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Male urinary incontinence (UI) affects quality of life and leads to a significant burden to the health care system. However, the contemporary prevalence and recent trends in UI and its subtypes among US men remain unknown.We evaluated 20-yr trends in the prevalence of UI and its subtype in US men aged ≥20 yr.A serial, cross-sectional analysis of the US nationally representative data from the National Health and Nutrition Examination Survey among men from 2001 to 2020.Prevalence of any, stress, urgency and overflow UI were derived. The frequency of UI was assessed in four categories: less than one time per month, a few times per month, a few times per week, and every day and/or night. All analyses were conducted using sample weights, stratification, and clustering of the complex sampling design. Sociodemographic and lifestyle correlates of UI over time were identified using multivariable logistic regressions.Data on 22994 US men (mean age, 46.6 yr [standard error, 0.20]; weighted population, 848642150) were analyzed. The prevalence of any UI increased from 2001-2002 (11.5% [95% confidence interval {CI}, 10.0-13.0]) to 2017-2020 (19.3% [95% CI, 17.2-21.3]), driven by urgency (from 9.0% [95% CI, 7.5-10.4]) to 15.2% [95% CI, 13.4-16.9]) and overflow UI (from 3.3% [95% CI, 2.7-4.0] to 5.5% [95% CI, 4.5-6.4]; all p for trend0.01). UI affects 38.5% US men ≥60 yr of age, with increasing trends in urgency and overflow UI and a decreasing trend in stress UI (all p for trend0.05). Racial/ethnic disparities were noted, with patterns differed by UI subtype. Compared with non-Hispanic White, non-Hispanic Black men were more likely to report urgency UI (odds ratio [OR], 1.94 [95% CI, 1.71-2.20]). Hispanic men were more likely to report urgency UI (OR, 1.33 [95% CI, 1.14-1.56]), but less likely to report stress (OR, 0.74 [95% CI, 0.56-0.98]) and overflow (OR, 0.75 [95% CI, 0.58-0.98]) UI. Men with higher body mass index and current smokers were more likely to report any, stress, and urgency UI than their counterparts. A higher prevalence of any UI was found in men with low family poverty ratios and chronic diseases, and those who were physically inactive.From 2001 to 2020, the overall prevalence of UI increased among US men, particularly for urgency and overflow UI.In this report, we looked at the prevalence of urinary incontinence among US men in a nationally representative sample. We found that urinary incontinence increased in the past 20 yr driving by the urgency and overflow urinary incontinence.

To raise awareness of the existence of extrarenal renal cell carcinoma (RCC).We report three patients with extrarenal RCC found in the renal proximity, but unattached to the kidney. None had a history of RCC or an identifiable primary renal neoplasm at the time of the diagnosis and on follow-up. The patients included two males and one female aged 57, 77, and 63 years, respectively. One carcinoma was found in the perirenal tissue adjacent to the adrenal, one involved the adrenal gland, and one was a retroperitoneal mass found within the lymph nodes. Two extrarenal RCCs represented clear-cell RCCs and one was an unclassifiable RCC. No patient had evidence of metastases at presentation and disease progression during the follow-up. This report adds to the literature on this unusual clinical scenario and further supports the concept of extrarenal RCC, which is not a well-recognized clinical phenomenon. We also reviewed other similar reports documenting the absence of identifiable renal primaries in the setting of either disseminated metastatic disease or isolated distant metastases of presumed renal origin. Similarly, some carcinomas of apparent renal derivation have been also identified during a work-up of metastatic carcinomas of unknown primary.There should be an awareness of this unusual and intriguing clinical scenario that currently lacks a definitive explanation and standardized therapy strategies. Establishing a correct diagnosis may allow treatment with specific targeted therapies in selected clinical cases.

Background: Approximately one in eight Canadian males will be diagnosed with prostate cancer. Longer survivorship horizons and resource constraints are leading to increasing strain on current models of specialist-led follow-up care delivery. Nurse-led digital health innovations can reduce demand on specialists if co-designed with health care professionals (HCPs). Methods: Using human-centred design, the purpose of this exploratory qualitative study with ten HCPs was to characterize their experiences with prostate cancer (PCa) follow-up and virtual care to optimally situate a nurse-led clinic within this ecosystem. Results: HCPs highlight how current follow-up care can be fragmented, so the scope of a nurse-led clinic should focus on the management of care with referral as needed. Despite an ambivalence for telemedicine arising from its implementation during the COVID-19 pandemic, HCPs see potential for improved care through digital health but note several concerns. Burn-out, weakened patient-provider relationships, and creeping scope of responsibilities were identified as pain points. We provide a health ecosystem readiness checklist to improve odds of acceptability, appropriateness, and feasibility synthesized from six HCP-defined facilitators mapped onto Proctor’s outcomes. Facilitators include: functionality testing (acceptability), technical support and usability (adoption), expectation management (appropriateness), resource allocation (cost), staff readiness (feasibility), and staff training (penetration). Conclusion: Intentional and empathetic co-design with HCPs during the development of digital health innovations, such as digital therapeutics, is necessary to ensure that HCPs can benefit from, instead of being burdened from, the rising tide of digital health in their clinical responsibilities.

