Total hip arthroplasty (THA) in hip arthritis with proximal femur deformity (PFD) is challenging particularly when the deformity is complex and below the trochanteric level. The preoperative altered hip biomechanics with poor abductor strength can impact the functional outcomes. In this review (https://www.crd.york.ac.uk/PROSPERO/view/CRD420261391431), we evaluated the functional outcomes and complications of THA in patients of PFD. It incorporated data from 19 studies, involving 929 patients and 1045 THAs, retrieved from searches conducted in PubMed, Embase, Scopus, and the Cochrane Library up to 29th April 2026. These included both retrospective and prospective studies with follow-up periods ranging from 2 to 15.8 years. The most frequent causes of PFD were developmental conditions like developmental dysplasia of the hip and Perthes disease, followed by post-traumatic origins and previous osteotomies. Common surgical interventions involved the posterior approach and proximal femoral osteotomies, particularly at the subtrochanteric level, with commonest use of non-modular femoral stems. Postoperative evaluations showed significant improvements in clinical scores and abductor muscle strength, effectively restoring hip function and significantly reducing limb length discrepancies (average postoperative discrepancy of 0.52 cm). Radiological assessments mostly confirmed correct stem alignment in most studies, though some variances such as varus and valgus malalignments were noted. Stem survivorship was excellent (>90% at 10 years). However, complications such as intraoperative and periprosthetic fractures, aseptic loosening necessitating revisions, and higher incidences of heterotopic ossification in certain conditions like Paget's disease were reported. Overall, THA in patients with PFD significantly enhances functional outcomes and demonstrates durable implant survivorship.

Pelvic and acetabular fractures, often resulting from high-impact trauma, pose significant challenges due to extensive blood loss and complex surgical procedures. Tranexamic acid (TXA), widely used in elective orthopedic surgeries, offers a potential strategy for managing blood loss. However, its efficacy and safety in pelvic-acetabular trauma surgeries have shown inconsistent results in prior studies. To systematically evaluate the safety and efficacy of intravenous TXA in reducing perioperative blood loss, transfusion requirements, and complications in pelvic and acetabular trauma surgeries. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. Literature searches of PubMed, Embase, and Cochrane databases identified relevant studies. Data on blood loss, transfusion rates, thromboembolic events, surgical time, and complications were extracted and analyzed using RevMan 5.4 software. A random-effects model was applied to account for heterogeneity. After screening, a total of 6 RCTs with 511 patients were included in this meta-analysis. TXA did not significantly reduce estimated blood loss (mean difference: 117.54 ml; 95

Current trials toward an HIV cure involve combination strategies aimed at achieving durable antiretroviral treatment (ART)-free viral control or HIV elimination, many relying on analytical treatment interruptions (ATIs) to evaluate efficacy. Given the physical, psychosocial, and interpersonal risks associated with ATIs, it is critical to monitor participants' experiences so that support can be provided when needed. While qualitative approaches have been used in similar settings, we designed and implemented a series of short, closed-ended participant surveys in the University of California, San Francisco-amfAR trial, a single-arm multi-intervention HIV cure-related trial with an extended ATI. Surveys were administered at relevant trial timepoints to capture participants' (n = 10) perspectives and experiences. These included their understanding of the trial, motivations, expectations, perceived risks, benefits, and burdens of trial participation, and their perspectives on restarting ART and partner protections. We describe these data using descriptive statistics and summarize lessons learned from implementing quantitative surveys in this complex trial. Our data indicate that all respondents understood the scientific goals and requirements of participating in the trial. Most were motivated to help advance research but many expressed anxiety about participating. During the trial, respondents had limited side effects, discomfort, and trial burnout. Those who completed surveys at ART restart reported mixed (positive and negative) feelings and challenges (e.g., missed doses) when restarting ART. Participants offered various methods for partner protection during ATIs and at ART restart. Many respondents expressed future willingness to participate in a similar HIV cure trial. While the number of respondents was small, these findings are consistent with concerns identified in guidance regarding these types of trials as well as qualitative findings from earlier studies. Moreover, we demonstrated that it is feasible to implement quantitative evaluations of participants' experiences. Such approaches should be implemented in future HIV cure trials to optimize human-centered research implementation.

