Plant-Based Diets and Disease Progression in Men With Prostate Cancer.

Importance: Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about postdiagnostic plant-based diet patterns in individuals with prostate cancer. Objective: To examine whether postdiagnostic plant-based dietary patterns are associated with risk of prostate cancer progression and prostate cancer-specific mortality. Design, Setting, and Participants: This longitudinal observational cohort study included men with biopsy-proven nonmetastatic prostate cancer (stage ≤T3a) from the diet and lifestyle substudy within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) enrolled at 43 urology practices across the US from 1999 to 2018. Participants completed a comprehensive diet and lifestyle questionnaire (including a validated food frequency questionnaire [FFQ]) between 2004 and 2016. Data were analyzed from August 2022 to April 2023. Exposures: Overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) scores were calculated from the FFQ. Main Outcomes and Measures: The primary outcome was prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer-specific mortality). The secondary outcome was prostate cancer-specific mortality. Results: Among 2062 participants (median [IQR] age, 65.0 [59.0-70.0] years), 61 (3%) identified as African American, 3 (<1%) identified as American Indian or Alaska Native, 9 (<1%) identified as Asian or Pacific Islander, 15 (1%) identified as Latino, and 1959 (95%) identified as White. Median (IQR) time from prostate cancer diagnosis to FFQ was 31.3 (15.9-62.0) months after diagnosis. During a median (IQR) follow-up of 6.5 (1.3-12.8) years after the FFQ, 190 progression events and 61 prostate cancer-specific mortality events were observed. Men scoring in the highest vs lowest quintile of PDI had a 47% lower risk of progression (HR, 0.53; 95% CI, 0.37-0.74; P for trend = .003). The hPDI was not associated with risk of progression overall. However, among 680 individuals with Gleason grade 7 or higher at diagnosis, the highest hPDI quintile was associated with a 55% lower risk of progression compared with the lowest hPDI quintile (HR 0.45; 95% CI, 0.25-0.81; P for trend = .01); no association was observed in individuals with Gleason grade less than 7. Conclusions and Relevance: In this cohort study of 2062 men with prostate cancer, higher intake of plant foods after prostate cancer diagnosis was associated with lower risk of cancer progression. These findings suggest nutritional assessment and counseling may be recommended to patients with prostate cancer to help establish healthy dietary practices and support well-being and overall health.

Barriers and confidence among colorectal and prostate cancer survivors participating in two behavioral intervention studies.

PURPOSE: Exercise and healthy diet are key components of cancer survivorship. We sought to explore perceived barriers to engaging in healthy diet and exercise, and whether these barriers change throughout remote-based behavioral interventions. METHODS: Smart Pace (SP) and Prostate 8 (P8) were two 12-week pilot randomized controlled trials (RCTs) among 42 colorectal cancer (CRC) survivors and 76 prostate cancer (PC) survivors, respectively, that encouraged participants to implement exercise (both) and healthy diet (P8 only) through text messaging and wearable fitness monitors; P8 also included web materials. Participants completed surveys on perceived barriers and confidence in their ability to implement healthy behaviors at enrollment and 12 weeks; P8 also included a 52-week assessment. RESULTS: At enrollment, CRC survivors commonly reported a lack of discipline/willpower (36%), time (33%), and energy (31%); PC survivors often reported a lack of knowledge about healthy dietary behaviors (26%). Not having anyone with whom to exercise with was a common barrier among both groups (21% in CRC, 20% in PC). Among the intervention groups in both studies, various enrollment barriers (overall, functional/psychological disability, aversiveness, excuses, and inconveniences) were associated with change in behavior over time. CONCLUSIONS: Among CRC and PC survivors, there are multiple potential barriers related to motivation, time, social support, and lack of knowledge, that can be addressed and overcome to improve healthy behaviors. Tailoring lifestyle interventions to participants' individual barriers and confidence is needed to promote and sustain behavior change long-term.

Protocol for a randomized controlled trial comparing a very low-carbohydrate diet or moderate-carbohydrate plate-method diet for type 2 diabetes: the LEGEND (Lifestyle Education about Nutrition for Diabetes) trial.

