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Background: There is a growing interest in reporting satisfaction levels of transgender women undergoing vaginoplasty surgery. The lack of information regarding satisfaction during the initial experience of the vaginoplasty technique, and the moderate morbidity related to the surgery, could discourage the immersion of new groups in initiating a program of this kind. Therefore, we aim to report patients' level of satisfaction during our initial experience in the penile inversion vaginoplasty technique., Methods: Retrospective study of patients who underwent penile inversion vaginoplasty in our center between September 2019 and August 2021. Surgery technique, demographic data, preoperative clinical variables, and short and long-term follow-up are described. Six months after surgery, a survey elaborated by the research team was conducted by phone. The score goes from 1 to 5, and it evaluates satisfaction on esthetics, functional, psychosocial, and global aspects., Results: Twenty patients underwent penile inversion vaginoplasty in our center during the described period. The average age was 35.6 years old, the mean body mass index (BMI) was 24.7 kg/m 2 , and they presented low comorbidity. Half of the patients presented at least one complication, most of which were minor. One patient was urgently reoperated due to bleeding, and three patients were reoperated on a scheduled basis from minor surgeries. 90% of the patients answered the questionnaire. The most common answers to all four areas covered (esthetics, functional, psychosocial, and global) were satisfied or very satisfied, resulting in a mean over four points in each one of the sections. Lastly, 94.4% of the patients reported being satisfied with their choice of having undergone surgery., Conclusions: Our initial experience in penile inversion vaginoplasty reveals good satisfaction results at short follow up., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-108/coif). The authors have no conflicts of interest to declare., (2022 Translational Andrology and Urology. All rights reserved.)

Background: Real-time prediction is key to prevention and control of infections associated with health-care settings. Contacts enable spread of many infections, yet most risk prediction frameworks fail to account for their dynamics. We developed, tested, and internationally validated a real-time machine-learning framework, incorporating dynamic patient-contact networks to predict hospital-onset COVID-19 infections (HOCIs) at the individual level., Methods: We report an international retrospective cohort study of our framework, which extracted patient-contact networks from routine hospital data and combined network-derived variables with clinical and contextual information to predict individual infection risk. We trained and tested the framework on HOCIs using the data from 51 157 hospital inpatients admitted to a UK National Health Service hospital group (Imperial College Healthcare NHS Trust) between April 1, 2020, and April 1, 2021, intersecting the first two COVID-19 surges. We validated the framework using data from a Swiss hospital group (Department of Rehabilitation, Geneva University Hospitals) during a COVID-19 surge (from March 1 to May 31, 2020; 40 057 inpatients) and from the same UK group after COVID-19 surges (from April 2 to Aug 13, 2021; 43 375 inpatients). All inpatients with a bed allocation during the study periods were included in the computation of network-derived and contextual variables. In predicting patient-level HOCI risk, only inpatients spending 3 or more days in hospital during the study period were examined for HOCI acquisition risk., Findings: The framework was highly predictive across test data with all variable types (area under the curve [AUC]-receiver operating characteristic curve [ROC] 0·89 [95% CI 0·88-0·90]) and similarly predictive using only contact-network variables (0·88 [0·86-0·90]). Prediction was reduced when using only hospital contextual (AUC-ROC 0·82 [95% CI 0·80-0·84]) or patient clinical (0·64 [0·62-0·66]) variables. A model with only three variables (ie, network closeness, direct contacts with infectious patients [network derived], and hospital COVID-19 prevalence [hospital contextual]) achieved AUC-ROC 0·85 (95% CI 0·82-0·88). Incorporating contact-network variables improved performance across both validation datasets (AUC-ROC in the Geneva dataset increased from 0·84 [95% CI 0·82-0·86] to 0·88 [0·86-0·90]; AUC-ROC in the UK post-surge dataset increased from 0·49 [0·46-0·52] to 0·68 [0·64-0·70])., Interpretation: Dynamic contact networks are robust predictors of individual patient risk of HOCIs. Their integration in clinical care could enhance individualised infection prevention and early diagnosis of COVID-19 and other nosocomial infections., Funding: Medical Research Foundation, WHO, Engineering and Physical Sciences Research Council, National Institute for Health Research (NIHR), Swiss National Science Foundation, and German Research Foundation., Competing Interests: Declaration of interests After the analysis in this paper was completed, AM and MB received funding from UKRI Research England via the MedTech SuperConnector (awarded on June 1, 2022) for commercial viability testing of infection prevention models. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Screenwide is a case-control study (2017−2021) including women with incident endometrial and ovarian cancers (EC and OC), BRCA1/2 and MMR pathogenic variant carriers, and age-matched controls from three centers in Spain. Participants completed a personal interview on their sociodemographic factors, occupational exposure, medication, lifestyle, and medical history. We collected biological specimens, including blood samples, self-collected vaginal specimens, cervical pap-brush samples, uterine specimens, and, when available, tumor samples. The planned analyses included evaluation of the potential risk factors for EC/OC; evaluation of molecular biomarkers in minimally invasive samples; evaluation of the cost-effectiveness of molecular tests; and the generation of predictive scores to integrate different epidemiologic, clinical, and molecular factors. Overall, 182 EC, 69 OC, 98 BRCA pathogenic variant carriers, 104 MMR pathogenic variant carriers, and 385 controls were enrolled. The overall participation rate was 85.7%. The pilot study using 61 samples from nine EC cases and four controls showed that genetic variants at the variant allele fraction > 5% found in tumors (n = 61 variants across the nine tumors) were detected in paired endometrial aspirates, clinician-collected cervical samples, and vaginal self-samples with detection rates of 90% (55/61), 79% (48/61), and 72% (44/61) by duplex sequencing, respectively. Among the controls, only one somatic mutation was detected in a cervical sample. We enrolled more than 800 women to evaluate new early detection strategies. The preliminary data suggest that our methodological approach could be useful for the early detection of gynecological cancers.

Dimension is a fundamental property of objects and the space in which they are embedded. Yet ideal notions of dimension, as in Euclidean spaces, do not always translate to physical spaces, which can be constrained by boundaries and distorted by inhomogeneities, or to intrinsically discrete systems such as networks. To take into account locality, finiteness and discreteness, dynamical processes can be used to probe the space geometry and define its dimension. Here we show that each point in space can be assigned a relative dimension with respect to the source of a diffusive process, a concept that provides a scale-dependent definition for local and global dimension also applicable to networks. To showcase its application to physical systems, we demonstrate that the local dimension of structural protein graphs correlates with structural flexibility, and the relative dimension with respect to the active site uncovers regions involved in allosteric communication. In simple models of epidemics on networks, the relative dimension is predictive of the spreading capability of nodes, and identifies scales at which the graph structure is predictive of infectivity. We further apply our dimension measures to neuronal networks, economic trade, social networks, ocean flows, and to the comparison of random graphs., (© 2022. The Author(s).)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Introduction: The need for beds and health personnel to treat coronavirus (COVID- 19) patients has led to the suspension of many elective sur-geries in Chile, including knee arthroplasties. This study aims to determine the incidence of knee arthroplasty in 2020, reflecting the effect of the COVID- 19 pandemic, and estimate the cost and time it would take to recover the waiting list prior to March 2020., Methods: A cross- sectional study was designed. We analyzed databases from The Department of Statistics and Health Information databases from Chile for 2019 and 2020, identifying patients with surgical discharges associated with knee arthroplasty codes. We estimated the time it would take to recover the surgeries unperformed in 2020 by simulating a monthly workload increase from the 2019 baseline. The costs of knee arthroplasty paid by the National Health Fund to institutions were estimated by diagnosis-related groups., Results: We found that the incidence rate of knee arthroplasty in 2020 decreased by 64% compared with 2019. The impact was higher in the public system (68%) and the National Health Found (63%). A simulated increase in knee arthroplasty productivity by 30% would allow recovering the postponed knee arthroplasty surgeries in 27 months, at a monthly cost to the public system of 318 million Chilean pesos (378 thousand US dollars)., Conclusions: The incidence rate of knee arthroplasty during 2020 decreased by 64%, revealing the extensive waiting line for people with knee osteoarthritis. An increase between 20- 40% in productivity compared with 2019 would allow recovering the unperformed surgeries in 20 to 41 months, at a monthly cost to the public network between 210 and 425 million Chilean pesos (250 to 506 thousand US dollars).