Advancements in long-acting (LA) HIV treatment and cure research with analytical treatment interruptions (ATIs) have generated important scientific and implementation questions. There is an urgent need to examine challenges navigating the evolving HIV treatment and cure research landscape. From August to October 2022, we conducted 26 semistructured interviews with biomedical researchers and community members representing a predominantly woman demographic to explore the complexity of navigating the rapidly evolving HIV therapeutic and HIV cure research landscape. We purposively sampled individuals recruited from the AIDS Clinical Trials Group and the Martin Delaney Collaboratories for HIV Cure Research. Audio files were transcribed verbatim and analyzed through a thematic approach, using an inductive and iterative process. Among 26 participants, 10 were biomedical researchers and 16 community members, including 11 were people with HIV. Three main themes emerged: (1) We are at a pivotal moment in the evolving landscape of HIV therapeutics and LA HIV treatment and HIV cure research should not be siloed but considered together; (2) There are challenges with engagement in HIV cure research and in switching between oral daily antiretroviral treatment and LA formulations and, mainly, the prolonged pharmacokinetic tail of these compounds matched with limited patient education about their impacts; and (3) There are unique opportunities as a result of this evolving therapeutic landscape, including the key role of decision support for people with HIV, centering around patient autonomy, and the need to learn from the lived experiences of people with HIV who choose LA treatment and/or participation in HIV cure research. Despite a bias toward the woman gender, our study identifies key considerations for navigating concurrent LA HIV treatment and HIV cure research with ATIs from both community members and biomedical researchers' perspectives. Achieving optimal HIV control remains a formidable challenge, necessitating robust interdisciplinary collaborations and engagement with key stakeholders.

INTRODUCTION:The Last Gift study at the University of California San Diego (UCSD), United States enrolls terminally ill people with HIV (PWH) in HIV cure research. METHODS:From 2017 to 2022, we conducted surveys with Last Gift participants and their next-of-kin/loved ones to evaluate willingness to participate in different types of HIV cure research at the end of life (EOL). We analyzed willingness data descriptively. RESULTS:We surveyed 17 Last Gift participants and 17 next-of-kin/loved ones. More than half of Last Gift participants ( n  = 10; 58.8%) expressed willingness to participate in studies involving totally new treatments or approaches ('first-in-human' studies), a combination of different approaches, the use of unique antibodies, proteins or molecules, or therapeutic vaccines. Under one-quarter of Last Gift participants ( n  = 4; 23.5%) expressed willingness to participate in research involving interventions that may shorten their life expectancy to benefit medical research. Most Last Gift participants and their next-of-kin/loved ones also expressed high acceptance for various types of donations and biopsies at the EOL (e.g. hair donations and skin, lymph node or gut biopsies). DISCUSSION:Knowing whether people would be willing to participate in different types of EOL HIV cure research can help inform the design of future innovative studies. As a research community, we have a duty to design studies with adequate safeguards to preserve the public trust in research and honor PWH's important gift to humanity.

The study by Zhao et al identifies the factors leading to the failure of unicompartmental knee arthroplasty (UKA) in their patients. These factors include substandard suturing of the wound, the presence of osteophytes and intra-articular loose bodies causing impingement, premature loosening of the tibial component, choosing unsuitable patients for the procedure, dislocation of the movable insert, and damage to the anterior cruciate ligament and medial collateral ligament. The findings suggest that employing the correct surgical techniques and indications is essential for successful outcomes in the UKA.

A man in his 30s came to our clinic with a year-long history of progressive pain and swelling in his knee. Diagnostic imaging revealed a displaced patellar fracture with an osteolytic, septated lesion and thinned expanded cortex in both fracture fragments. A core needle biopsy confirmed the diagnosis of giant cell tumour. Treatment involved wide excision of the tumour and the use of polypropylene mesh and a peroneal longus tendon autograft to reconstruct the extensor mechanism of the knee joint. One year postoperatively, the patient experienced no pain, demonstrated full range of motion and showed no signs of functional impairment or local tumour recurrence. This case highlights that reconstruction of the extensor mechanism of the knee after tumour excision with synthetic mesh is an affordable, user-friendly and widely accessible method. It can address large defects effectively while minimising the risks of disease transmission and graft lengthening, resulting in satisfactory outcomes.

