Inverse kinematic total knee arthroplasty using conventional instrumentation restores constitutional coronal alignment.

PURPOSE: Restricted inverse kinematic alignment (iKA) is a contemporary alignment strategy for total knee arthroplasty (TKA), commonly performed with robotic assistance. While superior clinical results are reported for kinematic-type alignment strategies, registry data indicate no survivorship benefit for navigation or robotic assistance. This study aimed to determine the efficacy of an instrumented, restricted iKA technique for achieving patient-specific alignment. METHODS: Seventy-nine patients undergoing 84 TKAs (five bilateral procedures) using an iKA technique were included for preoperative and postoperative lower limb alignment analysis. The mean age was 66.5 (range: 43-82) with 33 male and 51 female patients. Artificial intelligence was employed for radiographic measurements. Alignment profiles were classified using the Coronal Plane Alignment of the Knee (CPAK) system. Preoperative and postoperative alignment profiles were compared with subanalyses for preoperative valgus, neutral and varus profiles. RESULTS: The mean joint-line convergence angle (JLCA) reduced from 2.5° to -0.1° postoperatively. The mean lateral distal femoral angle (LDFA) remained unchanged postoperatively, while the mean medial proximal tibial angle (MPTA) increased by 2.5° (p = 0.001). By preservation of the LDFA and restoration of the MPTA, the mean hip knee ankle angle (HKA) moved through 3.5° varus to 1.2° valgus. The CPAK system was used to visually depict changes in alignment profiles for preoperative valgus, neutral and varus knees; with 63% of patients observing an interval change in classification. CONCLUSION: Encouraged by the latest evidence supporting both conventional instrumentation and kinematic-type TKA strategies, this study describes how a restricted, conventionally instrumented iKA technique may be utilised to restore constitutional lower limb alignment. LEVEL OF EVIDENCE: Level III.

Approach to Acute Traumatic and Nontraumatic Diaphragmatic Abnormalities.

Acute diaphragmatic abnormalities encompass a broad variety of relatively uncommon and underdiagnosed pathologic conditions, which can be subdivided into nontraumatic and traumatic entities. Nontraumatic abnormalities range from congenital hernia to spontaneous rupture, endometriosis-related disease, infection, paralysis, eventration, and thoracoabdominal fistula. Traumatic abnormalities comprise both blunt and penetrating injuries. Given the role of the diaphragm as the primary inspiratory muscle and the boundary dividing the thoracic and abdominal cavities, compromise to its integrity can yield devastating consequences. Yet, diagnosis can prove challenging, as symptoms may be vague and findings subtle. Imaging plays an essential role in investigation. Radiography is commonly used in emergency evaluation of a patient with a suspected thoracoabdominal process and may reveal evidence of diaphragmatic compromise, such as abdominal contents herniated into the thoracic cavity. CT is often superior, in particular when evaluating a trauma patient, as it allows rapid and more detailed evaluation and localization of pathologic conditions. Additional modalities including US, MRI, and scintigraphy may be required, depending on the clinical context. Developing a strong understanding of the acute pathologic conditions affecting the diaphragm and their characteristic imaging findings aids in efficient and accurate diagnosis. Additionally, understanding the appearance of diaphragmatic anatomy at imaging helps in differentiating acute pathologic conditions from normal variations. Ultimately, this knowledge guides management, which depends on the underlying cause, location, and severity of the abnormality, as well as patient factors. ©RSNA, 2024 Supplemental material is available for this article.

'I feel more part of the world': Participatory action research to develop post-diagnostic dementia support.

Many people living with dementia are 'on the margins', not accessing services and support, despite policy and care advancements. The COVID-19 pandemic exacerbated this, with the closure of face-to-face support during lockdowns in the UK and globally. The aim of the 'Beyond the Margins' project was to develop, implement, and evaluate a face-face programme of support with, by and for people with direct experience of dementia who are on the margins of existing services and support. In March 2020 the project was interrupted by the outbreak of the COVID-19 pandemic and it changed to an online format. The three-phase participatory action research project included 40 people living with dementia, 26 care partners and 31 health and social care practitioners. A seven-week online personal development programme called Getting On with Life (GO) was developed, delivered, and evaluated. This paper focuses on the participatory approaches used to develop and implement the GO programme, and the resulting aspects of its approach to facilitation and content. Key features include the GO Programme's principles of providing a safe and a respectful space, and the programme's values of: Everyone who comes already knows things, can learn things and can teach things; Doing things 'with' each other, rather than 'for' or 'to' each other; Personalised goals-led by the needs of participants rather than an imposed agenda. A key finding was the importance of developing post-diagnostic programmes as a 'sandwich', providing a safe space for learning that is preceded by understanding pathways to access the programme and followed by explicit consideration of the next steps in increasing social engagement.

