Specific considerations in female patients with patellar instability: current concepts.

Prior literature suggests that patellofemoral instability (PFI) is significantly more prevalent in women than in men. This higher prevalence is commonly attributed to anatomical differences between sexes, particularly with patellofemoral alignment. These differences encompass a higher rate of trochlear dysplasia (TD), patella alta, an increased Q angle, and soft tissue imbalances. In recent years worse outcomes have been reported in female patients after patellofemoral stabilization surgery using medial patellofemoral ligament reconstruction (MPFLr) alone or in combination with a tibial tubercle osteotomy (TTO), for this reason an "à la carte" plan (addressing the individuals anatomical risk factors) could be more appropriate for female patients.

Social class stigma and poorer health behaviors: Evidence from the eating in America study.

Although the association between objective markers of low socioeconomic status (SES) and poor health is well established, one underexamined possibility is that over and above objective SES, social class stigma-experiences and anticipation of discrimination based on social class-might undermine people's ability to engage in healthy behaviors. Participants (N = 2022) were recruited between December 2019 and January 2020 via a national Qualtrics panel that was census-matched to the U.S. population in age, gender, income, race/ethnicity, and census region. Participants completed measures of class stigma, alcohol use, disordered eating, comfort eating, sleep disturbance, physical activity, and demographics. Controlling for objective SES and demographics, generalized linear regression models indicated that class stigma was associated with significantly greater alcohol use, disordered eating, greater comfort eating, and sleep disturbance but not less physical activity. Class stigma was not associated with health behaviors after full adjustment for weight/racial discrimination and psychological factors. Results from this investigation suggest that beyond one's objective SES, the stigma associated with having low class may also contribute to poorer health behaviors.

Examining the effect of weight-related recruitment information on participant characteristics: A randomized field experiment.

Objective: Although 82% of American adults have a body mass index (BMI) of over 25, individuals with elevated BMI are considered difficult to recruit for studies. Effective participant identification and recruitment are crucial to minimize the likelihood of sampling bias. One understudied factor that could lead to sampling bias is the study information presented in recruitment materials. In the context of weight research, potential participants with higher weight may avoid studies that advertise weight-related procedures. Thus, this study experimentally manipulated the phrasing of weight-related information included in recruitment materials and examined its impact on participants' characteristics. Methods: Two visually similar flyers, either weight-salient or neutral, were randomly posted throughout a university campus to recruit participants (N = 300) for a short survey, assessing their internalized weight bias, anticipated and experienced stigmatizing experiences, eating habits, and general demographic characteristics. Results: Although the weight-salient (vs. neutral) flyer took 18.5 days longer to recruit the target sample size, there were no between flyer differences in respondents' internalized weight bias, anticipated/experienced weight stigma, disordered eating behaviors, BMI, or perceived weight. Absolute levels of these variables, however, were low overall. Conclusion: Providing detailed information about study procedures allows participants to have more autonomy over their participation without differentially affecting participant characteristics.

Return to sports in female athletes after anterior cruciate ligament reconstruction: A systematic review and metanalysis.

IMPORTANCE: Return to sport (RTS) is considered an indicator of successful recovery after anterior cruciate ligament reconstruction (ACLR). In recent years, there has been major interest in documenting RTS following anterior cruciate ligament (ACL) injury. Despite women being at increased risk for ACL injuries and a global increase in women's participation in sports, research has not adequately focused on female athletes. OBJECTIVE: The purpose of this study is to conduct a systematic review and meta-analysis evaluating the RTS rate in female athletes after ACLR. We hypothesize that most of the female athletes can RTS. EVIDENCE REVIEW: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Electronic databases (PubMed, Embase, and Epistemonikos) were searched for articles reporting RTS rates and contextual data in female athletes. The following search terms were used: "anterior cruciate ligament reconstruction" OR "ACL reconstruction" AND "female" OR "women" AND "return to sports" OR "return to play" to retrieve all relevant articles published between 2003 and 2023. A quality assessment of the included studies was conducted. FINDINGS: Fifteen articles were included, reporting on 1456 female athletes participating in pivoting sports. The included studies comprised 9 cohorts, 1 case-control study, 2 case series, 2 descriptive epidemiology studies, and 1 observational study. Eight out of fifteen studies focused solely on elite-level athletes. The participants had a mean age of 23.13 years. Soccer was the most prevalent sport among the participants, accounting for 49.7% of all athletes included. All 15 studies reported an RTS rate, yielding a meta-proportion of 69% [95% CI, 58-80%] for RTS. Nine articles reported the average time to RTS, which was 10.8 months [95% CI, 8.7-12.8 months]. CONCLUSIONS: This systematic review demonstrates that a majority of female athletes (69 â€‹%) can RTS participation at an average of 10.8 months, however, the available information is insufficient, and quantitative data and reasons for not returning to play are lacking. Future studies should establish return-to-play criteria in this population and determine reasons for not returning to play. LEVEL OF EVIDENCE: III.