Background: Prostate cancer survivors (PCa) can experience a range of unmet needs over a long horizon of survivorship. Thin healthcare services and specialist-led follow-up care models may not adequately address these needs. Digitally mediated nurse-led virtual care models may help support PCa survivors who have unmet survivorship needs in current healthcare systems. Methods: This qualitative descriptive study explores 10 patients’ experiences with follow-up and virtual care, informing the design of a nurse-led virtual clinic (the “Ned Nurse” Clinic) to provide integrated healthcare services. Results: Patient follow-up care experiences included uncertainty regarding care gaps despite new telemedicine modalities and the need for personalized wellbeing support. Patient recommendations for virtual care related to improving integration of existing care connections, supporting patient self-management, and addressing accessibility. Patients anticipate nurse-led PCa virtual care will: (1) clarify patient and provider roles and responsibilities; (2) improve care ease and access to care; (3) enhance mental wellbeing, and (4) reinforce continuity of care. Conclusion: Patients are keen to benefit from the flexibility and increased resources that digital health may provide, but remain concerned about digital literacy and service changes to support these innovations. Future work should evaluate the efficacy of digitally mediated nurse-led virtual care models to support PCa survivorship.

Urbanisation in east and southern Africa (ESA) has brought opportunity and wealth together with multiple dimensions of deprivation. Less well documented in published literature on the ESA region are features of urban practice that promote health equity. This work thus aimed to explore features of urban initiatives aimed at improving health and wellbeing in ESA countries and their contribution to different dimensions of health equity. A thematic analysis was implemented on evidence gathered from 52 documents from online searches and 10 case studies from Harare, Kampala, Lusaka, and Nairobi. Most of the initiatives found focused on social determinants affecting low income communities, particularly water, sanitation, waste management, food security and working and environmental conditions, arising from longstanding urban inequalities and from recent climate and economic challenges. The interventions contributed to changes in social and material conditions and system outcomes. Fewer reported on health status, nutrition, and distributional outcomes. The interventions reported facing contextual, socio-political, institutional, and resource challenges. Various enablers contributed to positive outcomes and helped to address challenges. They included investments in leadership and collective organisation; bringing multiple forms of evidence to planning, including from participatory assessment; building co-design and collaboration across multiple sectors, actors and disciplines; and having credible brokers and processes to catalyse and sustain change. Various forms of mapping and participatory assessment exposed often undocumented shortfalls in conditions affecting health, raising attention to related rights and duties to promote recognitional equity. Investment in social participation, organisation and capacities across the initiatives showed participatory equity to be a consistent feature of promising practice, with both participatory and recognitional equity acting as levers for other dimensions of equity. There was less evidence of distributional, structural and intergenerational equity. However, a focus on low income communities, links made between social, economic and ecological benefit, and investment in women and young people and in urban biodiversity indicated a potential for gains in these areas. The paper discusses learning on local process and design features to strengthen to promote these different dimensions of equity, and issues to address beyond the local level to support such equity-oriented urban initiatives.

