Optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test.

BACKGROUND: Many patients with low-stage cutaneous melanoma will experience tumor recurrence, metastasis, or death, and many higher staged patients will not. OBJECTIVE: To develop an algorithm by integrating the 31-gene expression profile test with clinicopathologic data for an optimized, personalized risk of recurrence (integrated 31 risk of recurrence [i31-ROR]) or death and use i31-ROR in conjunction with a previously validated algorithm for precise sentinel lymph node positivity risk estimates (i31-SLNB) for optimized treatment plan decisions. METHODS: Cox regression models for ROR were developed (n = 1581) and independently validated (n = 523) on a cohort with stage I-III melanoma. Using National Comprehensive Cancer Network cut points, i31-ROR performance was evaluated using the midpoint survival rates between patients with stage IIA and stage IIB disease as a risk threshold. RESULTS: Patients with a low-risk i31-ROR result had significantly higher 5-year recurrence-free survival (91% vs 45%, P < .001), distant metastasis-free survival (95% vs 53%, P < .001), and melanoma-specific survival (98% vs 73%, P < .001) than patients with a high-risk i31-ROR result. A combined i31-SLNB/ROR analysis identified 44% of patients who could forego sentinel lymph node biopsy while maintaining high survival rates (>98%) or were restratified as being at a higher or lower risk of recurrence or death. LIMITATIONS: Multicenter, retrospective study. CONCLUSION: Integrating clinicopathologic features with the 31-GEP optimizes patient risk stratification compared to clinicopathologic features alone.

Expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study.

OBJECTIVE: National Comprehensive Cancer Network (NCCN) guidelines for cutaneous melanoma (CM) recommend physicians consider increased surveillance for patients who typically have lower melanoma survival rates (stages IIB-IV as determined by the American Joint Committee on Cancer (AJCC), 8th edition). However, up to 15% of patients identified as having a low recurrence risk (stages I-IIA) experience disease recurrence, and some patients identified as having a high recurrence risk will not experience any recurrence. The 31-gene expression profile test (31-GEP) stratifies patient recurrence risk into low (Class 1) and high (Class 2) and has demonstrated risk-appropriate impact on disease management and clinical decisions. METHODS: Five-year plans for lab work, frequency of clinical visits, and imaging pre- and post-31-GEP test results were assessed for a cohort of 509 stage I-III patients following an interim subset analysis of 247 patients. RESULTS: After receiving 31-GEP results, 50.6% of patients had a change in management plans in at least one of the following categories-clinical visits, lab work, or surveillance imaging. The changes aligned with the risk predicted by the 31-GEP for 76.1% of patients with a Class 1 result and 78.7% of patients with a Class 2 result. A Class 1 31-GEP result was associated with changes toward low-intensity management recommendations, while a Class 2 result was associated with changes toward high-intensity management recommendations. CONCLUSION: The 31-GEP can stratify patient recurrence risk in patients with CM, and clinicians understand and apply the prognostic ability of the 31-GEP test to alter patient management in risk-appropriate directions.

When caught early, cancer of the skin can usually be removed, and patients have excellent chances of survival. However, some patients will have their cancer come back or spread to a new location in their body.The 31-gene expression profile (GEP) test measures the expression levels of 31 genes from an individual patient's tumor. A proprietary formula uses this information to identify the risk of recurrence or spread as low risk (Class 1) or high risk (Class 2). Cancers with low-risk 31-GEP scores have a lower chance of cancer recurrence or spread than patients with a high-risk score.In this study, we wanted to determine if doctors treated patients with low-risk scores differently from patients with high-risk scores. We found that doctors changed approximately half of patient treatment plans (doctor visits, lab work, or imaging to see if the cancer has come back) after learning the 31-GEP test results. Doctors usually planned less frequent follow-up visits for Class 1 results and more frequent follow up for Class 2 results.This study found doctors understand and make changes to their treatment plans based on the patient's 31-GEP test result.