Background: Global sustainability is an enmeshed system of complex socioeconomic, climatological, and ecological interactions. The numerous objectives of the UN's Sustainable Development Goals (SDGs) and the Paris Agreement have various levels of interdependence, making it difficult to ascertain the influence of changes to particular indicators across the whole system. In this analysis, we aimed to detect and rank the complex interlinkages between objectives of sustainability agendas., Methods: We developed a method to find interlinkages among the 17 SDGs and climate change, including non-linear and non-monotonic dependences. We used time series of indicators defined by the World Bank, consisting of 400 indicators that measure progress towards the 17 SDGs and an 18th variable (annual average temperatures), representing progress in the response to the climate crisis, from 2000 to 2019. This method detects significant dependencies among the time evolution of the objectives by using partial distance correlations, a non-linear measure of conditional dependence that also discounts spurious correlations originating from lurking variables. We then used a network representation to identify the most important objectives (using network centrality) and to obtain nexuses of objectives (defined as highly interconnected clusters in the network)., Findings: Using temporal data from 181 countries spanning 20 years, we analysed dependencies among SDGs and climate for 35 country groupings based on region, development, and income level. The observed significant interlinkages, central objectives, and nexuses identified varied greatly across country groupings; however, SDG 17 (partnerships for the goals) and climate change ranked as highly important across many country groupings. Temperature rise was strongly linked to urbanisation, air pollution, and slum expansion (SDG 11), especially in country groupings likely to be worst affected by climate breakdown, such as Africa. In several country groupings composed of developing nations, we observed a consistent nexus of strongly interconnected objectives formed by SDG 1 (poverty reduction), SDG 4 (education), and SDG 8 (economic growth), sometimes incorporating SDG 5 (gender equality), and SDG 16 (peace and justice)., Interpretation: The differences across groupings emphasise the need to define goals in accordance with local circumstances and priorities. Our analysis highlights global partnerships (SDG 17) as a pivot in global sustainability efforts, which have been strongly linked to economic growth (SDG 8). However, if economic growth and trade expansion were repositioned as a means instead of an end goal of development, our analysis showed that education (SDG 4) and poverty reduction (SDG 1) become more central, thus suggesting that these could be prioritised in global partnerships. Urban livelihoods (SDG 11) were also flagged as important to avoid replicating unsustainable patterns of the past., Funding: Engineering and Physical Sciences Research Council, UK Research and Innovation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

We show that the classification performance of graph convolutional networks (GCNs) is related to the alignment between features, graph, and ground truth, which we quantify using a subspace alignment measure (SAM) corresponding to the Frobenius norm of the matrix of pairwise chordal distances between three subspaces associated with features, graph, and ground truth. The proposed measure is based on the principal angles between subspaces and has both spectral and geometrical interpretations. We showcase the relationship between the SAM and the classification performance through the study of limiting cases of GCNs and systematic randomizations of both features and graph structure applied to a constructive example and several examples of citation networks of different origins. The analysis also reveals the relative importance of the graph and features for classification purposes.

Climate change has led to intensification and poleward migration of the Southeastern Pacific Anticyclone, forcing diverging regions of increasing, equatorward and decreasing, poleward coastal phytoplankton productivity along the Humboldt Upwelling Ecosystem, and a transition zone around 31° S. Using a 20-year dataset of barnacle larval recruitment and adult abundances, we show that striking increases in larval arrival have occurred since 1999 in the region of higher productivity, while slower but significantly negative trends dominate poleward of 30° S, where years of recruitment failure are now common. Rapid increases in benthic adults result from fast recruitment-stock feedbacks following increased recruitment. Slower population declines in the decreased productivity region may result from aging but still reproducing adults that provide temporary insurance against population collapses. Thus, in this region of the ocean where surface waters have been cooling down, climate change is transforming coastal pelagic and benthic ecosystems through altering primary productivity, which seems to propagate up the food web at rates modulated by stock-recruitment feedbacks and storage effects. Slower effects of downward productivity warn us that poleward stocks may be closer to collapse than current abundances may suggest.

Wound complications are an important cause of postoperative morbidity among patients with gynaecologic malignancies. We evaluated whether the placement of closed-incisional negative pressure therapy (ciNPT) at the time of laparotomy for gynaecologic cancer surgery reduced wound complication rates. A retrospective cohort study with primary wound closure performed by a gynaecologic oncologist was carried out. We evaluated two cohorts of patients who underwent surgery in 2017 with standard closure and patients who underwent surgery in 2019 with the placement of prophylactic ciNPT. Postoperative outcomes were examined. A total of 143 patients were included, 85 (59.4%) vs 58 (40.6%) with standard closure and ciNPT, respectively. The total complication rate in our sample was 38.71%. The rate of surgical complications in patients treated with ciNPT was 6.9% compared with 31.8% (P = .000) in patients treated with standard closure. In the analysis of complications, a significant reduction in infections (17.1%), seromas (15.4%), and wound dehiscence (17.1%) were observed when ciNPT was applied. The median hospital stay was 8 vs 6 days in the standard closure vs ciNPT groups (P = .048). The use of the prophylactic ciNPT following a laparotomy may decrease wound complications and hospital stays in oncological patients. ciNPT could be considered as part of clinical practice in patients at high risk of wound complications, such as patients with gynaecological malignancies., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

This study aimed to assess whether surgical practice had a significant impact on oncological outcomes among women who underwent robot-assisted radical hysterectomy for early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009). The secondary objective was to audit the pre-surgical quality indicators (QI) proposed by the European Society of Gynaecological Oncology (ESGO). The top 5 of 10 centers in Spain and Portugal were included in the analysis. The hospitals were divided into group A ( n = 118) and group B ( n = 97), with recurrence rates of <10% and >10%, respectively. After balancing both groups using the propensity score, the ORs for all events were higher and statistically significant for group B (recurrences OR = 1.23, 95% CI = 1.13-1.15, p -value = 0.001; death OR = 1.10, 95% CI = 1.02-1.18, p -value = 0.012; disease-specific mortality OR r = 1.11, 95% CI = 1.04-1.19, p -value = 0.002). A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed among the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes not only after robot-assisted surgery, but also after laparoscopies and open surgeries in the treatment of cervical cancer.