Background/Aims Pneumatosis intestinalis (PI) is a rare complication of systemic sclerosis (SSc), characterised by submucosal and/or subserosal collections of free gas, forming cystic lesions within the gastrointestinal (GI) tract. Methods A 67-year-old man with SSc-myositis overlap syndrome presented acutely unwell with worsening abdominal pain, bloating, bloody diarrhoea and vomiting for three weeks. He was afebrile and haemodynamically stable. His abdomen was distended with generalised tenderness but soft and regular bowel sounds were audible. There were no palpable organomegaly or signs of peritonism. He had raised CRP, serum amylase, serum lactate and pre-renal acute kidney injury. He tested positive for ANA Hep2 (speckled) and anti-Mi-2b. His contrast-enhanced CT abdomen and pelvis displayed extensive pneumatosis changes, moderately dilated small bowel loops and pneumoperitoneum without portal venous gas or acute thrombotic occlusion in the main-stem superior or inferior mesenteric arteries. He was managed conservatively with bowel rest, elemental diet, cycling antibiotics for small intestinal bacterial overgrowth (SIBO) and commenced on end-of-life care as surgical exploration was deemed too risky considering that he has exceedingly poor cardiac reserve. He made a surprisingly excellent recovery and his repeat CT scans at approximately 11 weeks showed a complete resolution of pneumatosis intestinalis and pneumoperitoneum. Results PI in SSc generally runs a benign course and is usually managed conservatively. The development of PI is multifactorial, involving a complex interplay between mechanical, biochemical, bacterial and drug factors. PI is usually asymptomatic but patients can present with GI and constitutional symptoms or peritonism. CT scan is the most preferred diagnostic modality for PI. Conservative management is preferable to surgical intervention after careful exclusion of acute surgical causes. The underlying cause of PI should be appropriately addressed and managed in all cases. The management of PI is based on the severity of symptoms and it includes bowel rest, elemental diet or parenteral nutrition, antibiotics, high concentration oxygen, hyperbaric oxygen therapy and/or octreotide. Our patient was managed conservatively as he did not exhibit clinical signs of peritonism or bowel ischaemia and surgical interventions were deemed too risky. He was treated with and has responded well to cycling oral antibiotics for SIBO which was thought to be contributory to his PI. Conclusion This case illustrates that PI with or without pneumoperitoneum could be a rare complication of SSc, and contrary to common belief, it is usually benign and managed conservatively with favourable outcome. An accurate interpretation of its clinical significance is crucial as acute presentations and ambiguous imaging findings can simulate acute surgical emergency leading to diagnostic dilemma and unnecessary or risky surgical interventions. However, emergency laparotomy should be considered in patients who exhibit signs of peritonism or bowel ischaemia and therefore timely involvement of surgeons and multidisciplinary team is essential. Disclosure K. Lim: None. S. Knights: None. J. Pauling: None. J. Gotto: None.

To describe patterns of practice of PSA testing and imaging for Ontario men receiving continuous ADT for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC).This was a retrospective, longitudinal, population-based study of administrative health data from 2008 to 2019. Men 65 years and older receiving continuous androgen deprivation therapy (ADT) with documented CRPC were included. An administrative proxy definition was applied to capture patients with nmCRPC and excluded those with metastatic disease. Patients were indexed upon progression to CRPC and were followed until death or end of study period to assess frequency of monitoring with PSA tests and conventional imaging. A 2-year look-back window was used to assess patterns of care leading up to CRPC as well as baseline covariates.At a median follow-up of 40.1 months, 944 patients with nmCRPC were identified. Their median time from initiation of continuous ADT to CRPC was 26.0 months. 60.7% of patients had their PSA measured twice or fewer in the year prior to index, and 70.7% patients did not receive any imaging in the year following progression to CRPC. Throughout the study period, 921/944 (97.6%) patients with CRPC progressed to high-risk (HR-CRPC) with PSA doubling time ≤ 10 months, of which more than half received fewer than three PSA tests in the year prior to developing HR-CRPC, and 30.9% received no imaging in the subsequent year.PSA testing and imaging studies are underutilized in a real-world setting for the management of nmCRPC, including those at high risk of developing metastatic disease. Infrequent monitoring impedes proper risk stratification, disease staging and detection of treatment failure and/or metastases, thereby delaying the necessary treatment intensification with life-prolonging therapies. Adherence to guideline recommendations and the importance of timely staging should be reinforced to optimize patient outcomes.

BACKGROUND Comprehensive models of survivorship care are necessary to improve access and coordination of care and to address the complexity of physical and psychosocial problems and long-term health needs experienced by patients following cancer treatment. Our group is building a nurse-led virtual clinic to support men living with prostate cancer (PCa) in the post-treatment follow-up phase of their survivorship journey. OBJECTIVE This paper presents our expert-informed, rules-based, survivorship algorithm to build a nurse-led model of survivorship care for prostate cancer survivors with “no evidence of disease” (Ned) to support more timely decision-making, enhanced safety and continuity of care. METHODS An initial rule-set was developed via a literature review and working groups with clinical experts across Canada (e.g., nurse experts, physician experts, scientists) (n=20), and patient partners (n=3). Algorithm priorities were defined through a multidisciplinary consensus meeting with clinical nurse specialists, nurse scientists, nurse practitioners, urologic oncologists, urologists, and radiation oncologists (n=17). The system was refined and validated using nominal group technique. RESULTS Four levels of alert classification were established, initiated by responses on the EPIC-CP survey, and mediated by changes in minimal clinically important different alert thresholds, alert history, clinical urgency with patient autonomy influencing clinical acuity. Patient autonomy was supported through tailored education as a first line of response, and alert escalation depending on a patient-initiated request for a nurse consultation. CONCLUSIONS The Ned algorithm is positioned to facilitate PCa nurse-led care models with a high nurse to patient ratio. This novel expert-informed PCa survivorship care algorithm contains a defined escalation pathway for clinically urgent symptoms while honoring patient preference. Though further validation is required through a pragmatic trial, we anticipate the Ned algorithm will support more timely decision-making, enhance continuity of care through automation of more frequent automated check points, while empowering patients to self-manage their symptoms more effectively than standard care. INTERNATIONAL REGISTERED REPORT RR2-10.1136/bmjopen-2020-045806

