post-injury weightbearing instructions - a multidisciplinary, nationally approved consensus policy.

Aims: Weightbearing instructions after musculoskeletal injury or orthopaedic surgery are a key aspect of the rehabilitation pathway and prescription. The terminology used to describe the weightbearing status of the patient is variable; many different terms are used, and there is recognition and evidence that the lack of standardized terminology contributes to confusion in practice. Methods: A consensus exercise was conducted involving all the major stakeholders in the patient journey for those with musculoskeletal injury. The consensus exercise primary aim was to seek agreement on a standardized set of terminology for weightbearing instructions. Results: A pre-meeting questionnaire was conducted. The one-day consensus meeting, including patient representatives, identified three agreed terms only to be used in defining the weightbearing status of the patient: 1) non-weightbearing; 2) limited weightbearing; and 3) unrestricted weightbearing. Conclusion: This study represents the first and only exercise in standardizing rehabilitation terminology in orthopaedics, as agreed by all major stakeholders in the patient pathway and the patients themselves. The standardization of language allows for higher-quality and more accurate research to be conducted, and is one small part of the bigger picture in increasing the mobility of patients after orthopaedic injury or surgery.

Synthesis and Catalytic Performance of Bimetallic Oxide-Derived CuO-ZnO Electrocatalysts for CO2 Reduction.

Steering the selectivity of electrocatalysts toward the desired product is crucial in the electrochemical reduction of CO2. A promising approach is the electronic modification of the catalyst's active phase. In this work, we report on the electronic modification effects on CuO-ZnO-derived electrocatalysts synthesized via hydrothermal synthesis. Although the synthesis method yields spatially separated ZnO nanorods and distinct CuO particles, strong restructuring and intimate atomic mixing occur under the reaction conditions. This leads to interactions that have a profound effect on the catalytic performance. Specifically, all of the bimetallic electrodes outperformed the monometallic ones (ZnO and CuO) in terms of activity for CO production. Surprisingly, on the other hand, the presence of ZnO suppresses the formation of ethylene on Cu, while the presence of Cu improves CO production of ZnO. In situ X-ray absorption spectroscopy studies revealed that this catalytic effect is due to enhanced reducibility of ZnO by Cu and stabilization of cationic Cu species by the intimate contact with partially reduced ZnO. This suppresses ethylene formation while favoring the production of H2 and CO on Cu. These results show that using mixed metal oxides with different reducibilities is a promising approach to alter the electronic properties of electrocatalysts (via stabilization of cationic species), thereby tuning the electrocatalytic CO2 reduction reaction performance.

Are there patients with an intracapsular fracture of the hip who may benefit from an uncemented hemiarthroplasty?

Aims: Cemented hemiarthroplasty is an effective form of treatment for most patients with an intracapsular fracture of the hip. However, it remains unclear whether there are subgroups of patients who may benefit from the alternative operation of a modern uncemented hemiarthroplasty - the aim of this study was to investigate this issue. Knowledge about the heterogeneity of treatment effects is important for surgeons in order to target operations towards specific subgroups who would benefit the most. Methods: We used causal forest analysis to compare subgroup- and individual-level treatment effects between cemented and modern uncemented hemiarthroplasty in patients aged > 60 years with an intracapsular fracture of the hip, using data from the World Hip Trauma Evaluation 5 (WHiTE 5) multicentre randomized clinical trial. EuroQol five-dimension index scores were used to measure health-related quality of life at one, four, and 12 months postoperatively. Results: Our analysis revealed a complex landscape of responses to the use of a cemented hemiarthroplasty in the 12 months after surgery. There was heterogeneity of effects with regard to baseline characteristics, including age, pre-injury health status, and lifestyle factors such as alcohol consumption. This heterogeneity was greater at the one-month mark than at subsequent follow-up timepoints, with particular regard to subgroups based on age. However, for all subgroups, the effect estimates for quality of life lay within the confidence intervals derived from the analysis of all patients. Conclusion: The use of a cemented hemiarthroplasty is expected to increase health-related quality of life compared with modern uncemented hemiarthroplasty for all subgroups of patients aged > 60 years with a displaced intracapsular fracture of the hip.