Social robot for older adults with cognitive decline: a preliminary trial.

The number of older adults living alone is rapidly increasing. Loneliness in older adults not only degrade their quality of life but also causes troubles such as heavy burden on the medical staff, especially when cognitive decline is present. Social robots could be used in several ways to reduce such problems. As a first step towards this goal, we introduced conversation robots into the homes of older adults with cognitive decline to evaluate the robot's availability and acceptance during several months. The study involved two steps, one for evaluating the robustness of the proposed robotic system, and the second one to examine the long-term acceptance of social robots by older adults with cognitive decline living alone. Our data shows that after several weeks of human-robot interaction, the participants continued to use the robot and successfully integrated them into their lives. These results open the possibility of further research involving how sustained interaction can be achieved, as well as which factors contributed to the acceptance of the robot.

Over 50% of self-reported burnout among Latin American orthopaedic surgeons: A cross-sectional survey on prevalence and risk factors.

OBJECTIVE: Assess the prevalence of self-reported burnout and identify risk and protective factors based on demographic and life quality aspects, among Latin American orthopaedic surgeons. METHODS: This study employed a cross-sectional analytical design. An original design survey was developed using multiple-choice and Likert-scale questions to gather self-reported burnout, demographic, work-related, social, personal, and mood-related data. The survey was electronically distributed to the Chilean Orthopaedic Surgery Society and the Latin American Society of Arthroscopy, Knee Surgery, and Sports Medicine members. Statistical analysis included Chi-square and Fisher's exact tests to determine associations between self-reported burnout and other variables. Subsequently, a multivariate logistic regression was carried out to identify key risk and protective factors (p â€‹< â€‹0.05). RESULTS: The survey's response rate was 20 â€‹% (n â€‹= â€‹358) out of the 1779 invitations that were sent. The most representative age range was 41-60 years (50 â€‹%) and 94 â€‹% were men. Of those surveyed, 50 â€‹% reported a burnout episode more than once per year, 60 â€‹% depersonalization when treating patients at least yearly, 13 â€‹% anhedonia, 11 â€‹% a depressive mood more than half of the month or almost every day, and 61 â€‹% weariness at the end of a working day. Burnout was statistically associated with age under 40 years old (p â€‹= â€‹0.012), fewer years as a specialist (p â€‹= â€‹0.037), fear of lawsuits (p â€‹< â€‹0.001), a non-healthy diet (p â€‹= â€‹0.003), non-doing recreational activities (p â€‹= â€‹0.004), depersonalization when treating their patients (p â€‹< â€‹0.001), weariness (p â€‹< â€‹0.001), anhedonia (p â€‹< â€‹0.001), depressive mood (p â€‹< â€‹0.001), and career dissatisfaction (p â€‹< â€‹0.001). The logistic regression demonstrated that fear of lawsuits (p â€‹< â€‹0.001), weariness at the end of a workday (p â€‹= â€‹0.016), and anhedonia (p â€‹= â€‹0.019) were those variables with stronger direct associations with self-reported burnout. A healthy diet was the strongest protective variable (p â€‹< â€‹0.001). CONCLUSION: Over 50 â€‹% of the Latin American orthopaedic surgeons who participated in the survey reported experiencing burnout episodes more than once a year, along with depersonalization when treating their patients at least once a year. Additionally, nearly 10 â€‹% of respondents experienced weekly depressive symptoms. Among the noteworthy risk factors for self-reported burnout were fear of lawsuits, weariness at the end of the workday, and anhedonia. Conversely, maintaining a healthy diet emerged as the most potent protective factor. LEVEL OF EVIDENCE: Level III.

