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Background: Patients with a displaced fracture of the distal radius are frequently offered surgical fixation. Manipulation of the fracture and moulded plaster casting is an alternative treatment that avoids metal implants, but evidence of its effectiveness is lacking., Objective: To compare functional outcomes, quality-of-life outcomes, complications and resource use among patients with a dorsally displaced fracture of the distal radius treated with manipulation and surgical fixation with Kirschner wires (K-wires) and those treated with manipulation and moulded cast., Design: Pragmatic, superiority, multicentre, randomised controlled trial with a health economic evaluation., Setting: A total of 36 orthopaedic trauma centres in the UK NHS., Participants: Patients (aged ≥ 16 years) treated for an acute dorsally displaced fracture of the distal radius were potentially eligible. Patients were excluded if their injury had occurred > 2 weeks previously, if the fracture was open, if it extended > 3 cm from the radiocarpal joint or if it required open reduction, or if the participant was unable to complete questionnaires., Interventions: Participants were randomly assigned in theatre (1 : 1) to receive a moulded cast (i.e. the cast group) or surgical fixation with K-wires (i.e. the K-wire group) after fracture manipulation., Main Outcome Measures: The primary outcome measure was the Patient-Rated Wrist Evaluation score at 12 months, analysed on an intention-to-treat basis. Health-related quality of life was recorded using the EuroQol-5 Dimensions, five-level version, and resource use was recorded from a health and personal social care perspective., Results: Between January 2017 and March 2019, 500 participants (mean age 60 years, 83% women) were randomly allocated to receive a moulded cast ( n  = 255) or surgical fixation with K-wire ( n  = 245) following a manipulation of their fracture. A total of 395 (80%) participants were included in the primary analysis at 12 months. There was no difference in the Patient-Rated Wrist Evaluation score at 1 year post randomisation [cast group: n  = 200, mean score 21.2 (standard deviation 23.1); K-wire group: n  = 195, mean score 20.7 (standard deviation 22.3); adjusted mean difference -0.34 (95% confidence interval -4.33 to 3.66); p  = 0.87]. A total of 33 (13%) participants in the cast group required surgical fixation for loss of fracture position in the first 6 weeks, compared with one participant in the K-wire group (odds ratio 0.02, 95% confidence interval 0.001 to 0.10). The base-case cost-effectiveness analysis showed that manipulation and surgical fixation with K-wires had a higher mean cost than manipulation and a moulded cast, despite similar mean effectiveness. The use of K-wires is unlikely to be cost-effective, and sensitivity analyses found this result to be robust., Limitations: Because the interventions were identifiable, neither patients nor clinicians could be blind to their treatment., Conclusions: Surgical fixation with K-wires was not found to be superior to moulded casting following manipulation of a dorsally displaced fracture of the distal radius, as measured by Patient-Rated Wrist Evaluation score. However, one in eight participants treated in a moulded cast required surgery for loss of fracture reduction in the first 6 weeks. After a successful closed reduction, clinicians may consider a moulded cast as a safe and cost-effective alternative to surgical fixation with K-wires., Future Work: Further research should focus on optimal techniques for immobilisation and manipulation of this type of fracture, including optimal analgesia, and for rehabilitation of the patient after immobilisation., Trial Registration: This trial is registered as ISRCTN11980540 and UKCRN Portfolio 208830., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 26, No. 11. See the NIHR Journals Library website for further project information.

Oncogenic extrachromosomal DNA elements (ecDNA) play an important role in tumor evolution, but our understanding of ecDNA biology is limited. We determined the distribution of single-cell ecDNA copy number across patient tissues and cell line models and observed how cell-to-cell ecDNA frequency varies greatly. The exceptional intratumoral heterogeneity of ecDNA suggested ecDNA-specific replication and propagation mechanisms. To evaluate the transfer of ecDNA genetic material from parental to offspring cells during mitosis, we established the CRISPR-based ecTag method. ecTag leverages ecDNA-specific breakpoint sequences to tag ecDNA with fluorescent markers in living cells. Applying ecTag during mitosis revealed disjointed ecDNA inheritance patterns, enabling rapid ecDNA accumulation in individual cells. After mitosis, ecDNAs clustered into ecDNA hubs, and ecDNA hubs colocalized with RNA polymerase II, promoting transcription of cargo oncogenes. Our observations provide direct evidence for uneven segregation of ecDNA and shed new light on mechanisms through which ecDNAs contribute to oncogenesis. SIGNIFICANCE: ecDNAs are vehicles for oncogene amplification. The circular nature of ecDNA affords unique properties, such as mobility and ecDNA-specific replication and segregation behavior. We uncovered fundamental ecDNA properties by tracking ecDNAs in live cells, highlighting uneven and random segregation and ecDNA hubs that drive cargo gene transcription. See related commentary by Henssen, p. 293 . This article is highlighted in the In This Issue feature, p. 275 ., (©2021 American Association for Cancer Research.)

Objective: To assess wrist function, quality of life, and complications in adult patients with a dorsally displaced fracture of the distal radius, treated with either a moulded cast or surgical fixation with K-wires., Design: Multicentre randomised clinical superiority trial, SETTING: 36 hospitals in the UK National Health Service (NHS)., Participants: 500 adults aged 16 or over with a dorsally displaced fracture of the distal radius, randomised after manipulation of their fracture (255 to moulded cast; 245 to surgical fixation)., Interventions: Manipulation and moulded cast was compared with manipulation and surgical fixation with K-wires plus cast. Details of the application of the cast and the insertion of the K-wires were at the discretion of the treating surgeon, according to their normal clinical practice., Main Outcome Measures: The primary outcome measure was the Patient Rated Wrist Evaluation (PRWE) score at 12 months (five questions about pain and 10 about function and disability; overall score out of 100 (best score=0 and worst score=100)). Secondary outcomes were PRWE score at three and six months, quality of life, and complications, including the need for surgery due to loss of fracture position in the first six weeks., Results: The mean age of participants was 60 years and 417 (83%) were women; 395 (79%) completed follow-up. No statistically significant difference in the PRWE score was seen at 12 months (cast group (n=200), mean 21.2 (SD 23.1); K-wire group (n=195), mean 20.7 (22.3); adjusted mean difference -0.34 (95% confidence interval -4.33 to 3.66), P=0.87). No difference was seen at earlier time points. In the cast group, 33 (13%) of participants needed surgical fixation for loss of fracture position in the first six weeks compared with one revision surgery in the K-wire group (odds ratio 0.02, 95% confidence interval 0.001 to 0.10)., Conclusions: Among patients with a dorsally displaced distal radius fracture that needed manipulation, surgical fixation with K-wires did not improve patients' wrist function at 12 months compared with a cast., Trial Registration: ISRCTN registry ISRCTN11980540., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the UK NIHR HTA Programme for the submitted work; MLC is an NIHR senior investigator and a member of the General Board for the NIHR HTA funding stream; SEL was on the HTA Additional Capacity Funding Board, HTA End of Life Care and Add-on Studies Board, HTA Prioritisation Group Board, HTA Trauma Board, and HTA MNCH Methods Group (2013-15) and was deputy chair of HTA Primary Care Themed Call Board (2013-14) and chair of the NIHR CTU Standing Advisory Committee (2012-16); JAC was a member of the HTA Efficient Study Designs Board (2014, 2015-16) and of the HTA End of Life Care and Add-on Studies Board (2015-16); JD receives grants from the NIHR HTA programmes (11/36/37 and 15/102/04); no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Transdural collaterals (TC) from the external carotid artery must be preserved when operating on patients with moyamoya vasculopathy. Several techniques have been used to identify the superficial temporal artery (STA) and middle meningeal artery (MMA) during surgery and prevent their damage. However, the use of neuronavigation for this specific purpose has never been described in the literature. We describe an operative case in which neuronavigation was used to preserve the TC (originating from the MMA), detailing our technique step by step and reviewing alternative methods previously reported., Case Presentation: A 6-year-old girl with moyamoya disease, who had developed marked bilateral TC from the MMA sparing the middle cerebral artery territory, underwent staged bilateral indirect revascularization surgery. Intraoperative neuronavigation was used to identify the STA and MMA with their main branches during skin incision, craniotomy, and dural opening. The neuronavigation matched the intraoperative findings exactly, and the target structures remained undamaged. The patient was discharged home after both surgeries with no neurological deficits. One year following surgery, the patient has excellent collateralization from both STAs and is asymptomatic and neurologically intact., Conclusion: With the use of intraoperative neuronavigation, the STA, MMA, and their main branches, as well as their relationship to the bone, can be identified and preserved. This approach can help in preventing undesirable injury to TC during surgery and may potentially prevent perioperative stroke in patients with moyamoya vasculopathy undergoing revascularization surgery., (© 2022 S. Karger AG, Basel.)