De novo urethral stricture disease in renal transplant recipients.

INTRODUCTION: With routine catheterization and low urine output pre-transplant, renal transplant recipients (RTRs) may be at risk of urethral stricture disease post-transplant. The objective of this study was to characterize new urethral stricture disease in males following renal transplant. METHODS: A retrospective chart review was carried out on all male RTRs at Vancouver General Hospital who developed urethral strictures from October 2009-2019. Descriptive analyses were conducted on patient characteristics. Comparative analyses against non-stricture RTRs were carried out. RESULTS: Of 636 RTRs, 18 (2.8%) developed a postoperative urethral stricture. Median time from transplant to stricture discovery was 56 days (range 8-618 days). One-third of stricture patients had prior risk factors for stricture formation. Post-transplant, 77.8% presented symptomatically, with 61.1% requiring intervention. Overall graft survival rate was 88.9% among the RTR stricture group; 16.7% experienced acute rejection and 22.2% had delayed graft function (DGF). There was no significant association between developing postoperative urethral stricture and urinary tract infection (Chi-squared [X2]=0.04, p=0.84; odds ratio [OR ] 0.81, 95% confidence interval [CI] 0.1-6.21), DGF (X2=0.14, p=0.70; OR 0.8, CI 0.26-2.48), or acute rejection (X2=2.02, p=0.14; OR 2.55, CI 0.71-9.12). CONCLUSIONS: De novo post-transplant urethral stricture rates appear to occur at a higher rate than the general population and contribute to patient morbidity. Stricture disease should be considered post-transplantation in patients with voiding dysfunction, even if they don't have prior risk factors. Multicenter studies should be considered to elucidate any relationship between urethral stricture and graft survival.

Autonomy lessons: Tips and tricks for building self-determination through the lens of a first time principal investigator.

Early career faculty face many challenges, including establishing a career direction, building skills, balancing work and personal life demands, finding mentors, and establishing collegial relationships within their departments. Early career funding has been shown to augment future success in academia; less is known about the impact of early career funding on the social, emotional, and professional identity aspects of work life. One theoretical perspective to examine this issue is self-determination theory, a broad psychological paradigm explaining motivation, well-being, and development. Self-determination theory is predicated on the idea that fulfillment of three basic needs leads to the achievement of integrated well-being. Optimizing autonomy (a sense of choice and control), competence (sense of mastery), and relatedness (a sense of belonging) accompanies greater motivation, productivity, and perceived success. The authors share how applying for and implementing an early career grant affected these three constructs. Early career funding manifested challenges and beneficial outcomes in relationship to each of the three psychological needs and led to important lessons that may be generally applicable to faculty across a wide range of disciplines. The authors offer broad principles as well as specific grant-related strategies for optimizing autonomy, competence, and relatedness while applying for and executing a grant.[Box: see text].

Clinically relevant T cell expansion media activate distinct metabolic programs uncoupled from cellular function.

Ex vivo expansion conditions used to generate T cells for immunotherapy are thought to adopt metabolic phenotypes that impede therapeutic efficacy in vivo. The comparison of five different culture media used for clinical T cell expansion revealed unique optima based on different output variables, including proliferation, differentiation, function, activation, and mitochondrial phenotypes. The extent of proliferation and function depended on the culture media rather than stimulation conditions. Moreover, the expanded T cell end products adapted their metabolism when switched to a different media formulation, as shown by glucose and glutamine uptake and patterns of glucose isotope labeling. However, adoption of these metabolic phenotypes was uncoupled to T cell function. Expanded T cell products cultured in ascites from ovarian cancer patients displayed suppressed mitochondrial activity and function irrespective of the ex vivo expansion media. Thus, ex vivo T cell expansion media have profound impacts on metabolism and function.

