Feasibility of a co-designed online nutrition education program for people with multiple sclerosis.

OBJECTIVE: Diet quality is important for people with multiple sclerosis (MS), but conflicting online information causes them confusion. People with MS want evidence-based MS-specific information to help them make healthy dietary changes, and we co-designed an asynchronous, online nutrition education program (Eating Well with MS) with the MS community. Our aim was to determine the feasibility of Eating Well with MS. METHODS: We used a single-arm pre-post design. The feasibility trial was a nine-week intervention with adults with confirmed MS. Feasibility outcomes: 1) demand (recruitment); 2) practicality (completion); 3) acceptability (Intrinsic Motivation Inventory: interest/enjoyment and value/usefulness subscales); and 4) limited efficacy testing (Diet Habits Questionnaire (DHQ); Critical Nutrition Literacy Tool (CNLT); Food Literacy Behaviour Checklist (FLBC), using intention-to-treat analysis). RESULTS: Recruitment (n = 70) exceeded the target (n = 48) within six weeks. Of the 70 enrolled, 84 % completed at least one module and 54 % completed the full program (five modules). The median interest/enjoyment rating was 5 out of 7 and median value/usefulness rating was 6 out of 7 (where 7 = 'very true'). Compared to pre-intervention, DHQ, CNLT, and FLBC scores all statistically significantly improved post-intervention. CONCLUSION: Eating Well with MS was well received by the MS community and improved their dietary behaviours; demonstrating feasibility. Our findings support the use of co-design methods when developing resources to improve dietary behaviours.

An Evaluation of Peer-Rated Surgical Skill and its Relationship With Detrusor Muscle Sampling in Transurethral Resection of Bladder Tumor.

OBJECTIVE: To assess the reliability of peer-review of TURBT videos as a means to evaluate surgeon skill and its relationship to detrusor sampling. METHODS: Urologists from an academic health system submitted TURBT videos in 2019. Ten blinded peers evaluated each surgeon's performance using a 10-item scoring instrument to quantify surgeon skill. Normalized composite skill scores for each surgeon were calculated using peer ratings. For surgeons submitting videos, we retrospectively reviewed all TURBT pathology results (2018-2019) to assess surgeon-specific detrusor sampling. A hierarchical logistic regression model was fit to evaluate the association between skill and detrusor sampling, adjusting for patient and surgeon factors. RESULTS: Surgeon skill scores and detrusor sampling rates were determined for 13 surgeons performing 245 TURBTs. Skill scores varied from -6.0 to 5.1 [mean: 0; standard deviation (SD): 2.40]. Muscle was sampled in 72% of cases, varying considerably across surgeons (mean: 64.5%; SD: 30.7%). Among 8 surgeons performing >5 TURBTs during the study period, adjusted detrusor sampling rate was associated with sending separate deep specimens (odds ratio [OR]: 1.97; 95% confidence interval [CI]: 1.02-3.81, P = .045) but not skill (OR: 0.81; 95% CI: 0.57-1.17, P = .191). CONCLUSION: Surgeon skill was not associated with detrusor sampling, suggesting there may be other drivers of variability of detrusor sampling in TURBT.

Selective Serotonin Reuptake Inhibitor (SSRI) Use is Not Associated With Impaired Semen Parameters.

OBJECTIVE: To examine the association between selective serotonin reuptake inhibitor (SSRI) use and semen quality. METHODS: We performed a retrospective review of all men undergoing semen analysis (SA) for fertility evaluation from 2002-2020 at a single academic medical center. Men were excluded if they had prior exposure to spermatotoxic medications, clomiphene citrate, gonadotropins, selective estrogen receptor modulators, or medical conditions known to impact male fertility. SSRI exposure was defined by an outpatient prescription within 90 days prior to any semen test. Differences between men with and without SSRI exposure were assessed with Wilcoxon rank sum for continuous variables and chi-squared testing for proportions. Univariable and multivariable linear regression models were fit to evaluate the relationship between SSRI use and individual semen parameters, controlling for age at the time of the semen analysis and non-SSRI drug use. RESULTS: A total of 8861 men were identified, of whom 153 men (1.7%) were exposed to SSRIs prior to SA. Median age was 35 years (interquartile range: 32-39) and was similar between groups (P = .999). Non-SSRI medication use was significantly higher in men taking SSRIs (78.4% vs 23.3%, < .001). On univariable and multivariable analyses, SSRI exposure was not associated with differences in semen volume, sperm concentration, motility, total motile sperm count, or normal morphology. CONCLUSION: In adult men undergoing fertility evaluation, SSRI exposure was not associated with impaired semen parameters. These data may help inform reproductive counseling and medical decision-making regarding SSRI use in men seeking paternity.