Introduction/Background Pneumatosis intestinalis (PI) is characterised by submucosal and/or subserosal collections of free gas, forming cystic lesions within the gastrointestinal (GI) tract, most commonly seen in the small intestine but it can also involve large intestine or the stomach. PI is idiopathic in about 15% of cases but the majority is secondary to conditions such as autoimmune, infectious, inflammatory, pulmonary, drug and/or traumatic aetiologies. PI is a rare and usually benign complication of systemic sclerosis (SSc), and most patients are relatively asymptomatic. Its pathogenesis is likely to involve complex interplay of mechanical, biochemical, bacterial and/or drug factors. Description/Method A 67-year-old man with SSc-myositis overlap syndrome for over nine years on long term Mycophenolate mofetil 500mg BD and Prednisolone 8mg OD presented acutely unwell with worsening abdominal pain, bloatedness, distension, intermittent bloody diarrhoea and vomiting for three weeks. He was afebrile but slightly hypotensive and tachycardic. His abdomen was distended with mild generalised tenderness but soft and regular bowel sounds were audible. There were no palpable organomegaly, guarding, rebound tenderness or other signs of peritonism. He had raised serum lactate at 3.1 and pre-renal acute kidney injury secondary to GI losses and reduced oral intake but his full blood count, liver blood tests, serum amylase, calcium profile, blood glucose, venous blood gas and C-reactive protein were all within normal range. His coeliac screen (IgA tTG) was normal. He tested positive for ANA Hep2 (speckled) but negative for ENA, anti-dsDNA and anti-centromere antibodies. His other SSc presentations include Raynaud’s phenomenon and diffuse scleroderma. His contrast-enhanced CT abdomen and pelvis on admission displayed extensive pneumatosis changes, moderately dilated small bowel loops and pneumoperitoneum. There are prominent atherosclerotic changes seen in aorta and its major branches with associated narrowing but there is no acute thrombotic occlusion seen in the main-stem superior or inferior mesenteric arteries or their major branches. The patient was managed conservatively with bowel rest, intravenous fluids and antibiotics, and was referred for palliative care as surgical exploration was deemed inappropriately risky given his underlying ischaemic heart disease and impaired cardiac reserve. He was discharged home following a short hospital stay with anticipatory medications and a short course of Rifaximin followed by monthly antibiotic cycling with Co-amoxiclav, Metronidazole and Ciprofloxacin. He made a surprisingly excellent recovery on the antibiotics and his repeat CT scans at 11 weeks showed complete resolution of the pneumatosis intestinalis. Discussion/Results PI with or without pneumoperitoneum is a rare gastrointestinal complication of SSc characterised by numerous intramural air-filled cysts within the GI tract. In spite of its usually extensive involvement of the GI tract, this condition generally runs a benign course and is managed conservatively in most cases. The development of PI in SSc is multifactorial, including mechanical (increased luminal pressure allowing gas to permeate into submucosal space through mucosal breach), biochemical (excessive hydrogen production via fermentation processes in gut), overgrowth of gas-producing bacteria and drugs such as corticosteroids that could possibly cause intestinal mucosa atrophy and breakdown. Symptoms of PI can include diarrhoea, constipation, abdominal pain, rectal bleeding and mucous discharge. CT scan has high sensitivity and is the best diagnostic modality for PI. The treatment of PI is based on the severity of symptoms. The underlying cause of PI should be appropriately addressed and managed in all cases. Patients with asymptomatic PI need no further treatment but regular clinical review and monitoring are advisable. Conservative management is preferable to surgical intervention after careful exclusion of acute surgical causes or complications such as bowel perforation, ischaemia or obstruction. For patients with mild symptoms who do not require hospitalisation, antibiotics and elemental diet are recommended. However, for acutely unwell patients with moderate to severe symptoms, hospitalisation is usually required for bowel rest or decompression, fluid and electrolyte replacements, elemental diet or parenteral nutrition, antibiotics, high concentration oxygen, hyperbaric oxygen therapy or octreotide infusion. Our patient was managed conservatively as he did not exhibit any clinical signs of peritonism or bowel ischaemia and surgical interventions were deemed too risky given his underlying cardiac status. He was treated with and has responded well to cycling oral antibiotics for small intestinal bacterial overgrowth which was thought to be contributory to his PI. Key learning points/Conclusion This case report illustrates that PI could be a rare gastrointestinal complication and presentation of SSc-myositis overlap syndrome, therefore clinicians should be aware of this uncommon manifestation of SSc. Other more common differentials such as inflammatory bowel disease, infections or even an underlying malignancy must be thoroughly assessed for and excluded. Pneumoperitoneum in the context of SSc-associated PI is generally benign in nature, spontaneous i.e. non-surgical and it occurs as a result of spontaneous rupture of the air-filled cysts within the gastrointestinal walls, rather than due to true bowel perforation. PI with or without pneumoperitoneum in patients with SSc is usually asymptomatic and only discovered incidentally on imaging or screening endoscopy. However, patients can present with more acute symptoms such as generalised abdominal pain/tenderness, distension and/or vomiting. These clinical presentations and imaging findings may simulate acute surgical abdomen such as bowel perforation and/or ischaemia, leading to diagnostic dilemma and unnecessary or inappropriately risky surgical interventions. Therefore, a precise diagnosis of PI and correct interpretation of its clinical significance are crucial, since PI is generally managed conservatively with favourable response. Surgical treatment is generally not preferred because GI involvement in SSc is almost always extensive, and operative manipulation is likely to result in post-operative complications. However, emergency laparotomy should be considered in patients who exhibit signs of peritonism or bowel ischaemia and therefore timely involvement of surgeons and multidisciplinary team is essential.