Activating Inducible T-cell Costimulator Yields Antitumor Activity Alone and in Combination with Anti-PD-1 Checkpoint Blockade.

In recent years, there has been considerable interest in mAb-based induction of costimulatory receptor signaling as an approach to combat cancer. However, promising nonclinical data have yet to translate to a meaningful clinical benefit. Inducible T-cell costimulator (ICOS) is a costimulatory receptor important for immune responses. Using a novel clinical-stage anti-ICOS immunoglobulin G4 mAb (feladilimab), which induces but does not deplete ICOS+ T cells and their rodent analogs, we provide an end-to-end evaluation of the antitumor potential of antibody-mediated ICOS costimulation alone and in combination with programmed cell death protein 1 (PD-1) blockade. We demonstrate, consistently, that ICOS is expressed in a range of cancers, and its induction can stimulate growth of antitumor reactive T cells. Furthermore, feladilimab, alone and with a PD-1 inhibitor, induced antitumor activity in mouse and humanized tumor models. In addition to nonclinical evaluation, we present three patient case studies from a first-time-in-human, phase I, open-label, dose-escalation and dose-expansion clinical trial (INDUCE-1; ClinicalTrials.gov: NCT02723955), evaluating feladilimab alone and in combination with pembrolizumab in patients with advanced solid tumors. Preliminary data showing clinical benefit in patients with cancer treated with feladilimab alone or in combination with pembrolizumab was reported previously; with example cases described here. Additional work is needed to further validate the translation to the clinic, which includes identifying select patient populations that will benefit from this therapeutic approach, and randomized data with survival endpoints to illustrate its potential, similar to that shown with CTLA-4 and PD-1 blocking antibodies. Significance: Stimulation of the T-cell activation marker ICOS with the anti-ICOS agonist mAb feladilimab, alone and in combination with PD-1 inhibition, induces antitumor activity across nonclinical models as well as select patients with advanced solid tumors.

Early Postoperative Results in Robotic-Arm-Assisted Total Knee Replacement versus Conventional Technique: First Latin American Experience.

Early results with robotic-arm-assisted total knee arthroplasty (TKA) are encouraging; nevertheless, literature might be unrepresentative, as it comes mostly from American, European, and Asian countries. There is limited experience and no comparative clinical reports in Latin America, a region of mainly low- and middle-income countries with limited access to these promising technologies. This study aims to compare the early postoperative results of the first Latin American experience with robotic-arm-assisted TKA versus conventional TKA. A cohort study was performed, including 181 consecutive patients (195 knees) with advanced symptomatic knee osteoarthritis (OA) undergoing primary TKA between March 2016 and October 2019. The cohort included 111 consecutive patients (123 knees) undergoing conventional TKA, followed by 70 consecutive patients (72 knees) undergoing robotic-arm-assisted TKA. The same surgical team (surgeon 1 and surgeon 2) performed all procedures. Patients with previous osteotomy, posttraumatic OA, and revision components were not considered. The same anesthetic and rehabilitation protocol was followed. The investigated clinical outcomes (for the first 60 postoperative days) were: surgical tourniquet time, time to home discharge, time to ambulation, postoperative daily pain (Visual Analog Scale), opioid use, range of motion, blood loss, complications, and postoperative mechanical axis. The early clinical postoperative results of this first Latin American comparative experience of robotic-arm-assisted TKA versus conventional technique showed lower opioids requirements and faster functional recovery of ambulation in those patients operated with the robotic system; nevertheless, surgical times were higher, without differences in total postoperative complications and other clinical outcomes.

Loss of smelling is an early marker of aging and is associated with inflammation and DNA damage in C57BL/6J mice.

