Citations

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0–72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3–82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.

The primary cilium, an antenna-like sensory organelle that protrudes from the surface of most eukaryotic cell types, has become a signaling hub of growing interest given that defects in its structure and/or function are associated with human diseases and syndromes, known as ciliopathies. With the continuously expanding role of primary cilia in health and diseases, identifying new players in ciliogenesis will lead to a better understanding of the function of this organelle. It has been shown that the primary cilium shares similarities with the immune synapse, a highly organized structure at the interface between an antigen-presenting or target cell and a lymphocyte. Studies have demonstrated a role for known cilia regulators in immune synapse formation. However, whether immune synapse regulators modulate ciliogenesis remains elusive. Here, we find that programmed death ligand 1 (PD-L1), an immune checkpoint protein and regulator of immune synapse formation, plays a role in the regulation of ciliogenesis. We found that PD-L1 is enriched at the centrosome/basal body and Golgi apparatus of ciliated cells and depleting PD-L1 enhanced ciliogenesis and increased the accumulation of ciliary membrane trafficking proteins Rab8a, BBS5, and sensory receptor protein PC-2. Moreover, PD-L1 formed a complex with BBS5 and PC-2. In addition, we found that depletion of PD-L1 resulted in the ciliary accumulation of Gli3 and the downregulation of Gli1. Our results suggest that PD-L1 is a new player in ciliogenesis, contributing to PC-2-mediated sensory signaling and the Hh signaling cascade.

AbstractBackgroundThis systematic review and meta‐analysis quantitatively examines the efficacy of angle‐based minimally invasive glaucoma surgery (MIGS) in normal tension glaucoma (NTG).MethodsA literature search was performed on Medline, Embase, PubMed, CINAHL and Cochrane Library from inception until 20 December 2022. Pilot, cohort, observational studies and randomised controlled trials including at least 5 subjects undergoing angle‐based MIGS (trabecular‐bypass devices, excisional trabeculotomy, goniotomy and ab‐interno canaloplasty) for NTG, with or without cataract surgery, were included. Meta‐analysis of continuous outcome using the meta routine in R version 2022.12.0+353 was performed to determine mean intraocular pressure (IOP) and anti‐glaucoma medication (AGM) reduction post‐operatively.ResultsOf the 846 studies initially identified, 15 studies with a pooled total of 367 eyes which underwent combined phacoemulsification and angle‐based MIGS were included for final meta‐analysis. Outcomes of the iStent were reported in 5 studies, iStent inject in 7 studies, Hydrus Microstent in 1 study, Kahook Dual Blade in 3 studies, and Trabectome in 2 studies. There was significant reduction in both IOP and AGM post‐operatively at 6 months (2.44 mmHg, 95%CI: 1.83–3.06; 1.21 AGM, 95%CI: 0.99–1.44), 12 months (2.28 mmHg, 95%CI: 1.71–2.84; 1.18 AGM, 95%CI: 0.90–1.47), 24 months (2.10 mmHg, 95%CI: 1.51–2.68; 1.26 AGM, 95%CI: 0.85–1.68) and 36 months (2.43 mmHg, 95%CI: 1.71–3.15, 0.87 AGM, 95%CI: 0.21–1.53) (all p < 0.05). Subgroup analysis on combined phacoemulsification‐iStent inject surgery demonstrated a reduction in both IOP (2.31 mmHg, 95%CI: 1.07–3.56, p < 0.001) and AGM (1.07 AGM, 95%CI: 0.86–1.29, p < 0.001) at 12 months post‐operatively.ConclusionsAngle‐based MIGS combined with phacoemulsification effectively reduces IOP and AGM in NTG eyes for up to 36 months after surgery.

Granulomatous dermatitis is a common tissue reaction pattern seen in the skin or systematically in various presentations. Granulomatous dermatitis can be subclassified into infectious and non-infectious categories. This article focuses on a patient with non-infectious granulomatous dermatitis followed for many years. Past medical history included bilateral total shoulder arthroplasty complicated by prosthetic joint infections. In its early stages, the axillary rash was painful and had many fluid-filled blisters. Ultimately, the histology of the rash deemed the lesion non-infectious and mostly due to an inflammatory process. Specifically, ionizing radiation was used for this patient. The category of granulomatous processes is broad and there are many subtypes. Other treatment options for non-infectious granulomatous processes may include corticosteroids, phototherapy, and interferon-gamma injections. The differential for granulomatous processes is extensive and treatment should be decided on a case-by-case basis.

Abstract Aims Patients with heart failure (HF) display metabolic alterations, including heightened ketogenesis, resulting in increased beta-hydroxybutyrate (β-OHB) formation. We aimed to investigate the determinants and prognostic impact of circulating β-OHB levels in patients with advanced HF and reduced ejection fraction (HFrEF). Methods and results A total of 867 patients with advanced HFrEF (age 57 ± 11 years, 83% male, 45% diabetic, 60% New York Heart Association class III), underwent clinical and echocardiographic examination, circulating metabolite assessment, and right heart catheterization (n = 383). The median β-OHB level was 64 (interquartile range [IQR] 33–161) μmol/L (normal 0–74 μmol/L). β-OHB levels correlated with increased markers of lipolysis (free fatty acids [FFA]), higher natriuretic peptides, worse pulmonary haemodynamics, and lower humoral regulators of ketogenesis (insulin/glucagon ratio). During a median follow-up of 1126 (IQR 410–1781) days, there were 512 composite events, including 324 deaths, 81 left ventricular assist device implantations and 107 urgent cardiac transplantations. In univariable Cox regression, increased β-OHB levels (T3 vs. T1: hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13–1.72, p = 0.002) and elevated FFA levels (T3 vs. T1: HR 1.39, 95% CI 1.09–1.79, p = 0.008) were both predictors of a worse prognosis. In multivariable Cox analysis evaluating the simultaneous associations of FFA and β-OHB levels with outcomes, only FFA levels remained significantly associated with adverse outcomes. Conclusions In patients with advanced HFrEF, increased plasma β-OHB correlate with FFA levels, worse right ventricular function, greater neurohormonal activation and other markers of HF severity. The association between plasma β-OHB and adverse outcomes is eliminated after accounting for FFA levels, suggesting that increased β-OHB is a consequence reflecting heightened lipolytic state, rather than a cause of worsening HF.

