Spatiotemporal immune atlas of a clinical-grade gene-edited pig-to-human kidney xenotransplant.

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. Here, we transplant a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and study the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells are uncommon in the porcine kidney cortex early after xenotransplantation and consist of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages express genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft is detectable. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression may be able to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

Inhibition of NFAT promotes loss of tissue resident uterine natural killer cells and attendant pregnancy complications in humans.

Uterine natural killer cells (uNKs) are a tissue resident lymphocyte population that are critical for pregnancy success. Although mouse models have demonstrated that NK deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here we identify uterus transplant (UTx) recipients as a human population with reduced endometrial NK cells and altered pregnancy phenotypes. We further show that the NK reduction in UTx is due to impaired transcriptional programming of NK tissue residency due to blockade of the transcription factor nuclear factor of activated T cells (NFAT). NFAT-dependent genes played a role in multiple molecular circuits governing tissue residency in uNKs, including early residency programs involving AP-1 transcription factors as well as TGFß-mediated upregulation of surface integrins. Collectively, our data identify a previously undescribed role for NFAT in uterine NK tissue residency and provide novel mechanistic insights into the biologic basis of pregnancy complications due to alteration of tissue resident NK subsets in humans. One Sentence Summary: Role of NFAT in uterine NK cell tissue residency.

Physiologic homeostasis after pig-to-human kidney xenotransplantation.

Demand for kidney grafts outpaces supply, limiting kidney transplantation as a treatment for kidney failure. Xenotransplantation has the potential to make kidney transplantation available to many more patients with kidney failure, but the ability of xenografts to support human physiologic homeostasis has not been established. A brain-dead adult decedent underwent bilateral native nephrectomies followed by 10 gene-edited (four gene knockouts, six human transgenes) pig-to-human xenotransplantation. Physiologic parameters and laboratory values were measured for seven days in a critical care setting. Data collection aimed to assess homeostasis by measuring components of the renin-angiotensin-aldosterone system, parathyroid hormone signaling, glomerular filtration rate, and markers of salt and water balance. Mean arterial blood pressure was maintained above 60 mmHg throughout. Pig kidneys secreted renin (post-operative day three to seven mean and standard deviation: 47.3 ± 9 pg/mL). Aldosterone and angiotensin II levels were present (post-operative day three to seven, 57.0 ± 8 pg/mL and 5.4 ± 4.3 pg/mL, respectively) despite plasma renin activity under 0.6 ng/mL/hr. Parathyroid hormone levels followed ionized calcium. Urine output down trended from 37 L to 6 L per day with 4.5 L of electrolyte free water loss on post-operative day six. Aquaporin 2 channels were detected in the apical surface of principal cells, supporting pig kidney response to human vasopressin. Serum creatinine down trended to 0.9 mg/dL by day seven. Glomerular filtration rate ranged 90-240 mL/min by creatinine clearance and single-dose inulin clearance. Thus, in a human decedent model, xenotransplantation of 10 gene-edited pig kidneys provided physiologic balance for seven days. Hence, our in-human study paves the way for future clinical study of pig-to-human kidney xenotransplantation in living persons.

Exploring User Perspectives of and Ethical Experiences With Teletherapy Apps: Qualitative Analysis of User Reviews.

BACKGROUND: Teletherapy apps have emerged as a promising alternative to traditional in-person therapy, especially after the COVID-19 pandemic, as they help overcome a range of geographical and emotional barriers to accessing care. However, the rapid proliferation of teletherapy apps has occurred in an environment in which development has outpaced the various regulatory and ethical considerations of this space. Thus, researchers have raised concerns about the ethical implications and potential risks of teletherapy apps given the lack of regulation and oversight. Teletherapy apps have distinct aims to more directly replicate practices of traditional care, as opposed to mental health apps, which primarily provide supplemental support, suggesting a need to examine the ethical considerations of teletherapy apps from the lens of existing ethical guidelines for providing therapy. OBJECTIVE: In this study, we examined user reviews of commercial teletherapy apps to understand user perceptions of whether and how ethical principles are followed and incorporated. METHODS: We identified 8 mobile apps that (1) provided teletherapy on 2 dominant mobile app stores (Google Play and Apple App Store) and (2) had received >5000 app reviews on both app stores. We wrote Python scripts (Python Software Foundation) to scrape user reviews from the 8 apps, collecting 3268 user reviews combined across 2 app stores. We used thematic analysis to qualitatively analyze user reviews, developing a codebook drawing from the ethical codes of conduct for psychologists, psychiatrists, and social workers. RESULTS: The qualitative analysis of user reviews revealed the ethical concerns and opportunities of teletherapy app users. Users frequently perceived unprofessionalism in their teletherapists, mentioning that their therapists did not listen to them, were distracted during therapy sessions, and did not keep their appointments. Users also noted technical glitches and therapist unavailability on teletherapy apps that might affect their ability to provide continuity of care. Users held varied opinions on the affordability of those apps, with some perceiving them as affordable and others not. Users further brought up that the subscription model resulted in unfair pricing and expressed concerns about the lack of cost transparency. Users perceived that these apps could help promote access to care by overcoming geographical and social constraints. CONCLUSIONS: Our study suggests that users perceive commercial teletherapy apps as adhering to many ethical principles pertaining to therapy but falling short in key areas regarding professionalism, continuity of care, cost fairness, and cost transparency. Our findings suggest that, to provide high-quality care, teletherapy apps should prioritize fair compensation for therapists, develop more flexible and transparent payment models, and invest in measures to ensure app stability and therapist availability. Future work is needed to develop standards for teletherapy and improve the quality and accessibility of those services.