Olfactory dysfunction is a prevalent symptom and an early marker of age-related neurodegenerative diseases in humans, including Alzheimer's and Parkinson's Diseases. However, as olfactory dysfunction is also a common symptom of normal aging, it is important to identify associated behavioral and mechanistic changes that underlie olfactory dysfunction in nonpathological aging. In the present study, we systematically investigated age-related behavioral changes in four specific domains of olfaction and the molecular basis in C57BL/6J mice. Our results showed that selective loss of odor discrimination was the earliest smelling behavioral change with aging, followed by a decline in odor sensitivity and detection while odor habituation remained in old mice. Compared to behavioral changes related with cognitive and motor functions, smelling loss was among the earliest biomarkers of aging. During aging, metabolites related with oxidative stress, osmolytes, and infection became dysregulated in the olfactory bulb, and G protein coupled receptor-related signaling was significantly down regulated in olfactory bulbs of aged mice. Poly ADP-ribosylation levels, protein expression of DNA damage markers, and inflammation increased significantly in the olfactory bulb of older mice. Lower NAD+ levels were also detected. Supplementation of NAD+ through NR in water improved longevity and partially enhanced olfaction in aged mice. Our studies provide mechanistic and biological insights into the olfaction decline during aging and highlight the role of NAD+ for preserving smelling function and general health.

Accuracy of Magnetic Resonance Imaging in the Diagnosis of Multiple Ligament Knee Injuries: A Multicenter Study of 178 Patients.

BACKGROUND: Magnetic resonance imaging (MRI) has shown limited diagnostic accuracy for multiple ligament knee injuries (MLKIs), especially posterolateral corner (PLC) injuries. HYPOTHESIS: The diagnostic accuracy of MRI for MLKIs will only be moderate for some knee structures. Patient-related factors and injury patterns could modify the diagnostic accuracy of MRI. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All patients with MLKIs surgically treated between January 2014 and December 2020 in the centers participating in the study were reviewed. We recorded sex, age, mechanism of injury, time from injury to MRI, and vascular and neurological associated lesions. Lesions to the anterior cruciate ligament (ACL), posterior cruciate ligament, medial collateral ligament, lateral collateral ligament (LCL), popliteus tendon, popliteofibular ligament, iliotibial band, biceps tendon, medial and lateral meniscus, and articular cartilage from MRI reports and surgical records were also collected. The sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, diagnostic odds ratio, positive and negative likelihood ratio, and intraclass correlation coefficient of MRI were calculated for each knee structure. With logistic regression, associations between patient and injury characteristics and MRI accuracy were assessed. RESULTS: A total of 178 patients (127 male; mean age, 33.1 years) were included. High-energy trauma was the most common mechanism of injury (50.6%), followed by sports trauma (38.8%) and low-energy trauma (8.4%). The ACL was the structure with the best diagnostic accuracy, diagnostic odds ratio, and positive predictive value (94.4%, 113.2, and 96.8%, respectively). PLC structures displayed the worst diagnostic accuracy among knee ligaments (popliteus tendon: 76.2%; LCL: 80.3%) and diagnostic odds ratio (popliteus tendon: 9.9; LCL: 17.0; popliteofibular ligament: 17.5). MRI was more reliable in detecting the absence of meniscal and chondral lesions than in identifying them. Logistic regression found that the diagnostic accuracy was affected by the Schenck classification, with higher Schenck grades having worse diagnostic accuracy for peripheral structures (iliotibial band, popliteus tendon, and biceps tendon) and improved diagnostic accuracy for the ACL and posterior cruciate ligament. CONCLUSION: The diagnostic accuracy of MRI for MLKIs largely varied among knee structures, with many of them at risk of a misdiagnosis, especially PLC, meniscal, and chondral lesions. The severity of MLKIs lowered the diagnostic accuracy of MRI for peripheral structures.

Navigation in anterior cruciate ligament reconstruction: State of the art.

Computer navigation (CN) for anterior cruciate ligament (ACL) surgery has been used mainly for two purposes: to enhance the accuracy of tunnel position and to evaluate the kinematics of the ACL reconstruction (ACLR) and the stability achieved by different surgical techniques. Many studies have shown that navigation may improve the accuracy of anatomical tunnel orientation and position during ACL reconstructive surgery compared with normal arthroscopic tunnel placement, especially regarding the femoral side. At the same time, it has become the gold-standard method for intraoperative knee kinematic assessment, as it permits a quantitative multidirectional knee joint laxity evaluation. CN in ACL surgery has been associated with diverse problems. First, in most optic systems additional skin incisions and drill holes in the femoral bone are required for fixation of a reference frame to the femur. Second, additional radiation exposure and extra medical cost to the patient for preoperative planning are usually needed. Third, CN, due to additional steps, has more opportunities for error during preoperative planning, intraoperative registration, and operation. Fourth, soft tissues, including the skin and subcutaneous tissues, are usually not considered during the preoperative planning, which can be a problem for kinematic and stability assessment. Many studies have concluded that ACLR using a CN system is more expensive than conventional surgery, it adds extra time to the surgery and it is not mitigated by better clinical outcomes. This, combined with costs and invasiveness, has limited the use of CN to research-related cases. Future technology should prioritize less invasive intra-operative surgical navigation.

