The effect of protein or amino acid provision on immobilization-induced muscle atrophy in healthy adults: A systematic review and meta-analysis.

Bed rest and limb immobilization are models of muscle disuse associated with skeletal muscle atrophy and reduced strength. The purpose of this systematic review was to examine the impact of protein or amino acid provision before and/or during a period of muscle disuse on muscle atrophy (primary outcome), strength and muscle protein synthesis (secondary outcomes) following a disuse period. We performed a systematic review of Embase, MEDLINE, Web of Science, PubMed and Clinical Trials in December 2022. Eligible studies were randomized controlled trials that combined a dietary protein or amino acid intervention versus control during an experimental model of disuse (bed rest or unilateral limb immobilization) in healthy individuals aged ≥18 years. Nine articles from eight independent trials were identified and rated for risk of bias by two authors. A meta-analysis of muscle mass data revealed no effect (standardized mean difference: 0.2; 95% confidence interval: -0.18 to 0.57, P = 0.31) of protein/amino acid intervention in preventing disuse-induced muscle atrophy. Although the meta-analysis was not conducted on strength or muscle protein synthesis data, there was insufficient evidence in the reviewed articles to support the use of protein/amino acid provision in mitigating the disuse-induced decline in either outcome measurement. Additional high-quality studies, including the reporting of randomization procedures and blinding procedures and the provision of statistical analysis plans, might be required to determine whether protein or amino acid provision serves as an effective strategy to attenuate muscle atrophy during periods of disuse.

The effect of combined ß-lactoglobulin supplementation and resistance exercise training prior to limb immobilisation on muscle protein synthesis rates in healthy young adults: study protocol for a randomised controlled trial.

BACKGROUND: The decline in skeletal muscle mass experienced following a short-term period (days to weeks) of muscle disuse is mediated by impaired rates of muscle protein synthesis (MPS). Previous RCTs of exercise or nutrition prehabilitation interventions designed to mitigate disuse-induced muscle atrophy have reported limited efficacy. Hence, the aim of this study is to investigate the impact of a complex prehabilitation intervention that combines ß-lactoglobulin (a novel milk protein with a high leucine content) supplementation with resistance exercise training on disuse-induced changes in free-living integrated rates of MPS in healthy, young adults. METHODS/DESIGN: To address this aim, we will recruit 24 healthy young (18-45 years) males and females to conduct a parallel, double-blind, 2-arm, randomised placebo-controlled trial. The intervention group will combine a 7-day structured resistance exercise training programme with thrice daily dietary supplementation with 23 g of ß-lactoglobulin. The placebo group will combine the same training programme with an energy-matched carbohydrate (dextrose) control. The study protocol will last 16 days for each participant. Day 1 will be a familiarisation session and days 2-4 will be the baseline period. Days 5-11 represent the 'prehabilitation period' whereby participants will combine resistance training with their assigned dietary supplementation regimen. Days 12-16 represent the muscle disuse-induced 'immobilisation period' whereby participants will have a single leg immobilised in a brace and continue their assigned dietary supplementation regimen only (i.e. no resistance training). The primary endpoint of this study is the measurement of free-living integrated rates of MPS using deuterium oxide tracer methodology. Measurements of MPS will be calculated at baseline, over the 7-day prehabilitation period and over the 5-day immobilisation period separately. Secondary endpoints include measurements of muscle mass and strength that will be collected on days 4 (baseline), 11 (end of prehabilitation) and 16 (end of immobilisation). DISCUSSION: This novel study will establish the impact of a bimodal prehabilitation strategy that combines ß-lactoglobulin supplementation and resistance exercise training in modulating MPS following a short-term period of muscle disuse. If successful, this complex intervention may be translated to clinical practice with application to patients scheduled to undergo, for example, hip or knee replacement surgery. TRIAL REGISTRATION: NCT05496452. Registered on August 10, 2022. PROTOCOL VERSION: 16-12-2022/1.

Chronic almond nut snacking alleviates perceived muscle soreness following downhill running but does not improve indices of cardiometabolic health in mildly overweight, middle-aged, adults.

Introduction: As a popular food snack rich in protein, fiber, unsaturated fatty acids, antioxidants and phytonutrients, almond nut consumption is widely associated with improvements in cardiometabolic health. However, limited data exists regarding the role of almond consumption in improving exercise recovery. Accordingly, we aimed to investigate the impact of chronic almond snacking on muscle damage and cardiometabolic health outcomes during acute eccentric exercise recovery in mildly overweight, middle-aged, adults. Methods: Using a randomized cross-over design, 25 mildly overweight (BMI: 25.8 ± 3.6 kg/m2), middle-aged (35.1 ± 4.7 y) males (n = 11) and females (n = 14) performed a 30-min downhill treadmill run after 8-weeks of consuming either 57 g/day of whole almonds (ALMOND) or an isocaloric amount (86 g/day) of unsalted pretzels (CONTROL). Muscle soreness (visual analogue scale), muscle function (vertical jump and maximal isokinetic torque) and blood markers of muscle damage (creatine kinase (CK) concentration) and inflammation (c-reactive protein concentration) were measured pre and post (24, 48, and 72 h) exercise. Blood biomarkers of cardiometabolic health (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol), body composition and psycho-social assessments of mood (POMS-2 inventory), appetite and well-being were measured pre and post intervention. Results: Downhill running successfully elicited muscle damage, as evidenced by a significant increase in plasma CK concentration, increased perception of muscle soreness, and impaired vertical jump performance (all p < 0.05) during acute recovery. No effect of trial order was observed for any outcome measurement. However, expressed as AUC over the cumulative 72 h recovery period, muscle soreness measured during a physical task (vertical jump) was reduced by ~24% in ALMOND vs. CONTROL (p < 0.05) and translated to an improved maintenance of vertical jump performance (p < 0.05). However, ALMOND did not ameliorate the CK response to exercise or isokinetic torque during leg extension and leg flexion (p > 0.05). No pre-post intervention changes in assessments of cardiometabolic health, body composition, mood state or appetite were observed in ALMOND or CONTROL (all p > 0.05). Conclusion: Chronic almond supplementation alleviates task-specific perceived feelings of muscle soreness during acute recovery from muscle damaging exercise, resulting in the better maintenance of muscle functional capacity. These data suggest that almonds represent a functional food snack to improve exercise tolerance in mildly overweight, middle-aged adults.