How to use X-ray templating to guide minimally invasive screw removal.

A How to Do It article describing the use of X-ray templating to guide minimally invasive surgical screw removal. By calibrating X-ray measurements using the screw itself as a template marker, we propose a method to reduce incision size and operative time to minimise the risks associated with screw removal.

Cdk5 mediates rotational force-induced brain injury.

Millions of traumatic brain injuries (TBIs) occur annually. TBIs commonly result from falls, traffic accidents, and sports-related injuries, all of which involve rotational acceleration/deceleration of the brain. During these injuries, the brain endures a multitude of primary insults including compression of brain tissue, damaged vasculature, and diffuse axonal injury. All of these deleterious effects can contribute to secondary brain ischemia, cellular death, and neuroinflammation that progress for weeks, months, and lifetime after injury. While the linear effects of head trauma have been extensively modeled, less is known about how rotational injuries mediate neuronal damage following injury. Here, we developed a new model of repetitive rotational head trauma in rodents and demonstrated acute and prolonged pathological, behavioral, and electrophysiological effects of rotational TBI (rTBI). We identify aberrant Cyclin-dependent kinase 5 (Cdk5) activity as a principal mediator of rTBI. We utilized Cdk5-enriched phosphoproteomics to uncover potential downstream mediators of rTBI and show pharmacological inhibition of Cdk5 reduces the cognitive and pathological consequences of injury. These studies contribute meaningfully to our understanding of the mechanisms of rTBI and how they may be effectively treated.

Spatiotemporal immune atlas of the first clinical-grade, gene-edited pig-to-human kidney xenotransplant.

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

The Effects of COVID-19 on Physicians' Perceived Ability to Provide Care for Patients With Type II Diabetes Mellitus.

Background and objective The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents multiple, diverse challenges to providing appropriate medical care, especially in terms of medication and treatment adherence for chronic diseases such as type 2 diabetes mellitus (T2DM). The COVID-19 pandemic has exacerbated these barriers by potentially forcing physicians to modify their treatment plans due to limitations on in-person visits and changes to patients' financial and social support systems. It remains uncertain whether physicians believe they can provide the same standard of care using telehealth technology or other means to their patients during the pandemic. The goal of this study was to explore physician perceptions about their ability to provide care to patients with T2DM during the COVID-19 pandemic. Methodology This cross-sectional study collected data between January 25, 2021, and February 2, 2021, using an anonymous, self-administered online survey involving DO and MD physicians including residents treating patients with T2DM. The survey was administered via REDCap and collected data on participant demographics, attitudes, perceptions, knowledge, and prior and current (COVID-19-era) experience with care for T2DM patients. Physicians registered with the Florida Department of Health with publicly available emails were invited to participate. Results The survey showed that during the COVID-19 pandemic, 57.9% of physicians (n=48) believed that their patients have a weaker social support system; 68.7% (n=57) modified their patient care plans due to patients' financial difficulties; 78.4% (n=65) believed a regular physical exam is necessary to properly treat patients; 48.2% (n=40) did not believe they had a more complete picture of the case with remote consultations; 47.0% (n=39) were not as satisfied with remote consultations as with face-to-face patient visits; 68.7% (n=57) believed telehealth is necessary to adequately treat patients; 38.5% (n=32) have been less likely to refer their patients to other providers or specialists; 45.8% (n=38) reported concerns over admitting their patients to the hospital for acute medical care; 61.5% (n=51) reported having more patients delay scheduling their routine follow-up care; 61.5% (n=51) believed their patients have been less compliant with the healthcare plans recommended to them. Conclusions The study showed that COVID-19 has significantly impacted physicians' perceptions and abilities to provide care for patients with T2DM. COVID-19 has negatively impacted several crucial aspects of diabetes management, including consistent in-person examinations, social support, and referral to other required services, which could result in long-term consequences for these patients. Furthermore, our study suggests that physicians may not be as satisfied with the care they are able to provide via remote consultations as they are with in-person visits, which has significant implications as we move toward a more telehealth-driven healthcare delivery system.