Membraneless organelles have emerged during the evolution of eukaryotic cells as intracellular domains in which multiple proteins organize into complex structures to perform specialized functions without the need of a lipid bilayer compartment. Here we describe the perinuclear space of eukaryotic cells as a highly organized network of cytoskeletal filaments that facilitates assembly of biomolecular condensates. Using bioinformatic analyses, we show that the perinuclear proteome is enriched in intrinsic disorder with several proteins predicted to undergo liquid-liquid phase separation. We also analyze immunofluorescence and transmission electron microscopy images showing the association between the nucleus and other organelles, such as mitochondria and lysosomes, or the labeling of specific proteins within the perinuclear region of cells. Altogether our data support the existence of a perinuclear dense sub-micron region formed by a well-organized three-dimensional network of structural and signaling proteins, including several proteins containing intrinsically disordered regions with phase behavior. This network of filamentous cytoskeletal proteins extends a few micrometers from the nucleus, contributes to local crowding, and organizes the movement of molecular complexes within the perinuclear space. Our findings take a key step towards understanding how membraneless regions within eukaryotic cells can serve as hubs for biomolecular condensates assembly, in particular the perinuclear space. Finally, evaluation of the disease context of the perinuclear proteins revealed that alterations in their expression can lead to several pathological conditions, and neurological disorders and cancer are among the most frequent., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To externally validate the CIPHER (Collaborative Integrated Pregnancy High-Dependency Estimate of Risk) prognostic model for pregnant and postpartum women admitted to the intensive care unit., Methods: A retrospective and a prospective validation study were conducted at two reference centers in Brazil. A composite outcome was defined as maternal death or need for prolonged organ support (more than 7 days) or acute lifesaving intervention. To evaluate the performance of the CIPHER model, a receiver operating characteristic curve was used and score calibration was assessed by the Hosmer-Lemeshow test. We conducted a descriptive analysis comparing the results of the current study with the results of the model development study., Results: A total of 590 women were included. The composite outcome was observed in 90 (15.2%) women. Of these, 13 (2.2%) were maternal deaths and 77 (13%) required one or more component of organ support or lifesaving intervention. The CIPHER model's area under the curve (AOC) did not show significant predictive ability (AOC 0.53, 95% CI 0.46-0.60), and consequently its calibration was poor (Hosmer-Lemeshow test P<.05)., Conclusion: The CIPHER model for prediction of mortality and need for interventions in critically ill obstetric patients did not perform well in our Brazilian population. Different predictors of morbidity and mortality may need to be used for patients receiving care in public hospitals in low- and middle-income countries., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The aim of this study was to evaluate the clinical, epidemiological and laboratory aspects of SARS-CoV-2 infection during pregnancy and postpartum in 16 maternity hospitals., Methods and Analysis: A prospective multicentre study, with five axes. First, the prevalence of SARS-CoV-2 infection among women admitted for childbirth will be described in a cross-sectional study. Second, maternal and perinatal outcomes will be assessed in a prospective cohort study including pregnant or postpartum women with suspected COVID-19. Third, a cohort of positive COVID-19 cases with sampling of a variety of biological material. Histopathological and viral analysis of biological maternal and neonatal samples will be performed, and the assessment of nutritional variables to evaluate the association between vitamin D and severity of infection. Fourth, a monitoring and evaluation committee to collect relevant healthcare information and plan actions in centres facing the pandemic. Furthermore, qualitative studies will be performed to study pregnant women, their families and health professionals. Fifth, an ecological study will monitor the number of live births, stillbirths and other outcomes to explore any trend among the periods before, during and after the pandemic. Data will systematically be collected in an electronic platform following standardised operational procedures. For quantitative study components, an appropriate statistical approach will be used for each analysis. For qualitative data, in-depth interviews recorded in audio will be transcribed, checking the text obtained with the recording. Subsequently, thematic analysis with the aid of the NVivo programme will be performed., Ethics and Dissemination: Ethical approval was obtained (letters of approval numbers 4.047.168, 4.179.679 and 4.083.988). All women will be fully informed to sign the consent form before enrolment in the study. Findings will be disseminated through peer-reviewed journals and scientific conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Deep surgical site infection (SSI) is common after lower limb fracture. We compared the diagnosis of deep SSI using alternative methods of data collection and examined the agreement of clinical photography and in-person clinical assessment by the Centers for Disease Control and Prevention (CDC) criteria after lower limb fracture surgery., Methods: Data from two large, UK-based multicentre randomized controlled major trauma trials investigating SSI and wound healing after surgical repair of open lower limb fractures that could not be primarily closed (UK WOLLF), and surgical incisions for fractures that were primarily closed (UK WHiST), were examined. Trial interventions were standard wound care management and negative pressure wound therapy after initial surgical debridement. Wound outcomes were collected from 30 days to six weeks. We compared the level of agreement between wound photography and clinical assessment of CDC-defined SSI. We are also assessed the level of agreement between blinded independent assessors of the photographs., Results: Rates of CDC-defined deep SSI were 7.6% (35/460) after open fracture and 6.3% (95/1519) after closed incisional repair. Photographs were obtained for 77% and 73% of WOLLF and WHiST cohorts respectively (all participants n = 1,478). Agreement between photographic-SSI and CDC-SSI was fair for open fracture wounds (83%; k = 0.27 (95% confidence interval (CI) 0.14 to 0.42)) and for closed incisional wounds (88%; k = 0.29 (95% CI 0.20 to 0.37)) although the rate of photographically detected deep SSIs was twice as high as CDC-SSI (12% vs 6%). Agreement between different assessors for photographic-SSI (WOLLF 88%, k = 0.63 (95% CI 0.52 to 0.72); WHiST 89%; k = 0.61 (95% CI 0.54 to 0.69)); and wound healing was good (WOLLF 90%; k = 0.80 (95% CI 0.73 to 0.86); WHiST 87%; k = 0.57 (95% CI 0.50 to 0.64))., Conclusion: Although wound photography was feasible within the research context and inter-rater assessor agreement substantial, digital photographs used in isolation overestimated deep SSI rates, when compared to CDC criteria. Wound photography should not replace clinical assessment in pragmatic trials but may be useful for screening purposes where surgical infection outcomes are paramount. Cite this article: Bone Joint J  2021;103-B(12):1802-1808.

Objective:  To study maternal anxiety in pregnant women without comorbidities in the context of the COVID-19 outbreak in Brazil and to study maternal knowledge and concerns about the pandemic., Methods:  This is a secondary analysis from a national multicenter cross-sectional study performed in 10 cities, from June to August, 2020, in Brazil. Interviewed postpartum women, without medical or obstetrical comorbidities, were included in the present subanalysis. A structured questionnaire and the Beck Anxiety Inventory (BAI) were applied., Results:  Out of the 1,662 women, 763 (45.9%) met the criteria for the current analysis and 16.1% presented with moderate and 11.5% with severe maternal anxiety. Moderate or severe maternal anxiety was associated with high school education (odds ratio [OR]:1.58; 95% confidence interval [CI]:1.04-2.40). The protective factor was cohabiting with a partner (OR: 0.46; 95%CI: 0.29-0.73). There was a positive correlation between the total BAI score and receiving information about care in the pandemic (r partial 0.15; p  < 0.001); concern about vertical transmission of COVID-19 (r partial 0.10; p  = 0.01); receiving information about breastfeeding (r partial 0.08; p  = 0.03); concerns about prenatal care (r partial 0.10; p  = 0.01), and concerns about the baby contracting COVID-19 (r partial 0.11; p  = 0.004). The correlation was negative in the following aspects: self-confidence in protecting from COVID-19 (r partial 0.08; p  = 0.04), having learned (r partial 0.09; p  = 0.01) and self-confidence in breastfeeding (r partial 0.22; p  < 0.001) in the context of the pandemic., Conclusion:  The anxiety of pregnant women without medical or obstetrical comorbidities was associated to high school educational level and not living with a partner during the COVID-19 pandemic. Self-confidence in protecting against COVID-19 and knowledge about breastfeeding care during the pandemic reduced maternal anxiety., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Adolescent and young women (10-24 years old) are habitually a neglected group in humanitarian settings. Menstrual hygiene management (MHM) is an unmet aspect of sexual and reproductive health (SRH) and an additional challenge if lack of hygiene products, inadequate access to safe, clean, and private toilets identified as period poverty. Our objective was to provide an overview of the main MHM issues affecting Venezuelan migrant adolescents and young women in the north-western border of Venezuela-Brazil., Method: A cross-sectional study was conducted, early in 2021, with the use of a self-responded questionnaire, in Spanish, adapted from the Menstrual Practice Needs Scale (MPNS-36). All identified adolescents and young women aged between 12 and 24 years old were invited to participate (convenience sample-167 women). Women with complete questionnaires and who menstruate were included. Information on access to and quality of hygiene kits and toilets were retrieved, and a descriptive analysis performed, with an evaluation of frequencies for categorical variables (n, %) and mean (± SD-standard deviation) for continuous variables. In addition to the open-ended questions, we included one open question about their personal experience with menstruation., Results: According to official reports, at the moment of the interviews, there were 1.603 Venezuelans living on the streets in Boa Vista. A total of 167 young women were invited, and 142 further included, mean age was 17.7 years, almost half of the participants who menstruate (46.4%) did not receive any hygiene kits, 61% were not able to wash their hands whenever they wanted, and the majority (75.9%) did not feel safe to use the toilets. Further, menstruation was often described with negative words., Conclusions: Migrant Venezuelan adolescents and young women have their MHM needs overlooked, with evident period poverty, and require urgent attention. It is necessary to assure appropriate menstrual materials, education, and sanitation facilities, working in partnership among governmental and non-governmental organizations to guarantee menstrual dignity to these young women., (© 2021. The Author(s).)