Objectives: With a growing role for health services in managing population health, there is a need for early identification of populations with high need. Segmentation approaches partition the population based on demographics, long-term conditions (LTCs) or healthcare utilisation but have mostly been applied to adults. Our study uses segmentation methods to distinguish patterns of healthcare utilisation in children and young people (CYP) and to explore predictors of segment membership., Design: A retrospective cohort study., Setting: Routinely collected primary and secondary healthcare data in Northwest London from the Discover database., Participants: 378 309 CYP aged 0-15 years registered to a general practice in Northwest London with 1 full year of follow-up., Primary and Secondary Outcome Measures: Assignment of each participant to a segment defined by seven healthcare variables representing primary and secondary care attendances, and description of utilisation patterns by segment. Predictors of segment membership described by age, sex, ethnicity, deprivation and LTCs., Results: Participants were grouped into six segments based on healthcare utilisation. Three segments predominantly used primary care, two moderate utilisation segments differed in use of emergency or elective care, and a high utilisation segment, representing 16 632 (4.4%) children accounted for the highest mean presentations across all service types. The two smallest segments, representing 13.3% of the population, accounted for 62.5% of total costs. Younger age, residence in areas of higher deprivation and the presence of one or more LTCs were associated with membership of higher utilisation segments, but 75.0% of those in the highest utilisation segment had no LTC., Conclusions: This article identifies six segments of healthcare utilisation in CYP and predictors of segment membership. Demographics and LTCs may not explain utilisation patterns as strongly as in adults, which may limit the use of routine data in predicting utilisation and suggest children have less well-defined trajectories of service use than adults., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

The current mental health crisis is a growing public health issue requiring a large-scale response that cannot be met with traditional services alone. Digital support tools are proliferating, yet most are not systematically evaluated, and we know little about their users and their needs. Shout is a free mental health text messaging service run by the charity Mental Health Innovations, which provides support for individuals in the UK experiencing mental or emotional distress and seeking help. Here we study a large data set of anonymised text message conversations and post-conversation surveys compiled through Shout. This data provides an opportunity to hear at scale from those experiencing distress; to better understand mental health needs for people not using traditional mental health services; and to evaluate the impact of a novel form of crisis support. We use natural language processing (NLP) to assess the adherence of volunteers to conversation techniques and formats, and to gain insight into demographic user groups and their behavioural expressions of distress. Our textual analyses achieve accurate classification of conversation stages (weighted accuracy = 88%), behaviours (1-hamming loss = 95%) and texter demographics (weighted accuracy = 96%), exemplifying how the application of NLP to frontline mental health data sets can aid with post-hoc analysis and evaluation of quality of service provision in digital mental health services., 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 Liu, Peach, Lawrance, Noble, Ungless and Barahona.)

In order to increase the economic profitability of Avileña-Negra Ibérica beef production, the inclusion of corn silage in total mixed rations was proposed during the fattening period. Twenty-four Avileña-Negra Ibérica breed entire young bulls were used to evaluate the effects of two feeding systems-concentrate (CON) and corn silage (SIL)-and two packaging systems-vacuum (VAC) and modified atmosphere (MAP)-on the lipid oxidation, color evolution and visual color acceptability of meat throughout display with either oxygen-permeable film (FILM) or modified atmosphere (MAP). Two muscles were assessed: Longissimus thoracis (LT) and Semitendinosus (ST). Meat from SIL-fed animals had higher TBA values than CON-fed animals after 7 days in MAP packaging. Lipid oxidation was prevented more effectively by VAC packaging than MAP. Display time highly influenced lipid oxidation, since oxidation rates were lower with VAC than MAP packaging. After 14 days of display in MAP, the LT from CON was lighter than the ST. Meat discoloration after 7 days of display was significantly different between packaging systems. Vacuum-packaged meat kept the same color throughout the storage time. Visual color acceptability for the LT was higher throughout display than for the ST. Samples from the MAP were well accepted by consumers, especially the meat from the SIL group. Alternatively, feeding with corn silage could be used for this type of animals without affecting important aspects of meat quality.

Background: To characterise the longitudinal dynamics of C-reactive protein (CRP) and Procalcitonin (PCT) in a cohort of hospitalised patients with COVID-19 and support antimicrobial decision-making., Methods: Longitudinal CRP and PCT concentrations and trajectories of 237 hospitalised patients with COVID-19 were modelled. The dataset comprised of 2,021 data points for CRP and 284 points for PCT. Pairwise comparisons were performed between: (i) those with or without significant bacterial growth from cultures, and (ii) those who survived or died in hospital., Results: CRP concentrations were higher over time in COVID-19 patients with positive microbiology (day 9: 236 vs 123 mg/L, p < 0.0001) and in those who died (day 8: 226 vs 152 mg/L, p < 0.0001) but only after day 7 of COVID-related symptom onset. Failure for CRP to reduce in the first week of hospital admission was associated with significantly higher odds of death. PCT concentrations were higher in patients with COVID-19 and positive microbiology or in those who died, although these differences were not statistically significant., Conclusions: Both the absolute CRP concentration and the trajectory during the first week of hospital admission are important factors predicting microbiology culture positivity and outcome in patients hospitalised with COVID-19. Further work is needed to describe the role of PCT for co-infection. Understanding relationships of these biomarkers can support development of risk models and inform optimal antimicrobial strategies., (© 2021. The Author(s).)

Purpose: Currently, patient-reported outcome measures (PROMs) are the standard instruments used to compare arthroplasty results. Goodman et al. recently published a well-constructed scale with excellent psychometric properties that can be quickly administered. The main objective of our study was to translate, culturally adapt, and validate a Spanish version of the Goodman questionnaire in patients who underwent total hip arthroplasty (THA)., Methods: The original Goodman scale was translated into Spanish and cross-culturally adapted. Then, the data from this version were tested for psychometric quality. We designed a cross-sectional study for data collection. This study enrolled 2 institutions. Patients who underwent hip replacement due to primary osteoarthritis secondary to dysplasia between 1 January 2018 and 31 December 2019 were included. A total of 153 patients were contacted twice to record the Goodman and Oxford hip scales (OHS) to assess the validity of the questionnaire. Reliability was tested using the Cronbach's alpha, Concordance using 3 test: intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC), and the Bradley-Blackwood F test. The spearman correlation was used to asses correlation between the OHS and the Spanish-adapted Goodman scale., Results: The overall satisfaction after THA was reported to be "very satisfied" by 137 patients (75%), and only 14 patients reported some degree of dissatisfaction (6%). The improvement in quality of life was reported to be "more than I ever dreamed possible" by 41% patients. Cronbach's alpha was acceptable, reaching a coefficient of 0.95 (95% confidence interval, 0.82-1). No statistical difference (t test, p = 0.55) was found in the original version, with great internal validity. Test re-test concordance was optimal among the 3 tests used. A moderate correlation was found between the OHS and the Spanish-adapted Goodman scale., Conclusion: The Spanish version of the Goodman questionnaire in THA is a reliable, consistent, and feasible scale to evaluate patient satisfaction and improvement in the quality of life in Spanish speakers., (© 2021. The Author(s).)

Purpose To analyze the impact of the coronavirus disease 2019 (COVID-19) outbreak during the first pandemic year in a single country. Methods A cross-sectional study was designed. The free access database of the Chilean Department of Statistics and Health Information (DEIS) was used to compare the number of orthopedic procedures between 2019 and 2020. Country mobility was exported from the Institute of Complex Engineering Systems (ISCI) free-access database; this corresponds to a direct measurement of the degree of confinement of the country. Spearman correlation (rho) was used to analyze the total monthly COVID infection trend and mobility to orthopedics procedures. Results The number of orthopedic surgeries fell by 22.8% during the first year of the pandemic. All surgical procedures were adversely affected, with the fracture/trauma surgeries being the least affected. The maximum adverse impact was seen in knee arthroplasty (-64%), followed by hip arthroplasty (-41%) and knee ligament reconstruction (-44%). The number of orthopedic procedures had a mild correlation to the monthly number of COVID-19 cases (rho=-0.53, p=0.08) and a strong correlation with the country's mobility (rho=0.94, p=0.0001). Conclusions The COVID-19 outbreak diminished the number of orthopedic procedures during 2020, and the impact was directly correlated to the country's mobility. The public health network did have a more significant adverse impact in elective surgeries due to a slower recovery than private institutions. An increase in the waiting list should be expected, which will widen the difference in access to orthopedic surgery in Chile., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Barahona et al.)