In Situ X-ray Absorption Spectroscopy of LaFeO3 and LaFeO3/LaNiO3 Thin Films in the Electrocatalytic Oxygen Evolution Reaction.

We study the electrocatalytic oxygen evolution reaction using in situ X-ray absorption spectroscopy (XAS) to track the dynamics of the valence state and the covalence of the metal ions of LaFeO3 and LaFeO3/LaNiO3 thin films. The active materials are 8 unit cells grown epitaxially on 100 nm conductive La0.67Sr0.33MnO3 layers using pulsed laser deposition (PLD). The perovskite layers are supported on monolayer Ca2Nb3O10 nanosheet-buffered 100 nm SiNx membranes. The in situ Fe and Ni K-edges XAS spectra were measured from the backside of the SiNx membrane using fluorescence yield detection under electrocatalytic reaction conditions. The XAS spectra show significant spectral changes, which indicate that (1) the metal (co)valencies increase, and (2) the number of 3d electrons remains constant with applied potential. We find that the whole 8 unit cells react to the potential changes, including the buried LaNiO3 film.

The rate of nonunion in the MRI-detected occult scaphoid fracture.

Aims: There is a lack of published evidence relating to the rate of nonunion seen in occult scaphoid fractures, diagnosed only after MRI. This study reports the rate of delayed union and nonunion in a cohort of patients with MRI-detected acute scaphoid fractures. Methods: This multicentre cohort study at eight centres in the UK included all patients with an acute scaphoid fracture diagnosed on MRI having presented acutely following wrist trauma with normal radiographs. Data were gathered retrospectively for a minimum of 12 months at each centre. The primary outcome measures were the rate of acute surgery, delayed union, and nonunion. Results: A total of 1,989 patients underwent acute MRI for a suspected scaphoid fracture during the study period, of which 256 patients (12.9%) were diagnosed with a previously occult scaphoid fracture. Of the patients with scaphoid fractures, six underwent early surgical fixation (2.3%) and there was a total of 16 cases of delayed or nonunion (6.3%) in the remaining 250 patients treated with cast immobilization. Of the nine nonunions (3.5%), seven underwent surgery (2.7%), one opted for non-surgical treatment, and one failed to attend follow-up. Of the seven delayed unions (2.7%), one (0.4%) was treated with surgery at two months, one (0.4%) did not attend further follow-up, and the remaining five fractures (1.9%) healed after further cast immobilization. All fractures treated with surgery had united at follow-up. There was one complication of surgery (prominent screw requiring removal). Conclusion: MRI-detected scaphoid fractures are not universally benign, with delayed or nonunion of scaphoid fractures diagnosed only after MRI seen in over 6% despite appropriate initial immobilization, with most of these patients with nonunion requiring surgery to achieve union. This study adds weight to the evidence base supporting the use of early MRI for these patients.

Focus on POCUS Point of Care Ultrasound in the Upper Extremity.

Ultrasound technologies are infrequently utilized in orthopedics as a first line diagnostic method, however, advances in technology and the applied techniques have opened the door for how and when ultrasound can be used. One specific avenue is the use of point of care ultrasound in which ultrasound is used at the time of initial patient evaluation by the evaluating physician. This use expedites time to diagnosis and can even guide therapeutic interventions. In the past two decades there have been numerous studies demonstrating the effectiveness of ultrasound for the diagnosis of many orthopedic conditions in the upper extremity, often demonstrating that it can be used in the place of and with greater diagnostic accuracy than magnetic resonance imaging. This review elaborates on these topics and lays a groundwork for how to incorporate point of care ultrasound into a modern orthopedic practice.

Impoverished language in early childhood affects the development of complex sentence structure.