Introduction: The novel coronavirus pandemic poses a challenge to healthcare systems' balance. Since children apparently have milder disease courses, COVID-19 guidelines were not easily adapted to pediatrics. We intend to characterize how the national departments of pediatrics adapted to the pandemic at the beginning and describe the measures that were taken to protect healthcare workers., Methods: An unvalidated online questionnaire was sent to all departments of pediatrics directors of Portuguese public health system hospitals regarding course of actions taken between April and May 2020 to face the new coronavirus pandemic. Neonatology units were excluded., Results: Thirty-eight questionnaires were included (93% of public health system departments). All departments divided the pediatric emergency unit into non-COVID-19 and COVID-19 areas: 68% in different areas, 47% divided the same space with a physical barrier and 16% with a line on the floor. Healthcare workers were divided into non-COVID-19 and COVID-19 teams in 71% of the departments. Personal protective equipment mostly used in COVID-19 areas consisted of face shield/goggles (97%) and respirators (95%). Others wore surgical masks (8%). The main clinical criteria for testing were Direção-Geral da Saúde criteria (84%). Presential appointments were maintained in 68% of departments with selected follow-up (81%) and priority-first appointments (73%)., Discussion: National departments of pediatrics faced the pandemic differently and measures taken in the emergency department were more similar. Personal protective equipment was adequate in all wards with occasional overuse, considering national and international guidelines., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by The Author(s). Published by S. Karger AG, Basel on behalf of NOVA National School of Public Health.)

Physical activity levels during the COVID-19 pandemic have been decreasing and this may be a risk factor for development of emotional eating and its associated factors. The aim of the study was to analyze the factors associated with emotional eating among individuals with different physical activity levels during the COVID-19 pandemic. Data relating to the pandemic on physical activity, emotional eating, sociodemographic data, perceptions about lifestyle habits, body satisfaction, and perceptions about eating habits and food consumption were collected. Factors associated with emotional eating in the group of active and inactive individuals were observed using multiple linear regression controlled for age, sex, BMI, and monthly income. Emotional eating for the active group was associated with perceived stress, body dissatisfaction, and increased consumption of sweets and desserts. In addition to these factors found among the active group, working or studying >8 h/day, sleep worsening, increased amount of food consumed, increased purchase of food through delivery, and increased vegetable consumption were also associated with emotional eating for the inactive group. These findings suggest a potential protective role of physical activity in the appearance of factors associated with emotional eating during the COVID-19 pandemic.

A close interaction between basic science and applied medicine is to be expected. Therefore, it is important to measure how far apart the field of cell biology and medicine are. Our approach to estimating the distance between these fields was to compare their vocabularies and to quantify the difference in word repertoire. We compared the vocabulary of the title and abstract of articles available in PubMed in two selected high-impact journals in each field: cell biology, medicine, and translational science. Although each journal has its own editorial policy, we showed that within each field there is a small vocabulary difference between the two journals. We developed a word similarity index that can measure how much journals share a common vocabulary. We found a high similarity index between each cell biology (91%), medical (71-74%), and translational journal (65%). In contrast, the comparison between medicine and biology journals produced low correlation values (22-36%), suggesting that their vocabularies are quite dissimilar. Translational medicine journals had medium similarity values when compared to cell biology journals (52-70%) and medicine journals (27-59%). This approach was also performed in 10-year periods to evaluate the evolution of each field. Using the "onomics" strategy presented here, we observed that differences in vocabulary of basic science and medicine have been increasing over time. Since translational medicine has an intermediate vocabulary, we confirmed that translational medicine is an efficient approach to bridge this gap.

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: COVID-19 pandemic posed major challenges in obstetric health care services. Preparedness, development, and implementation of new protocols were part of the needed response. This study aims to describe the strategies implemented and the perspectives of health managers on the challenges to face the pandemic in 16 different maternity hospitals that comprise a multicenter study in Brazil, called REBRACO (Brazilian network of COVID-19 during pregnancy)., Methods: Mixed-method study, with quantitative and qualitative approaches. Quantitative data on the infrastructure of the units, maternal and perinatal health indicators, modifications on staff and human resources, from January to July/2020. Also, information on total number of cases, and availability for COVID-19 testing. A qualitative study by purposeful and saturation sampling was undertaken with healthcare managers, to understand perspectives on local challenges in facing the pandemic., Results: Most maternities early implemented their contingency plan. REBRACO centers reported 338 confirmed COVID-19 cases among pregnant and post-partum women up to July 2020. There were 29 maternal deaths and 15 (51.8%) attributed to COVID-19. All maternities performed relocation of beds designated to labor ward, most (75%) acquired mechanical ventilators, only the minority (25%) installed new negative air pressure rooms. Considering human resources, around 40% hired extra health professionals and increased weekly workload and the majority (68.7%) also suspended annual leaves. Only one center implemented universal screening for childbirth and 6 (37.5%) implemented COVID-19 testing for all suspected cases, while around 60% of the centers only tested moderate/severe cases with hospital admission. Qualitative results showed that main challenges experienced were related to the fear of the virus, concerns about reliability of evidence and lack of resources, with a clear need for mental health support among health professionals., Conclusion: Study findings suggest that maternities of the REBRACO initiative underwent major changes in facing the pandemic, with limitations on testing, difficulties in infrastructure and human resources. Leadership, continuous training, implementation of evidence-based protocols and collaborative initiatives are key to transpose the fear of the virus and ascertain adequate healthcare inside maternities, especially in low and middle-income settings. Policy makers need to address the specificities in considering reproductive health and childbirth during the COVID-19 pandemic and prioritize research and timely testing availability., Competing Interests: The authors have declared that no competing interests exist.

Importance: Platelet-rich plasma injections are used as a treatment for chronic midportion Achilles tendinopathy, but evidence for this treatment is limited., Objective: In adults with midportion Achilles tendinopathy, to assess the effects of a single platelet-rich plasma injection, compared with sham injection, on the outcome of the Victorian Institute of Sport Assessment-Achilles (VISA-A) score (a single composite measure of Achilles tendinopathy severity)., Design, Setting, and Participants: A participant-blinded, multicenter randomized clinical trial that included 240 people from 24 sites assigned to either a platelet-rich plasma injection or a sham injection between April 2016 and February 2020. Final follow-up was July 2020. Participants were older than 18 years with midportion Achilles tendon pain for more than 3 months as confirmed by ultrasound, magnetic resonance imaging, or both., Interventions: A single intratendinous platelet-rich plasma injection (n = 121) or a single sham injection (insertion of a subcutaneous dry needle not entering the tendon) (n = 119)., Main Outcomes and Measures: The primary outcome was the VISA-A score, measured 6 months after treatment allocation. The VISA-A score contains 8 questions that cover 3 domains of pain, function, and activity, analyzed as a composite score (range, 0 [worst symptoms] to 100 [no symptoms]; minimal clinically important difference in score, 12 points). The primary analysis was adjusted for laterality, age, sex, and baseline VISA-A score., Results: Among 240 patients assigned to a platelet-rich plasma or sham injection (mean age, 52 years; 138 [58%] women), 221 (92%) completed the trial. At 6-month follow-up, mean VISA-A score values in the plasma-rich plasma group vs the sham injection group were 54.4 vs 53.4 (adjusted mean difference, -2.7 [95% CI, -8.8 to 3.3]). The most common adverse events compared between patients in the platelet-rich plasma group vs the sham group were injection site discomfort (97 vs 73 patients), swelling (56 vs 52 patients) and bruising (48 vs 49 patients)., Conclusions and Relevance: Among patients with chronic midportion Achilles tendinopathy, treatment with a single injection of intratendinous platelet-rich plasma, compared with insertion of a subcutaneous dry needle, did not reduce Achilles tendon dysfunction at 6 months. These findings do not support the use of this treatment for chronic midportion Achilles tendinopathy., Trial Registration: isrctn.org Identifier: ISRCTN13254422.

