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Studies of complications resulting from surgery or radiotherapy for prostate cancer have mainly focused on incontinence and erectile dysfunction. We aimed to assess other important complications associated with these treatments for prostate cancer. We did a population-based retrospective cohort study, in which we used administrative hospital data, physician billing codes, and cancer registry data for men who underwent either surgery or radiotherapy alone for prostate cancer between 2002 and 2009 in Ontario, Canada. We measured the 5-year cumulative incidence of five treatment-related complication endpoints: hospital admissions; urological, rectal, or anal procedures; open surgical procedures; and secondary malignancies. In the 32 465 patients included in the study, the 5-year cumulative incidence of admission to hospital for a treatment-related complication was 22·2% (95% CI 21·7–22·7), but was 2·4% (2·2–2·6) for patients whose length of stay was longer than 1 day. The 5-year cumulative incidence of needing a urological procedure was 32·0% (95% CI 31·4–32·5), that of a rectal or anal procedure was 13·7% (13·3–14·1), and that of an open surgical procedure was 0·9% (0·8–1·1). The 5-year cumulative incidence of a second primary malignancy was 3·0% (2·6–3·5). These risks were significantly higher than were those of 32 465 matched controls with no history of prostate cancer. Older age and comorbidity at the time of index treatment were important predictors for a complication in all outcome categories, but the type of treatment received was the strongest predictor for complications. Patients who were given radiotherapy had higher incidence of complications for hospital admissions, rectal or anal procedures, open surgical procedures, and secondary malignancies at 5 years than did those who underwent surgery (adjusted hazard ratios 2·08–10·8, p<0·0001). However, the number of urological procedures was lower in the radiotherapy than in the surgery group (adjusted hazard ratio 0·66, 95% CI 0·63–0·69; p<0·0001) Complications after prostate cancer treatment are frequent and dependent on age, comorbidity, and the type of treatment. Patients and physicians should be aware of these risks when choosing treatment for prostate cancer, and should balance them with the clinical effectiveness of each therapy. Ajmera Family Chair in Urologic Oncology.

Microneedles (MNs), renowned for their painless and minimally invasive qualities, exhibit significant potential for facilitating effective drug delivery, vaccination, and targeted sample extraction. Extracellular vesicles (EVs), serving as cargo for MNs, are naturally occurring nanovesicles secreted by cells and characterized by novel biomarkers, low immunogenicity, and cell-source-specific traits. MNs prove instrumental in extracting EVs from the sample fluid, thereby facilitating a promising diagnostic and prognostic tool. To harness the therapeutic potential of EVs in tissue repair, MNs with sustained delivery of EVs leverage micron-sized channels to enhance targeted site concentration, demonstrating efficacy in treating various diseases, such as Achillea tendinopathy, hair loss, spinal cord injury, and diabetic ulcers. EV-loaded MNs emerge as a promising platform for repair applications of skin, cardiac, tendon, hair, and spinal cord tissues. This review commences with an overview of MNs, subsequently delving into the role of EVs as cargo for MNs. The paper then synthesizes the latest advancements in the use of EV-loaded MNs for tissue regenerative repair, extending to research progress in extracting EVs from MNs for disease diagnosis and prognostic evaluations. It aims to offer valuable insights and forecast future research trajectories with the hope of inspiring innovative ideas among researchers in this field.

BackgroundThe 2017 American College of Cardiology/American Heart Association guidelines defined hypertension at ≥130/80 mm Hg. Studies on patients with connective tissue diseases were not considered. Our aim was to assess the impact of this definition on atherosclerotic vascular events (AVEs) in systemic lupus erythematosus.Patients methodsIndividuals from the Toronto Lupus Clinic with at least 2 years of follow-up and no prior AVE were divided in three groups according to their mean blood pressure (BP) over that period (≥140/90 mm Hg, 130-139/80-89 mm Hg and <130/80 mm Hg). They were followed until the first occurrence of an AVE (fatal or non-fatal coronary artery disease, cerebrovascular event and peripheral vascular disease) or last visit. Groups were compared as per the baseline atherosclerotic risk factors. A multivariable time-dependent analysis was performed to adjust for the presence of other risk factors.ResultsOf 1532 patients satisfying the inclusion criteria, 155 (10.1%) had a BP ≥140/90 mm Hg, 316 (20.6%) 130–139/80–89 mm Hg and 1061 (69.3%) were normotensives. After a mean follow-up of 10.8 years, 124 AVEs were documented. The incidence rates were 18.9, 11.5 and 4.5 per 1000 patient-years for the three groups, respectively (p=0.0007 between the 130–139/80–89 mm Hg group and the normotensives). A mean BP of 130–139/80–89 mm Hg over the first 2 years was independently associated with the occurrence of AVEs (HR 1.73, 95% CI 1.13 to 2.65, p=0.011).ConclusionPatients with lupus with a sustained mean BP of 130–139/80–89 mm Hg over 2 years had a significantly higher incidence of AVEs compared with normotensive individuals. This BP level should be the target for antihypertensive therapy to minimise their cardiovascular risk.