The hypothesis that impoverished language experience affects complex sentence structure development around the end of early childhood was tested using a fully randomized, sentence-to-picture matching study in American Sign Language (ASL). The participants were ASL signers who had impoverished or typical access to language in early childhood. Deaf signers whose access to language was highly impoverished in early childhood (N = 11) primarily comprehended structures consisting of a single verb and argument (Subject or Object), agreeing verbs, and the spatial relation or path of semantic classifiers. They showed difficulty comprehending more complex sentence structures involving dual lexical arguments or multiple verbs. As predicted, participants with typical language access in early childhood, deaf native signers (N = 17) or hearing second-language learners (N = 10), comprehended the range of 12 ASL sentence structures, independent of the subjective iconicity or frequency of the stimulus lexical items, or length of ASL experience and performance on non-verbal cognitive tasks. The results show that language experience in early childhood is necessary for the development of complex syntax. RESEARCH HIGHLIGHTS: Previous research with deaf signers suggests an inflection point around the end of early childhood for sentence structure development. Deaf signers who experienced impoverished language until the age of 9 or older comprehend several basic sentence structures but few complex structures. Language experience in early childhood is necessary for the development of complex sentence structure.

The Neural Separability of Emotion Reactivity and Regulation.

One foundational distinction in affective science is between emotion reactivity and regulation. This conceptual distinction has long been assumed to be instantiated in spatially separable brain systems (a typical example: amygdala/insula for reactivity and frontoparietal areas for regulation). In this research, we begin by reviewing previous findings that support and contradict the neural separability hypothesis concerning emotional reactivity and regulation. Further, we conduct a direct test of this hypothesis with empirical data. In five studies involving healthy and clinical samples (total n = 336), we assessed neural responses using fMRI while participants were asked to either react naturally or regulate their emotions (using reappraisal) while viewing emotionally evocative stimuli. Across five studies, we failed to find support for the neural separability hypothesis. In univariate analyses, both presumptive "reactivity" and "regulation" brain regions demonstrated equal or greater activation for the reactivity contrast than for the regulation contrast. In multivariate pattern analyses (MVPA), classifiers decoded reactivity (vs. neutral) trials more accurately than regulation (vs. reactivity) trials using multivoxel data in both presumptive "reactivity" and "regulation" regions. These findings suggest that emotion reactivity and regulation-as measured via fMRI-may not be as spatially separable in the brain as previously assumed. Our secondary whole-brain analyses revealed largely consistent results. We discuss the two theoretical possibilities regarding the neural separability hypothesis and offer thoughts for future research. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00227-9.

In infertile women with subclinical hypothyroidism, with or without thyroid peroxidase antibodies, serum TSH during pregnancy follows preconception values and thyroid hormones remain stable.

STUDY QUESTION: How does subclinical hypothyroidism, defined in infertile women during preconception by thyroid-stimulating hormone (TSH) >2.5 or >4.5 mIU/l, with or without thyroid peroxidase antibodies (anti-TPO) >100 IU/ml, impact thyroid hormone levels during pregnancy and after birth? SUMMARY ANSWER: During pregnancy, TSH levels remain similar to those in preconception, even with supplementary thyroxine, whereas the serum levels of anti-TPO progressively decline. WHAT IS KNOWN ALREADY: Overt hypothyroidism impacts both pregnancy and offspring but randomized clinical trials and cohort studies failed to detect the benefit of treatment with thyroxine in cases with low-threshold TSH or with anti-TPO during pregnancy. STUDY DESIGN SIZE DURATION: First, the prevalence and reproducibility of two candidate cut-off levels of subclinical hypothyroidism in a cohort of 177 infertile women was compared with 171 women not aiming for pregnancy. Second, the impact of distinct setpoints of TSH in preconception (with or without anti-TPO) was monitored during pregnancy in 87 previously infertile women by high-frequency monitoring of thyroid function. Both studies were carried out from 2007 to 2019. PARTICIPANTS/MATERIALS SETTING METHODS: Reproducibility and prevalence of subclinical hypothyroidism were examined in infertile women presenting in the fertility care unit of an academic institution. Women not aiming for pregnancy participated as controls. In both groups, TSH and anti-TPO were measured two times on different occasions. In addition, a group of previously infertile women with known preconception setpoints of TSH (with or without anti-TPO) were followed up prospectively throughout pregnancy and after birth. During pregnancy, serum was sampled weekly until Week 12, then monthly until delivery, and once after birth. Only cases with preconception TSH >4.5 mIU/l were supplemented with thyroxine. After collection of all samples, the serum levels of anti-TPO and the major thyroid hormones were measured. Prolactin with known fluctuations during pregnancy was used as reference. MAIN RESULTS AND THE ROLE OF CHANCE: Measures of both TSH and anti-TPO at two different time points were accurate and reproducible. The odds of subclinical hypothyroidism in infertile women and controls were similar. During pregnancy, TSH closely followed preconception TSH levels, whereas serum levels of the thyroid hormones predominantly remained within or above (not below) the reference. Treatment of infertile women with preconception TSH >4.5 mIU/l with thyroxine resulted in higher free thyroxine (fT4) serum levels. The serum levels of anti-TPO declined as pregnancies evolved. LIMITATIONS REASONS FOR CAUTION: The numbers of participants both in the prevalence study and in pregnancy did not reach the a priori estimated numbers. For ethical reasons, the patients with preconception TSH >4.5 mIU/l were treated with thyroxine. The findings apply to infertile women only. WIDER IMPLICATIONS OF THE FINDINGS: We propose to use >4.5 mIU/l as the serum TSH threshold for supplementing women with thyroxine before pregnancy. During pregnancy, fT4 may be the better marker to monitor thyroid function. The consistent decrease of anti-TPO antibody levels during ongoing pregnancies must be considered a protective element. STUDY FUNDING/COMPETING INTERESTS: The prevalence part of this study was supported by Merck-Serono, Geneva (TH006/EMR200007-603). The hormone measurements of the serum samples collected during the follow-up pregnancies were made possible by financial support of Roche Diagnostica (November 1721, 2017, Rotkreuz, Switzerland). I.D.G. was supported by a grant of the Repronatal Foundation, Basel, Switzerland. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: Research Database of UniBasel, project no. 576691 (2007).