The adverse association between stimulant use for attention deficit hyperactivity disorder (ADHD) and semen parameters.

This study examined the relationship between stimulant medications used for the treatment of attention deficit hyperactivity disorder and semen parameters. We performed a retrospective cohort study at a large, academic institution between 2002 and 2020. We included men with a semen analysis without prior spermatotoxic medication use, empiric medical therapy exposure or confounding medical diagnoses (varicocele, Klinefelter's syndrome, cryptorchidism, cystic fibrosis, diabetes, cancer or cancer-related treatment, and azoospermia). Men were stratified by stimulant exposure (methylphenidate or amphetamines). A multivariable linear regression was fit to assess the association between individual semen parameters, age, stimulant exposure and non-stimulant medication use. Of 8,861 men identified, 106 men had active prescriptions for stimulants within 90 days prior to semen testing. After controlling for age and exposure to non-stimulant medications, stimulant use was associated with decreased total motile sperm count (ß: -18.00 mil/ejaculate and standard error: 8.44, p = 0.033) in the setting of decreased semen volume (ß: -0.35 ml, and standard error: 0.16, p = 0.035), but not sperm concentration, motility and morphology. These findings suggest a role for reproductive physicians and mental health providers to consider counselling men on the potential negative impact of stimulants prescribed for attention deficit hyperactivity disorder on semen volume during fertility planning.

In Vivo Expansion of Antigen-Specific Regulatory T Cells through Staggered Fc.IL-2 Mutein Dosing and Antigen-Specific Immunotherapy.

In mice, Ag administration in the absence of adjuvant typically elicits tolerogenic immune responses through the deletion or inactivation of conventional CD4 T cells and the formation or expansion of regulatory CD4 T cells (Treg). Although these "Ag-specific immunotherapy" (ASI) approaches are currently under clinical development to treat autoinflammatory conditions, efficacy and safety may be variable and unpredictable because of the diverse activation states of immune cells in subjects with autoimmune and allergic diseases. To reliably induce Ag-specific tolerance in patients, novel methods to control T cell responses during ASI are needed, and strategies that permanently increase Treg frequencies among Ag-specific CD4 T cells may provide long-lasting immunosuppression between treatments. In this study, we present an approach to durably increase the frequency of Ag-specific Treg in mice by administering ASI when Treg numbers are transiently increased with individual doses of a half-life-extended Treg-selective IL-2 mutein. Repeated weekly cycles of IL-2 mutein doses (day 0) followed by ASI (day 3) resulted in a 3- to 5-fold enrichment in Treg among Ag-responsive CD4 T cells. Expanded Ag-specific Treg persisted for more than 3 wk following treatment cessation, as well as through an inflammatory T cell response to an Ag-expressing virus. Combining Treg enrichment with ASI has the potential to durably treat autoimmune disease or allergy by increasing the Treg/conventional CD4 T cell ratio among autoantigen- or allergen-specific T cells.

Peyronie's disease: pharmacological treatments and limitations.

Introduction: Peyronie's disease (PD) is a disorder of the tunica albuginea from disordered and excessive deposition of collagen resulting in a palpable scar, pain, erect penile deformity and erectile dysfunction that significantly impacts patients both physically and emotionally.Areas Covered: Several treatment options have been described for PD, including shockwave therapy, traction therapy, both oral and intralesional pharmacological options, and surgery. This review seeks to examine the data for different types of non-surgical treatments for PD. We review how various treatment modalities impact several relevant clinical endpoints for Peyronie's disease, including effects on pain, penile curvature, plaque formation, and erectile function. We performed a literature search using PubMed and SCOPUS while referencing AUA, EAU, and CUA guidelines for management of Peyronie's Disease for studies published 1980-2020.Expert opinion: Intralesional collagenase injections have the strongest evidence and are the only FDA approved intralesional treatment for PD. Penile traction therapy (PTT) is low risk and may be beneficial in patients willing to invest significant time using the devices. Furthermore, oral combination therapy with other modalities may provide some benefit. Further investigation is required to better understand pathophysiology of PD and clarify the therapeutic utility of existing treatments, potentially with a multimodal strategy.