During the surgical resolution of intertrochanteric and subtrochanteric hip fractures on an orthopedic table, a fluoroscope needs to be used in orthogonal planes. This requires that the contralateral leg does not obstruct the radioscopic view, so patients are often placed in a hemilithotomy position. This position, also called the Lloyd-Davis position, involves hip flexion, hip abduction, hip external rotation, and knee flexion. However, rare complications, such as acute leg posterior compartment syndrome, have been described. In addition, patients with severe osteoarthritis and joint stiffness or a history of total hip arthroplasty may have difficulty achieving this position, and the well leg may be at risk of injury in a hemilithotomy position. A previously described position called the "scissor position" is, in our opinion, a safer and more efficient technique for placing the well leg on the orthopedic table, using only a pillow and a self-adhesive compression bandage. This simple position allows a lateral fluoroscopic view of the injured femur without overlapping or interference from the other limb., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Barrientos et al.)

Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through x-ray structure determination and Markov transient and Deuterium exchange analyses, we identified the allosteric binding site and revealed how this compound blocks RSK4 kinase activation through binding to an allosteric site and mimicking a kinase autoinhibitory mechanism involving the RSK4's hydrophobic motif. Last, we show that patients undergoing chemotherapy and adhering to prophylactic levofloxacin in the large placebo-controlled randomized phase 3 SIGNIFICANT trial had significantly increased ( P = 0.048) long-term overall survival times. Hence, we suggest that RSK4 inhibition may represent an effective therapeutic strategy for treating lung and bladder cancer., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The investigation of allosteric effects in biomolecular structures is of great current interest in diverse areas, from fundamental biological enquiry to drug discovery. Here we present ProteinLens, a user-friendly and interactive web application for the investigation of allosteric signalling based on atomistic graph-theoretical methods. Starting from the PDB file of a biomolecule (or a biomolecular complex) ProteinLens obtains an atomistic, energy-weighted graph description of the structure of the biomolecule, and subsequently provides a systematic analysis of allosteric signalling and communication across the structure using two computationally efficient methods: Markov Transients and bond-to-bond propensities. ProteinLens scores and ranks every bond and residue according to the speed and magnitude of the propagation of fluctuations emanating from any site of choice (e.g. the active site). The results are presented through statistical quantile scores visualised with interactive plots and adjustable 3D structure viewers, which can also be downloaded. ProteinLens thus allows the investigation of signalling in biomolecular structures of interest to aid the detection of allosteric sites and pathways. ProteinLens is implemented in Python/SQL and freely available to use at: www.proteinlens.io., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

This study aims to correlate the tibial tubercle to trochlear groove (TT-TG) distance with knee axial alignment. The hypothesis is that as internal torsion of the distal femur or external torsion of the proximal tibial increases, the TT-TG distance increases. We designed a cross-sectional study approved by our institutional ethics review board. We reviewed 32 computed tomography angiographies of patients that have nonjoint or bone-related symptoms. Distal femoral torsion, proximal tibial torsion, knee articular torsion (AT), and TT-TG distance were measured. A regression analysis between the TT-TG distance and the AT was performed. A positive correlation between the TT-TG distance and the AT was found. An increase in external torsion of the proximal tibial or an increase in internal torsion of the distal femur increases the TT-TG distance. For a correct interpretation of the TT to trochlear groove distance, we propose that the axial alignment should be included in the regular analysis of patellofemoral disease., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Several benefits are published supporting patient-specific instrumentation (PSI) in total ankle arthroplasty (TAA). This study seeks to determine if TAA with PSI yields different radiographic outcomes vs standard instrumentation (SI)., Methods: Sixty-seven primary TAA patients having surgery using PSI or SI between 2013 and 2015 were retrospectively reviewed using weightbearing radiographs at 6-12 weeks postsurgery. Radiographic parameters analyzed were the medial distal tibia angle (MDTA), talar-tilt angle (TTA), anatomic sagittal distal tibia angle (aSDTA), lateral talar station (LTS), and talar component inclination angle (TCI). A comparison of the 2 groups for each radiologic parameter's distribution was performed using a nonparametric median test and Fisher exact test. Furthermore, TAAs with all radiographic measurements within acceptable limits were classified as "perfectly aligned." The rate of "perfectly aligned" TAAs between groups was compared using a Fisher exact test with a significance of .05., Results: Of the 67 TAAs, 51 were done with PSI and 16 with SI. There were no differences between groups in MDTA ( P = .174), TTA ( P = .145), aSDTA ( P = .98), LTS ( P = .922), or TCI angle ( P = .98). When the rate of "perfectly aligned TAA" between the 2 groups were compared, there was no significant difference ( P = .35)., Conclusion: No significant radiographic alignment differences were found between PSI and SI implants. This study showed that both techniques achieve reproducible TAA radiographic coronal and sagittal alignment for the tibial component when performed by experienced surgeons. The talar component's sagittal alignment is similar whether or not PSI was used but is noticeably different from normal anatomic alignment by design., Level of Evidence: Level III, retrospective cohort study using prospectively collected data.

Objective: There is scarce evidence available about the benefit of combining technetium ( 99m Tc) and indocyanine green (ICG) for sentinel lymph node (SLN) biopsy in endometrial cancer. The aim of this study was to compare the overall and bilateral pelvic detection rates of SLNs in two retrospective cohorts: ICG exclusive vs. combined ICG+ 99m Tc., Methods: The COMBITEC study (COMBined ICG and Technetium for SLN detection in Endometrial Cancer) consisted of a multicentre retrospective study (February 2015-June 2020) including patients diagnosed with endometrial atypical hyperplasia or early-stage endometrial carcinoma who underwent SLN biopsy by cervical injection of ICG with or without 99m Tc in four different referral centers in Spain., Results: A total of 180 patients were included, 51% (n = 92) in ICG group and 49% (n = 88) in ICG+ 99m Tc group. Eighty-seven percent of the patients presented endometrioid histology, and over 99% of the procedures were performed by a minimally invasive approach. Both groups were comparable regarding their basal characteristics, except for a higher body mass index in ICG+ 99m Tc group and a bigger proportion of robotic-assisted procedures in ICG group. Overall detection rate was 92.8% without significant differences between groups (ICG: 94.6% vs ICG+ 99m Tc: 90.9%, p = .34). No significant differences were observed neither in bilateral pelvic nor aortic mapping rate. When 99m Tc was used, surgical procedures were significantly longer. In 7.3% of mapped patients, at least one positive SLN was found (ICG: 10.3% vs ICG+ 99m Tc: 3.9%, p = .109). Empty node packet rates and number of SLNs retrieved per patient were also similar between cohorts., Conclusion: Combining preoperative 99m Tc to intraoperative ICG did not improve SLN detection in endometrial cancer, but resulted in longer procedures., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest related to the above presented work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: This study aimed to review the current knowledge on the utility of intraoperative fluorescence imaging in gynecologic surgery and to give evidence-based recommendations to improve the quality of care for women who undergo gynecologic surgery., Methods: A computer-based systematic review of the MEDLINE, CENTRAL, Pubmed, EMBASE, and SciSearch databases as well as institutional guidelines was performed. The time limit was set at 2000-2019. For the literature search, PRISMA guidelines were followed. A modified-Delphi method was performed in three rounds by a panel of experts to reach a consensus of conclusions and recommendations., Results: Indocyanine green (ICG) is used primarily in gynecology for sentinel node-mapping. In endometrial and cervical cancer, ICG is a feasible, safe, time-efficient, and reliable method for lymphatic mapping, with better bilateral detection rates. Experience in vulvar cancer is more limited, with ICG used together with Tc-99 m as a dual tracer and alone in video endoscopic inguinal lymphadenectomy. In early ovarian cancer, results are still preliminary but promising. Indocyanine green fluorescence imaging also is used for ureteral assessment, allowing intraoperative ureteral visualization, to reduce the risk of ureteral injury during gynecologic surgery., Conclusions: For most gynecologic cancers, ICG fluorescence imaging is considered the tracer of choice for lymphatic mapping. The use of this new technology expands to a better ureteral assessment.