Using video-based assessment (VBA) to document fellow improvement in safely completing the jejunojejunostomy portion of laparoscopic Roux-en-Y gastric bypass (RYGB) surgery.

BACKGROUND: Surgical assessment instruments are used for formative and summative trainee evaluations. To characterize the features of existing instruments and a novel 12-item objective, procedure-specific assessment tool for Roux-en-Y Gastric Bypass (RYGB-OPSA), we evaluated the progress of a single surgical fellow over 17 consecutive surgeries. METHODS: Seventeen consecutive RYGB videos completed between 8/2021 and 1/2022 by an academic hospital surgical fellow were de-identified and assessed by four board-certified bariatric surgeons using Global Operative Assessment of Laparoscopic Skills (GOALS), General Assessment of Surgical Skill (GASS), and RYGB-OPSA which includes the reflection of transverse colon, identification of ligament of Treitz, biliopancreatic and Roux limbs orientation, jejunal division point selection, stapler use, mesentery division, bleeding control, jejunojejunostomy (JJ) anastomotic site selection, apposition of JJ anastomotic site, JJ creation, common enterotomy closure of JJ, and integrity of anastomosis. The GASS measured economy of motion, tissue handling, appreciating operative anatomy, bimanual dexterity, and achievement of hemostasis. RYGB-OPSA and GASS items were scored "poor-unsafe," "acceptable-safe," or "good-safe." Change in performance was measured by linear trendline slope. RESULTS: Over the course of 17 procedures, significant improvement was demonstrated by three GOALS items, GOALS overall score, GASS bimanual dexterity, and three RYGB-OPSA tasks: JJ creation, jejunal division point selection, and stapler use. Achievement of hemostasis declined but never rated "poor-unsafe." Overall RYGB-OPSA and GOALS trendlines documented significant increase across the 17 procedures. CONCLUSION: This examination of a bariatric surgery fellow's operative training experience as measured by three surgical assessment instruments demonstrated anticipated improvements in general skills and safe completion of procedure-specific tasks. Effective surgical assessment instruments have enough sensitivity to show improvement to enable meaningful trainee feedback (low-stakes assessments) as well as the ability to determine safe surgical practice to enable promotion to greater autonomous practice.

Five-year outcomes for patients with a displaced fracture of the distal tibia.