Physician Assistant Students' Perceptions and Competencies Concerning Lifestyle Medicine.

PURPOSE: With nearly two-thirds of chronic disease attributed to lifestyle, there is a need for physician assistants (PA) to develop competencies in Lifestyle Medicine (LM). The purpose of this study was to assess PA students' skill competencies in exercise and dietary prescription to guide curriculum implementation efforts. METHODS: An online survey was administered to PA students at a single institution. RESULTS: Overall, 74 (63%) students completed the survey, self-reporting moderate competence (range: 1-6) in conducting a physical exam to approve an exercise program (4.17 ± 1.22), designing a nutritional plan (3.76 ± 1.32), and designing an exercise prescription (3.50 ± 1.32). Only about half of the clinical students felt competent in conducting a physical examination to approve an exercise program (56%), determine maximal heart rate (54%), and design a nutritional plan (58%), and only 25% reported competence in designing an exercise prescription. Additionally, 84% of clinical students reported time spent on LM in their program as "poor" or inadequate, and 100% wanted to learn more. CONCLUSIONS: PA students reported inadequate competence and knowledge in LM but expressed an unanimous interest in learning more about LM during their educational training.

1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer.

Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a notable enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared with ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete the tumor-promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a potential immunotherapy target to treat human cancer.

Multi-scale tissue architecture analysis of favorable-risk prostate cancer: Correlation with biochemical recurrence.

PURPOSE: Prostate cancer (PCa) with biopsy-based grade group (GG) 1 or 2 characteristics has a favorable outcome, yet some cases still progress after radical prostatectomy and present with biochemical recurrence (BCR). We hypothesized that the multi-scale tissue architecture (MSTA) analysis score would correlate with the aggressive PCa phenotype and could be used as a tool for risk assessment to improve the management of patients with favorable-risk PCa. MATERIALS AND METHODS: MSTA was evaluated in needle-biopsy samples from 115 patients with favorable-risk PCa, as defined by GG1 and GG2, a prostate-specific antigen (PSA) level of <10 ng/mL, a clinical stage of cT1c to cT2b, and general Gleason GG (GGG) and expert pathologist-assessed GG (EGG). Algorithms based on Voronoi diagrams were applied to all Feulgen-thionin-stained diagnostic areas. One hundred tissue architecture features were calculated and an MSTA score, a linear combination of the most discriminant features, was generated. Correlation of MSTA score with BCR and other clinical variables was investigated. RESULTS: In a univariate regression model, EGG, clinical stage, and MSTA were significant predictors of BCR (respective p-values: 0.0016, 0.016, and 0.028). Survival analysis showed that patients with a high MSTA score were more likely to experience BCR than were patients with a low MSTA score (odds ratio, 2.9). Combining MSTA with GG assessment resulted in a significant stratification of risk for BCR. CONCLUSIONS: MSTA score could be used as an objective adjunct risk stratification tool to pathologist assessments and could improve the management of patients with favorable-risk PCa.

Educating physician-assistant students as agents of lifestyle medicine.

BACKGROUND: The burden of chronic disease in the USA necessitates a shift in medicine and medical education from disease treatment to health and wellness promotion. At the forefront of this shift is the field of lifestyle medicine - the evidence-based use of lifestyle modification to prevent, treat and reverse disease. Health care providers, including physician assistants (PAs), can be the vehicle of behaviour change for patients, families and communities, and must receive adequate training to practice lifestyle medicine. METHODS: We describe a pilot lifestyle medicine curriculum implemented through a PA training programme run in the USA in the academic year 2016/2017. The curriculum included four taught modules on lifestyle medicine, two assessment activities and a survey of self-perceived competency, measured before and after the programme. RESULTS: Forty students participated in the curriculum. Results showed a significant increase in self-perceived competencies in seven of nine lifestyle medicine areas (p < 0.001). After the curriculum, all students were successfully able to provide a written lifestyle medicine prescription for a mock patient, with the most common prescription topics including nutrition-related prescriptions (41%), followed by physical activity (26%), addressing substance use (10%), mental health or stresses (10%) and sleep (7%). Furthermore, on average students were able to correctly identify 70% of the desired recommendations for a mock patient. CONCLUSION: Lifestyle medicine curricula can be successfully integrated into existing PA curricula, with demonstrated increases in self-assessments of competency and practical skills.