Background The management of neglected traumatic knee dislocations is challenging and is commonly associated with suboptimal outcomes. In this article we present two cases of neglected knee dislocations in two young trauma victims who presented late due to restrictions during the COVID-19 pandemic. Methods Two young patients presented at our center with neglected knee fracture-dislocations after eight weeks and six months of trauma. Comprehensive evaluation was performed using radiographs, computed tomography scans, and magnetic resonance imaging. Surgical intervention included open reduction and internal fixation of the mal-aligned intra-articular fracture fragments. Additionally, articular congruency was restored and repair or reconstruction of the posterior cruciate ligament, anterior cruciate ligament, and meniscus was conducted using suitable tendinous autografts and implants. Following surgery, the knees were immobilized for six weeks, followed by aggressive physical therapy. Results After three months of surgical intervention, fracture union and joint stability were achieved. At the >36-month follow-up appointments, both patients were pain-free at rest with a stable knee joint, achieving ≥90 degrees of knee flexion and without extensor deficits. Concurrent with radiographic evidence of osteoarthritic changes in the knee joint, there was mild pain (VAS 2) after prolonged knee movement activities and walking for long distances (>1 km). Conclusion Open reduction and internal fixation, along with simultaneous menisco-ligamentous reconstructions in neglected fracture-dislocations of the knee result in satisfactory clinical outcomes. This approach proves to be an effective joint preservation procedure in young patients, even in delayed and neglected conditions.

The use of broadly neutralizing antibodies (bNAbs) as a cure-related research strategy for human immunodeficiency virus (HIV) has gained attention from the scientific community. bNAbs are specialized antibodies that target HIV-1 by binding to proteins on the surface of the virus, preventing the infection of human cells. In HIV-1 clinical studies assessing the use of bNAbs, it has been common practice to prescreen potential participants for bNAb sensitivity. However, the use of pre-screening in HIV-1 bNAb clinical trials is a topic of ongoing debate, with regard to its potential benefits and limitations. In this paper, we examine the possible benefits and limitations of pre-screening for bNAb sensitivity in HIV-1 cure-related studies, and suggest alternative methods which may be more effective or efficient at saving costs and time. Ultimately, the decision to use pre-screening in HIV-1 bNAb clinical trials should be based on a careful assessment of the potential benefits and limitations of this approach, as well as the specific needs, goals, design, and population of the study in question.

Introduction:Although current antiretroviral therapy allows most people with HIV (PWH) to experience normal longevity with a good quality of life, an HIV cure remains elusive due to HIV reservoir formation within deep tissues. An HIV cure remains highly desirable to the community of PWH. This study reports on the perceived risks and benefits of participation in the Last Gift study, a study aimed at characterizing HIV reservoirs via post-mortem autopsy, among PWH at the end of life (EOL) and their next-of-kin (NOK)/loved ones.Methods:Last Gift participants (PWH with a terminal illness and/or near the end of life) and their NOK/loved ones were surveyed for perceptions of risks, benefits, and meaning for participation in the Last Gift study.Results:The average age of the 17 Last Gift participants was 66.6 years, 3 were females, 1 person identified as Hispanic, and 15 as Caucasian. The average age of the 17 NOK/loved ones was 56.7 years, and relationships to Last Gift participants included partner/spouse, sibling, friend, child, parent, grandparent, and nephew. The only perceived personal risk of the Last Gift among participants was the blood draws (3/17). NOK/loved ones perceived the following risks: blood draws (2/17), physical pain (3/17), worry that something bad will happen (2/17), and unpleasant side effects (1/17). Participants in Last Gift and NOK/loved ones indicated the study had various positive social effects. For both participants and NOK/loved ones, the most frequent perceived personal benefit of the Last Gift was the satisfaction of supporting HIV cure research.Discussion:Participants perceived minimal personal and societal risks and valued the altruistic benefits of participating in the Last Gift study. Last Gift participants and NOK/loved ones were cautious about possible personal risks of EOL HIV cure research but still viewed that the emotional, psychological and societal benefits of participation outweighed potential risks.