Aims: To report the outcomes of patients with a fracture of the distal tibia who were treated with intramedullary nail versus locking plate in the five years after participating in the Fixation of Distal Tibia fracture (FixDT) trial. Methods: The FixDT trial reported the results for 321 patients randomized to nail or locking plate fixation in the first 12 months after their injury. In this follow-up study, we report the results of 170 of the original participants who agreed to be followed up until five years. Participants reported their Disability Rating Index (DRI) and health-related quality of life (EuroQol five-dimension three-level questionnaire) annually by self-reported questionnaire. Further surgical interventions related to the fracture were also recorded. Results: There was no evidence of a difference in patient-reported disability, health-related quality of life, or the need for further surgery between participants treated with either type of fixation at five years. Considering the combined results for all participants, there was no significant change in DRI scores after the first 12 months of follow-up (difference between 12 and 24 months, 3.3 (95% confidence interval -1.8 to 8.5); p = 0.203), with patients reporting around 20% disability at five years. Conclusion: This study shows that the moderate levels of disability and reduced quality of life reported by participants 12 months after a fracture of the distal tibia persist in the medium term, with little evidence of improvement after the first year.

Global assessment of surgical skills (GASS): validation of a new instrument to measure global technical safety in surgical procedures.

BACKGROUND: Broad implementation of the American Board of Surgery's entrustable professional activities initiative will require assessment instruments that are reliable and easy to use. Existing assessment instruments of general laparoscopic surgical skills have limited reliability, efficiency, and validity across the spectrum of formative (low-stakes) and summative (high-stakes) assessments. A novel six-item global assessment of surgical skills (GASS) instrument was developed and evaluated with a focus upon safe versus unsafe surgical practice scoring rubric. METHODS: The GASS was developed by iterative engagement with expert laparoscopic surgeons and includes six items (economy of motion, tissue handling, appreciating operative anatomy, bimanual dexterity, achievement of hemostasis, overall performance) with a uniform three-point scoring rubric ("poor-unsafe", "adequate-safe", "good-safe"). To test inter-rater reliability, a cross-sectional study of four bariatric surgeons with experience ranging from 4 to 28 years applied the GASS and the global operative assessment of laparoscopic skills (GOALS) to 30 consecutive Roux-en-Y gastric bypass procedure operative videos. Inter-rater reliability was assessed for a simplified dichotomous "safe" versus "unsafe" scoring rubric using Gwet's AC2. RESULTS: The GASS inter-rater reliability was very high across all six domains (0.88-1.00). The GASS performed comparably to the GOALS inter-rater reliability scores (0.96-1.00). The economy of motion and bimanual dexterity items had the highest percentage of unsafe ratings (9.2% and 5.8%, respectively). CONCLUSION: The GASS, a novel six-item instrument of general laparoscopic surgical skills, was designed with a simple scoring rubric (poor-safe, adequate-safe, good-safe) to minimize rater burden and focus feedback to trainees and promotion evaluations on safe surgical performance. Initial evaluation of the GASS is promising, demonstrating high inter-rater reliability. Future research will seek to assess the GASS against a broader spectrum of laparoscopic procedures.

International orthopaedic trials.

Musculoskeletal diseases are having a growing impact worldwide. It is therefore crucial to have an evidence base to most effectively and efficiently implement future health services across different healthcare systems. International trials are an opportunity to address these challenges and have many potential benefits. They are, however, complex to set up and deliver, which may impact on the efficient and timely delivery of a project. There are a number of models of how international trials are currently being delivered across a range of orthopaedic patient populations, which are discussed here. The examples given highlight that the key to overcoming these challenges is the development of trusted and equal partnerships with collaborators in each country. International trials have the potential to address a global burden of disease, and in turn optimize the benefit to patients in the collaborating countries and those with similar health services and care systems.

Exploring the potential of using simulation games for engaging with sheep farmers about lameness recognition.