Quantification of large scale DNA organization for predicting prostate cancer recurrence.

This study investigates whether Genomic Organization at Large Scales (which we propose to call GOALS) as quantified via nuclear phenotype characteristics and cell sociology features (describing cell organization within tissue) collected from prostate tissue microarrays (TMAs) can separate biochemical failure from biochemical nonevidence of disease (BNED) after radical prostatectomy (RP). Of the 78 prostate cancer tissue cores collected from patients treated with RP, 16 who developed biochemical relapse (failure group) and 16 who were BNED patients (nonfailure group) were included in the analyses (36 cores from 32 patients). A section from this TMA was stained stoichiometrically for DNA using the Feulgen-Thionin methodology, and scanned with a Pannoramic MIDI scanner. Approximately 110 nuclear phenotypic features, predominately quantifying large scale DNA organization (GOALS), were extracted from each segmented nuclei. In addition, the centers of these segmented nuclei defined a Voronoi tessellation and subsequent architectural analysis. Prostate TMA core classification as biochemical failure or BNED after RP using GOALS features was conducted (a) based on cell type and cell position within the epithelium (all cells, all epithelial cells, epithelial >2 cell layers away from basement membrane) from all cores, and (b) based on epithelial cells more than two cell layers from the basement membrane using a Classifier trained on Gleason 6, 8, 9 (16 cores) only and applied to a Test set consisting of the Gleason 7 cores (20 cores). Successful core classification as biochemical failure or BNED after RP by a linear classifier was 75% using all cells, 83% using all epithelial cells, and 86% using epithelial >2 layers. Overall success of predicted classification by the linear Classifier of (b) was 87.5% using the Training Set and 80% using the Test Set. Overall success of predicted progression using Gleason score alone was 75% for Gleason >7 as failures and 69% for Gleason >6 as failures. © 2017 International Society for Advancement of Cytometry.

"We're all thrown in the same boat ": A qualitative analysis of peer support in dementia care.

Peer support is well established in fields such as the disability movement and mental health and is increasingly recognised as one way of enabling support by and for people with a diagnosis of dementia and their immediate carers. It was central to the implementation of the National Dementia Strategy (NDS) for England, when 40 demonstration sites were established. This mixed-methods study included in-depth qualitative interviews with people living with dementia (n = 101) and staff/stakeholders (n = 82) at 8 of the 40 sites. Data analysis was a five-stage process: coding framework developed (using 25 transcripts); further development of the framework (using a further 70 transcripts); development of emerging themes; modelling of themes and verification of models based on the entire data set. Peer support had positive emotional and social impact that was rooted in identification with others, a commonality of experience and reciprocity of support. There was also a contrast between the quality of peer support and support from professionals. This emphasises the significance of lived experience and promoting a strength-based approach to interpersonal support that is enabling and challenges a deficit approach to understanding dementia.

Organisational space for partnership and sustainability: lessons from the implementation of the National Dementia Strategy for England.

National policy initiatives are faced with challenges in their partnership development and sustainability. The National Dementia Strategy for England recommended Dementia Adviser (DA) and Peer Support Network (PSN) services and 40 demonstration sites were established. In this paper, we report on the national evaluation of these demonstration sites, with specific reference to aspects of organisational development. The research used a mixed-methods design with three main strands: (i) activity and outcome monitoring; (ii) organisational surveys and collaborative discussion; (iii) in-depth case studies in eight of the 40 sites. This paper focuses primarily on three rounds of organisational surveys distributed to all 40 demonstration sites over a period of 21 months and interviews in the case studies. Data identify the significance of infrastructure within immediate services as well as the position of services within the external infrastructure of the wider health and social care landscape. Partnership - both internally and externally - was key to establishing and sustaining services that flourished. When working well, DAs and PSNs acted as a link between services and people with dementia at the same time as filling gaps in existing support, providing information, advice and interpersonal support that was tailored to individual needs and circumstances. In conclusion, to achieve the full potential and sustainability of services requires them to be in an organisational space that allows them to work in partnership and collaboration with other services, and that values their distinct knowledge of their communities.