Mode of action of p-quinone derivatives with trypanocidal activity studied by experimental and in silico models.

Quinones are attractive pharmacological scaffolds for developing new agents for the treatment of different transmissible and non-transmissible human diseases due to their capacity to alter the cell redox homeostasis. The bioactivity and potential mode of action of 19 p-quinone derivatives fused to different aromatic rings (carbo or heterocycles) and harboring distinct substituents were investigated in infective Trypanosoma brucei brucei. All the compounds, except for a furanequinone (EC50=38 µM), proved to be similarly or even more potent (EC50 = 0.5-5.5 µM) than the clinical drug nifurtimox (EC50 = 5.3 µM). Three furanequinones and one thiazolequinone displayed a higher selectivity than nifurtimox. Two of these selective hits resulted potent inhibitors of T. cruzi proliferation (EC50=0.8-1.1 µM) but proved inactive against Leishmania infantum amastigotes. Most of the p-quinones induced a rapid and marked intracellular oxidation in T. b. brucei. DFT calculations on the oxidized quinone (Q), semiquinone (Q•-) and hydroquinone (QH2) suggest that all quinones have negative ΔG for the formation of Q•-. Qualitative and quantitative structure-activity relationship analyses in two or three dimensions of different electronic and biophysical descriptors of quinones and their corresponding bioactivities (killing potency and oxidative capacity) were performed. Charge distribution over the quinone ring carbons of Q and Q.- and the frontier orbitals energies of SUMO (Q.-) and LUMO (Q) correlate with their oxidative and trypanocidal activity. QSAR analysis also highlighted that both bromine substitution in the p-quinone ring and a bulky phenyl group attached to the furane and thiazole rings (which generates a negative charge due to the π electron system polarized by the nearby heteroatoms) are favorable for activity. By combining experimental and in silico procedures, this study disclosed important information about p-quinones that may help to rationally tune their electronic properties and biological activities.

¿Existen discrepancias entre la planificación preoperatoria y la evaluación intraoperatoria realizada por el cirujano en la artroplastia total de rodilla con asistencia robótica? / Are there discrepancies between preoperative planning and intraoperative evaluation by the surgeon in robotically assisted total knee arthroplasty?

Introducción: Existe poca evidencia respecto de la concordancia entre el plan preoperatorio mediante artroplastia total de rodilla asistida por robot y el plan posterior al balance protésico realizado por el cirujano. El objetivo de este trabajo es evaluar el grado de concordancia entre la planificación preoperatoria de la artroplastia total de rodilla con asistencia robótica semiactiva (Mako) y la planificación efectuada por el traumatólogo durante la cirugía. Materiales y métodos: estudio retrospectivo y descriptivo de prótesis primarias instaladas entre octubre de 2018 y junio de 2019 con planificación preoperatoria realizada por el software MAKOplasty®. Se excluyeron las prótesis no colocadas por el sistema robótico o con información clínica incompleta. Esto se comparó con la planificación intraoperatoria del traumatólogo. Variables analizadas: alineación coronal y sagital, rotación y tamaño de los componentes e inserto. Los datos se analizaron con el softwareSTATA v.16.0. Se realizó un análisis descriptivo univariante cualitativo, con un intervalo de confianza del 95%. Resultados: se incluyeron cincuenta y una rodillas operadas de cuarenta y nueve pacientes, el 69% fueron mujeres. El nivel de concordancia para el componente femoral fue: axial 86.3% (IC = 73.7 - 94.2), coronal 88.2% (IC = 76.1 - 95.5), sagital 88.2% (IC = 76.1 - 95.5). Componente tibial: axial 98% (IC = 89.5 ­ 99.9), coronal 96.1% (IC = 86.5 ­ 99.5), sagital 96.1% (IC = 86.5 ­ 99.5). Tamaño del componente: fémur 94.1% (IC = 83.7 ­ 98.7), tibia 84.3% (IC = 71.4 ­ 92.9), inserto 27.4% (IC = 15.8 ­ 41.7). Conclusión: la planificación preoperatoria mediante el uso de la asistencia robótica semiactiva de Mako presenta un buen nivel de concordancia con la planificada intraoperatoriamente, a excepción del tamaño del inserto. El traumatólogo es determinante en la modificación del plan preoperatorio. Nivel de Evidencia: III