Introduction: Computer simulation games are increasingly being used in agriculture as a promising tool to study, support and influence real-life farming practices. We explored the potential of using simulation games to engage with sheep farmers on the ongoing challenge of reducing lameness. Working with UK stakeholders, we developed a game in which players are challenged with identifying all the lame sheep in a simulated flock. Here, we evaluate the game's potential to act as a tool to help assess, train and understand farmers' ability to recognize the early signs of lameness. Methods: Participants in the UK were invited to play the game in an online study, sharing with us their in-game scores alongside information relating to their real-life farming experience, how they played the game, and feedback on the game. Mixed methods were used to analyze this information in order to evaluate the game. Quantitative analyses consisted of linear modeling to test for statistical relationships between participants' in-game recall (% of the total number of lame sheep that were marked as lame), and the additional information they provided. Qualitative analyses of participants' feedback on the game consisted of thematic analysis and a Likert Scale questionnaire to contextualize the quantitative results and identify additional insights from the study. Results: Quantitative analyses identified no relationships between participants' (n = 63) recall scores and their real life farming experience, or the lameness signs they looked for when playing the game. The only relationship identified was a relationship between participants' recall score and time spent playing the game. Qualitative analyses identified that participants did not find the game sufficiently realistic or engaging, though several enjoyed playing it and saw potential for future development. Qualitative analyses also identified several interesting and less-expected insights about real-life lameness recognition practices that participants shared after playing the game. Discussion: Simulation games have potential as a tool in livestock husbandry education and research, but achieving the desired levels of realism and/or engagingness may be an obstacle to realizing this. Future research should explore this potential further, aided by larger budgets and closer collaboration with farmers, stockpeople, and veterinarians.

A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation.

Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single-nucleotide polymorphism rs55705857, which confers a sixfold greater risk of isocitrate dehydrogenase (IDH)-mutant low-grade glioma (LGG). We reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the Myc promoter and increased Myc expression. Mutating the orthologous mouse rs55705857 locus accelerated tumor development in an Idh1R132H-driven LGG mouse model from 472 to 172 days and increased penetrance from 30% to 75%. Our work reveals mechanisms of the heritable predisposition to lethal glioma in ~40% of LGG patients.

The extinct shark Otodus megalodon was a transoceanic superpredator: Inferences from 3D modeling.

Although shark teeth are abundant in the fossil record, their bodies are rarely preserved. Thus, our understanding of the anatomy of the extinct Otodus megalodon remains rudimentary. We used an exceptionally well-preserved fossil to create the first three-dimensional model of the body of this giant shark and used it to infer its movement and feeding ecology. We estimate that an adult O. megalodon could cruise at faster absolute speeds than any shark species today and fully consume prey the size of modern apex predators. A dietary preference for large prey potentially enabled O. megalodon to minimize competition and provided a constant source of energy to fuel prolonged migrations without further feeding. Together, our results suggest that O. megalodon played an important ecological role as a transoceanic superpredator. Hence, its extinction likely had large impacts on global nutrient transfer and trophic food webs.

Effects of reducing the standardized ileal digestible lysine and tryptophan to lysine ratio to slow growth of finishing pigs.

The COVID-19 global pandemic greatly affected pork processing plants in the United States. These pork processing plants were forced to either temporarily close or operate at reduced capacity due to the increased number of health-related employee absences. Because finishing pigs could not be timely marketed, methods to reduce growth performance were required to keep pigs from becoming too heavy at slaughter weight. Therefore, our objective was to determine the extent that reducing dietary standardized ileal digestible (SID) Lys and tryptophan-to-lysine ratio (Trp:Lys) ratio would slow finishing pig average daily gain (ADG) in a commercial setting. A total of 1,080 finishing pigs (327 × 1050, PIC; initially 32.3 kg) were used in a 119-d growth trial. Pigs were allotted by initial body weight (BW) and randomly assigned to 1 of 4 dietary treatments in a completely randomized block design with 27 pigs per pen and 10 pens per treatment. Three dietary regimes were formulated to contain either 100%, 90%, or 80% of the estimated SID Lys requirement for pigs in this facility, with a SID Trp:Lys ratio of 19%, with the exception of the last dietary phase formulated to 17% SID Trp:Lys. Seven different dietary phases were fed. The SID Lys concentrations in the 100% diets were: 1.10%, 1.01%, 0.91%, 0.83%, 0.79%, 0.71%, or 0.67% SID Lys from 32 to 40, 40 to 51, 51 to 72, 72 to 85, 85 to 98, 98 to 112, and 112 to 130 kg, respectively. A fourth regime was formulated to 80% SID Lys with a SID Trp:Lys ratio of 16% (80-16% SID Trp:Lys) throughout all phases. Overall from d 0 to 119, ADG (linear, P < 0.001), final BW (linear, P < 0.001), and gain-to-feed (G:F) decreased (linear, P = 0.087) as SID Lys decreased from 100% to 80% of the estimated requirement. Pigs fed the 80-16% SID Trp:Lys diets had an additional decrease in ADG (P < 0.05) and G:F (P < 0.10) compared with pigs fed 80% of the SID Lys requirement with the normal Trp:Lys ratio. The reduction in SID Lys (from 100% to 80%) and reduction in SID Lys and Trp:Lys ratio resulted in an 8.6 and 11.7 kg, respectively, decrease in final BW compared with pigs fed Lys and Trp at the requirement (100%). This study provides alternatives for pork producers to reduce growth rate of finishing pigs.