Designing Flexible Longitudinal Regimens: Supporting Clinician Planning for Discontinuation of Psychiatric Drugs.

Clinical decision support tools have typically focused on one-time support for diagnosis or prognosis, but have the ability to support providers in longitudinal planning of patient care regimens amidst infrastructural challenges. We explore an opportunity for technology support for discontinuing antidepressants, where clinical guidelines increasingly recommend gradual discontinuation over abruptly stopping to avoid withdrawal symptoms, but providers have varying levels of experience and diverse strategies for supporting patients through discontinuation. We conducted two studies with 12 providers, identifying providers' needs in developing discontinuation plans and deriving design guidelines. We then iteratively designed and implemented AT Planner, instantiating the guidelines by projecting taper schedules and providing flexibility for adjustment. Provider feedback on AT Planner highlighted that discontinuation plans required balancing interpersonal and infrastructural constraints and surfaced the need for different technological support based on clinical experience. We discuss the benefits and challenges of incorporating flexibility and advice into clinical planning tools.

Electronic bridge to mental health for college students: A randomized controlled intervention trial.

OBJECTIVE: Suicide is the second leading cause of death among college students in the United States, and the percentage of students reporting suicidal thoughts is increasing. Nevertheless, many students at risk do not seek mental health (MH) services. This randomized controlled trial (RCT) examined the efficacy of Electronic Bridge to Mental Health for College Students (eBridge) for increasing at-risk students' linkage to MH services. METHOD: Students from four universities were recruited via email; 40,347 (22.6%) completed the online suicide risk screen; and 3,363 (8.3%) met criteria for randomization based on suicide risk factors and lack of current treatment (62.2% female, 35.0% male, 2.8% transgender/nonbinary; 73.2% White, 7.0% Black, 19.9% Asian, 11.7% other; 12.4% Hispanic, 76.2% undergraduate). These students were randomized to eBridge [personalized feedback (PF) with option of online counseling] or Control (PF). The primary outcome was linkage to MH services within 6 months. RESULTS: Among students assigned to eBridge, 355 students (21.0%) posted ≥1 message, and 168 (10.0%) posted ≥2 messages to the counselor. In intent-to-treat analyses, there was no eBridge effect on obtaining MH services. However, within the eBridge group, students who posted ≥1 message were significantly more likely to link to MH services. CONCLUSIONS: eBridge shows promise for reaching a relatively small subset of college students at risk for suicide; however, engagement in eBridge was low. This study underscores the urgent need for more effective strategies to engage young adults in online mental health interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Attitudes towards vaccines and intention to vaccinate against COVID-19: a cross-sectional analysis-implications for public health communications in Australia.

OBJECTIVE: To examine SARS-CoV-2 vaccine confidence, attitudes and intentions in Australian adults as part of the iCARE Study. DESIGN AND SETTING: Cross-sectional online survey conducted when free COVID-19 vaccinations first became available in Australia in February 2021. PARTICIPANTS: Total of 1166 Australians from general population aged 18-90 years (mean 52, SD of 19). MAIN OUTCOME MEASURES: Primary outcome: responses to question 'If a vaccine for COVID-19 were available today, what is the likelihood that you would get vaccinated?'.Secondary outcome: analyses of putative drivers of uptake, including vaccine confidence, socioeconomic status and sources of trust, derived from multiple survey questions. RESULTS: Seventy-eight per cent reported being likely to receive a SARS-CoV-2 vaccine. Higher SARS-CoV-2 vaccine intentions were associated with: increasing age (OR: 2.01 (95% CI 1.77 to 2.77)), being male (1.37 (95% CI 1.08 to 1.72)), residing in least disadvantaged area quintile (2.27 (95% CI 1.53 to 3.37)) and a self-perceived high risk of getting COVID-19 (1.52 (95% CI 1.08 to 2.14)). However, 72% did not believe they were at a high risk of getting COVID-19. Findings regarding vaccines in general were similar except there were no sex differences. For both the SARS-CoV-2 vaccine and vaccines in general, there were no differences in intentions to vaccinate as a function of education level, perceived income level and rurality. Knowing that the vaccine is safe and effective and that getting vaccinated will protect others, trusting the company that made it and vaccination recommended by a doctor were reported to influence a large proportion of the study cohort to uptake the SARS-CoV-2 vaccine. Seventy-eight per cent reported the intent to continue engaging in virus-protecting behaviours (mask wearing, social distancing, etc) postvaccine. CONCLUSIONS: Most Australians are likely to receive a SARS-CoV-2 vaccine. Key influencing factors identified (eg, knowing vaccine is safe and effective, and doctor's recommendation to get vaccinated) can inform public health messaging to enhance vaccination rates.