Predictors of use and overall survival for patients undergoing metastasectomy for bladder cancer in a national cohort.

OBJECTIVES: To determine the use of surgical resection of metastatic disease in a large national sample and its association with overall survival. METHODS: The National Cancer Database was queried for patients with metastatic bladder cancer (2004-2016). Overall survival was assessed using Kaplan-Meier and multivariable Cox analyses. The associations between covariates and use of metastasectomy were assessed with multivariable logistic regression. RESULTS: Of the 16 382 patients with metastatic bladder cancer included, 6.8% underwent metastasectomy. Its use increased over time (4.7% in 2004 to 6.6% in 2016; per year odds ratio 1.02, 95% confidence interval 1.00-1.04, P = 0.019). Median survival was 7.0 months for patients who received metastasectomy and 5.1 months for those who did not (hazard ratio 0.85, 95% confidence interval 0.79-0.91, P < 0.001). In subgroup analyses, metastasectomy predicted longer survival in patients with lung (hazard ratio 0.73, 95% confidence interval 0.61-0.88, P = 0.001) or brain metastases (hazard ratio 0.58, 95% confidence interval 0.35-0.96, P = 0.035) and in patients with variant histology (hazard ratio 0.80, 95% confidence interval 0.69-0.93, P = 0.003). CONCLUSIONS: In a national sample, the use of metastasectomy for bladder cancer is low. Furthermore, metastasectomy is associated with longer survival overall and in multiple subgroups. However, these results should be validated in future studies.

Marijuana, Lower Urinary Tract Symptoms, and Pain in the Urologic Patient.

OBJECTIVE: To describe marijuana's clinical role for urologic symptoms. METHODS: Studies related to marijuana, voiding dysfunction, lower urinary tract symptoms (LUTS), and pain through January 2019 from PubMed were evaluated for relevance and quality. RESULTS: Forty-eight studies were reviewed. Cannabinoids have mixed efficacy for neurogenic LUTS and little evidence for non-neurogenic LUTS, chronic non-cancer-related and perioperative pain. For cancer-related pain, high-level studies demonstrate cannabinoids are well-tolerated with unclear benefit. CONCLUSION: Cannabinoids appear well-tolerated in the short-term, but their efficacy and long-term impact is unproven and unknown in urologic discomfort. Cannabinoids for urologic symptoms should be further explored with well-designed randomized controlled trials.

A Comparison of Fucoidan Conjugated to Paclitaxel and Curcumin for the Dual Delivery of Cancer Therapeutic Agents.

BACKGROUND: The aim of this study was to develop and compare polymeric micelles of fucoidan, a sulfated polysaccharide, and hydrophobic drugs such as paclitaxel and curcumin. Paclitaxel and curcumin are both known for their medicinal properties, including anticancer efficacy. However, their very low water solubility, absorption and rapid metabolism leads to reduced bioavailability. To redress these problems and enhance anti-cancer therapeutics using fucoidan, polymeric micelles were synthesized from conjugates of fucoidan and hydrophobic drugs. METHODS: The chemical conjugation of fucoidan and hydrophobic drugs has been achieved by utilizing reactive functional groups on the molecules, such as carboxylic groups and hydroxyl groups. RESULTS: The micelles revealed a homogeneous spherical morphology, size, negative surface charge. Fourier transform infrared spectroscopy was used to investigate the physicochemical properties of the polymeric micelles, which form a self-assembled polymeric micelle in aqueous medium. The results of the in vitro release of curcumin and fucoidan showed that their release rates were higher at a pH of 4.5 than at a pH of 7.4. In contrast, the paclitaxel conjugate had a similar release profile at pH of 4.5 and pH of 7.4. CONCLUSION: In the present work, we also found an effective drug delivery system that had the ability to release two types of anticancer drugs, fucoidan and hydrophobic drugs, in the tumour environment.

Contemporary survival trends in penile cancer: Results from the National Cancer Database.