The Last Gift is an observational HIV cure-related research study conducted with people with HIV at the end of life (EOL) at the University of California San Diego. Participants agree to voluntarily donate blood and other biospecimens while living and their bodies for a rapid research autopsy postmortem to better understand HIV reservoir dynamics throughout the entire body. The Last Gift study was initiated in 2017. Since then, 30 volunteers were enrolled who are either (1) terminally ill with a concomitant condition and have a prognosis of 6 months or less or (2) chronically ill with multiple comorbidities and nearing the EOL. Multiple ethical and logistical challenges have been revealed during this time; here, we share our lessons learnt and ethical analysis. Issues relevant to healthcare research include surrogate informed consent, personal and professional boundaries, challenges posed conducting research in a pandemic, and clinician burnout and emotional support. Issues more specific to EOL and postmortem research include dual roles of clinical care and research teams, communication between research personnel and clinical teams, legally required versus rapid research autopsy, identification of next of kin/loved ones and issues of inclusion. Issues specific to the Last Gift include logistics of body donation and rapid research autopsy, and disposition of the body as a study benefit. We recommend EOL research teams to have clear provisions around surrogate informed consent, rotate personnel to maintain boundaries, limit direct contact with staff associated with clinical care and have a clear plan for legally required versus research autopsies, among other recommendations.

Background: HIV cure-directed clinical trials using analytical treatment interruptions (ATIs) require participants to adhere to frequent monitoring visits for viral load tests. Novel viral load monitoring strategies are needed to decrease participant burden during ATIs. Objective: To examine acceptability of a novel home-based blood collection device for viral load testing in the context of two ongoing ATI trials in Philadelphia, PA, United States. Methods: From January 2021 to February 2022, participants completed three in-depth interviews via teleconference during their participation in an ATI: (1) within two weeks of enrollment in the device study, (2) approximately four weeks after beginning to use the device, and (3) within two weeks of the end of the ATI when ART was re-initiated. We used conventional content analysis to analyze the data. Results: We recruited 17 participants: 15 were cisgender males, 1 cisgender female, and 1 transgender woman. We observed an overall 87% success rate in drawing blood with the device from home collection and found overall high acceptance of the device. A mean of 91.5 devices per participant were used for home-based blood collection. Most PWH viewed the device as relatively convenient, painless, easy to use, and a simple solution to frequent blood draws. The main challenge encountered was the inability to completely fill up devices with blood in some cases. Most participants reported positive experiences with mailing blood samples and could see themselves using the device on a regular basis outside of ATIs. Conclusions: Our study showed participant valued the novel home-based peripheral blood collection for viral load testing in the context of ATI trials. More research will be necessary to optimize implementation of the device and to assess whether blood collected can reliably measure viral loads in the context of ATI trials.

Background One of the next frontiers in HIV research is focused on finding a cure. A new priority includes people with HIV (PWH) with non-AIDS terminal illnesses who are willing to donate their bodies at the end-of-life (EOL) to advance the search towards an HIV cure. We endeavored to understand perceptions of this research and to identify ethical and practical considerations relevant to implementing it. Methods We conducted 20 in-depth interviews and 3 virtual focus groups among four types of key stakeholders in the United States (PWH, biomedical HIV cure researchers, HIV clinicians, and bioethicists) to obtain triangulated viewpoints because little was known about the ethics of this topic. Each group was queried as to ethical considerations, safeguards, and protections for conducting HIV cure-related research at the EOL to ensure this research remains acceptable. Results All four key stakeholder groups generally supported HIV cure-related research conducted at the EOL because of the history of altruism within the PWH community and the potential for substantial scientific knowledge to be gained. Our informants expressed that: (1) Strong stakeholder and community involvement are integral to the ethical and effective implementation, as well as the social acceptability of this research; (2) PWH approaching the EOL should not inherently be considered a vulnerable class and their autonomy must be respected when choosing to participate in HIV cure-related research at the EOL; (3) Greater diversity among study participants, as well as multi-disciplinary research teams, is necessitated by HIV cure-related research at the EOL; (4) The sensitive nature of this research warrants robust oversight to ensure a favorable risk/benefit balance and to minimize the possibility of therapeutic misconception or undue influence; and (5) Research protocols should remain flexible to accommodate participants' comfort and needs at the EOL. Conclusion Because of the ethical issues presented by HIV cure-related research at the EOL, robust ethical safeguards are of utmost importance. The proposed ethical and practical considerations presented herein is a first step in determining the best way to maximize this research's impact and social value. More much inquiry will need to be directed towards understanding context-specific and cultural considerations for implementing EOL HIV cure research in diverse settings.