Developing a minimum common dataset for hip fracture audit to help countries set up national audits that can support international comparisons.

AIMS: The aim of this study was to explore current use of the Global Fragility Fracture Network (FFN) Minimum Common Dataset (MCD) within established national hip fracture registries, and to propose a revised MCD to enable international benchmarking for hip fracture care. METHODS: We compared all ten established national hip fracture registries: England, Wales, and Northern Ireland; Scotland; Australia and New Zealand; Republic of Ireland; Germany; the Netherlands; Sweden; Norway; Denmark; and Spain. We tabulated all questions included in each registry, and cross-referenced them against the 32 questions of the MCD dataset. Having identified those questions consistently used in the majority of national audits, and which additional fields were used less commonly, we then used consensus methods to establish a revised MCD. RESULTS: A total of 215 unique questions were used across the ten registries. Only 72 (34%) were used in more than one national audit, and only 32 (15%) by more than half of audits. Only one registry used all 32 questions from the 2014 MCD, and five questions were only collected by a single registry. Only 21 of the 32 questions in the MCD were used in the majority of national audits. Only three fields (anaesthetic grade, operation, and date/time of surgery) were used by all ten established audits. We presented these findings at the Asia-Pacific FFN meeting, and used an online questionnaire to capture feedback from expert clinicians from different countries. A draft revision of the MCD was then presented to all 95 nations represented at the Global FFN conference in September 2021, with online feedback again used to finalize the revised MCD. CONCLUSION: The revised MCD will help aspirant nations establish new registry programmes, facilitate the integration of novel analytic techniques and greater multinational collaboration, and serve as an internationally-accepted standard for monitoring and improving hip fracture services. Cite this article: Bone Joint J 2022;104-B(6):721-728.

Five-year outcomes for patients sustaining severe fractures of the lower limb : mid-term results from the Wound management for Open Lower Limb Fracture (WOLLF) trial.

AIMS: The aim of this study was to report the outcomes of patients with severe open fractures of the lower limb in the five years after they took part in the Wound management for Open Lower Limb Fracture (WOLLF) trial. METHODS: The WOLLF trial compared standard dressings to negative pressure wound therapy (NPWT) applied at the end of the first surgical wound debridement, and patients were followed-up for 12 months. At 12 months, 170 of the original 460 participants agreed to take part in this medium-term follow-up study. Patients reported their Disability Rating Index (DRI) (0 to 100, where 100 is total disability) and health-related quality of life (HRQoL) using the EuroQol five-dimension three-level health questionnaire (EQ-5D-3L) annually by self-reported questionnaire. Further surgical interventions related to the open fracture were also recorded. RESULTS: There was no evidence of a difference in patient-reported disability, HRQoL, or the need for further surgery between patients treated with NPWT versus standard dressings at five years. Considering the combined results for all participants, there was a small but statistically significant change in DRI scores over time (1.6 units per year; p = 0.005), but no evidence that EQ-5D-3L scores changed significantly during years two to five (p = 0.551). CONCLUSION: This study shows that the high levels of disability and reduced HRQoL reported by patients 12 months after severe open fractures of the lower limb persist in the medium term, with little evidence of improvement between years two and five. Cite this article: Bone Joint J 2022;104-B(5):633-639.