Introduction: There is little evidence regarding the concordance between the preoperative plan using robotic-assisted total knee arthroplasty and that after the prosthetic balance by the surgeon. Our aim is to evaluate the level of agreement between the preoperative planning of total knee arthroplasty with semiactive robotic assistance (Mako) and the planning made by the orthopedic surgeon during the surgery. Materials and methods: descriptive study of prostheses installed between October 2018 and June 2019 with preoperative planning performed by the MAKOplasty® software. This was compared with intraoperative planning by the Orthopedic Surgeon. Variables analyzed: coronal and sagittal alignment, rotation and size of the components and insert. The data was analyzed with the STATA v.16.0 software. A qualitative univariate descriptive analysis was performed, with a 95% confidence interval. Results: fifty-one operated knees from forty-nine patients were included, 69% were women. The level of agreement was: Femoral component: axial 86.3% [CI = 73.7 - 94.2], coronal 88.2% [CI = 76.1 - 95.5], sagittal 88.2% [CI = 76.1 - 95.5]. Tibial component: axial 98% [CI = 89.5 - 99.9], coronal 96.1% [CI = 86.5 - 99.5], sagittal 96.1% [CI = 86.5 - 99.5]. Component size: femur 94.1% [CI = 83.7 - 98.7], tibia 84.3% [CI = 71.4 - 92.9], insert 27.4% [CI = 15.8 - 41.7]. Conclusion: preoperative planning through the use of Mako semiactive robotic assistance presents a good level of agreement with that planned intraoperatively, with the exception of the insert size. The orthopedic surgeon is decisive in modifying the preoperative plan. Level of Evidence: III

Expanding the molecular versatility of an optogenetic switch in yeast.

In the budding yeast Saccharomyces cerevisiae, the FUN-LOV (FUNgal Light Oxygen and Voltage) optogenetic switch enables high levels of light-activated gene expression in a reversible and tunable fashion. The FUN-LOV components, under identical promoter and terminator sequences, are encoded in two different plasmids, which limits its future applications in wild and industrial yeast strains. In this work, we aim to expand the molecular versatility of the FUN-LOV switch to increase its biotechnological applications. Initially, we generated new variants of this system by replacing the promoter and terminator sequences and by cloning the system in a single plasmid (FUN-LOVSP). In a second step, we included the nourseothricin (Nat) or hygromycin (Hph) antibiotic resistances genes in the new FUN-LOVSP plasmid, generating two new variants (FUN-LOVSP-Nat and FUN-LOVSP-Hph), to allow selection after genome integration. Then, we compared the levels of light-activated expression for each FUN-LOV variants using the luciferase reporter gene in the BY4741 yeast strain. The results indicate that FUN-LOVSP-Nat and FUN-LOVSP-Hph, either episomally or genome integrated, reached higher levels of luciferase expression upon blue-light stimulation compared the original FUN-LOV system. Finally, we demonstrated the functionality of FUN-LOVSP-Hph in the 59A-EC1118 wine yeast strain, showing similar levels of reporter gene induction under blue-light respect to the laboratory strain, and with lower luciferase expression background in darkness condition. Altogether, the new FUN-LOV variants described here are functional in different yeast strains, expanding the biotechnological applications of this optogenetic tool.

Return to sport soccer after anterior cruciate ligament reconstruction: ISAKOS consensus.