Abstract Presentation Date: 6/8/2024 Presentation Start Time: 6:00 PM Background Sickle cell disease patients often lack awareness of how the disease progresses in their bodies, leading to inadequate self-care and adherence to treatment recommendations. This can result in irreversible damage, such as stroke, and affect their psychological health, leading to feelings of isolation, depression, anxiety, and frustration. The 3D Sickle Cell Patient Education Model can help bridge the gap by providing patients with a comprehensive and detailed explanation of their disease, illustrating how red blood cells function within different areas of the body, and showcasing the complications and ramifications of the disease. It can also promote consistency with treatment programs for all patients, making it an essential tool for SCD communities and healthcare industries worldwide. Methods Rochester, MN, Mayo Clinic Comprehensive Pediatric Sickle Cell Clinic, we utilized an innovative approach by incorporating a 3D model to educate children diagnosed with SCD. Results During our session at the Mayo Clinic Comprehensive Pediatric Sickle Cell Clinic, we utilized an innovative approach by incorporating a 3D model to educate children diagnosed with SCD. We were pleasantly surprised to witness a significant improvement in their understanding of SCD. The 3D Sickle Cell Patient Education Model is an incredibly effective tool that SCD communities and healthcare industries can leverage to promote better education and awareness of SCD. Conclusions SCD can be complex for patients and their loved ones to manage. However, with proper care and management, those affected by the disease can still live a better life. These Sickle Cell Patient Learning resources can provide valuable tools and resources for caregivers and healthcare providers to manage the condition more effectively, leading to improved patient outcomes. Additionally, this model can also serve as an educational tool in schools from diverse backgrounds, including urban, rural, and suburban areas where access to education resources may be limited. By utilizing these resources, we can help ensure that those affected by SCD have the support and tools they need to thrive. 3D Sickle Cell Patient Education Model

Abstract Introduction Sexual pain has a profound impact on individuals, regardless of their sexual orientation or gender identity, and affects women more often than men. It adversely affects both sexual function and interpersonal relationships. Despite its prevalence, sexual pain in women often remains unaddressed and untreated. Various underlying causes contribute to sexual pain, sometimes involving multiple factors. We explore treatment options and offer clinical insights into the evaluation and management of 4 common conditions which cause sexual pain in women. In this article, we use the term “women” to indicate cisgender women. Objectives Our aim is to highlight the most common clinical scenarios of sexual pain and provide comprehensive discussions on each, to improve patient care and outcomes in the management of sexual pain. Methods We conducted a comprehensive review of literature and clinical cases to explore the various causes and management strategies for sexual pain in women. We systematically searched databases such as PubMed, Google Scholar, and relevant medical journals. We included peer-reviewed articles, case studies, and clinical trials published between 2000 and 2023. Additionally, we analyzed real-life cases from our clinical practice at our academic institution. Results Our review identified various factors contributing to sexual pain in women, ranging from hormonal imbalances to neuroproliferative and inflammatory conditions affecting the genitourinary system. Each case should be approached individually to offer optimal management strategies accordingly. Conclusion The management of sexual pain in women requires a comprehensive approach that addresses the multifactorial nature of the condition. Patient education and counseling play a crucial role in the management of sexual pain, empowering individuals to advocate for their own health and well-being. The collaboration between healthcare providers and patients can improve our understanding and management of this complex condition.

ABSTRACT Background The aim of this study was to determine the long-term effect of increasing water intake in patients with autosomal dominant polycystic kidney disease (ADPKD) on longitudinal changes in health-related quality of life (HRQoL) in the setting of a clinical trial. Methods Self-completed HRQoL (using the KDQoL-SF, v.1.3 questionnaire) was assessed annually in participants of a 3-year randomized controlled clinical trial (n = 187), allocated (1:1) either to increase water intake to reduce urine osmolality to ≤270 mosmol/kg (implemented by dietetic coaching, self-monitoring tools, text messaging) or continue usual water intake. Results Overall, 96% and 81.8% of participants (n = 187) completed the questionnaire at the baseline and final study visits, respectively. At baseline, the physical component summary score (PCS) and mental component summary score (MCS) were similar in the two groups (P &gt; 0.05) and the five dimensions with the lowest scores in both groups were: energy and fatigue; general and overall health; sleep; emotional well-being; and pain. Within each group, there were no longitudinal changes over time. At the final visit, the PCS was higher in the increased water intake group (51.3 ± 7.6, mean ± standard deviation) compared to the usual water intake group 48.8 ± 9.3; P = 0.037) whereas the MCS was numerically similar. The improvement in the PCS was due to higher sub-scale values for physical functioning and pain (both P &lt; 0.05). By multivariate analysis, only baseline PCS and height-corrected total kidney volume were associated with the final PCS (P &lt; 0.05). Conclusion HRQoL scores remained stable over a 3 year period, and were not adversely affected by the intervention to increase water intake. Future studies should evaluate the clinical significance of the higher PCS in the increased water intake group.