BACKGROUND: Optimal carbohydrate intake is an important and controversial area in the nutritional management of type 2 diabetes. Some evidence indicates that reducing overall carbohydrate intake with a low- or very low-carbohydrate eating plan can improve glycemic control compared to following eating plans that involve greater carbohydrate intake. However, critical knowledge gaps currently prevent clear recommendations about carbohydrate intake levels. METHODS: The LEGEND (Lifestyle Education about Nutrition for Diabetes) Trial aims to compare a very low-carbohydrate diet to a moderate-carbohydrate plate-method diet for glycemic control in adults with type 2 diabetes. This two-site trial plans to recruit 180 adults with type 2 diabetes. We will randomize participants to either a 20-session group-based diet and lifestyle intervention that teaches either a very low-carbohydrate diet or a moderate-carbohydrate plate-method diet. We will assess participants at study entry and 4 and 12 months later. The primary outcome is HbA1c, and secondary outcomes include inflammation (high sensitivity C-reactive protein), body weight, changes in diabetes medications, lipids (small particle LDL, HDL, triglycerides), skeletal metabolism (bone mineral density from dual-energy x-ray absorptiometry and bone turnover markers serum procollagen type I N propeptide and serum C-terminal telopeptide of type I collagen), and body composition (percent body fat, percent lean body mass). DISCUSSION: The LEGEND trial is a randomized controlled trial to assess optimal carbohydrate intake in type 2 diabetes by evaluating the effects of a very low-carbohydrate diet vs. a moderate-carbohydrate plate-method diet over a year-long period. The research addresses important gaps in the evidence base for the nutritional management of type 2 diabetes by providing data on potential benefits and adverse effects of different levels of carbohydrate intake. TRIAL REGISTRATION: ClinicalTrials.gov NCT05237128. Registered on February 11, 2022.

Actigraphy: An Adjunctive Method to Measure Irritability in Opioid-Exposed Newborns.

Background and purpose: Conventional measures of withdrawal in newborns with prenatal opioid exposure (POE) rely on nursing assessments, including the subjective judgment of infant irritability. This study investigated limb movement actigraphy as a tool for providing an objective, quantifiable measure of underlying distress. Methods: Correlational analyses compared continuous physiological-detected movement actigraphy and clinical intervallic-scored symptomology (modified Finnegan system) obtained from a control cohort of 37 term neonates with POE studied in their crib in the newborn unit (1-8 days). Results: Infants spent 15% crib time in high movement activity (>100 movements/minute; index irritability) and 38% crib time in low activity (0-5 movements/minute; index calm). There was a significant positive association between actigraphy and Finnegan composite score (r = .28, P = .001) and between actigraphy and subcomponent scores (i.e., central nervous system, gastrointestinal, and metabolic-vasomotor-respiratory). Conclusion: Movement activity via actigraphy captures underlying distress and calm not measured by conventional assessments. Such objective, quantifiable measures can serve to promote equitable assessment and treatment of hospitalized newborns with POE.

Evaluating the Impact of Exclusion Criteria on the Generalizability of Hidradenitis Suppurativa Treatment Research.

Exclusion criteria can limit the generalizability and translation of research findings into clinical practice. The objective of this study is to characterize the trends of exclusion criteria and explore the impact of exclusion criteria on participant diversity, length of enrollment, and the number of enrolled participants. A detailed search was performed using PubMed and clinicaltrials.gov. Nineteen published randomized controlled trials were included, where 2,664 patients were screened, and 2,234 patients (mean age: 37.6 years, 56.6% female) were enrolled from 25 countries. On average, there were 10.1 (standard deviation: 6.14, range: 3-25) exclusion criteria per randomized controlled trial. There was a weak to moderate positive correlation between the number of exclusion criteria and the proportion of enrolled participants (R = 0.49, P value = 0.040). However, no association was seen between the number of exclusion criteria, number of enrolled Black participants (R = 0.86, p value = 0.08), and enrollment length (R = 0.083, P value = 0.74). In addition, there was no discernable trend in the number of exclusion criteria over time (R = -0.18, P value = 0.48). Although the number of exclusion criteria appeared to impact the number of enrolled participants, the lack of skin of color representation in hidradenitis suppurativa randomized controlled trials does not appear to be influenced by the number of exclusion criteria.