Aims: The aim of this study was to assess the effect of time to surgical intervention from admission on mortality and morbidity for patients with hip fractures., Methods: MEDLINE and Embase were searched from inception to June 2020. Reference lists were manually assessed to identify additional papers. Primary comparative research studies that recruited patients aged over 60 years, with non-pathological primary proximal femoral fractures that were treated surgically, were included. Studies that did not include a group operated on within 24 hours or which reported time to surgery in calendar days were excluded. Two investigators extracted data on study characteristics, methods, and outcomes. The pre-defined primary outcome was 30-day mortality. Secondary outcomes were complications and mortality at other time points. Relative risks (RRs) with 95% confidence intervals (CIs) were aggregated and were grouped by study-level characteristics., Results: This review included 46 studies (January 1991 to June 2020), comprising 521,857 hip fractures with 64,047 postoperative deaths. No randomized controlled trials were eligible for inclusion. In a pooled analysis of 15 studies, RR of mortality at 30 days comparing time to surgery < 24 hours with > 24 hours was 0.86 (95% CI 0.82 to 0.91; I 2 = 69%; 95% CI 50% to 81%; p-value for heterogeneity < 0.001). The association was stronger in observational studies that did not adjust for confounders than in those that adjusted for multiple covariates. In a pooled analysis of six studies, the RR of mortality at 30 days comparing time to surgery < 24 hours with 24 to 36 hours was 0.87 (95% CI 0.81 to 0.93; I 2 = 65%; 95% CI 16% to 85%; p-value for heterogeneity = 0.014)., Conclusion: This meta-analysis indicates reduced mortality for patients operated within 24 hours compared with those operated on beyond 24 hours or within 24 to 36 hours. Where resources allow and there is no specific reversible contraindication to early surgery, we recommend that hip fractures should be surgically treated within 24 hours. Cite this article: Bone Joint J  2021;103-B(7):1176-1186.

Aims: The aim of the Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) was to determine the optimal treatment for adults with a bicortical undisplaced or minimally displaced fracture of the waist of the scaphoid, comparing early surgical fixation with initial cast immobilization, with immediate fixation being offered to patients with nonunion., Methods: A cost-effectiveness analysis was conducted to assess the relative merits of these forms of treatment. The differences in costs to the healthcare system and quality-adjusted life years (QALYs) of the patients over the one-year follow-up of the trial in the two treatment arms were estimated using regression analysis., Results: Our base case analysis found that patients randomized to early surgical fixation had statistically significantly higher mean costs to the NHS of £1,295 more than for the cast immobilization arm (p < 0.001), primarily due to the cost of surgery. They also had a marginally better quality of life, over the period, of 0.0158 QALYs; however, this was not statistically significant (p = 0.379). The mean combined cost per additional QALY was £81,962, well above the accepted threshold for cost-effectiveness used in the UK and internationally. The probability of early surgery being cost-effective in this setting was only 5.6%., Conclusion: Consistent with the clinical findings of SWIFFT, these results indicate that initial cast immobilization of minimally displaced scaphoid fractures, with immediate fixation only offered to patients with nonunion, is the optimal form of treatment, resulting in comparable outcomes with less cost to the healthcare system. Cite this article: Bone Joint J  2021;103-B(7):1277-1283.

Introduction:  Preeclampsia (PE) is a pregnancy complication associated with increased maternal and perinatal morbidity and mortality. The disease presents with recent onset hypertension (after 20 weeks of gestation) and proteinuria, and can progress to multiple organ dysfunction, with worse outcomes among early onset preeclampsia (EOP) cases (< 34 weeks). The placenta is considered the root cause of PE; it represents the interface between the mother and the fetus, and acts as a macromembrane between the two circulations, due to its villous and vascular structures. Therefore, in pathological conditions, macroscopic and microscopic evaluation can provide clinically useful information that can confirm diagnosis and enlighten about outcomes and future therapeutic benefit., Objective:  To perform an integrative review of the literature on pathological placental findings associated to preeclampsia (comparing EOP and late onset preeclampsia [LOP]) and its impacts on clinical manifestations., Results:  Cases of EOP presented worse maternal and perinatal outcomes, and pathophysiological and anatomopathological findings were different between EOP and LOP placentas, with less placental perfusion, greater placental pathological changes with less villous volume (villous hypoplasia), greater amount of trophoblastic debris, syncytial nodules, microcalcification, villous infarcts, decidual arteriolopathy in EOP placentas when compared with LOP placentas. Clinically, the use of low doses of aspirin has been shown to be effective in preventing PE, as well as magnesium sulfate in preventing seizures in cases of severe features., Conclusion:  The anatomopathological characteristics between EOP and LOP are significantly different, with large morphological changes in cases of EOP, such as hypoxia, villous infarctions, and hypoplasia, among others, most likely as an attempt to ascertain adequate blood flow to the fetus. Therefore, a better understanding of the basic macroscopic examination and histological patterns of the injury is important to help justify outcomes and to determine cases more prone to recurrence and long-term consequences., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Aims: To identify the prevalence of neuropathic pain after lower limb fracture surgery, assess associations with pain severity, quality of life and disability, and determine baseline predictors of chronic neuropathic pain at three and at six months post-injury., Methods: Secondary analysis of a UK multicentre randomized controlled trial (Wound Healing in Surgery for Trauma; WHiST) dataset including adults aged 16 years or over following surgery for lower limb major trauma. The trial recruited 1,547 participants from 24 trauma centres. Neuropathic pain was measured at three and six months using the Doleur Neuropathique Questionnaire (DN4); 701 participants provided a DN4 score at three months and 781 at six months. Overall, 933 participants provided DN4 for at least one time point. Physical disability (Disability Rating Index (DRI) 0 to 100) and health-related quality-of-life (EuroQol five-dimension five-level; EQ-5D-5L) were measured. Candidate predictors of neuropathic pain included sex, age, BMI, injury mechanism, concurrent injury, diabetes, smoking, alcohol, analgaesia use pre-injury, index surgery location, fixation type, Injury Severity Score, open injury, and wound care., Results: The median age of the participants was 51 years (interquartile range 35 to 64). At three and six months post-injury respectively, 32% (222/702) and 30% (234/787) had neuropathic pain, 56% (396/702) and 53% (413/787) had chronic pain without neuropathic characteristics, and the remainder were pain-free. Pain severity was higher among those with neuropathic pain. Linear regression analyses found that those with neuropathic pain at six months post-injury had more physical disability (DRI adjusted mean difference 11.49 (95% confidence interval (CI) 7.84 to 15.14; p < 0.001) and poorer quality of life (EQ-5D utility -0.15 (95% CI -0.19 to -0.11); p < 0.001) compared to those without neuropathic characteristics. Logistic regression identified that prognostic factors of younger age, current smoker, below knee fracture, concurrent injuries, and regular analgaesia pre-injury were associated with higher odds of post-injury neuropathic pain., Conclusion: Pain with neuropathic characteristics is common after lower limb fracture surgery and persists to six months post-injury. Persistent neuropathic pain is associated with substantially poorer recovery. Further attention to identify neuropathic pain post-lower limb injury, predicting patients at risk, and targeting interventions, is indicated. Cite this article: Bone Joint J  2021;103-B(6):1047-1054.