OBJECTIVE: To investigate contemporary survival trends in penile cancer. METHODS: The National Cancer Database was queried for men with penile cancer diagnosed between 1998 and 2009. Patient, tumor, treatment, and facility characteristics were obtained. Overall survival (OS) was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards regression model for all cases and stratified by stage. RESULTS: A total of 8,122 cases of penile cancer were reported from 1998 to 2009 in the National Cancer Database. Complete staging, survival, and covariate data were available for 5,043 cases. The estimated crude 5-year OS for the entire cohort was 61.0%. For all patients, no significant differences in crude 5-year OS were detected between 2006 to 2009 and 2002 to 2005 compared to 1998 to 2001. On multivariable analysis, OS did not significantly differ across all eras. Regional lymph node dissection was associated with improved OS (hazard ratio [HR] = 0.777, P ≤ 0.0001). In patients who underwent lymph node dissection, dissection of ≥8 nodes significantly improved survival (HR = 0.672; P = 0.0011). Additional modeling stratified by stage revealed that OS for stage II cancers increased significantly in 2006 to 2009 compared to 1998 to 2001 (HR = 0.714; P = 0.0034). CONCLUSIONS: Survival in penile cancer has remained unchanged as a whole and for each stage, except for stage II disease. An improved survival trend was detected in stage II penile cancer. Performing a lymph node dissection, especially extensive dissections, may benefit long-term survival.

Metastatic progression is associated with dynamic changes in the local microenvironment.

Most cancer-associated deaths result from metastasis. However, it remains unknown whether the size, microenvironment or other features of a metastatic lesion dictate its behaviour or determine the efficacy of chemotherapy in the adjuvant (micrometastatic) setting. Here we delineate the natural history of metastasis in an autochthonous model of pancreatic ductal adenocarcinoma (PDAC), using lineage tracing to examine the evolution of disseminated cancer cells and their associated microenvironment. With increasing size, lesions shift from mesenchymal to epithelial histology, become hypovascular and accumulate a desmoplastic stroma, ultimately recapitulating the primary tumours from which they arose. Moreover, treatment with gemcitabine and nab-paclitaxel significantly reduces the overall number of metastases by inducing cell death in lesions of all sizes, challenging the paradigm that PDAC stroma imposes a critical barrier to drug delivery. These results illuminate the cellular dynamics of metastatic progression and suggest that adjuvant chemotherapy affords a survival benefit by directly targeting micrometastases.

Inverse Relationship Between Organ-Specific Autoantibodies and Systemic Immune Mediators in Type 1 Diabetes and Type 2 Diabetes: Action LADA 11.

OBJECTIVE: We related organ-specific autoantibodies, including diabetes-associated autoantibodies (DAAs) and non-DAAs to systemic cytokines/chemokines in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: From the European Action LADA (latent autoimmune diabetes in adults) cohort, patients with adult-onset type 1 diabetes (n = 80, of whom 50 had LADA and 30 had classic type 1 diabetes) and type 2 diabetes (n = 626) were analyzed for DAAs (GAD antibody [GADA], IA-2 antigen, islet cell antibody, and zinc transporter T8), non-DAAs (transglutaminase, thyroid peroxide autoantibodies, parietal cell antibodies), and 10 immune mediator concentrations (measured by LUMINEX). RESULTS: Type 1 diabetes patients (whether having classic type 1 diabetes or LADA), apart from their clinical phenotype, could not be distinguished by either autoantibodies (both DAAs and non-DAAs) or immune mediators. In type 1 diabetes, most immune mediators (9 of 10) were negatively correlated with DAA titers. Type 2 diabetes patients, who by definition were without DAAs, had fewer non-DAAs (P < 0.0005), but had higher levels of proinflammatory immune mediators, especially compared with patients with type 1 diabetes who had high GADA titers (interleukin [IL]-6 [P < 0.001], soluble E-selectin [P < 0.01], and IL-1 receptor antagonist [P = 0.052], for trend). CONCLUSIONS: Patients with type 1 diabetes had more DAAs and non-DAAs than did those with type 2 diabetes, whereas the frequency and nature of these autoantibodies was broadly similar in classic type 1 diabetes and LADA. Systemic immune mediator levels, in the main, were negatively correlated with DAA titers, and, for some, were higher in patients with type 2 diabetes, especially when compared with patients who had high GADA titers. Differences in the clinical classification of diabetes are associated with graded differences in adaptive and innate immune reactivity.