Lichen planus associated with secukinumab treatment for plaque psoriasis.

Secukinumab and ixekizumab are IL17A inhibitors most commonly used to treat psoriasis. Common side effects include upper respiratory tract infections, injection site reactions, and mucocutaneous candidiasis. Recently, these medications have been reported to trigger lichen planus and lichenoid reactions have also been reported as an emerging side effect of biologics, especially tumor necrosis factor inhibitors. Herein, we report a patient with lichen planus that appeared after initiation of secukinumab for the treatment of psoriasis.

Protocol for a 4-arm randomized controlled trial testing remotely delivered exercise-only, diet-only, and exercise + diet interventions among men with prostate cancer treated with radical prostatectomy (Prostate 8-II).

BACKGROUND: Nutrition and physical activity are associated with prostate cancer recurrence and mortality. Few randomized controlled trials (RCT) have examined the effects of long-term exercise and diet changes on prostate cancer clinical, biological, and patient-reported outcomes. METHODS: Prostate 8-II is a 4-arm RCT among 200 men with prostate cancer who chose radical prostatectomy (RP) as their primary treatment. Men are enrolled prior to RP and randomized to exercise-only, diet-only, exercise + diet, or usual care (50/arm). Participants begin their assigned intervention 0-5 weeks prior to RP and continue for 24-months following surgery. The 3 active intervention arms receive access to a web-portal and text messages, coaching calls, and other intervention resources (e.g., heart rate sensor and resistance bands and/or recipe booklet). Weekly exercise goals for the exercise intervention groups are 150 min moderate or 75 min vigorous aerobic exercise, 2 strength sessions, and 2 flexibility sessions. Diet intervention groups work with a dietitian to customize their goals (e.g., increase cruciferous vegetables, cooked tomatoes, healthy fats, fish; limit processed meats, whole milk). The primary endpoint is biochemical recurrence. Secondary endpoints include change in tumor biomarkers from biopsy to RP as well as patient-reported outcomes (e.g., quality-of-life), blood and urine biomarkers, and anthropometry at 0, 6, 12, and 24 months. CONCLUSION: This 4-arm RCT will examine the impact of change in exercise and diet (alone or in combination) on prostate cancer recurrence, biology, and quality-of-life.

Management of Primary Focal Hyperhidrosis: An Algorithmic Approach.

Hyperhidrosis (HH) is defined as perspiration beyond the level required to maintain temperature regulation. HH affects nearly 4.8% of the population in the United States. It can have a great impact on patient’s quality of life by disturbing daily activity, performance, confidence, social interactions, and mental health. In the majority of patients with HH (93%), the etiology of excess sweating is idiopathic, which classifies it as primary focal HH. Mild HH may be controlled with topical antiperspirants and lifestyle modifications. Based on the location of involvement, iontophoresis and botulinum toxin may be considered if the patient does not respond to topical therapies. Despite minimizing sweating, chronic use of systemic anticholinergics, in particular oxybutynin, may result in detrimental adverse effects such as dementia. Local surgery, radiofrequency, microwave, and lasers are other potential modalities for HH. Sympathectomy can be a last resort for the treatment of focal HH of the palmar, plantar, axillary, and craniofacial areas after failure of less invasive therapeutic options. In this review, we conducted a comprehensive search in the PubMed electronic database to summarize an algorithmic approach for the treatment of HH. This can help broaden options for managing this difficult disease. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5774.

New-onset cutaneous lupus erythematosus after the COVID-19 vaccine.

Vaccine development for COVID-19 has progressed expeditiously. To date, the Food and Drug Administration (FDA) has authorized the Moderna/mRNA-1273, Pfizer-BioNTech (BNT162b2), and Johnson & Johnson's Janssen (JNJ-78436735) vaccines for use in the United States. Immediate side effects have included myalgia fatigue, chills, fever, and headache. We report an elderly patient with a history of lung cancer and no prior history of autoimmune disease who developed cutaneous lupus erythematosus two ½ months after the second dose of the Pfizer-BioNTech COVID-19 vaccine.

Chronic IL-1 Exposed AR+ PCa Cell Lines Show Conserved Loss of IL-1 Sensitivity and Evolve Both Conserved and Unique Differential Gene Expression Profiles.