INTRODUCTION: Many factors can affect the return to pivoting sports, after an Anterior Cruciate Ligament Reconstruction. Prehabilitation, rehabilitation, surgical and psychological aspects play an essential role in the decision to return to sports. The purpose of this study is to reach an international consensus about the best conditions for returning to sports in soccer-one of the most demanding level I pivoting sports after anterior cruciate ligament (ACL) reconstruction. METHODS: 34 International experts in the management of ACL injuries, representing all the Continents were convened and participated in a process based on the Delphi method to achieve a consensus. 37 statements related to ACL reconstruction were reviewed by the experts in three rounds of surveys in complete anonymity. The statements were prepared by the working group based on previous literature or systematic reviews. Rating agreement through a Likert Scale: strongly agree, agree, neither agree or disagree, disagree and strongly disagree was used. To define consensus, it was established that the assertions should achieve a 75% of agreement or disagreement. RESULTS: Of the 37 statements, 10 achieved unanimous consensus, 18 non-unanimous consensus and 9 did not achieve consensus. In the preoperative, the correction of the range of motion deficit, the previous high level of participation in sports and a better knowledge of the injury by the patient and compliance to participate in Rehabilitation were the statements that reached unanimous consensus. During the surgery, the treatment of associated injuries, as well as the use of autografts, and the addition of a lateral extra-articular tenodesis in some particular cases (active young athletes, <25 years old, hyperlaxity, high rotatory laxity and revision cases) obtained also 100% consensus. In the postoperative period, psychological readiness and its validation with scales, adequate physical preparation, as well as not basing the RTSS purely on the time of evolution after surgery, were the factors that reached unanimous Consensus. CONCLUSIONS: The consensus statements derived from this international ISAKOS leaders, may assist clinicians in deciding when to return to sports soccer in patients after an ACL reconstruction. Those statements that reached 100% consensus have to be strongly considered in the final decision to RTS soccer.

Postoperative Infection After Anterior Cruciate Ligament Reconstruction: Prevention and Management.

Because septic arthritis after anterior cruciate ligament reconstruction is an uncommon complication, information on prevention strategies has not been extensively studied. Recommendations that can be made from the available evidence are as follows: (1) prophylactic intravenous antibiotics should be given preoperatively; (2) patellar tendon autograft use decreases the possibility of a postoperative infection; and (3) vancomycin presoaking of grafts is strongly recommended, especially when performing hamstring autograft anterior cruciate ligament reconstruction. When septic arthritis presents after anterior cruciate ligament reconstruction, early management is crucial to allow a satisfactory outcome. Accordingly, early clinical suspicion is the most important factor to achieve a timely diagnosis. The treatment of choice is arthroscopic lavage with intravenous antibiotic treatment. Graft retention, when possible, is important for obtaining better functional results.

Influence of Steric Effect on the Pseudo-Multicomponent Synthesis of N-Aroylmethyl-4-Arylimidazoles.

A pseudo-three-component synthesis of N-aroylmethylimidazoles 3 with three new C-N bonds formed regioselectively under microwave conditions was developed. Products were obtained by reacting two equivalents of aroylmethyl bromide (ArCOCH2Br, 1) with the appropriate amidine salt (RCN2H3.HX, 2) and with K2CO3 as a base in acetonitrile. The bicomponent reaction also occurred, giving the expected 4(5)-aryl-1H-imidazoles 4. Notably, the ratio of products 3 and 4 is governed by steric factors of the amidine 2 (i.e., R = H, CH3, Ph). Therefore, a computational study was carried out to understand the reaction course regarding product ratio (3/4), regioselectivity, and the steric effects of the amidine substituent group.

Vancomycin Presoaking of the Graft Appears to Prevent Infection After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

Background: Vancomycin presoaking of the graft has been shown to decrease infection rates in some case series of anterior cruciate ligament (ACL) reconstruction. Purpose: We sought to substantiate the efficacy of vancomycin presoaked grafts for the prevention of infection after ACL reconstruction. Methods: We performed a systematic review of Medline and OVID to assess the incidence of postoperative infection in studies comparing patients undergoing ACL reconstruction with the use of vancomycin presoaked ACL grafts and a control group of patients undergoing ACL reconstruction without the use of presoaked grafts. The efficacy of vancomycin presoaking was calculated using the Agresti-Coull confidence interval. Relative risk (RR) was calculated for every study and the total sample. Results: The 11 studies that met inclusion criteria comprised 24,298 patients. In patients with vancomycin presoaking of the graft, 1 infection was reported in 8764 cases (0.01% rate). In the studies with control groups that did not have vancomycin presoaked grafts, there were 125 infections in 15,534 ACL reconstructions (0.8% rate). The efficacy of vancomycin presoaking in preventing infection after ACL reconstruction was 99.9% (0.999%-1.000% CI). The overall RR obtained was 0.07 (0.03-0.16 CI). All included studies were retrospective cohort studies (level III). Conclusions: Vancomycin presoaking of the graft has been shown to decrease infection rates after ACL reconstruction in studies of low evidence level. This suggests the need for prospective randomized controlled trials addressing this issue so that recommendations on the routine use of vancomycin presoaking of ACL grafts can be made with confidence.