Effects of Multi-ingredient Preworkout Supplements on Physical Performance, Cognitive Performance, Mood State, and Hormone Concentrations in Recreationally Active Men and Women.

ABSTRACT: Beckner, ME, Pihoker, AA, Darnell, ME, Beals, K, Lovalekar, M, Proessl, F, Flanagan, SD, Arciero, PJ, Nindl, BC, and Martin, BJ. Effects of multi-ingredient preworkout supplements on physical performance, cognitive performance, mood state, and hormone concentrations in recreationally active men and women. J Strength Cond Res 36(9): 2493-2501, 2022-Performance enhancement supplement research has primarily focused on the effectiveness of individual ingredients, rather than the combination. This study investigated the acute effects of 2 multi-ingredient preworkout supplements (MIPS), with beta-alanine and caffeine (BAC) and without (NBAC), compared with placebo (PLA) on anaerobic performance, endurance capacity, mood state, cognitive function, vascular function, and anabolic hormones. Thirty exercise-trained individuals (24.4 ± 4.9 years, 15 men and 15 women) completed a fatiguing exercise protocol on 3 separate occasions, 30 minutes after ingestion of BAC, NBAC, or PLA. Outcomes were analyzed using one-way or two-way repeated-measures analysis of variance, as appropriate (alpha = 0.05). Anaerobic power was greater when supplementing with NBAC (10.7 ± 1.2 W·kg -1 ) and BAC (10.8 ± 1.4 W·kg -1 ) compared with PLA (10.4 ± 1.2 W·kg -1 ) ( p = 0.014 and p = 0.022, respectively). BAC improved V̇ o2 peak time to exhaustion ( p = 0.006), accompanied by an increase in blood lactate accumulation ( p < 0.001), compared with PLA. Both NBAC and BAC demonstrated improved brachial artery diameter after workout ( p = 0.041 and p = 0.005, respectively), but PLA did not. L-arginine concentrations increased from baseline to postsupplement consumption of BAC ( p = 0.017). Reaction time significantly decreased after exercise for all supplements. There was no effect of supplement on mood states. Exercise-trained individuals looking to achieve modest improvements in power and endurance may benefit from consuming MIPS before exercise.

The effects of 16-weeks of prebiotic supplementation and aerobic exercise training on inflammatory markers, oxidative stress, uremic toxins, and the microbiota in pre-dialysis kidney patients: a randomized controlled trial-protocol paper.

BACKGROUND: Chronic kidney disease (CKD) is characterized by dysbiosis, elevated levels of uremic toxins, systemic inflammation, and increased markers of oxidative stress. These factors lead to an increased risk of cardiovascular disease (CVD) which is common among CKD patients. Supplementation with high amylose maize resistant starch type 2 (RS-2) can change the composition of the gut microbiota, and reduce markers of inflammation and oxidative stress in patients with end-stage renal disease. However, the impact of RS-2 supplementation has not been extensively studied in CKD patients not on dialysis. Aerobic exercise training lowers certain markers of inflammation in CKD patients. Whether combining aerobic training along with RS-2 supplementation has an additive effect on the aforementioned biomarkers in predialysis CKD patients has not been previously investigated. METHODS: The study is being conducted as a 16-week, double-blind, placebo controlled, parallel arm, randomized controlled trial. Sixty stage 3-4 CKD patients (ages of 30-75 years) are being randomized to one of four groups: RS-2 & usual care, RS-2 & aerobic exercise, placebo (cornstarch) & usual care and placebo & exercise. Patients attend four testing sessions: Two baseline (BL) sessions with follow up visits 8 (wk8) and 16 weeks (wk16) later. Fasting blood samples, resting brachial and central blood pressures, and arterial stiffness are collected at BL, wk8 and wk16. A stool sample is collected for analysis of microbial composition and peak oxygen uptake is assessed at BL and wk16. Blood samples will be assayed for p-cresyl sulphate and indoxyl sulphate, c-reactive protein, tumor necrosis factor α, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, malondialdehyde, 8-isoprostanes F2a, endothelin-1 and nitrate/nitrite. Following BL, subjects are randomized to their group. Individuals randomized to conditions involving exercise will attend three supervised moderate intensity (55-65% peak oxygen uptake) aerobic training sessions (treadmills, bikes or elliptical machine) per week for 16 weeks. DISCUSSION: This study has the potential to yield information about the effect of RS-2 supplementation on key biomarkers believed to impact upon the development of CVD in patients with CKD. We are examining whether there is an additive effect of exercise training and RS-2 supplementation on these key variables. TRIAL REGISTRATION: Clinicaltrials.gov Trial registration# NCT03689569 . 9/28/2018, retrospectively registered.