Background: Research on stakeholder perspectives of HIV cure research has involved people with HIV (PWH), who generally cite the importance of HIV clinician advice in making decisions about trial participation. However, there has been little exploration of non-researcher community HIV clinician perspectives, which are clearly critical to the success of HIV cure-related research.Objective: We aimed to learn how community HIV clinicians perceive HIV cure research and identify factors that would lead them to support or discourage HIV cure trial participation by their patients.Methods: We recruited a purposive sample of 12 community HIV clinicians in metro-Seattle, WA to participate in structured interviews. We completed 11 interviews via teleconference and received one written response. We used conventional content analysis to analyze the data.Results: Overall, community HIV clinicians were supportive of patient participation in HIV cure trials. Factors affecting support included knowledge of local trials, ease of referral, patient immune function and health stability, study risks and benefits, burden of study requirements, patient characteristics, patient life stability, potential impact on engagement in care, study communication plans, and beliefs that patients should have the autonomy to decide to participate. Participants had concerns about trials requiring treatment delays or interruptions and HIV transmission risk. While their knowledge of the field was limited, they were interested in learning more about open HIV cure trials.Conclusions: It would benefit the HIV cure research community if those leading HIV cure trials make stronger efforts to engage community clinicians who care for PWH, but are not active researchers, early in the trial design process. Such engagement prior to launching HIV cure trials will improve trial designs, leading to better enrollment and retention within these important studies.

Background HIV cure research involving cell and gene therapy has intensified in recent years. There is a growing need to identify ethical standards and safeguards to ensure cell and gene therapy (CGT) HIV cure research remains valued and acceptable to as many stakeholders as possible as it advances on a global scale. Methods To elicit preliminary ethical and practical considerations to guide CGT HIV cure research, we implemented a qualitative, in-depth interview study with three key stakeholder groups in the United States: (1) biomedical HIV cure researchers, (2) bioethicists, and (3) community stakeholders. Interviews permitted evaluation of informants’ perspectives on how CGT HIV cure research should ethically occur, and were transcribed verbatim. We applied conventional content analysis focused on inductive reasoning to analyze the rich qualitative data and derive key ethical and practical considerations related to CGT towards an HIV cure. Results We interviewed 13 biomedical researchers, 5 community members, and 1 bioethicist. Informants generated considerations related to: perceived benefits of CGT towards an HIV cure, perceived risks, considerations necessary to ensure an acceptable benefit/risk balance, CGT strategies considered unacceptable, additional ethical considerations, and considerations for first-in-human CGT HIV cure trials. Informants also proposed important safeguards to developing CGT approaches towards an HIV cure, such as the importance of mitigating off-target effects, mitigating risks associated with long-term duration of CGT interventions, and mitigating risks of immune overreactions. Conclusion Our study identified preliminary considerations for CGT-based HIV cure across three key stakeholder groups. Respondents identified an ideal cure strategy as one which would durably control HIV infection, protect the individual from re-acquisition, and eliminate transmission to others. Known and unknown risks should be anticipated and perceived as learning opportunities to preserve and honor the altruism of participants. Preclinical studies should support these considerations and be transparently reviewed by regulatory experts and peers prior to first-in-human studies. To protect the public trust in CGT HIV cure research, ethical and practical considerations should be periodically revisited and updated as the science continues to evolve. Additional ethics studies are required to expand stakeholder participation to include traditionally marginalized groups and clinical care providers.

As end-of-life (EOL) HIV cure-related research expands, understanding perspectives of participants’ next-of-kin (NOK) is critical to maintaining ethical study conduct. We conducted two small focus groups and two one-on-one interviews using focus group guides with the NOK of Last Gift study participants at the University of California, San Diego (UCSD). Participating NOK included six individuals ( n = 5 male and n = 1 female), including a grandmother, grandfather, partner, spouse, and two close friends. Researchers double-coded the transcripts manually for overarching themes and sub-themes using an inductive approach. We identified six key themes: 1) NOK had an accurate, positive understanding of the Last Gift clinical study; 2) NOK felt the study was conducted ethically; 3) Perceived benefits for NOK included support navigating the dying/grieving process and personal growth; 4) Perceived drawbacks included increased sadness, emotional stress, conflicted wishes between NOK and study participants, and concerns around potential invasiveness of study procedures at the EOL; 5) NOK expressed pride in loved ones’ altruism; and 6) NOK provided suggestions to improve the Last Gift study, including better communication between staff and themselves. These findings provide a framework for ethical implementation of future EOL HIV cure-related research involving NOK.

Background The pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research. Methods We conducted a scoping review of the growing HIV cure research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing. Discussion Despite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation). Conclusion HIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time.