Pragmatic cluster randomised control trial using Vaxcards as an age-appropriate tool to incentivise and educate school students about vaccination.

OBJECTIVE: This trial aimed to determine if return rates of consent forms for vaccination could be improved when Vaxcards were offered as an incentive to school children. SETTING: Nineteen schools in South East Melbourne participated. INTERVENTIONS: Students in the experimental arm received a pack of Vaxcards when they returned their government consent form. OUTCOME MEASURES: Return of 'yes' consent forms for vaccination as part of a local government council vaccine programme was the primary outcome of this trial. Return rates were compared between the intervention and control schools and with historical return rates. RESULTS: Secondary school students (N=3087) from 19 schools participated. Compared with historical returns, a small global reduction in 'yes' responses to consent forms of -4.21% in human papilloma virus consent 'yes' responses and -4.69% for diphtheria, tetanus and pertussis was observed across all schools. No difference between the experimental and control groups was observed. CONCLUSIONS: Low 'yes' consent rates and reduction in consent rates between 2018 and 2019 for all groups are concerning. This finding highlights the need for behaviour change interventions across all groups to increase vaccine confidence. Lack of effect of incentivisation with Vaxcards in this study may have been due to the timing of receiving the cards (after the decision to vaccinate had been made, not before) and the limited intensity of the intervention. Optimising the timing and the intensity of exposure to Vaxcards could improve the outcome. TRIAL REGISTRATION NUMBER: ACTRN12618001753246.

Understanding People's Use of and Perspectives on Mood-Tracking Apps: Interview Study.

BACKGROUND: Supporting mental health and wellness is of increasing interest due to a growing recognition of the prevalence and burden of mental health issues. Mood is a central aspect of mental health, and several technologies, especially mobile apps, have helped people track and understand it. However, despite formative work on and dissemination of mood-tracking apps, it is not well understood how mood-tracking apps used in real-world contexts might benefit people and what people hope to gain from them. OBJECTIVE: To address this gap, the purpose of this study was to understand motivations for and experiences in using mood-tracking apps from people who used them in real-world contexts. METHODS: We interviewed 22 participants who had used mood-tracking apps using a semistructured interview and card sorting task. The interview focused on their experiences using a mood-tracking app. We then conducted a card sorting task using screenshots of various data entry and data review features from mood-tracking apps. We used thematic analysis to identify themes around why people use mood-tracking apps, what they found useful about them, and where people felt these apps fell short. RESULTS: Users of mood-tracking apps were primarily motivated by negative life events or shifts in their own mental health that prompted them to engage in tracking and improve their situation. In general, participants felt that using a mood-tracking app facilitated self-awareness and helped them to look back on a previous emotion or mood experience to understand what was happening. Interestingly, some users reported less inclination to document their negative mood states and preferred to document their positive moods. There was a range of preferences for personalization and simplicity of tracking. Overall, users also liked features in which their previous tracked emotions and moods were visualized in figures or calendar form to understand trends. One gap in available mood-tracking apps was the lack of app-facilitated recommendations or suggestions for how to interpret their own data or improve their mood. CONCLUSIONS: Although people find various features of mood-tracking apps helpful, the way people use mood-tracking apps, such as avoiding entering negative moods, tracking infrequently, or wanting support to understand or change their moods, demonstrate opportunities for improvement. Understanding why and how people are using current technologies can provide insights to guide future designs and implementations.

Tabletop Board Game Elements and Gamification Interventions for Health Behavior Change: Realist Review and Proposal of a Game Design Framework.