Aims: To determine the role of early MRI in the management of suspected scaphoid fractures., Methods: A total of 337 consecutive patients presenting to an emergency department (ED) following wrist trauma over a 12-month period were prospectively included in this service evaluation project. MRI was not required in 62 patients with clear diagnoses, and 17 patients were not managed as per pathway, leaving a total of 258 patients with normal scaphoid series radiographs who were then referred directly from ED for an acute wrist MRI scan. Patient demographics, clinical details, outcomes, and complications were recorded at a minimum of a year following injury., Results: The median time from injury to ED presentation was one day and the median number of positive clinical signs was two out of three (snuffbox tenderness, tubercle tenderness, pain on telescoping). Of 258 patients referred for acute MRI, 208 scans were performed as 50 patients either did not tolerate (five patients) or did not attend their scan (45 patients). MRI scans demonstrated scaphoid fracture (13%), fracture of another bone (22%), scaphoid contusion (6%), other contusion/ligamentous injury (20%), or solely degenerative pathology (10%). Only 29% of scans showed no abnormality. Almost 50% of those undergoing MRI (100 patients) were discharged by ED with advice, with only one re-presentation. Of the 27 undisplaced occult scaphoid fractures, despite prompt cast immobilization, two experienced delayed union which was successfully treated with surgery., Conclusion: The use of MRI direct from ED enables prompt diagnosis and the early discharge of a large proportion of patients with normal radiographs following wrist trauma. Cite this article: Bone Jt Open  2021;2(6):447-453.

Aims: The aim of this study was to explore parents and young people's experience of having a medial epicondyle fracture, and their thoughts about the uncertainty regarding the optimal treatment., Methods: Families were identified after being invited to participate in a randomized controlled trial of surgery or no surgery for displaced medial epicondyle fractures of the humerus in children. A purposeful sample of 25 parents (22 females) and five young people (three females, mean age 11 years (7 to 14)) from 15 UK hospitals were interviewed a mean of 39 days (14 to 78) from injury. Qualitative interviews were informed by phenomenology and themes identified to convey participants' experience., Results: The results identify parents' desire to do the best for their child expressed through two themes: 1) 'uncertainty' (being uncertain about the best treatment option); and 2) 'facilitating recovery' (sharing the experience). Parents and young people were shocked when confronted with uncertainty about treatment and they felt responsible for the decision. They searched for further information, drew on their own experience, and struggled to weigh up risks of the treatments. Discussion with surgeons provided crucial support for decision-making, and young people were involved to a varying degree. In facilitating recovery, parents balanced increasing activity with protecting their child, but lacked knowledge about pain management, and how to improve strength and function of the arm. They hoped for a return to normal, including competitive sports., Conclusion: Surgeons are aware of the impact of injury on children and their parents; however, they may be less aware of the turmoil created by treatment uncertainty. Confident surgeons who appreciate and contextualize the importance of pre-existing experience and beliefs are best placed to help the family develop confidence to embrace uncertainty, particularly regarding participation in clinical trials. Cite this article: Bone Jt Open  2021;2(6):359-364.

The mechanisms involved in the development of skeletal muscle fibers have been studied in the last 70 years and yet many aspects of this process are still not completely understood. A myriad of in vivo and in vitro invertebrate and vertebrate animal models has been used for dissecting the molecular and cellular events involved in muscle formation. Among the most used animal models for the study of myogenesis are the rodents rat and mouse, the fruit fly Drosophila, and the birds chicken and quail. Here, we describe the robustness and advantages of the chick primary muscle culture model for the study of skeletal myogenesis. In the myoblast culture obtained from embryonic chick pectoralis muscle it is possible to analyze all the steps involved in skeletal myogenesis, such as myoblast proliferation, withdrawal from cell cycle, cell elongation and migration, myoblast alignment and fusion, the assembly of striated myofibrils, and the formation of multinucleated myotubes. The fact that in vitro chick myotubes can harbor hundreds of nuclei, whereas myotubes from cell lines have only a dozen nuclei demonstrates the high level of differentiation of the autonomous chick myogenic program. This striking differentiation is independent of serum withdrawal, which points to the power of the model. We also review the major pro-myogenic and anti-myogenic molecules and signaling pathways involved in chick myogenesis, in addition to providing a detailed protocol for the preparation of embryonic chick myogenic cultures. Moreover, we performed a bibliometric analysis of the articles that used this model to evaluate which were the main explored topics of interest and their contributors. We expect that by describing the major findings, and their advantages, of the studies using the embryonic chick myogenic model we will foster new studies on the molecular and cellular process involved in muscle proliferation and differentiation that are more similar to the actual in vivo condition than the muscle cell lines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Costa, Jurberg and Mermelstein.)

Background: There are no accurate estimates of the prevalence of non-severe maternal morbidities. Given the lack of instruments to fully assess these morbidities, the World Health Organization (WHO) developed an instrument called WOICE. We aimed to evaluate the prevalence of non-severe maternal morbidities in puerperal women and factors associated to impaired clinical, social and mental health conditions., Method: A cross-sectional study with postpartum women at a high-risk outpatient clinic in southeast Brazil, from November 2017 to December 2018. The WOICE questionnaire included three sections: the first with maternal and obstetric history, sociodemographic data, risk and environment factors, violence and sexual health; the second considers functionality and disability, general symptoms and mental health; and the third includes data on physical and laboratory tests. Data collection was supported by Tablets with REDCAP software. Initially, a descriptive analysis was performed, with general prevalence of all variables contained in the WOICE, including scales on anxiety and depression (GAD-7 and PHQ-9- impaired if ≥10), functionality (WHODAS- high disability scores when ≥37.4) and data on violence and substance use. Subsequently, an evaluation of cases with positive findings was performed, with a Poisson regression to investigate factors associated to impaired non-clinical and clinical conditions., Results: Five hundred seventeen women were included, majority (54.3%) multiparous, between 20 and 34 years (65.4%) and with a partner (75,6%). Over a quarter had (26.2%) preterm birth. Around a third (30.2%) reported health problems informed by the physician, although more than 80% considered having good or very good health. About 10% reported any substance use and 5.9% reported exposure to violence. Anxiety was identified in 19.8% of cases, depression in 36.9% and impaired functioning in 4.4% of women. Poisson regression identified that poor overall health rating was associated to increased anxiety/depression and impaired functioning. Having a partner reduced perception of women on the presence of clinical morbidities., Conclusion: During postpartum care of a high-risk population, over one third of the considered women presented anxiety and depression; 10% reported substance use and around 6% exposure to violence. These aspects of women's health need further evaluation and specific interventions to improve quality of care.

The use of tourniquets in lower limb trauma surgery to control bleeding and improve the surgical field is a long established practice. In this article, we review the evidence relating to harms and benefits of tourniquet use in lower limb fracture fixation surgery and report the results of a survey on current tourniquet practice among trauma surgeons in the UK.

Aims: The aim of this study was to determine whether national standards of best practice are associated with improved health-related quality of life (HRQoL) outcomes in hip fracture patients., Methods: This was a multicentre cohort study conducted in 20 acute UK NHS hospitals treating hip fracture patients. Patients aged ≥ 60 years treated operatively for a hip fracture were eligible for inclusion. Regression models were fitted to each of the "Best Practice Tariff" indicators and overall attainment. The impact of attainment on HRQoL was assessed by quantifying improvement in EuroQol five-dimension five-level questionnaire (EQ-5D-5L) from estimated regression model coefficients., Results: A total of 6,532 patients provided both baseline and four-month EQ-5D-5L, of whom 1,060 participants had died at follow-up. Best practice was achieved in the care of 57% of participants; there was no difference in age, cognitive ability, and mobility at baseline for the overall attainment and non-attainment groups. Attaining at least 'joint care by surgeon and orthogeriatrician', 'delirium assessment', and 'falls assessment' was associated with a large, clinically relevant increase in four months EQ-5D-5L of 0.094 (bootstrapped 95% confidence interval (CI) 0.046 to 0.146)., Conclusion: National standards with enhanced remuneration in hip fracture care results in improvement in individual patients' HRQoL. Cite this article: Bone Joint J  2021;103-B(5):881-887.