Green tea extract does not affect exogenous glucose appearance but reduces insulinemia with glucose ingestion in exercise recovery.

We reported that supplementation with green tea extract (GTE) lowered the glycemic response to an oral glucose load following exercise, but via an unknown mechanism (Martin BJ, MacInnis MJ, Gillen JB, Skelly LE, Gibala MJ. Appl Physiol Nutr Metab 41: 1057-1063, 2016. Here we examined the effect of supplementation with GTE on plasma glucose kinetics on ingestion of a glucose beverage during exercise recovery. Eleven healthy, sedentary men (21 ± 2 yr old; body mass index = 23 ± 4 kg/m2, peak O2 uptake = 38 ± 7 ml·kg-1·min-1; means ± SD) ingested GTE (350 mg) or placebo (PLA) thrice daily for 7 days in a double-blind, crossover design. In the fasted state, a primed constant infusion of [U-13C6]glucose was started, and 1 h later, subjects performed a graded exercise test (25 W/3 min) on a cycle ergometer. Immediately postexercise, subjects ingested a 75-g glucose beverage containing 2 g of [6,6-2H2]glucose, and blood samples were collected every 10 min for 3 h of recovery. The rate of carbohydrate oxidation was lower during exercise after GTE vs. PLA (1.26 ± 0.34 vs. 1.48 ± 0.51 g/min, P = 0.04). Glucose area under the curve (AUC) was not different between treatments after drink ingestion (GTE = 1,067 ± 133 vs. PLA = 1,052 ± 91 mM/180 min, P = 0.91). Insulin AUC was lower after GTE vs. PLA (5,673 ± 2,153 vs. 7,039 ± 2,588 µIU/180 min, P = 0.05), despite similar rates of glucose appearance (GTE = 0.42 ± 0.16 vs. PLA = 0.43 ± 0.13 g/min, P = 0.74) and disappearance (GTE = 0.43 ± 0.14 vs. PLA = 0.44 ± 0.14 g/min, P = 0.57). We conclude that short-term GTE supplementation did not affect glucose kinetics following ingestion of an oral glucose load postexercise; however, GTE was associated with attenuated insulinemia. These findings suggest GTE lowers the insulin required for a given glucose load during postexercise recovery, which warrants further mechanistic studies in humans.

National physical activity recommendations: systematic overview and analysis of the situation in European countries.