Objective Surgical techniques are learned gradually throughout an orthopedic residency. Training on real patients carries drawbacks such as limited access and elevated risk. Alternatively, surgical simulation allows residents to practice in a safe environment with greater access to standardized surgical tasks. Virtual reality simulators display images inside an artificial joint, often providing real-time haptic feedback to allow for realistic interaction. The objective of this study was to evaluate the construct validity of a virtual reality simulator for knee arthroscopy by analyzing the capacity of system parameters to distinguish between expert and novice surgeons. Design This comparative cross-sectional study contrasts the automated performance reports for novice and expert orthopedic surgeons after executing surgical tasks on the ARTHRO Mentor virtual reality simulator. Setting Surgical simulation center at the University of Chile Clinical Hospital, Santiago, Chile. Participants The novice group consisted of 20 second-year orthopedic and traumatology residents at the University of Chile School of Medicine. The expert group consisted of 10 experienced arthroscopic surgeons. All participants carried out standardized tasks in the knee arthroscopy virtual reality simulator. The median performance scores of the two groups were compared, and multivariate logistic regression was performed to assess the capacity of the system to discriminate between the two groups. Results Median performance on the vast majority of surgical tasks was superior for the expert group. The expert group had performance values equal to or higher than the novice group on 43 of the 44 variables recorded for the basic tasks and 74 of the 75 advanced task variables. The multivariate logistic regression analysis discriminated expert from novice users with 100% accuracy. Conclusion The virtual reality simulator for knee arthroscopy showed good construct validity, with performance metrics accurately discriminating between expert and novice users., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Palet et al.)

The use of agroindustry by-products in animal diets allows the use of residues that are not fit for human consumption. In this study, it was investigated whether fattening commercial rabbits during 30 days with a non-medicated feed, with 20% addition of grape pomace (GPD), affected production traits and the fatty acid composition, antioxidants properties, and the shelf life of the meat compared to a conventional strategy (CON). Furthermore, it was tested, by chromatographic analysis, whether this alternative diet allowed the transfer of phenolic compounds to the meat. Thirty-six weaned rabbits were allotted to the two treatments. In each treatment, 18 rabbits were fattened in three indoor cages, each housing three males and three female rabbits. No significant differences were found in live weights ( p > 0.05), but the feed conversion rate and carcass weight and yield were found to be impaired in the GPD group ( p ≤ 0.05). The GPD group had a higher intramuscular fat percentage (2.01 vs. 1.54), improved polyunsaturated/saturated fatty acids ratio (0.75 vs. 0.66), and better atherogenicity (0.71 vs. 0.83) and thrombogenicity (1.14 vs. 1.24) indexes, while the n -6 /n -3 ratio was higher (25.4 vs. 20.3). Total volatile basic nitrogen in meat was lower in the GPD group ( p = 0.01), suggesting a delayed spoilage. However, no improvements in total phenolic content, antioxidant capacity, reducing power, and lipid oxidation ( p > 0.05) were found in the meat. Even though the GPD pellets offered to the animals had several grape-derived phenolic compounds, and higher antioxidant properties compared to the CON diet, none of the phenolic compounds detected in feeds were detected in the meat samples.

Purpose To describe the trends of orthopedic surgery in Chile since 2004 in terms of the number and gender of surgeons, the incidence of procedures per 100,000 inhabitants (IR), and access by health insurance and type of health center. Methods A cross-sectional study was designed. Three databases were analyzed: the free access database of the Chilean Department of Statistics and Health Information (DEIS), which had information on all procedures performed in health institutions in Chile from 2004 to 2020. Then, the orthopedic surgeon registry was requested from the National Superintendence of Health (NSH). Finally, the database of the Chilean Society of Orthopaedic Surgeons (SCHOT) was analyzed. Spearman's correlation was used to determine significant trends during the analyzed period. Results The NSH reported 1770 orthopedic surgeons in 2020; 56% were affiliated with SCHOT. An upward trend in the proportion of female orthopedic surgeons was found, from 4.8% in 2004 to 7.6% in 2020. Since 2004, the IR of orthopaedic surgeries has been increasing significantly in both health insurances; the growth in public insurance follows a linear model (R 2  = 0.970) of parameters β 0  = - 55982.6 (p <0.000) and β 1 = 28.02 (p <0.000) while in private insurance, the growth is also linear (R 2  = 0.890) but with a greater slope: β 0  = - 104136 (p <0.000) and β 1  = 52.15 (p <0.000). A significant downward trend was found in the proportion of surgeries performed in the public health network (rho = -0.797, p = 0.0002). Conclusions There is a significant increase in the number of orthopedic surgeons and the number of procedures per 100,000 inhabitants. Nevertheless, there is evident inequity in access to orthopedic surgery in Chile and low gender diversity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Barahona et al.)

Cancer cells can survive chemotherapy-induced stress, but how they recover from it is not known. Using a temporal multiomics approach, we delineate the global mechanisms of proteotoxic stress resolution in multiple myeloma cells recovering from proteasome inhibition. Our observations define layered and protracted programs for stress resolution that encompass extensive changes across the transcriptome, proteome, and metabolome. Cellular recovery from proteasome inhibition involved protracted and dynamic changes of glucose and lipid metabolism and suppression of mitochondrial function. We demonstrate that recovering cells are more vulnerable to specific insults than acutely stressed cells and identify the general control nonderepressable 2 (GCN2)-driven cellular response to amino acid scarcity as a key recovery-associated vulnerability. Using a transcriptome analysis pipeline, we further show that GCN2 is also a stress-independent bona fide target in transcriptional signature-defined subsets of solid cancers that share molecular characteristics. Thus, identifying cellular trade-offs tied to the resolution of chemotherapy-induced stress in tumor cells may reveal new therapeutic targets and routes for cancer therapy optimization., Competing Interests: Competing interest statement: H.W.A. acknowledges research support by Amgen. Amgen did not have a role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript., (Copyright © 2021 the Author(s). Published by PNAS.)

Traditional classification tasks learn to assign samples to given classes based solely on sample features. This paradigm is evolving to include other sources of information, such as known relations between samples. Here, we show that, even if additional relational information is not available in the dataset, one can improve classification by constructing geometric graphs from the features themselves, and using them within a Graph Convolutional Network. The improvement in classification accuracy is maximized by graphs that capture sample similarity with relatively low edge density. We show that such feature-derived graphs increase the alignment of the data to the ground truth while improving class separation. We also demonstrate that the graphs can be made more efficient using spectral sparsification, which reduces the number of edges while still improving classification performance. We illustrate our findings using synthetic and real-world datasets from various scientific domains., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Networks are widely used as mathematical models of complex systems across many scientific disciplines. Decades of work have produced a vast corpus of research characterizing the topological, combinatorial, statistical, and spectral properties of graphs. Each graph property can be thought of as a feature that captures important (and sometimes overlapping) characteristics of a network. In this paper, we introduce HCGA, a framework for highly comparative analysis of graph datasets that computes several thousands of graph features from any given network. HCGA also offers a suite of statistical learning and data analysis tools for automated identification and selection of important and interpretable features underpinning the characterization of graph datasets. We show that HCGA outperforms other methodologies on supervised classification tasks on benchmark datasets while retaining the interpretability of network features. We exemplify HCGA by predicting the charge transfer in organic semiconductors and clustering a dataset of neuronal morphology images., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