Objective:  The coronavirus disease 2019 (COVID-19) is a pandemic viral disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The impact of the disease among the obstetric population remains unclear, and the study of the placenta can provide valuable information. Adequate sampling of the placental tissue can help characterize the pathways of viral infections., Methods:  A protocol of placental sampling is proposed, aiming at guaranteeing representativity of the placenta and describing the adequate conservation of samples and their integrity for future analysis. The protocol is presented in its complete and simplified versions, allowing its implementation in different complexity settings., Results:  Sampling with the minimum possible interval from childbirth is the key for adequate sampling and storage. This protocol has already been implemented during the Zika virus outbreak., Conclusion:  A protocol for adequate sampling and storage of placental tissue is fundamental for adequate evaluation of viral infections on the placenta. During the COVID-19 pandemic, implementation of this protocol may help to elucidate critical aspects of the SARS-CoV-2 infection., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Segmental tibial fractures are fractures in two or more areas of the tibial diaphysis resulting in a separate intercalary segment of the bone. Surgical fixation is recommended for patients with segmental tibial fractures as non-operative treatment outcomes are poor. The most common surgical interventions are intramedullary nailing (IMN) and circular frame external fixation (CFEF), but evidence about which is better is of poor quality. An adequately powered randomised controlled trial (RCT) to determine optimum treatment is required. STIFF-F aimed to assess the feasibility of a multicentre RCT comparing IMN with CFEF for segmental tibial fracture., Methods: STIFF-F was a mixed-methods feasibility study comprising a pilot RCT conducted at six UK Major Trauma Centres, qualitative interviews drawing on Phenomenology and an online survey of rehabilitation. The primary outcome was recruitment rate. Patients, 16 years and over, with a segmental tibial fracture (open or closed) deemed suitable for IMN or CFEF were eligible to participate. Randomisation was stratified by site using random permuted blocks of varying sizes. Participant or assessor blinding was not possible. Interviews were undertaken with patients about their experience of injury, treatment, recovery and participation. Staff were interviewed to identify contextual factors affecting trial processes, their experience of recruitment and the treatment pathway. An online survey was developed to understand the rehabilitation context of the treatments., Results: Eleven patients were screened and three recruited to the pilot RCT. Nineteen staff and four patients participated in interviews, and 11 physiotherapists responded to the survey. This study found the following: (i) segmental tibial fractures were rarer than anticipated, (ii) the complexity of the injury, study setup times and surgeon treatment preferences impeded recruitment, (iii) recovery from a segmental tibial fracture is challenging, and rehabilitation protocols are inconsistent and (iv) despite the difficulty recruiting, staff valued this research question and strived to find a way forward., Conclusion: The proposed multicentre RCT comparing IMN with CFEF is not feasible. This study highlighted the difficulty of recruiting patients to an RCT of a complex rare injury over a short time period., Trial Registration: The study was registered with the International Standard Randomised Controlled Trials Number Registry: ISRCTN11229660.

Aims: This study sought to compare the rate of deep surgical site infection (SSI), as measured by the Centers for Disease Control and Prevention (CDC) definition, after surgery for a fracture of the hip between patients treated with standard dressings and those treated with incisional negative pressure wound therapy (iNPWT). Secondary objectives included determining the rate of recruitment and willingness to participate in the trial., Methods: The study was a two-arm multicentre randomized controlled feasibility trial that was embedded in the World Hip Trauma Evaluation cohort study. Any patient aged > 65 years having surgery for hip fracture at five recruitment centres in the UK was considered to be eligible. They were randomly allocated to have either a standard dressing or iNPWT after closure of the wound. The primary outcome measure was deep SSI at 30 and 90 days, diagnosed according to the CDC criteria. Secondary outcomes were: rate of recruitment; further surgery within 120 days; health-related quality of life (HRQoL) using the EuroQol five-level five-dimension questionnaire (EQ-5D-5L); and related complications within 120 days as well as mobility and residential status at this time., Results: A total of 462 valid randomizations were carried out (232 and 230 in the standard dressing and iNPWT groups, respectively). In the standard dressing group, 14 of 218 patients (6.4%) developed deep SSI. In the iNPWT group, four of 214 patients (1.9%) developed deep SSI. This gives a total rate of SSI of 4.2% (95% confidence interval (CI) 2.7% to 6.5%). Patients and surgeons were willing to participate in the study with 462 patients being recruited from a possible 749 (62.3%)., Conclusion: The rate of deep SSI 30 days after surgery for a fracture of the hip was 4%, which makes a study comparing the clinical effectiveness of standard dressings and iNPWT feasible. Cite this article: Bone Joint J  2021;103-B(4):755-761.

Aims: A pilon fracture is a severe ankle joint injury caused by high-energy trauma, typically affecting men of working age. Although relatively uncommon (5% to 7% of all tibial fractures), this injury causes among the worst functional and health outcomes of any skeletal injury, with a high risk of serious complications and long-term disability, and with devastating consequences on patients' quality of life and financial prospects. Robust evidence to guide treatment is currently lacking. This study aims to evaluate the clinical and cost-effectiveness of two surgical interventions that are most commonly used to treat pilon fractures., Methods: A randomized controlled trial (RCT) of 334 adult patients diagnosed with a closed type C pilon fracture will be conducted. Internal locking plate fixation will be compared with external frame fixation. The primary outcome and endpoint will be the Disability Rating Index (a patient self-reported assessment of physical disability) at 12 months. This will also be measured at baseline, three, six, and 24 months after randomization. Secondary outcomes include the Olerud and Molander Ankle Score (OMAS), the five-level EuroQol five-dimenison score (EQ-5D-5L), complications (including bone healing), resource use, work impact, and patient treatment preference. The acceptability of the treatments and study design to patients and health care professionals will be explored through qualitative methods., Discussion: The two treatments being compared are the most commonly used for this injury, however there is uncertainty over which is most clinically and cost-effective. The Articular Pilon Fracture (ACTIVE) Trial is a sufficiently powered and rigorously designed study to inform clinical decisions for the treatment of adults with this injury. Cite this article: Bone Jt Open  2021;2(3):150-163.

Objective: To evaluate the impact of pre-eclampsia on cesarean delivery by using the Robson classification., Methods: A retrospective cross-sectional study including all women who delivered in a referral maternity hospital in southeast Brazil from January 2017 to February 2018. Women were classified into 1 of 10 Robson groups and then further subdivided into pre-eclampsia (PE) and non-PE (NPE) groups. Frequency of cesarean was determined for each group and compared by using χ 2 and prevalence ratio., Results: Overall, 3102 women were included, of whom 1578 (50.9%) delivered by cesarean. Classification in Robson group 5 was the most frequent among all women (n=727, 23.4%). In the PE group (n=258, 8.3%), group 10 was the most frequent classification (n=120, 46.5%); in NPE, Robson group 5 was the most frequency (n=682, 24.0%). Pre-eclampsia was associated with a higher occurrence of cesarean (77.5% vs 48.4%; prevalence ratio, 2.29; 95% confidence interval, 1.82-2.82), owing to higher rates in Robson groups 1, 5, and 10., Conclusion: Pre-eclampsia was associated with a higher occurrence of cesarean delivery in some Robson groups. Robson classification may be used to evaluate the impact of specific conditions at a facility level to help plan future interventions to optimize the use of cesarean., (© 2020 International Federation of Gynecology and Obstetrics.)

Objective: Severe maternal morbidity (SMM) is already known to be associated with adverse neonatal outcomes, however, its association with long-term deficits of weight and height, and impairment in neurodevelopment among children was not yet fully assessed. We aim to evaluate whether SMM has repercussions on the weight and height-for-age and neurodevelopmental status of the child., Methods: A retrospective cohort analysis with women who had SMM events in a tertiary referral center in Brazil. They were compared to a control group of women who had not experienced any SMM. Childbirth and perinatal characteristics, weight and height-for-age deficits and neurodevelopmental impairment suspicion by Denver II Test were comparatively assessed in both groups using RR and 95% CI. Multiple regression analysis was used addressing deficit of weight-for-age, height-for-age and an altered Denver Test, estimating their independent adjusted RR and 95% CI., Results: 634 women with perinatal outcomes available (311 with SMM and 323 without) and 571 children were assessed. Among women with SMM, increased rates in perinatal deaths, Apgar lower than 7 at five minutes, shorter breastfeeding period, preterm birth (49.0% × 11.1%), low birthweight (45.8% × 11.5%), deficits of weight-for-age [RR 3.11 (1.60-6.04)] and height-for-age [RR 1.52 (1.06-2.19)] and altered Denver Test [RR 1.5 (1.02-2.36)] were more frequently found than in the control group. SMM was not identified as independently associated with any of the main outcomes., Conclusion: SMM showed to be associated with a negative impact on growth and neurodevelopment aspects of perinatal and infant health. These findings suggest that effective health policies directed towards appropriate care of pregnancy may have an impact on the reduction of maternal, neonatal and infant morbidity and mortality.