The application of machine learning to assess plaque risk phenotypes on cardiovascular CT angiography (CTA) is an area of active investigation. Studies using accepted histologic definitions of plaque risk as ground truth for machine learning models are uncommon. The aim was to evaluate the accuracy of a machine-learning software for determining plaque risk phenotype as compared to expert pathologists (histologic ground truth).Sections of atherosclerotic plaques paired with CTA were prospectively collected from patients undergoing carotid endarterectomy at two centers. Specimens were annotated for lipid-rich necrotic core, calcification, matrix, and intraplaque hemorrhage at 2 mm spacing and classified as minimal disease, stable plaque, or unstable plaque according to a modified American Heart Association histological definition. Phenotype is determined in two steps: plaque morphology is delineated according to histological tissue definitions, followed by a machine learning classifier. The performance in derivation and validation cohorts for plaque risk categorization and stenosis was compared to histologic ground truth at each matched cross-section.A total of 496 and 408 vessel cross-sections in the derivation and validation cohorts (from 30 and 23 patients, respectively). The software demonstrated excellent agreement in the validation cohort with histological ground truth plaque risk phenotypes with weighted kappa of 0.82 [0.78-0.86] and area under the receiver operating curve for correct identification of plaque type was 0.97 [0.96, 0.98], 0.95 [0.94, 0.97], 0.99 [0.99, 1.0] for unstable plaque, stable plaque, and minimal disease, respectively. Diameter stenosis correlated poorly to histologically defined plaque type; weighted kappa 0.25 in the validation cohort.A machine-learning software trained on histological ground-truth tissue inputs demonstrated high accuracy for identifying plaque stability phenotypes as compared to expert pathologists.

We witness an era with more screens than ever before, and within each screen, a multitude of visual varieties. Lisa Gotto investigates this medial diversity as a field of tension between large and small forms of digital image culture. This includes, on the one hand, the immersive potential of large image arrangements, such as digital 3D cinema, and, on the other hand, the compactness of mobile image forms, such as those of the smartphone film or the media practices of Instagram. Weaving together a rich variety of examples and sources, this book presents a multifaceted collection of essays that explore the transformational potential of digital media culture, contextualize its media-technical conditions, and reflect on its social consequences.