There is a high prevalence of knee osteoarthritis that affects only the medial tibiofemoral compartment. In this group of patients with severe disease, the medial unicompartmental knee arthroplasty (UKA) is an excellent choice. However, this technique has a great learning curve due to the lower tolerance of improper positioning and alignment. In this context, the robotic-assisted surgery (RAS) arises as an option to improve the accuracy and secondarily enhance the clinical outcomes related to the UKA. The objective in this study is to determine if there are significant advantages with the use of RAS over conventional surgery (CS). In the systematic review of the literature, classification of the results in three main subjects: (A) precision and alignment; (B) functional results and clinical parameters; (C) survivorship. We found 272 studies, of which 15 meet the inclusion and exclusion criteria. There is mostly described that RAS significantly improves the accuracy in position (80-100% of planned versus performed P < 0.05), alignment (2-3 times less error variance P < 0.05) and selection of the proper size of the implants (69.23% of correct size femoral implants versus 16.67% using CS P < 0.0154). Recently, there is mild evidence about benefits in the early rehabilitation and post-operative pain, but in all studies reviewed, there is no advantages of RAS in the long-term functional evaluation. There is no strong literature that supports a longer survival of the prothesis with RAS, being the longest mean follow-up reported of 29.6 months. RAS is a useful tool in increasing the precision of the medial UKA implant placement. However, there is still a lack of evidence that properly correlates this improvement in accuracy with better clinical, functional and survival results.

Sequential behaviour is often compositional and organised across multiple time scales: a set of individual elements developing on short time scales (motifs) are combined to form longer functional sequences (syntax). Such organisation leads to a natural hierarchy that can be used advantageously for learning, since the motifs and the syntax can be acquired independently. Despite mounting experimental evidence for hierarchical structures in neuroscience, models for temporal learning based on neuronal networks have mostly focused on serial methods. Here, we introduce a network model of spiking neurons with a hierarchical organisation aimed at sequence learning on multiple time scales. Using biophysically motivated neuron dynamics and local plasticity rules, the model can learn motifs and syntax independently. Furthermore, the model can relearn sequences efficiently and store multiple sequences. Compared to serial learning, the hierarchical model displays faster learning, more flexible relearning, increased capacity, and higher robustness to perturbations. The hierarchical model redistributes the variability: it achieves high motif fidelity at the cost of higher variability in the between-motif timings., Competing Interests: The authors have declared that no competing interests exist.

Background: The use of unicompartmental knee arthroplasty (UKA) has increased and new technologies have been developed to improve patient survival and satisfaction, soft tissue balance, alignment, and component size. Robot-assisted systems offer an increase in surgical precision and accuracy. The purpose of this study is to evaluate the precision of component position using five radiological parameters in conventional and robotic-assisted medial UKA using the NAVIO system., Methods: A cohort study was designed for patients who underwent medial UKA between April 2017 and March 2019 in a single center. Patients were allocated in the conventional (UKA-C) or robotic-assisted (UKA-R) group. The variables analyzed were age, gender, affected knee side, length of hospital stay, surgical time, and radiological measurements such as anatomical medial distal femoral angle (aMDFA), anatomical medial proximal tibial angle (aMPTA), tibial slope, the sagittal femoral angle, and the component size. A target was defined for each measurement, and a successful UKA was defined if at least four radiological measures were on target after surgery. Also, patients' reported outcomes were evaluated using the Oxford Knee Score (OKS) and a numeric rating scale (NRS) for pain., Results: Thirty-four patients were included, 18 of them underwent UKA-R. The success rate for UKA in the UKA-R group was 87%; meanwhile, in the UKA-C group this was 28%, this difference was significant and powered (Fisher's exact test, p = 0.001; 1 - β = 0.95). Also, a 5-point difference in favor of the UKA-R group in the median OKS (p = 0.01), and a significantly lower median NRS for pain (p < 0.000) were found after surgery., Conclusions: UKA-R achieved more precision in the radiological parameters' measure in this study. Also, UKA-R has a trend towards a better OKS and a lower NRS for pain at short-term follow-up.

The intrinsic temporality of learning demands the adoption of methodologies capable of exploiting time-series information. In this study we leverage the sequence data framework and show how data-driven analysis of temporal sequences of task completion in online courses can be used to characterise personal and group learners' behaviors, and to identify critical tasks and course sessions in a given course design. We also introduce a recently developed probabilistic Bayesian model to learn sequential behaviours of students and predict student performance. The application of our data-driven sequence-based analyses to data from learners undertaking an on-line Business Management course reveals distinct behaviors within the cohort of learners, identifying learners or groups of learners that deviate from the nominal order expected in the course. Using course grades a posteriori, we explore differences in behavior between high and low performing learners. We find that high performing learners follow the progression between weekly sessions more regularly than low performing learners, yet within each weekly session high performing learners are less tied to the nominal task order. We then model the sequences of high and low performance students using the probablistic Bayesian model and show that we can learn engagement behaviors associated with performance. We also show that the data sequence framework can be used for task-centric analysis; we identify critical junctures and differences among types of tasks within the course design. We find that non-rote learning tasks, such as interactive tasks or discussion posts, are correlated with higher performance. We discuss the application of such analytical techniques as an aid to course design, intervention, and student supervision.

Metabolism plays a central role in cell physiology because it provides the molecular machinery for growth. At the genome-scale, metabolism is made up of thousands of reactions interacting with one another. Untangling this complexity is key to understand how cells respond to genetic, environmental, or therapeutic perturbations. Here we discuss the roles of two complementary strategies for the analysis of genome-scale metabolic models: Flux Balance Analysis (FBA) and network science. While FBA estimates metabolic flux on the basis of an optimization principle, network approaches reveal emergent properties of the global metabolic connectivity. We highlight how the integration of both approaches promises to deliver insights on the structure and function of metabolic systems with wide-ranging implications in discovery science, precision medicine and industrial biotechnology., 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. The handling editor declared a past co-authorship with one of the author, DO., (Copyright © 2021 Dusad, Thiel, Barahona, Keun and Oyarzún.)

Background: Understanding nosocomial acquisition, outbreaks, and transmission chains in real time will be fundamental to ensuring infection-prevention measures are effective in controlling coronavirus disease 2019 (COVID-19) in healthcare. We report the design and implementation of a hospital-onset COVID-19 infection (HOCI) surveillance system for an acute healthcare setting to target prevention interventions., Methods: The study took place in a large teaching hospital group in London, United Kingdom. All patients tested for SARS-CoV-2 between 4 March and 14 April 2020 were included. Utilizing data routinely collected through electronic healthcare systems we developed a novel surveillance system for determining and reporting HOCI incidence and providing real-time network analysis. We provided daily reports on incidence and trends over time to support HOCI investigation and generated geotemporal reports using network analysis to interrogate admission pathways for common epidemiological links to infer transmission chains. By working with stakeholders the reports were co-designed for end users., Results: Real-time surveillance reports revealed changing rates of HOCI throughout the course of the COVID-19 epidemic, key wards fueling probable transmission events, HOCIs overrepresented in particular specialties managing high-risk patients, the importance of integrating analysis of individual prior pathways, and the value of co-design in producing data visualization. Our surveillance system can effectively support national surveillance., Conclusions: Through early analysis of the novel surveillance system we have provided a description of HOCI rates and trends over time using real-time shifting denominator data. We demonstrate the importance of including the analysis of patient pathways and networks in characterizing risk of transmission and targeting infection-control interventions., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Aberrant neural oscillations hallmark numerous brain disorders. Here, we first report a method to track the phase of neural oscillations in real-time via endpoint-corrected Hilbert transform (ecHT) that mitigates the characteristic Gibbs distortion. We then used ecHT to show that the aberrant neural oscillation that hallmarks essential tremor (ET) syndrome, the most common adult movement disorder, can be transiently suppressed via transcranial electrical stimulation of the cerebellum phase-locked to the tremor. The tremor suppression is sustained shortly after the end of the stimulation and can be phenomenologically predicted. Finally, we use feature-based statistical-learning and neurophysiological-modelling to show that the suppression of ET is mechanistically attributed to a disruption of the temporal coherence of the aberrant oscillations in the olivocerebellar loop, thus establishing its causal role. The suppression of aberrant neural oscillation via phase-locked driven disruption of temporal coherence may in the future represent a powerful neuromodulatory strategy to treat brain disorders.