Antimalarials exert a cardioprotective effect in lupus patients: Insights from the Spanish Society of Rheumatology Lupus Register (RELESSER) analysis of factors associated with heart failure.

BACKGROUND/OBJECTIVES: Factors associated with chronic heart failure (CHF) in patients with systemic lupus erythematosus (SLE) have received little attention. Recent data on the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection have cast doubt on its cardiac safety. The factors associated with CHF, including therapy with antimalarials, were analyzed in a large multicenter SLE cohort. METHODS: Cross-sectional study including all patients with SLE (ACR-1997 criteria) included in the Spanish Society of Rheumatology Lupus Register (RELESSER), based on historically gathered data. Patients with CHF prior to diagnosis of SLE were excluded. A multivariable analysis exploring factors associated with CHF was conducted. RESULTS: The study population comprised 117 patients with SLE (ACR-97 criteria) and CHF and 3,506 SLE controls. Ninety percent were women. Patients with CHF were older and presented greater SLE severity, organ damage, and mortality than those without CHF. The multivariable model revealed the factors associated with CHF to be ischemic heart disease (7.96 [4.01-15.48], p < 0.0001), cardiac arrhythmia (7.38 [4.00-13.42], p < 0.0001), pulmonary hypertension (3.71 [1.84-7.25], p < 0.0002), valvulopathy (6.33 [3.41-11.62], p < 0.0001), non-cardiovascular damage (1.29 [1.16-1.44], p < 0.000) and calcium/vitamin D treatment (5.29 [2.07-16.86], p = 0.0015). Female sex (0.46 [0.25-0.88], p = 0.0147) and antimalarials (0.28 [0.17-0.45], p < 0.000) proved to be protective factors. CONCLUSIONS: Patients with SLE and CHF experience more severe SLE. Treatment with antimalarials appears to confer a cardioprotective effect.

Engineering Cancer Antigen-Specific T Cells to Overcome the Immunosuppressive Effects of TGF-ß.

Adoptive T cell therapy with T cells expressing affinity-enhanced TCRs has shown promising results in phase 1/2 clinical trials for solid and hematological tumors. However, depth and durability of responses to adoptive T cell therapy can suffer from an inhibitory tumor microenvironment. A common immune-suppressive agent is TGF-ß, which is secreted by tumor cells and cells recruited to the tumor. We investigated whether human T cells could be engineered to be resistant to inhibition by TGF-ß. Truncating the intracellular signaling domain from TGF-ß receptor (TGFßR) II produces a dominant-negative receptor (dnTGFßRII) that dimerizes with endogenous TGFßRI to form a receptor that can bind TGF-ß but cannot signal. We previously generated specific peptide enhanced affinity receptor TCRs recognizing the HLA-A*02-restricted peptides New York esophageal squamous cell carcinoma 1 (NY-ESO-1)157-165/l-Ag family member-1A (TCR: GSK3377794, formerly NY-ESO-1c259) and melanoma Ag gene A10254-262 (TCR: ADP-A2M10, formerly melanoma Ag gene A10c796). In this article, we show that exogenous TGF-ß inhibited in vitro proliferation and effector functions of human T cells expressing these first-generation high-affinity TCRs, whereas inhibition was reduced or abolished in the case of second-generation TCRs coexpressed with dnTGFßRII (e.g., GSK3845097). TGF-ß isoforms and a panel of TGF-ß-associated genes are overexpressed in a range of cancer indications in which NY-ESO-1 is commonly expressed, particularly in synovial sarcoma. As an example, immunohistochemistry/RNAscope identified TGF-ß-positive cells close to T cells in tumor nests and stroma, which had low frequencies of cells expressing IFN-γ in a non-small cell lung cancer setting. Coexpression of dnTGFßRII may therefore improve the efficacy of TCR-transduced T cells.