BACKGROUND: Developing national physical activity (PA) recommendations is an essential element of an effective national approach to promote PA. METHODS: Systematic overview and analysis of national PA recommendations across the European Region of the World Health Organization (WHO). The WHO European national information focal points provided information which was complemented through online searches and input from other experts. RESULTS: Information received until summer 2012 from 37 countries was analyzed. Sixteen countries did not have national recommendations while 21 countries did. For 17 countries, the source document was accessible. Seventeen recommendations referred to adults, 14 to young people and 6 to older adults. Most national recommendations for children and young people are quite similar: 12 countries recommend at least 60 minutes of moderate- to vigorous-intensity PA each day, in line with the WHO global recommendation. Three countries recommend longer durations and one a lower one. In some countries, slight variations were found regarding the recommended intensity and minimum bouts. Only one country was fully in line with the WHO recommendations. Two countries have issued separate recommendations for pre-school children. For adults, most countries still follow the 1995 United States recommendations of "at least 30 minutes on 5 days a week". Three countries were fully in line with the WHO recommendations. Four countries give specific recommendations on reducing weight, avoiding weight gain or continuing weight maintenance. The six identified national PA recommendations for older adults are mainly similar to those for adults but underline that particularly for this age group also less activity has important health benefits; four countries also recommend balance training. CONCLUSIONS: About half of the countries for which information was available and likely less than 40% of all 53 countries in the WHO European Region have developed national PA recommendations. Further investment is needed to address this important step towards a comprehensive PA promotion approach. Much remains to be done for the 2010 WHO recommendations to be fully reflected in national documents across all parts of the Region and all age groups. In addition, avoiding extended periods of inactivity and overweight are only addressed by a minority of countries yet.

Oral manifestations of hyperparathyroidism secondary to familial hypophosphatemic rickets.

A 14-year-old male with familial hypophosphatemic rickets, being treated with oral phosphate and calcitriol therapy, presented to the Division of Pediatric Dentistry, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pa. A panoramic radiograph showed multifocal, multilocular lesions in the mandible leading to surgical exploration and biopsy. Histopathological evaluation of the largest lesion showed features consistent with central giant cell granuloma. Given the patient's history, hyperparathyroidism was suspected. Laboratory data showed an elevated parathyroid hormone of 152 pg/ml (normal range equals nine to 69). This confirmed the diagnosis of multiple brown tumors in the mandible associated with secondary hyperparathyroidism, which was attributed to high-dose phosphate treatment. After endocrinology consultation, calcitriol therapy was increased. Improvement of the patient's brown tumors is expected with medical therapy. The purpose of this case report was to raise awareness among pediatric dentists about the maxillofacial ramifications of secondary hyperparathyroidism.

No effect of short-term green tea extract supplementation on metabolism at rest or during exercise in the fed state.

UNLABELLED: Supplementation with green tea extract (GTE) in animals has been reported to induce numerous metabolic adaptations including increased fat oxidation during exercise and improved performance. However, data regarding the metabolic and physiological effects of GTE during exercise in humans are limited and equivocal. PURPOSE: To examine the effects of short-term GTE treatment on resting energy expenditure (REE), wholebody substrate utilization during exercise and time trial performance. METHODS: Fifteen active men (24 ± 3 y; VO(2)peak = 48 ± 7 ml · kg · min(-1); BMI = 26 ± 3 kg · m(2)((-1))) ingested GTE (3x per day = 1,000 mg/d) or placebo (PLA) for 2 day in a double-blind, crossover design (each separated by a 1 week wash-out period). REE was assessed in the fasted state. Subjects then ingested a standardized breakfast (~5.0 kcal · kg(-1)) and 90 min later performed a 60 min cycling bout at an intensity corresponding to individual maximal fat oxidation (44 ± 11% VO(2)peak), followed by a 250 kJ TT. RESULTS: REE, whole-body oxygen consumption (VO2) and substrate oxidation rates during steady-state exercise were not different between treatments. However, mean heart rate (HR) was lower in GTE vs. PLA (115 ± 16 vs. 118 ± 17 beats · min(-1); main effect, p = .049). Mixed venous blood [glycerol] was higher during rest and exercise after GTE vs. PLA (p = .006, main effect for treatment) but glucose, insulin and free-fatty acids were not different. Subsequent time trial performance was not different between treatments (GTE = 25:38 ± 5:32 vs. PLA = 26:08 ± 8:13 min; p = .75). CONCLUSION: GTE had minimal effects on whole-body substrate metabolism but significantly increased plasma glycerol and lowered heart rate during steady-state exercise, suggesting a potential increase in lipolysis and a cardiovascular effect that warrants further investigation.