Purpose: To describe patient-reported outcomes, radiological results, and revision to total hip replacement in patients with hip dysplasia that underwent periacetabular osteotomy as isolated treatment or concomitant with hip arthroscopy., Methods: Case series study. Between 2014 and 2017, patients were included if they complained of hip pain and had a lateral center-edge angle ≤ of 20°. Exclusion criteria included an in-maturate skeleton, age of 40 or older, previous hip surgery, concomitant connective tissue related disease, and Tönnis osteoarthritis grade ≥ 1. All patients were studied before surgery with an anteroposterior pelvis radiograph, false-profile radiograph, and magnetic resonance imaging. Magnetic resonance imaging was used to assess intraarticular lesions, and if a labral or chondral injury was found, concomitant hip arthroscopy was performed. The non-parametric median test for paired data was used to compare radiological measures (anterior and lateral center-edge angle, Tönnis angle, and extrusion index) after and before surgery. Survival analysis was performed using revision to total hip arthroplasty as a failure. Kaplan Meier curve was estimated. The data were processed using Stata., Results: A total of 15 consecutive patients were included; 14 (93%) were female patients. The median follow-up was 3.5 years (range, 2 to 8 years). The median age was 20 (range 13 to 32). Lateral center-edge angle, Tönnis angle, and extrusion index correction achieved statistical significance. Seven patients (47%) underwent concomitant hip arthroscopy; three of them (47%) were bilateral (10 hips). The labrum was repaired in six cases (60%). Three patients (15%) required revision with hip arthroplasty, and no hip arthroscopy-related complications are reported in this series., Conclusion: To perform a hip arthroscopy concomitant with periacetabular osteotomy did not affect the acetabular correction. Nowadays, due to a lack of conclusive evidence, a case by case decision seems more appropriate to design a comprehensive treatment.

Metabolic heterogeneity is widely recognized as the next challenge in our understanding of non-genetic variation. A growing body of evidence suggests that metabolic heterogeneity may result from the inherent stochasticity of intracellular events. However, metabolism has been traditionally viewed as a purely deterministic process, on the basis that highly abundant metabolites tend to filter out stochastic phenomena. Here we bridge this gap with a general method for prediction of metabolite distributions across single cells. By exploiting the separation of time scales between enzyme expression and enzyme kinetics, our method produces estimates for metabolite distributions without the lengthy stochastic simulations that would be typically required for large metabolic models. The metabolite distributions take the form of Gaussian mixture models that are directly computable from single-cell expression data and standard deterministic models for metabolic pathways. The proposed mixture models provide a systematic method to predict the impact of biochemical parameters on metabolite distributions. Our method lays the groundwork for identifying the molecular processes that shape metabolic heterogeneity and its functional implications in disease., 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 © 2020 Tonn, Thomas, Barahona and Oyarzún.)

Introduction The purpose of this study is to describe the incidence rate (IR) per 100,000 inhabitants of arthroplasty in Chile between 2004 and 2019, emphasizing knee and hip arthroplasty. Methods This is a cross-sectional study. Patients who underwent arthroplasty between 2004 and 2019 were identified in the free access database of the Chilean Department of Statistics and Health Information (DEIS), which depends directly on the Ministry of Health. This register stores all hospital discharges of the country from private or public health centers. The trend during the period of study was analyzed using Spearman's correlation. Results From a total of 111,303 patients, 133,518 arthroplasties were performed. Hip arthroplasty (HA) accounted for 73.35%, followed by knee arthroplasty (KA) (23,92%). A significant upward trend was found in HA (rho=0.95, p<0.000) and KA (rho=0.98, p<0.000). Most of the surgeries were done within the Public Health Network (61,6%), but 20% of patients affiliated with public insurance underwent arthroplasty in a private center. Patients above 60 years of age affiliated with private insurance underwent 1.8 HA and 2.5 KA for every one HA and KA undergone by patients of the same age group who were affiliated with public insurance. Conclusion HA was more frequent than KA. A significant gap was found in the incidence of arthroplasty as compared to countries belonging to the Organization for Cooperation and Economic Development, given by a less aged population and by inequity in health access. Wider coverage and a national registry for arthroplasty must be considered in Chilean health policies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Barahona et al.)

Background: The purpose of this study is to determine if patients with osteoarthritis that undergo hip or knee arthroplasty jeopardize their life expectancy in Chile., Methods: A survival analysis study was designed and approved by our institutional ethics review board. Patients were included if they underwent surgery for hip or knee osteoarthritis and were 50 years or older at the time of surgery. Patients were excluded if arthroplasty was performed for fracture, hemophilia arthropathy, or tumor. A multiparametric Weibull regression was estimated, and the hazard ratio was reported. For internal validity, a bootstrap of 200 repetitions was performed., Results: A total of 4 094 arthroplasties were included. The Kaplan-Meier curve estimates a higher survival than the general population up to 12 years, after which the median survival is less than the general population. The bootstrap multiparametric Weibull regression estimated a hazard ratio of 1.53 (95% confidence interval: 1.27 to 1.84) for women, 1.09 (1.08 to 1.10) for every year older, and 1.29 (1.07 to 1.53) for hip arthroplasty patients., Conclusion: Mortality after hip and knee arthroplasty in Chile follows a bimodal behavior similar to reports from the United States and Europe. At first, mortality is lower than the general population but worsens after 12 to 15 years of surgery.

Background and Aims: Among all transplanted abdominal organs, the small intestine is one of the most ischemia sensitive. Appropriate graft selection, procurement, and preservation are crucial for optimum graft and patient survival. We evaluated ischemic damage in human small intestine grafts under different hypothermic preservation conditions (cold static and continuous perfusion) and solutions: histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW)., Methods: Fourteen small intestinal grafts were procured from deceased donors. HTK and UW were used for the vascular perfusion at the cross clamp, and UW, HTK, or Ringer Lactate were used for the luminal flush at the back table. Therefore, part of the same harvested intestine was stored in cold static storage and in continuous perfusion preservation (with intestinal perfusion unit) simultaneously. Histological samples were collected from the jejunum and ileum at different time points and different preservation conditions. The samples were collected before the initiation of cold storage (T0), after 8 hours of cold static (ST8), or after 8 hours of continuous perfusion preservation (PT8) (n = 161 samples). Blinded histological evaluation was conducted and ischemic damage was determined using the Park/Chiu scale., Results: The ileum had less ischemic damage than the jejunum, regardless of using static or continuous perfusion preservation. There was no significantly ischemic damage difference between intestinal grafts flushed and perfused with UW or HTK., Conclusion: The jejunum is more susceptible to ischemic injury than the ileum. UW and HTK are equivalent to preserve intestinal graft. This suggests that selective transplantation of ileum could reduce ischemia-related postoperative complications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To compare joint line restoration after unicompartmental knee arthroplasty (UKA) between conventional and robotic-assisted surgery. Previous studies have shown that joint line distalization can lead to higher failure rates. The hypothesis was that robotic-assisted UKA is associated with less femoral component distalization and a precise tibial cut, which allows a more anatomical restitution of the knee joint line., Methods: Retrospective cohort study of patients undergoing medial or lateral UKA between May 2018 and March 2020. Preoperative and postoperative radiologic assessment of the joint line was performed by two observers, using three different methods, one for tibial slope and one for tibial resection. Robotic assisted UKA and conventional UKA groups were compared., Results: Sixty UKA were included, of which 48 (77.42%) were medial. Robotic-assisted UKA were 40 (64.52%) and 22(35.48%) were conventional The distalization of the femoral component was higher in the conventional group despite the method of measurement used In both Weber methods, the difference was statistically different: Conventional 2.3 (0.9 to 5.6) v/s Robotic 1.5 (- 1.1 to 4.1) (p =0.0025*). A higher proportion of patients achieved a femoral component position ≤ two millimeters from the joint line using robotic-assisted UKA compared to the conventional technique . No statistical difference between robotic-assisted and conventional UKA was found in tibial resection and slope., Conclusion: Robotic-assisted UKA shows a better rate of joint line restoration due to less femoral component distalization than conventional UKA. No difference was found in the amount of tibial resection between groups in this study., Level of Evidence: III.