Objective: To evaluate the use of analgesia during labor in women who had a vaginal birth and to determine the factors associated with its use., Methods: A secondary analysis was performed of the WHO Multicountry Survey on Maternal and Newborn Health, a cross-sectional, facility-based survey including 359 healthcare facilities in 29 countries. The prevalence of analgesia use for vaginal birth in different countries was reported according to the Human Development Index (HDI). Sociodemographic and obstetric characteristics of the participants with and without analgesia were compared. The prevalence ratios were compared across countries, HDI groups, and regions using a design-based χ 2 test., Results: Among the 221 345 women who had a vaginal birth, only 4% received labor analgesia, mainly epidural. The prevalence of women receiving analgesia was significantly higher in countries with a higher HDI than in countries with a lower HDI. Education was significantly associated with increased use of analgesia; nulliparous women and women undergoing previous cesarean delivery had a significantly increased likelihood of receiving analgesia., Conclusion: Use of analgesia for women undergoing labor and vaginal delivery was low, specifically in low-HDI countries. Whether low use of analgesia reflects women's desire or an unmet need for pain relief requires further studies., (© 2020 International Federation of Gynecology and Obstetrics.)

Objective: To estimate the generalizability of treatment effects observed in a randomized trial of hip fracture surgery implants to a broader population of people undergoing hip surgery in the United Kingdom., Study Design and Setting: In 2018, the WHiTE-3 trial (n = 958) demonstrated that a modular hemiarthroplasty implant conferred no additional benefit over the traditional monoblock implant for quality of life and length of hospital stay. We compared and weighted the trial sample against two target populations: WHiTE-cohort (n = 2,457) and UK-National Hip Fracture Database (NHFD, n = 190,894), and re-estimate expected treatment effects for the target populations., Results: Despite differences in baseline characteristics of the trial sample and target populations, the re-estimated treatment effects were comparable. For quality of life, the differences between the trial estimate and WHiTE-cohort and NHFD estimates were 0.01 points on the EuroQol (EQ5D). For length of stay, the difference between the trial estimate and WHiTE-cohort was 0.50 days; and the difference between the trial estimate and NHFD estimate was -0.47 days., Conclusion: This generalizability analysis of the WHiTE-3 trial found that the inferences from the trial can be generalized to a wider population of individuals in the UK NHFD and the WHiTE-cohort who met the inclusion criteria for WHiTE-3., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Introduction: human growth is the result of an interaction between genetic, hormonal, nutritional, and environmental factors. It is not yet fully understood what is predominant and decisive in determining an individual's weight and height. Objective: the aim of this study was to evaluate the cardiometabolic profile of exclusively breastfed children born small for gestational age (SGA). Methods: this is a prospective cohort study of children born at term who were classified as SGA, and as appropiate for gestational age (AGA), who were followed up to pre-school age. Anthropometric measures and body composition parameters were obtained. Breastfeeding duration was calculated in days, and achievement of catch up of weight was considered an increase in Z-score ≥ 0.67. The cardiometabolic profile was evaluated in the first month of life and repeated at pre-school age. At pre-school age, fasting blood glucose, insulin, HOMA-IR, and blood pressure were measured. Results: twenty SGA and 12 AGA children were studied. The mean duration of exclusive breastfeeding (EBF) was 180 days in both groups. Of SGA children, 85 % had recovery anthropometric parameters for age within the first six months, with a speed of weight gain significantly higher than the that of AGAs (p < 0.001). SGAs continued to be thinner and smaller than AGAs at pre-school age. There was no diagnosis of overweight or obesity in the studied sample, and no differences were foun between groups in laboratory tests. Conclusion: these findings suggest that EBF may confer protection until pre-school age in children born SGA, who are considered at higher risk for chronic non-communicable diseases.

Background: Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 strain, was first identified in late 2019 in China. The outcomes of patients affected by the virus can worsen, developing acute respiratory failure and other serious complications, especially in older individuals and people with obesity and comorbidities. Thus, obese patients tend to have a more severe course of COVID-19. Thus, this review aims to synthesize the evidence in the literature that associates COVID-19 and the severity of clinical outcomes in infected obese patients., Methods: This protocol was designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols Statement. Scientific and gray literature will be systematically selected from PubMed/MEDLINE, Latin American Literature in Health Sciences, Online Scientific Electronic Library, Scopus, ScienceDirect, Web of Science, Embase, and Cochrane. The selection of articles will be limited to studies published in English, Portuguese, and Spanish from December 2019 onwards. The main clinical outcomes will be clinical severity in obese patients with COVID-19 as tachypnea (respiratory rate, ≥ 30 breaths per minute), hypoxemia (oxygen saturation, ≤ 93%), the ratio of the partial pressure of arterial oxygen to fraction of inspired oxygen (< 300), lung infiltrate (> 50% of the lung field involved within 24-48 h), diagnosis of the severe acute respiratory syndrome, need of invasive mechanical ventilation, and mortality. Two reviewers will independently screen all citations, full-text articles, and abstract data. Selection bias will be minimized by excluding studies published before December 2019. Conflicts will be resolved through a third reviewer and consensus-building. Moreover, findings will be reported using narrative synthesis and tabulation of the summaries., Discussion: Given the need for early detection of the possible implications and treatment for patients with obesity diagnosed with COVID-19, the scoping review will be useful to capture the state of the current literature, identify the gaps, and make recommendations for future research for directing the conduct and optimization of therapies in these patients by the multiprofessional teams., Systematic Review Registration: Open Science Framework: https://osf.io/xrkec.

Background: The coronavirus disease 2019 (COVID-19) pandemic may have an effect on maternal anxiety and influence postpartum experience., Objective: To study the prevalence of maternal anxiety in late pregnancy in the context of the COVID-19 outbreak in Brazil and to analyze its association with maternal knowledge and concerns about the pandemic., Methods: This was a national multicenter cross-sectional study performed in 10 different public university hospitals, between 1 June and 31 August 2020, in Brazil. The inclusion criteria were: maternal age more than 18 years; gestational age more than 36 weeks at childbirth; single alive newborn without malformations; and absence of mental disorders. We applied a structured questionnaire to explore the knowledge and concerns about COVID-19. Maternal anxiety was assessed using the Beck Anxiety Inventory (BAI)., Results: Of the 1662 women interviewed, the BAI score in late pregnancy indicated that 13.9% presented moderate and 9.6% severe maternal anxiety. Moderate or severe maternal anxiety was independently associated with the fear of being unaccompanied at childbirth (aOR1.12, 95% CI 1.10-1.35), and independent protective factors were confidence in knowing how to protect oneself from COVID-19 (aOR0.89, 95% CI 0.82-0.97) and how to safely breastfeed (aOR0.89, 95% CI 0.83-0.95)., Conclusion: The COVID-19 pandemic has a significant impact on maternal anxiety.

Aims: Surgical treatment of hip fracture is challenging; the bone is porotic and fixation failure can be catastrophic. Novel implants are available which may yield superior clinical outcomes. This study compared the clinical effectiveness of the novel X-Bolt Hip System (XHS) with the sliding hip screw (SHS) for the treatment of fragility hip fractures., Methods: We conducted a multicentre, superiority, randomized controlled trial. Patients aged 60 years and older with a trochanteric hip fracture were recruited in ten acute UK NHS hospitals. Participants were randomly allocated to fixation of their fracture with XHS or SHS. A total of 1,128 participants were randomized with 564 participants allocated to each group. Participants and outcome assessors were blind to treatment allocation. The primary outcome was the EuroQol five-dimension five-level health status (EQ-5D-5L) utility at four months. The minimum clinically important difference in utility was pre-specified at 0.075. Secondary outcomes were EQ-5D-5L utility at 12 months, mortality, residential status, mobility, revision surgery, and radiological measures., Results: Overall, 437 and 443 participants were analyzed in the primary intention-to-treat analysis in XHS and SHS treatment groups respectively. There was a mean difference of 0.029 in adjusted utility index in favour of XHS with no evidence of a difference between treatment groups (95% confidence interval -0.013 to 0.070; p = 0.175). There was no evidence of any differences between treatment groups in any of the secondary outcomes. The pattern and overall risk of adverse events associated with both treatments was similar., Conclusion: Any difference in four-month health-related quality of life between the XHS and SHS is small and not clinically important. There was no evidence of a difference in the safety profile of the two treatments; both were associated with lower risks of revision surgery than previously reported. Cite this article: Bone Joint J 2021;103-B(2):256-263.