Wound healing in diabetic patients is mainly hindered by a combination of long-term glycosylation, persistent inflammatory response, and immunosuppressive state. The interaction of these factors not only results in considerable prolongation of the wound healing process but also elevates the likelihood of recurrent ulcer development, profoundly affecting patients’ quality of life. Traditional treatments, including surgical debridement, anti-infection, dressing application, vascular intervention, and glycaemic control, can only relieve some symptoms. However, they are often ineffective in addressing the underlying cause of impaired wound healing. It is of concern that the importance of the immune microenvironment in diabetic wound healing has not yet been fully appreciated and investigated, and the homeostasis of the immune microenvironment is crucial for promoting cell proliferation, angiogenesis, and tissue repair. However, this microenvironment is often dysregulated in the diabetic state. This paper reviews the key factors leading to dysregulation of the immune microenvironment, including immune cell dysfunction, abnormal cytokine expression, and disruption of key signalling pathways, and introduces an innovative silicone-based microneedle drug delivery method, which takes advantage of microneedle’s precise targeting and highly efficient drug loading capacity to deliver drugs with immunomodulatory functions directly to the wound in a sustained manner, activate the corresponding signalling pathways, promote the polarization of M1 macrophages into the M2 phenotype, and stimulate neovascularization, providing a low inflammatory and pro-angiogenic immune microenvironment for diabetic wound healing, which provides a new therapeutic idea and means for diabetic wound healing.

To estimate the level of medication adherence and barriers to adherence among systemic lupus erythematosus (SLE) patients. Patients taking antimalarials, immunosuppressives, and/or steroids to treat SLE were included. Adherence was measured using the Medication Adherence Self Report Inventory (MASRI) and adherence rates < 80% were considered nonadherent while rates ≥ 80% sufficiently adherent. Pill counts were conducted in a proportion of participants. Barriers to adherence were identified using the Identification of Medication Adherence Barriers Questionnaire 30 (IMAB-Q 30). Associations between adherence and patient demographics and disease-specific characteristics were explored. A total of 94 patients were studied and 28 pill counts conducted. 10 patients were classified as nonadherent and 84 patients as sufficiently adherent. 46% of patients were taking steroids, 77.7% antimalarials, and 55.3% immunosuppressives. 88% of patients were taking ≥ 1 medication for non-SLE conditions. The mean medication adherence rate for the SLE patients was 90.7%. Important barriers to adherence reported by nonadherent patients were: concern about harmful side effects (50%), being easily distracted (50%), life getting in the way (50%), being unsure or disagreeing that their condition will worsen without medications (50%), and having personal reasons for not taking medications (50%). Non-adherent patients reported significantly more barriers than sufficiently adherent patients (p < 0.001). The adherence rate in our population was higher than expected, reaching 90%. Barriers to medication adherence were identified and should be addressed on a population and individualized basis to improve patient outcomes.

Objectives Patients with systemic lupus erythematosus (SLE) are usually treated with glucocorticosteroids even during periods of clinically quiescent disease. A recent study showed that abrupt glucocorticoid withdrawal was associated with an increased likelihood of flare in the next 12 months. The aim of the present study was to assess clinical flare rates and damage accrual in patients who tapered glucocorticosteroids gradually. Methods Patients from the Toronto Lupus Clinic with 2 consecutive years of clinically quiescent disease were retrieved from the database. Individuals who maintained a low prednisone dose (5 mg/day) comprised the maintenance group, whereas patients who gradually tapered prednisone within these two years comprised the withdrawal group. All individuals were followed for 2 years after prednisone discontinuation or the corresponding date for the maintenance group. Propensity score matching was implemented to adjust for certain baseline differences. Outcomes included clinical flares and damage accrual. Results Of 270 eligible patients, 204 were matched (102 in each group). Flare rate (any increase in clinical SLE Disease Activity Index 2000) was lower in the withdrawal group both at 12 (17.6% versus 29.4%; P = 0.023) and 24 months (33.3% versus 50%; P = 0.01). Moderate to severe flares (requiring systemic treatment escalation) were not different at 12 months (10.8% versus 13.7%; P = 0.467) but were less frequent at 24 months (14.7% versus 27.5%; P = 0.024). Damage accrual was less frequent in the withdrawal group (6.9% versus 17.6%; P = 0.022). No predictors for clinical flares were identified. Conclusion Gradual glucocorticoid withdrawal is safe in clinically quiescent SLE and is associated with fewer clinical flares and less damage accrual at 24 months.