Purpose The purpose of the study is to compare the survival after hip fracture in patients older than 50 years after hip fracture between a private and a public health center in Chile. We hypothesize that treatment at a private health center (PRH) may be associated with lower one-year mortality and longer median survival time after hip fracture (adjusted by gender and age) compared to a public health center (PLH). Methods PRH and PLH patients who were coded with a diagnosis of hip fracture were included in this study. PRH patients were included between 2002 to 2018, and PLH patients were included from 2012 to 2018. One-year mortality was estimated by logistic regression; meanwhile, median survival time was estimated by exponential regression. A survival analysis study was designed and approved by our institutional ethics review board. Results A total of 2130 patients were included in the PLH cohort, and a total of 1110 patients were included in the PRH. The one-year mean mortality, adjusted by age and gender, was 0.23 (range: 0.21 to 0.25) in the PLH and 0.16 (range: 0.13 to 0.18) in the PRH cohort. The median survival time, adjusted by age and gender, was 4.2 years (range: 4.1 to 4.4) in the PLH and 6.8 years (range: 6.3 to 7.29) in the PRH cohort. Conclusion Patients older than 50 years treated in a private health center have a higher median survival time and a lower probability of dying one year after a hip fracture., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Barahona et al.)

This retrospective analysis aimed to assess the risk factors for recurrence in patients diagnosed with early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009) undergoing robot-assisted radical hysterectomy in Spain and Portugal between 2009 and 2018. A second primary objective was to audit the oncological outcomes according to quality indicators (QI) proposed by the European Society of Gynecology Oncology (ESGO). The study population included 239 women. After a median follow-up of 51 months, recurrence occurred in 26 patients (10.9%). Independent factors for recurrence were clinical tumor size > 20 mm (hazard ratio (HR) 2.37), adenocarcinoma as histological type (HR 2.51), positive pelvic lymph nodes (HR 4.83), tumor grade 2 (HR 4.99), tumor grade 3 (HR 8.06), and having not performed sentinel lymph node biopsy (SLNB) (HR 4.08). All 5 QI selected were surpassed by our results. In patients with early-stage cervical cancer undergoing robotic radical hysterectomy, clinicians should be aware that tumor grade 2 and 3, tumor size > 20 mm, adenocarcinoma, positive pelvic nodes, and lack of performance of SLNB are risk factors for recurrence. Fulfillment of QI targets of the ESGO might be considered as an objective oncological outcome indicator supporting the minimally invasive approach for early-stage cervical cancer treatment.

Urinary tract infection (UTI) is one of the most common infectious complications among renal transplant patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is routinely used as first-line prophylaxis against Pneumocystis pneumonia (PCP) and other opportunistic infections including UTI. Aerosolized pentamidine is an alternate agent used for PCP prophylaxis; however, it does not provide coverage against uropathogens. This is a retrospective study of 81 renal transplant recipients who received TMP-SMX or aerosolized pentamidine for PCP prophylaxis at our center over 1 year. Survival analysis demonstrated increased cumulative incidence of UTI among patients receiving pentamidine for PCP prophylaxis compared to those receiving TMP-SMX (log-rank test P < .001). Univariate and multivariate Cox proportional hazard regression model showed pentamidine prophylaxis (HR 3.740; 95% CI 1.745-8.016; P = .001) and female sex (HR 4.025; 95% CI 1.770-9.154; P = .001) to independently increase UTI risk. Age, induction agent, graft type, diabetes, and delayed graft function (DGF) were not associated with increased risk. This study concludes that the use of pentamidine for PCP prophylaxis compared to TMP-SMX is associated with increased risk of UTI. Secondary UTI prophylaxis may be considered for patients who are unable to tolerate TMP-SMX and who have other risk factors for UTI; however, the efficacy of this has not been studied., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The suspension of elective surgery during the COVID-19 pandemic is unprecedented and has resulted in record volumes of patients waiting for operations. Novel approaches that maximise capacity and efficiency of surgical care are urgently required. This study applies Markov multiscale community detection (MMCD), an unsupervised graph-based clustering framework, to identify new surgical care models based on pooled waiting-lists delivered across an expanded network of surgical providers., Design: Retrospective observational study using Hospital Episode Statistics., Setting: Public and private hospitals providing surgical care to National Health Service (NHS) patients in England., Participants: All adult patients resident in England undergoing NHS-funded planned surgical procedures between 1 April 2017 and 31 March 2018., Main Outcome Measures: The identification of the most common planned surgical procedures in England (high-volume procedures (HVP)) and proportion of low, medium and high-risk patients undergoing each HVP. The mapping of hospitals providing surgical care onto optimised groupings based on patient usage data., Results: A total of 7 811 891 planned operations were identified in 4 284 925 adults during the 1-year period of our study. The 28 most common surgical procedures accounted for a combined 3 907 474 operations (50.0% of the total). 2 412 613 (61.7%) of these most common procedures involved 'low risk' patients. Patients travelled an average of 11.3 km for these procedures. Based on the data, MMCD partitioned England into 45, 16 and 7 mutually exclusive and collectively exhaustive natural surgical communities of increasing coarseness. The coarser partitions into 16 and seven surgical communities were shown to be associated with balanced supply and demand for surgical care within communities., Conclusions: Pooled waiting-lists for low-risk elective procedures and patients across integrated, expanded natural surgical community networks have the potential to increase efficiency by innovatively flexing existing supply to better match demand., Competing Interests: Competing interests: JK reports consultancy for Verb robotics/Ethicon and is a shareholder of OneWelbeck Day Surgery., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Purpose: To estimate survival curves in patients with hip fracture according to gender, age, type of fracture, and waiting time for surgery and to compare them with the life expectancy of the general population. The study hypothesis is that survival after hip fractures is significantly lower than in the general population, especially in cases that underwent delayed surgery, regardless of age and gender., Methods: A survival analysis study was designed and approved by our institutional ethics review board. All patients who were coded with a diagnosis of hip fracture from 2002 to 2018 were included in the study. A total of 1176 patients were included, and the median age was 81 years (18-105 years). Kaplan-Meier curves and log-rank tests were performed to compare survival curves between those who underwent surgery on time and those with surgical delays. An exponential multivariate regression model was estimated, and a hazard ratio (HR) was reported for age, gender, and wait time for surgery. A significance of 5% was used, and a confidence interval level of 95% was reported., Results: The Kaplan-Meier curves for delayed surgery (log-rank, p  = 0.00) and the age group (log-rank, p  = 0.00) were significantly different. Exponential regression estimated an HR 1.05 (1.05-1.07) for age, HR 1.80 (1.51-2.13) for men, and HR 1.93 (1.61-2.31) for each day of wait for surgery., Conclusions: The 2 significant findings of this study are that hip fracture patients over 40 years old have a higher risk of dying at any time compared to the general population and that the waiting time for surgery (a modifiable factor) decreases survival rates at any time.