Robots don’t seem to be vain creatures taking snapshots of themselves. As functional machines, their purpose is to create a picture of the world without dwelling on the pleasures of self-presentation and self-admiration. However, robots have been taking selfies for quite a while. When Gigapan, a robotic camera mount designed to capture pictures of artwork for Google’s Art Project, traveled through the world’s most famous museums, it took a whole series of selfies by reflecting itself in the galleries’ mirrors. Another prominent photogenic robot is NASA’s Science Laboratory rover Curiosity. When it landed on Mars, it held its camera at robotic arm’s length to take head shots: truly authentic selfies, as they seem. Robot selfies raise questions about self-reflection and the concepts that are associated with it. Why does a robot take a selfie? What does it mean for a machine to capture and present itself? Is the robot selfie a way of android self-recognition and self-monitoring? Could it be that camera robots do not just circulate images but are capable of creating machinic self-awareness? The chapter addresses these issues to discuss what new territories the form of the robot selfie could explore. The first section considers the optical effect of reflection and its contribution to the formation of robotic self-depiction; the second discusses the process of technological transformation and the shift of knowledge constellations that is linked to it. The peculiarity of robot selfies, Gotto argues, lies in their aptitude to mediate between self-reflection and self-transformation. Robot selfies exist both as an effect and an alternative mode of selfie culture. As such, they are a prime site for investigating not only the logics and aesthetics of selfies but also the future potential of digital media culture.

Plasma HDL-cholesterol concentrations correlate negatively with the risk of atherosclerotic cardiovascular disease (ASCVD). According to a widely cited model, HDL elicits its atheroprotective effect through its role in reverse cholesterol transport, which comprises the efflux of cholesterol from macrophages to early forms of HDL, followed by the conversion of free cholesterol (FCh) contained in HDL into cholesteryl esters, which are hepatically extracted from the plasma by HDL receptors and transferred to the bile for intestinal excretion. Given that increasing plasma HDL-cholesterol levels by genetic approaches does not reduce the risk of ASCVD, the focus of research has shifted to HDL function, especially in the context of macrophage cholesterol efflux. In support of the reverse cholesterol transport model, several large studies have revealed an inverse correlation between macrophage cholesterol efflux to plasma HDL and ASCVD. However, other studies have cast doubt on the underlying reverse cholesterol transport mechanism: in mice and humans, the FCh contained in HDL is rapidly cleared from the plasma (within minutes), independently of esterification and HDL holoparticle uptake by the liver. Moreover, the reversibility of FCh transfer between macrophages and HDL has implicated the reverse process - that is, the transfer of FCh from HDL to macrophages - in the aetiology of increased ASCVD under conditions of very high plasma HDL-FCh concentrations.

Human female infertility, 20% of which is idiopathic, is a public health problem for which better diagnostics and therapeutics are needed. A novel cause of infertility emerged from studies of female mice deficient in the HDL receptor gene (Scarb1). These mice are infertile and have high plasma HDL cholesterol (C) concentrations, due to elevated HDL-free cholesterol (FC), which transfers from HDL to all tissues. Previous studies have indicated that oral delivery of probucol, an HDL-lowering drug, to female Scarb1

Aim: In humans, very high plasma HDL-cholesterol concentrations are associated with increased all cause- and atherosclerotic cardiovascular disease (ASCVD)-mortality. The HDL receptor-deficient mouse (Scarb1 -/- ) is a robust model of this phenotype having high free cholesterol (FC) bioavailability due to too many FC-rich HDL particles. Clinically, plasma LDL and HDL are quantified according to total cholesterol = FC + cholesteryl esters (CE), which likely contribute to ASCVD pathophysiology differently. Despite higher HDL, Scarb1 -/- mice have more ASCVD on a Western diet, and increased mol% FC in ovaries, erythrocytes, heart, lung, female liver and macrophages, tissues that are associated with female infertility, impaired cell maturation, cardiac dysfunction and atherosclerosis. Bacterial serum opacity factor (SOF) reduces plasma cholesterol ~ 40% by diverting HDL-cholesterol to the hepatic LDLR. Hypothesis: Adeno-associated virus delivery of SOF (AAV SOF ) normalizes plasma and tissue FC accretion and reverses the pathologies associated with Scarb1 -/- mice. Methods: The lipid compositions of plasma, HDL, erythrocytes, and tissues of Scarb1 -/- mice treated with AAV SOF at 12-13 weeks of age for three weeks were compared with age- and sex-matched wild type (WT) C57BL6 and Scarb1 -/- mice. Results: As hypothesized, AAV SOF reduced plasma and HDL-FC and CE, as well as mol% FC in Scarb1 -/- mice towards WT levels. Erythrocyte FC levels also fell, but mol% FC remained elevated. Some changes were sex-specific: AAV SOF reduced the elevated FC only in female livers to WT levels. AAV SOF reduced FC and CE in lungs of females to WT levels, but not among males; the mol% FC remained high in both sexes. In steroidogenic tissues, adrenals, ovaries and testis, AAV SOF treatment increased FC. Unexpectedly, in Scarb1 -/- mice, AAV SOF increased mol% FC and FC in heart beyond already elevated levels. Conclusions: These findings support the hypothesis that plasma and HDL cholesterol levels determine tissue cholesterol levels that drive the pathologies specific to Scarb1 -/- mice. This evolving model of the role of HDL-FC in RCT provides a rationale for human studies to determine the utility of HDL-FC bioavailability as a risk factor for ASCVD and other pathologies.