ObjectivesThis study aimed to evaluate the prevalence and incidence of herpes zoster (HZ) events and describe its associated factors in a study of patients with SLE.Methods491 consecutive SLE participants were screened for HZ events using a patient-reported questionnaire to capture outcomes on pain and other characteristics associated with HZ events. Sociodemographic, clinical and laboratory measures were also analysed, and time-dependent Cox regression survival analyses were performed to investigate factors associated with HZ events.ResultsPrevalence of HZ was 30.5%, incidence was 14.3 cases per 1000 person-years. Lymphopenia and glucocorticoid dosing were significantly associated with HZ events.ConclusionsHZ is highly prevalent in SLE, which may be linked to disease-related and treatment-related effects on cellular immunity. Our results suggest that the presence of certain risk factors may be useful to allow identification of patients at risk of HZ and improve its management in patients with SLE.

Silicon microneedle (Si-MN) systems are a promising strategy for transdermal drug delivery due to their minimal invasiveness and ease of processing and application. Traditional Si-MN arrays are usually fabricated by using micro-electro-mechanical system (MEMS) processes, which are expensive and not suitable for large-scale manufacturing and applications. In addition, Si-MNs have a smooth surface, making it difficult for them to achieve high-dose drug delivery. Herein, we demonstrate a solid strategy to prepare a novel black silicon microneedle (BSi-MN) patch with ultra-hydrophilic surfaces for high drug loading. The proposed strategy consists of a simple fabrication of plain Si-MNs and a subsequent fabrication of black silicon nanowires. First, plain Si-MNs were prepared via a simple method consisting of laser patterning and alkaline etching. The nanowire structures were then prepared on the surfaces of the plain Si-MNs to form the BSi-MNs through Ag-catalyzed chemical etching. The effects of preparation parameters, including Ag+ and HF concentrations during Ag nanoparticle deposition and [HF/(HF + H2O2)] ratio during Ag-catalyzed chemical etching, on the morphology and properties of the BSi-MNs were investigated in detail. The results show that the final prepared BSi-MN patches exhibit an excellent drug loading capability, more than twice that of plain Si-MN patches with the same area, while maintaining comparable mechanical properties for practical skin piercing applications. Moreover, the BSi-MNs exhibit a certain antimicrobial activity that is expected to prevent bacterial growth and disinfect the affected area when applied to the skin.

Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte levels in SLE patients based on their cognitive performance, independently from the attribution to SLE, and exploring the potential for various serum analytes to differentiate between SLE patients with and without CI. Two hundred ninety individuals aged 18-65 years who met the 2019-EULAR/ACR classification criteria for SLE were included. Cognitive function was measured utilizing the adapted ACR-Neuropsychological Battery (ACR-NB). CI was defined as a z-score of ≤-1.5 in two or more domains. The serum levels of nine analytes were measured using ELISA. The data were randomly partitioned into a training (70%) and a test (30%) sets. Differences in the analyte levels between patients with and without CI were determined; and their ability to discriminate CI from non-CI was evaluated. Of 290 patients, 40% (n=116) had CI. Serum levels of S100A8/A9 and MMP-9, were significantly higher in patients with CI (p=0.006 and p=0.036, respectively). For most domains of the ACR-NB, patients with CI had higher S100A8/A9 serum levels than those without. Similarly, S100A8/A9 had a negative relationship with multiple CI tests and the highest AUC (0.74, 95%CI: 0.66-0.88) to differentiate between patients with and without CI. In this large cohort of well-characterized SLE patients, serum S100A8/A9 and MMP-9 were elevated in patients with CI. S100A8/A9 had the greatest discriminatory ability in differentiating between patients with and without CI.