Aims: Patients receiving cemented hemiarthroplasties after hip fracture have a significant risk of deep surgical site infection (SSI). Standard UK practice to minimize the risk of SSI includes the use of antibiotic-loaded bone cement with no consensus regarding type, dose, or antibiotic content of the cement. This is the protocol for a randomized clinical trial to investigate the clinical and cost-effectiveness of high dose dual antibiotic-loaded cement in comparison to low dose single antibiotic-loaded cement in patients 60 years and over receiving a cemented hemiarthroplasty for an intracapsular hip fracture., Methods: The WHiTE 8 Copal Or Palacos Antibiotic Loaded bone cement trial (WHiTE 8 COPAL) is a multicentre, multi-surgeon, parallel, two-arm, randomized clinical trial. The pragmatic study will be embedded in the World Hip Trauma Evaluation (WHiTE) (ISRCTN 63982700). Participants, including those that lack capacity, will be allocated on a 1:1 basis stratified by recruitment centre to either a low dose single antibiotic-loaded bone cement or a high dose dual antibiotic-loaded bone cement. The primary analysis will compare the differences in deep SSI rate as defined by the Centers for Disease Control and Prevention within 90 days of surgery via medical record review and patient self-reported questionnaires. Secondary outcomes include UK Core Outcome Set for hip fractures, complications, rate of antibiotic prescription, resistance patterns of deep SSI, and resource use (more specifically, cost-effectiveness) up to four months post-randomization. A minimum of 4,920 patients will be recruited to obtain 90% power to detect an absolute difference of 1.5% in the rate of deep SSI at 90 days for the expected 3% deep SSI rate in the control group., Conclusion: The results of this trial will provide evidence regarding clinical and cost-effectiveness between low dose single and high dose dual antibiotic-loaded bone cement, which will inform policy and practice guidelines such as the National Institute for Health and Care Excellence guidance on management of hip fractures. Cite this article: Bone Jt Open  2021;2(2):72-78.

Microscopy is the main technique to visualize and study the structure and function of cells. The impact of optical and electron microscopy techniques is enormous in all fields of biomedical research. It is possible that different research areas rely on microscopy in diverse ways. Here, we analyzed comparatively the use of microscopy in pharmacology and cell biology, among other biomedical sciences fields. We collected data from articles published in several major journals in these fields. We analyzed the frequency of use of different optical and electron microscopy techniques: bright field, phase contrast, differential interference contrast, polarization, conventional fluorescence, confocal, live cell imaging, super resolution, transmission and scanning electron microscopy, and cryoelectron microscopy. Our analysis showed that the use of microscopy has a distinctive pattern in each research area, and that nearly half of the articles from pharmacology journals did not use any microscopy method, compared to the use of microscopy in almost all the articles from cell biology journals. The most frequent microscopy methods in all the journals in all areas were bright field and fluorescence (conventional and confocal). Again, the pattern of use was different: while the most used microscopy methods in pharmacology were bright field and conventional fluorescence, in cell biology the most used methods were conventional and confocal fluorescence, and live cell imaging. We observed that the combination of different microscopy techniques was more frequent in cell biology, with up to 6 methods in the same article. To correlate the use of microscopy with the research theme of each article, we analyzed the proportion of microscopy figures with the use of cell culture. We analyzed comparatively the vocabulary of each biomedical sciences field, by the identification of the most frequent words in the articles. The collection of data described here shows a vast difference in the use of microscopy among different fields of biomedical sciences. The data presented here could be valuable in other scientific and educational contexts., Competing Interests: The authors have declared that no competing interests exist.

Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents an important cause of maternal and perinatal morbidity and mortality. The screening of the disease is a subject of studies, but the complexity and uncertainties regarding its etiology make this objective a difficult task. In addition, the costs related to screening protocols, the heterogeneity of the most affected populations and the lack of highly effective prevention methods reduce the potential of current available algorithms for screening. Thus, the National Specialized Commission of Hypertension in Pregnancy of the Brazilian Association of Gynecology and Obstetrics Federation (Febrasgo, in the Portuguese acronym) (NSC Hypertension in Pregnancy of the Febrasgo) considers that there are no screening algorithms to be implemented in the country to date and advocates that Aspirin and calcium should be widely used., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Maternal mortality is unacceptably high in our region. In 2015, the Latin American Center for Perinatology and Women´s Reproductive Health (CLAP) created a regional network of institutions including 16 countries, committed to improving epidemiological surveillance and healthcare of women in a situation of abortion or near miss event, using a common platform, the Perinatal Information System (SIP). The objective of the current pilot project was to test a new method of study called EviSIP (Evidence from SIP), a method of generating information on maternal near miss and abortion for the region. We describe the implementation of this initiative in reproductive healthcare facilities using SIP. Junior researchers/clinicians from these countries were included, along with expert researchers in reproductive health from across the world. Articles were produced with data on maternal near miss and abortion gathered from the SIP of each participating sentinel center; and recommendations from experts. EviSIP was the first joint workspace to discuss patient outcomes after treatment of abortion or near miss cases, with data analysis of each Sentinel Center; discuss and analyze data among centers, at a country and regional level; discuss the main outcomes and their impact on changing procedures and policies; strengthen the operational research capacity of the centers; develop and encourage the publication of scientific articles. The EviSIP initiative also promoted training of healthcare professionals in research. EviSIP provided a unique opportunity to train for research and mentorship and was pivotal to the production of scientific knowledge of reproductive health in the region.

Introduction: Hypertension is a very important cause of maternal morbidity and mortality worldwide, despite efforts on prevention. The lack of a tool to provide effective and early prediction of hypertension for a high-risk group may contribute to improving maternal and fetal outcomes. Metabolomics has figured out as a promised technology to contribute to the improvement of hypertension in pregnancy prediction., Methods and Analysis: Our primary outcome is hypertensive disorders of pregnancy. A detailed systematic literature search will be performed in electronic databases PubMed, EMBASE, Scopus, Web of Science, Latin America and Caribbean Health Sciences Literature, Scientific Electronic Library Online, Health Technology Assessment and Database of Abstracts of Reviews of Effects using controlled terms 'pre-eclampsia', 'hypertensive disorders', 'metabolomics' and 'prediction' (and their variations). Studies from the latest 20 years will be included, except case reports, reviews, cross-sectional studies, letter to editors, expert opinions, commentaries papers or non-human research. If possible, we will perform a meta-analysis. Two peer-reviewers will independently perform the search and in cases of discordance, a third reviewer will be consulted., Ethics and Dissemination: As a systematic review, ethics approval is not required. The results of this review will present the current use and performance of metabolomics for predicting gestational hypertension. Such data could potentially guide future studies and interventions to improve existing prediction models., Prospero Registration Number: CRD42018097409., Competing Interests: Competing interests: None declared., (©World Health Organization 2020. Licensee BMJ.)

Objectives: To perform a multidimensional assessment of women who experienced severe maternal morbidity (SMM) and its short-term and medium-term impact on the lives and health of women and their children., Design: A retrospective cohort study., Setting: A tertiary maternity hospital from the southeast region of Brazil., Participants: The exposed population was selected from intensive care unit admissions if presenting any diagnostic criteria for SMM. Controls were randomly selected among women without SMM admitted to the same maternity and same time of childbirth., Primary and Secondary Outcome Variables: Validated tools were applied, addressing post-traumatic stress disorder (PTSD) and quality of life (SF-36) by phone, and then general and reproductive health, functioning (WHO Disability Assessment Schedule), sexual function (Female Sexual Function Index (FSFI)), substance abuse (Alcohol, Smoking and Substance Involvement Screening Test 2.0) and growth/development (Denver Developmental Screening Test) of children born in the index pregnancy in a face-to-face interview., Results: All instruments were applied to 638 women (315 had SMM; 323 were controls, with the assessment of 264 and 307 children, respectively). SF-36 score was significantly lower in the SMM group, while PTSD score was similar between groups. Women who had SMM became more frequently sterile, had more abnormal clinical conditions after the index pregnancy and a higher score for altered functioning, while proportions of FSFI score or any drug use were similar between groups. Furthermore, children from the SMM group were more likely to have weight (threefold) and height (1.5 fold) for age deficits and also impaired development (1.5-fold)., Conclusion: SMM impairs some aspects of the lives of women and their children. The focus should be directed towards monitoring these women and their children after birth, ensuring accessibility to health services and reducing short-term and medium-term repercussions on physical, reproductive and psychosocial health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)