BACKGROUND: Games, when used as interventional tools, can influence behavior change by incentivizing, reinforcing, educating, providing feedback loops, prompting, persuading, or providing meaning, fun, and community. However, not all game elements will appeal to all consumers equally, and different elements might work for different people and in different contexts. OBJECTIVE: The aim of this study was to conduct a realist review of tabletop games targeting behavior change and to propose a framework for designing effective behavior change games. METHODS: A realist review was conducted to inform program theory in the development of tabletop games for health behavior change. The context, mechanisms used to change behavior, and outcomes of included studies were reviewed through a realist lens. RESULTS: Thirty-one papers met the eligibility criteria and were included in the review. Several design methods were identified that enhanced the efficacy of the games to change behavior. These included design by local teams, pilot testing, clearly defined targets of behavior change, conscious attention to all aspects of game design, including game mechanics, dynamics, aesthetics, and the elicitation of emotions. Delivery with other mediums, leveraging behavioral insights, prior training for delivery, and repeated play were also important. Some design elements that were found to reduce efficacy included limited replayability or lack of fun for immersive engagement. CONCLUSIONS: Game designers need to consider all aspects of the context and the mechanisms to achieve the desired behavior change outcomes. Careful design thinking should include consideration of the game mechanics, dynamics, aesthetics, emotions, and contexts of the game and the players. People who know the players and the contexts well should design the games or have significant input. Testing in real-world settings is likely to lead to better outcomes. Careful selection and purposeful design of the behavior change mechanisms at play is essential. Fun and enjoyment of the player should be considered, as without engagement, there will be no desired intervention effect.

Patient-Chosen Gap Payment: an exploratory qualitative review of patients and general practitioner attitudes toward an alternative funding model for general practice.

We explored patients' and GPs' perceptions of an alternative payment system, a Patient-Chosen Gap Payment, where a gap fee is determined by the patient based on their perceived value of the service, including the choice to pay nothing. Semi-structured, in-depth interviews held with GPs (n=10) and patients (n=10) were audio-recorded, transcribed and analysed for emerging themes. We found three emergent themes: (1) the cost of quality: health care was difficult to value for both GPs and patients; there was belief in universal coverage and the importance of quality, but trade-offs in quality of care were a common perception; (2) the doctor-patient relationship: patient-centred care was a common goal and perceived as a good measure of quality care and a way for patients to place a value on the service/care; and (3) the business of general practice: participants wanted to see sustainable business models for primary care that incentivised quality of care. A Patient-Chosen Gap Payment (PCGP) funding model could incentivise doctors to provide better care without limiting access to health care. Further research is needed to model real-world application.

Goals, life events, and transitions: examining fertility apps for holistic health tracking.

OBJECTIVE: Fertility is becoming increasingly supported by consumer health technologies, especially mobile apps that support self-tracking activities. However, it is not clear whether the apps support the variety of goals and life events of those who menstruate, especially during transitions between them. METHODS: Thirty-one of the most popular fertility apps were evaluated, analyzing data from three sources: the content of app store pages, app features, and user reviews. FINDINGS: Results suggest that fertility apps are designed to support specific life goals of people who menstruate, offering several data collection features and limited feedback options. However, users often desire holistic tracking that encompasses a variety of goals, life events, and the transitions among them. DISCUSSION: These findings suggest fertility patients can benefit more from holistic self-tracking and provide insights for future design of consumer health technologies that better support holistic fertility tracking. CONCLUSION: Fertility apps have the potential to support varied experiences of people who menstruate. But to achieve that, apps need to expand their support by offering ways for more users to perform holistic, personalized, and personally meaningful tracking, so they can derive long-term benefit from the data they collect.

Lisfranc Fixation Techniques and Postoperative Functional Outcomes: A Systematic Review.

The optimal method of fixation of acute Lisfranc injuries is yet to be established. We aim to systematically review the literature to identify the impact of fixation method on postoperative functional outcomes. A systematic review was undertaken using the PRISMA framework to identify all studies reporting postoperative functional outcomes in patients who underwent open-reduction internal fixation of acute Lisfranc injuries. Studies reporting outcomes of numerous fixation methods were divided into fixation subcohorts. Studies comparing bridge plate with transarticular screw fixation were included for meta-analysis, conducted using a random-effects model. Seventeen studies (20 subcohorts) with 462 patients were included. Mean patient age was 29.6 (rang, 15-81) years. Mean follow-up was 38.7 (range 11 to 287) months. American Academy of Orthopaedic Surgeons midfoot score (AOFAS-MF) was the most frequently reported functional outcome (16/20 subcohorts). Overall weighted mean AOFAS-MF was 76.3 ± 9.4 for all cases, with 74.2 ± 9.4 for transarticular screws and 79.2 ± 8.3 for bridge plates. The mean difference between screw and plate was not statistically significant (mean difference = 5.0, 95% confidence interval, -4.8 - 14.8, p = .3). A single study reported AOFAS-MF mean of 92 using suture button fixation. Meta-analysis of the 2 available comparative studies revealed higher postoperative AOFAS-MF with bridge plate fixation (pooled standardized mean difference, 0.51; 95% confidence interval, 0.15-0.87, p = .006). There is scarcity of literature examining the impact of fixation method on postoperative functional outcomes in acute Lisfranc injuries. A small number of studies have reported superior functional outcomes with use of bridge plate fixation. Further evidence is needed to ascertain which injuries are best managed with each fixation method or whether 1 fixation construct is universally superior.