Head and Neck Soft Tissue Sarcomas Treated with Radiation Therapy.

Head and neck soft tissue sarcomas (HNSTSs) are rare and heterogeneous cancers in which radiation therapy (RT) has an important role in local tumor control (LC). The purpose of this study was to evaluate outcomes and patterns of treatment failure in patients with HNSTS treated with RT. A retrospective review was performed of adult patients with HNSTS treated with RT from January 1, 1998, to December 31, 2012. LC, locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and predictors thereof were assessed. Forty-eight patients with HNSTS were evaluated. Five-year Kaplan-Meier estimates of LC, LRC, DFS, and OS were 87, 73, 63, and 83%, respectively. Angiosarcomas were found to be associated with worse LC, LRC, DFS, and OS. Patients over the age of 60 had lower rates of DFS. HNSTSs comprise a diverse group of tumors that can be managed with various treatment regimens involving RT. Angiosarcomas have higher recurrence and mortality rates.

Once-daily radiation therapy for inflammatory breast cancer.

PURPOSE: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. METHODS AND MATERIALS: A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof were assessed. RESULTS: Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). CONCLUSIONS: Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC, particularly among these subsets of patients.

The rare cancer network: ongoing studies and future strategy.

The Rare Cancer Network (RCN) was formed in the early 1990's to create a global network that could pool knowledge and resources in the studies of rare malignancies whose infrequency prevented both their study with prospective clinical trials. To date, the RCN has initiated 74 studies resulting in 46 peer reviewed publications. The First International Symposium of the Rare Cancer Network took place in Nice in March of 2014. Status updates and proposals for new studies were heard for fifteen topics. Ongoing studies continue for cardiac sarcomas, thyroid cancers, glomus tumors, and adult medulloblastomas. New proposals were presented at the symposium for primary hepatic lymphoma, solitary fibrous tumors, Rosai-Dorfman disease, tumors of the ampulla of Vater, salivary gland tumors, anorectal melanoma, midline nuclear protein in testes carcinoma, pulmonary lymphoepithelioma-like carcinoma, adenoid cystic carcinoma of the trachea, osteosarcomas of the mandible, and extra-cranial hemangiopericytoma. This manuscript presents the abstracts of those proposals and updates on ongoing studies, as well a brief summary of the vision and future of the RCN.

Pharmacological interventions to treat or prevent neurocognitive decline after brain radiation.

After surgery, radiation is the most effective treatment for the majority of brain tumors in both children and adults. Although improvements in radiotherapy delivery and targeting have resulted in reduction in neurologic morbidity, radiotherapy is still associated with acute and late toxicities that are dependent on a variety of treatment- and patient-specific variables. Variables of treatment include radiation dose, fractionation, volume, technique, photons or protons, and concomitant or adjuvant chemotherapy. Patient- and tumor-specific variables include tumor type, location and patient age. Side effects of treatment are also variable and can range from mild fatigue to significant memory difficulties and even death. This review will focus on the hypothesized mechanisms of cognitive dysfunction after radiation therapy and will discuss possible intervention strategies including behavioral and pharmacological prevention and treatment.

Late tumor pseudoprogression followed by complete remission after lung stereotactic ablative radiotherapy.

Lung stereotactic ablative radiotherapy (SABR) has recently become more common in the management of patients with early-stage non-small cell lung cancer (NSCLC) and metastatic lung lesions who are not surgical candidates. By design, SABR is applied to small treatment volumes, using fewer but significantly higher dose fractions, and steep dose gradients. This treatment theoretically maximizes tumor cell death and decreases the risk of damage to the surrounding normal tissues. Local control rates for SABR in early stage lung cancer remain high. Since the numbers of primary tumor recurrences is small, some debate exists as to the appropriate definition of treatment failure. Controversies remain regarding the most appropriate interpretation of imaging tests obtained to evaluate treatment outcomes after lung SABR. Most definitions of progression include an increasing diameter of target lesion which can be problematic given the known mass-like consolidation seen on CT imaging after ablative therapy. Here, we present a case report illustrative of the pitfalls of relying solely on anatomic imaging to determine SABR treatment failure.