Although plasma HDL-C levels negatively correlate with atherosclerotic cardiovascular disease (ACVD), attempts to reduce ACVD risk by raising plasma HDL have disappointed. Thus, hypotheses about salutary HDL effects have shifted from higher-is-better to function-is-more-important. The SRBI-/- mouse is an extreme model of HDL dsyfunctionality; compared to WT mice, SRB1-/- mice have higher plasma HDL levels and an HDL surface that is free cholesterol (FC)-rich (60 vs. 15 mol%). This would be expected to increase HDL-FC bioavailability to cytotoxic levels. HDL dysfunctionality among SRB1-/- mice is associated with multiple metabolic abnormalities—impaired cell membrane structure and function and atherosusceptibility, despite having high plasma HDL-C levels, and infertility among female SRB1-/- mice. Dietary probucol, an HDL-lowering drug, partially reverses infertility in SR-B1-/- mice. The mechanisms underlying ovaritoxicity is not known and interventions that fully reverse this state has not been identified. We hypothesized that a bacterial protein, serum opacity factor (SOF), which acts on HDL and lowers cholesterol in WT mice by 43% in 3 hours, would normalize HDL functionality and rescue infertility in SRBI-/- female mice. SOF DNA was cloned into a TBG-AAV8 plasmid and virus produced by UPENN Vector Lab. The AAV-SOF was delivered by IP injection leading to the endogenous expression of SOF. Probucol-fed and AAV-GFP mice were used as controls. SOF expression drastically decreased plasma cholesterol and normalized the size of HDL in SRBI-/- females comparable to that of WT mice. Fertility was restored in female mice injected with SOF while GFP controls remained infertile. Compared to Probucol-fed mice, AAV-SOF females had a higher percentage of fertile females and shorter time to first litter drop. We concluded that SOF performed equally or better than probucol in rescuing fertility and normalizing HDL.

Background When technically feasible, partial nephrectomy (pN) is preferred over radical nephrectomy (rN) due to similar oncological control with preservation of renal function. Here, we evaluate the incorporation of pN into practice for small renal masses and examine the associated outcomes. Methods We included patients who had undergone either a partial or radical nephrectomy in Alberta, Canada for renal cell carcinomas with pathology tumor stage T1a between 2002 and 2014 (N=1449). Patients were excluded if they had multiple tumors or if they were on dialysis prior to nephrectomy. Results pN use increased over the duration of the study period. Patients treated after the introduction of guidelines (2007) recommending the use of pN were significantly more likely to receive a pN (OR: 2.709, 95% CI: 1.944-3.775; p

The possibility of obtaining potassium sulfate by converting calcium sulfate (phosphogypsum) and potassium chloride in an ammonia solution was investigated. The optimal conditions for the process at various concentrations of ammonia solution were determined. When using a 25% solution of NH3, the stirring time is 30–60 min, the consumption rate of KCl is 160% from stoichiometry. When using a 40% ammonia solution, the stirring time has practically no effect on the conversion, and the KCl consumption rate is only 120% from stoichiometry. The conversion temperature in both cases should be 15–20°C; the mass ratio of gypsum and ammonia should be 1 : (3–5).

76 Background: In recent years, treatment intensification beyond androgen deprivation therapy (ADT) with several novel therapies have shown survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). Given the rapidly evolving landscape in mCSPC treatment, there is a need to better understand how treatment strategies fit in real-world clinical practice and are combined/sequenced with other available therapies. Methods: Using electronic medical records and administrative data, a population-based retrospective cohort study was conducted. Patients aged ≥18 years of age who were newly diagnosed with de novo mCSPC and initiated ADT post-diagnosis between 2010 to 2020 in Alberta, Canada, were included. Treatment intensification was defined as the receipt of apalutamide, abiraterone acetate, enzalutamide, or chemotherapy (e.g. docetaxel) within 180 days of ADT initiation. Results: A total of 2,515 de novo mCSPC were identified during study period with 2,098 (83%) patients initiating ADT post-diagnosis. Of those, 525 (25%) received intensification beyond ADT. The percentage of patients who were intensified was 3% in 2010-2013 and gradually increased to 67% in 2020. Between 2014-2017, docetaxel was the most common therapy for intensification, but its use decreased considerably in 2018-2020 with abiraterone acetate, apalutamide and enzalutamide becoming increasingly available in the mCSPC setting. Upon progression, 46% and 22% in the intensified group versus 38% and 13% in the ADT-alone group initiated one and two-lines of subsequent therapies respectively. Abiraterone acetate and enzalutamide were the most common subsequent therapy for both the intensified (32% and 31% respectively) and the ADT-alone (56% and 38% respectively) groups. Docetaxel (24%) was used as subsequent therapy among mCSPC patients who were intensified with oral systemic agents. In multivariable logistic regression analyses of patients diagnosed in 2014-2020, significant predictors of intensification were younger age at diagnosis, lower Charlson comorbidity index, greater number of metastatic sites, shorter time to ADT initiation, referral to a specialists/cancer centres, surgery or radiation prior to ADT, and more recent year of diagnosis (all p

Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse.To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins.This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort). The primary endpoint for all studies was the percent change from baseline to week 12 in LDL-C levels. Safety and tolerability were assessed by laboratory values and adverse events.In the Phase 3 No Statin Cohort, bempedoic acid (n = 394) lowered LDL-C levels at week 12 significantly more than placebo (n = 192; -26.5% [95% CI, -29.7%, -23.2%]; P0.001). The fixed-dose combination of bempedoic acid with ezetimibe lowered LDL-C by 39.2% (95% CI, -51.7% to -26.7%; P0.001). Muscle-related disorders occurred at a rate of 26.4 and 28.6 per 100 person-years with bempedoic acid and placebo, respectively.In patients with hypercholesterolemia unable to take statins, bempedoic acid lowered LDL-C levels by a mean of 26.5% vs placebo and bempedoic acid + ezetimibe fixed-dose combination lowered LDL-C by 39.2%. The treatments were generally well tolerated, suggesting that bempedoic acid may be efficacious and well tolerated in this challenging-to-treat patient population.

The adoption of docetaxel for systemic treatment of metastatic prostate cancer (PCa), in both castration-sensitive (mCSPC) and castration-resistant (mCRPC) settings, is poorly understood. This study examined the real-world utilization of docetaxel in these patients and their outcomes.A retrospective population-based study used administrative data from Ontario, Canada, to identify men aged ≥66 years who were diagnosed with de novo mCSPC or mCRPC between 2014 and 2019 and received docetaxel. The study assessed treatment tolerability and toxicity, and survival in both cohorts. Descriptive and comparative statistical analysis were conducted.The study identified 11.2% (399/3556) and 13.2% (203/1534) patients diagnosed with de novo mCSPC and with mCRPC who received docetaxel respectively. The median age in both cohorts was 72 years (IQR: 68-76). Overall, 43.9% (n = 175) patients with de novo mCSPC and 52.1% (n = 85) with mCRPC completed ≥6 cycles of docetaxel. Over two-fifth also needed dose adjustments in both cohorts. Hospitalization or emergency department visit for febrile neutropenia were noted in 15.8% (n = 63) of de novo mCSPC patients and similarly in 19% (n = 31) of mCRPC cohort. The median survival of PCa patients who completed ≥6 cycles of docetaxel was significantly longer relative to those who completed4 cycles: 32.7 vs. 23.5 months (p 0.001) for mCSPC and 20.5 vs. 10.7 (p = 0.012) for mCRPC respectively.In this population-based study of elderly patients with metastatic PCa, treatment with docetaxel was associated with poor tolerability and higher toxicity compared with clinical trials. Receipt of limited cycles and reduced overall dose of docetaxel were associated with inferior overall survival.

Prostate cancer (PCa) is one of the most commonly diagnosed types of malignancy and is the second leading cause of cancer-related death in men in developed countries. Cyclin dependent kinase 2 associate protein 1(CDK2AP1) is an epigenetic and cell cycle regulator gene which has been downregulated in several malignancies, but its involvement in PCa has not yet been investigated in a clinical setting. We assessed the prognostic value of CDK2AP1 expression in a cohort of men diagnosed with PCa (n = 275) treated non-surgically by transurethral resection of the prostate (TURP) and studied the relationship between CDK2AP1 expression to various PCa molecular subtypes (ERG, PTEN, p53 and AR) and evaluated the association with clinical outcome. Further, we used bioinformatic tools to analyze the available TCGA PRAD transcriptomic data to explore the underlying mechanism. Our data confirmed increased expression of CDK2AP1 with higher Gleason Grade Group (GG) and metastatic PCa (p