INTRODUCTION: Inflammation drives prostate cancer (PCa) progression. While inflammation is a cancer hallmark, the underlying mechanisms mediating inflammation-induced PCa are still under investigation. Interleukin-1 (IL-1) is an inflammatory cytokine that promotes cancer progression, including PCa metastasis and castration resistance. We previously found that acute IL-1 exposure represses PCa androgen receptor (AR) expression concomitant with the upregulation of pro-survival proteins, causing de novo accumulation of castration-resistant PCa cells. However, acute inflammation is primarily anti-tumorigenic, while chronic inflammation is pro-tumorigenic. Thus, using the LNCaP PCa cell line as model, we found that PCa cells can evolve insensitivity to chronic IL-1 exposure, restoring AR and AR activity and acquiring castration resistance. In this paper we expanded our chronic IL-1 model to include the MDA-PCa-2b PCa cell line to investigate the response to acute versus chronic IL-1 exposure and to compare the gene expression patterns that evolve in the LNCaP and MDA-PCa-2b cells chronically exposed to IL-1. METHODS: We chronically exposed MDA-PCa-2b cells to IL-1α or IL-1ß for several months to establish sublines. Once established, we determined subline sensitivity to exogenous IL-1 using cell viability assay, RT-qPCR and western blot. RNA sequencing was performed for parental and subline cells and over representation analysis (ORA) for geneset enrichment of biological process/pathway was performed. RESULTS: MDA-PCa-2b cells repress AR and AR activity in response to acute IL-1 exposure and evolve insensitivity to chronic IL-1 exposure. While cell biological and molecular response to acute IL-1 signaling is primarily conserved in LNCaP and MDA-PCa-2b cells, including upregulation of NF-κB signaling and downregulation of cell proliferation, the LNCaP and MDA-PCa-2b cells evolve conserved and unique molecular responses to chronic IL-1 signaling that may promote or support tumor progression. CONCLUSIONS: Our chronic IL-1 subline models can be used to identify underlying molecular mechanisms that mediate IL-1-induced PCa progression.

Feasibility and Acceptability of a Web-Based Dietary Intervention with Text Messages for Colorectal Cancer: A Randomized Pilot Trial.

BACKGROUND: Diet is associated with colorectal cancer survival. Yet, adherence to nutrition guidelines is low among colorectal cancer survivors. METHODS: We conducted a pilot trial among colorectal cancer survivors to evaluate a 12-week remote dietary intervention. Participants received print materials and were randomized (1:1) to intervention (website, text messages) or wait-list control. Primary outcomes included feasibility and acceptability. We also explored change in diet from 0 to 12 and 24 weeks and change from 0 to 12 weeks in anthropometry and circulating biomarkers (Trial Registration: NCT02965521). RESULTS: We randomized 50 colorectal cancer survivors (25 intervention, 25 control). Retention was 90% at 12 weeks and 84% at 24 weeks. Participants had a median age of 55 years and were 66% female, 70% non-Hispanic white, and 96% had a college degree. The intervention arm responded to a median 15 (71%) of 21 text messages that asked for a reply [interquartile range (IQR) = 8, 19] and visited the website a median of 13 (15%) days (IQR = 1, 33) of the 84 study days. CONCLUSIONS: We developed a Web-based dietary intervention for colorectal cancer survivors. Our pilot results suggest that colorectal cancer survivors may engage more with text messages than a study website. Research to improve tailoring of text messages, while maintaining scalability, is needed. IMPACT: Remote dietary interventions using text messages may be feasible for colorectal cancer survivors.See all articles in this CEBP Focus section, "Modernizing Population Science."

Cancer-associated mutations in human pyruvate kinase M2 impair enzyme activity.

Mammalian pyruvate kinase catalyzes the final step of glycolysis, and its M2 isoform (PKM2) is widely expressed in proliferative tissues. Mutations in PKM2 are found in some human cancers; however, the effects of these mutations on enzyme activity and regulation are unknown. Here, we characterized five cancer-associated PKM2 mutations, occurring at various locations on the enzyme, with respect to substrate kinetics and activation by the allosteric activator fructose-1,6-bisphosphate (FBP). The mutants exhibit reduced maximal velocity, reduced substrate affinity, and/or altered activation by FBP. The kinetic parameters of five additional PKM2 mutants that have been used to study enzyme function or regulation also demonstrate the deleterious effects of mutations on PKM2 function. Our findings indicate that PKM2 is sensitive to many amino acid changes and support the hypothesis that decreased PKM2 activity is selected for in rapidly proliferating cells.

Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies.

Mitochondrial apoptosis can be effectively targeted in lymphoid malignancies with the FDA-approved B cell lymphoma 2 (BCL-2) inhibitor venetoclax, but resistance to this agent is emerging. We show that venetoclax resistance in chronic lymphocytic leukemia is associated with complex clonal shifts. To identify determinants of resistance, we conducted parallel genome-scale screens of the BCL-2-driven OCI-Ly1 lymphoma cell line after venetoclax exposure along with integrated expression profiling and functional characterization of drug-resistant and engineered cell lines. We identified regulators of lymphoid transcription and cellular energy metabolism as drivers of venetoclax resistance in addition to the known involvement by BCL-2 family members, which were confirmed in patient samples. Our data support the implementation of combinatorial therapy with metabolic modulators to address venetoclax resistance.

Aspects of the parent-child relationship and parent metabolic outcomes.

Much is known about the effect of parent-child relationships on child health; less is known about how parent-child relationships influence parent health. To assess the association between aspects of the parent-child relationship and parent metabolic outcomes, and whether these associations are moderated by parent gender. Five metabolic outcomes (systolic and diastolic blood pressure, heart rate, total cholesterol and glycated hemoglobin) were assessed among 261 parents (45.83 ± 5.50 years) of an adolescent child (14.57 ± 1.072 years). Parents completed questionnaires assessing their child's hassles and the quality of their days with their child. Parents' perceptions of their child's hassles were associated with parent heart rate (B = 2.954, SE = 1.267, p = 0.021) and cholesterol (B = 0.028, SE = 0.011, p = 0.010), such that greater perceived child hassles were associated with higher heart rate and cholesterol levels, on average. These associations were not moderated by parent gender (all ps > 0.30). Parent report of their day with their child was not associated with parent metabolic outcomes (all ps > 0.20). Parent gender moderated the association between parent report of their day with their child and parent systolic blood pressure (B = 13.861, SE = 6.200, p = 0.026), such that less positive reports were associated with higher blood pressure readings among fathers, but not mothers. This study suggests that parent metabolic health may in part be influenced by aspects of the parent-child relationship.

Accurate detection of atrial fibrillation and atrial flutter using the electrocardiomatrix technique.

BACKGROUND: Atrial fibrillation (AFIB) and atrial flutter (AFL) are two common cardiac arrhythmias that predispose patients to serious medical conditions. There is a need to accurately detect these arrhythmias to prevent diseases and reduce mortality. Apart from accurately detecting these arrhythmias, it is also important to distinguish between AFIB and AFL due to differing clinical treatments. METHODS: In this study, we applied a new technology, the electrocardiomatrix (ECM) invented in our lab, in detecting AFIB and AFL in human patients. ECM converts 2D ECG signals into a 3D color matrix, which renders arrhythmia detection intuitive, fast, and accurate. Using ECM, we analyzed the ECG signals from the online MIT-BIH Atrial Fibrillation Database (PhysioNet), and compared our ECM-based results to manual annotations based on ECG by physicians. RESULTS: Results demonstrate that ECM and PhysioNet annotations of AFIB and AFL agree more than 99% of the time. The sensitivities of the ECM for AFIB and AFL detection were 99.2% and 98.0%, respectively, and the specificities of the ECM for AFIB and AFL were both at 99.8% and 99.8%. CONCLUSIONS: This study demonstrates that ECM is a reliable method for accurate identification of AFIB and AFL.

The Role of Pyruvate Kinase M2 in Cancer Metabolism.

The M2 isoform of pyruvate kinase is expressed preferentially in cancer cells over other pyruvate kinase isoforms. PKM2 is unique in its ability to be regulated allosterically by nutrients and growth signaling pathways, allowing cells to adapt their metabolic program to match physiological needs in different environments. Here, we discuss the role of pyruvate kinase M2 in glioma and in cancer metabolism.