Proximal Femoral Erosion: A Sequelae of Psuedoaneursym Formation Following Operative Fixation of an Intertrochanteric Neck of Femur Fracture.

A 72-year-old male sustained a left intertrochanteric neck of femur fracture following a fall. He underwent operative fixation with a dynamic hip screw and was discharged home. Fifteen months later, the patient presented again with ongoing left thigh pain and swelling. A pelvic radiograph showed scalloping of the medial proximal femoral cortex. Further investigation revealed a left profunda femoris artery pseudoaneurysm. Vascular injury during operative fixation of intratrochanteric fractures is a rare complication, which may be missed due to a delayed presentation. Treating physicians should be mindful of late presentations of vascular injury following the surgical fixation of proximal femoral fractures.

Epithelial tissue cut-out following needle insertion into a joint: a potential complication during arthroscopy.

BACKGROUND: Knee arthroscopy is a common orthopaedic procedure and often involves insertion of a needle through skin into a joint. This needle insertion can create epithelial tissue cut-outs possibly containing commensal bacteria that can be flushed into the joint, and potentially lead to post-arthroscopy septic arthritis. This study aims to assess the frequency of epithelial tissue cut-out creation on insertion of different needle sizes at different angles to the skin. METHODS: Using an ex-vivo porcine limb tissue model, needles of various gauge (14-23G) were inserted at angles of 90, 60, 45 and 30° to the skin surface. Ten passes were undertaken at each angle. Needle lumen contents were then examined for solid tissue cut-out. RESULTS: Two hundred and eighty needle passes were performed resulting in 70 tissue cut-outs (25%) containing solid material. This was more common amongst lower gauge needles. 8 of the 70 (11.4%) tissue cut-outs contained macroscopic evidence of epithelium. The overall rate of epithelial tissue cut-out was 2.9%. The 23G needle had the lowest rate of tissue cut-out creation, occurring twice out of 40 passes (P = 0.002). Neither of these contained macroscopic epithelial tissue. CONCLUSION: Hypodermic needle insertion through skin into a joint can create epithelial tissue cut-out. Epithelial tissue cut-out occurs more frequently with use of lower gauge needles. This study suggests use of a 23G needle during arthroscopy, inserted either at 60 or 90° to the skin, to reduce epithelial tissue cut-out and any potential contribution to post-arthroscopy septic arthritis.

Live Observation of Two Parallel Membrane Degradation Pathways at Axon Terminals.

Neurons are highly polarized cells that require continuous turnover of membrane proteins at axon terminals to develop, function, and survive. Yet, it is still unclear whether membrane protein degradation requires transport back to the cell body or whether degradation also occurs locally at the axon terminal, where live observation of sorting and degradation has remained a challenge. Here, we report direct observation of two cargo-specific membrane protein degradation mechanisms at axon terminals based on a live-imaging approach in intact Drosophila brains. We show that different acidification-sensing cargo probes are sorted into distinct classes of degradative "hub" compartments for synaptic vesicle proteins and plasma membrane proteins at axon terminals. Sorting and degradation of the two cargoes in the separate hubs are molecularly distinct. Local sorting of synaptic vesicle proteins for degradation at the axon terminal is, surprisingly, Rab7 independent, whereas sorting of plasma membrane proteins is Rab7 dependent. The cathepsin-like protease CP1 is specific to synaptic vesicle hubs, and its delivery requires the vesicle SNARE neuronal synaptobrevin. Cargo separation only occurs at the axon terminal, whereas degradative compartments at the cell body are mixed. These data show that at least two local, molecularly distinct pathways sort membrane cargo for degradation specifically at the axon terminal, whereas degradation can occur both at the terminal and en route to the cell body.