Comparison of long-term outcomes of breast conservation and reconstruction after mastectomy using BREAST-Q.

AIMS: Patients' post-operative wellbeing determines the impact and effectiveness of breast reshaping and reconstruction procedures. The aim of the study was to evaluate and compare four different types of breast reconstruction: bilateral therapeutic mammaplasty, DIEP flap, ELD with immediate lipomodelling and implant-based reconstruction using BREAST-Q. METHODS: Patients who underwent breast reconstruction by one of the above-mentioned methods were identified from a retrospective register and sent BREAST-Q questionnaires. Univariate and multivariate analysis of BREAST-Q scores and clinical characteristics were performed for identifying trends between and within groups. RESULTS: A total of 240 patients were identified with a response rate of 57%. Patients receiving implants were statistically less satisfied with breast reconstruction (mean 57%) and tended to be younger with lower BMI in comparison to other groups. There were no statistical differences in psychosocial wellbeing or patient experience between groups. Despite the fact that clinically these groups were heterogeneous, satisfaction with breast was similar in the remaining three autologous groups (range 70-75%). Detailed analysis and interpretation of quality-of-life scores, clinical differences and trends identified in the multivariate analysis along with nuances between surgical techniques used in our unit for breast reshaping and reconstruction, have been performed. CONCLUSIONS: The most important goal of breast reconstruction is to restore patients' quality of life and satisfaction with breast. Identifying factors which can potentially predict poor outcomes will improve the informed consent process and patient selection.

The relationship between muscle protein content and CT-derived muscle radio-density in patients with upper GI cancer.

INTRODUCTION: Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle loss. Cross-sectional analysis of CT scans is a recognized research method for assessing skeletal muscle volume. However, little is known about the relationship between CT-derived estimates of muscle radio-density (SMD) and muscle protein content. We assessed the relationship between CT-derived body composition variables and the protein content of muscle biopsies from cancer patients. METHODS: Rectus abdominis biopsies from cancer patients (n = 32) were analysed for protein content and correlated with phenotypic data gathered using CT body composition software. RESULTS: Skeletal muscle protein content varied widely between patients (median µg/mg wet weight = 89.3, range 70-141). There was a weak positive correlation between muscle protein content and SMD (r = 0.406, p = 0.021), and a weak positive correlation between protein content and percentage weight change (r = 0.416, p = 0.018). CONCLUSION: The protein content of skeletal muscle varies widely in cancer patients and cannot be accurately predicted by CT-derived muscle radio-density.

Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia.

BACKGROUND: Sarcopenia is defined as the age-related loss of skeletal muscle mass and function. While all humans lose muscle with age, 2-5% of elderly adults develop functional consequences (disabilities). The aim of this study was to investigate muscle myogenesis in healthy elderly adults, with or without sarcopenia, compared with middle-aged controls using both in vivo and in vitro approaches to explore potential biomarker or causative molecular pathways associated with sarcopenic versus non-sarcopenic skeletal muscle phenotypes during ageing. METHODS: Biomarkers of multiple molecular pathways associated with muscle regeneration were analysed using quantitative polymerase chain reaction in quadriceps muscle samples obtained from healthy elderly sarcopenic (HSE, n = 7) or non-sarcopenic (HENS, n = 21) and healthy middle-aged control (HMC, n = 22) groups. An in vitro system of myogenesis (using myoblasts from human donors aged 17-83 years) was used to mimic the environmental challenges of muscle regeneration over time. RESULTS: The muscle biopsies showed evidence of satellite cell activation in HENS (Pax3, P < 0.01, Pax7, P < 0.0001) compared with HMC. Early myogenesis markers Myogenic Differentiation 1 (MyoD1) and Myogenic factor 5 (Myf5) (P < 0.0001) and the late myogenesis marker myogenin (MyoG) (P < 0.01) were increased in HENS. In addition, there was a 30-fold upregulation of TNF-α in HENS compared with HMC (P < 0.0001). The in vitro system demonstrated age-related upregulation of pro-inflammatory cytokines (2-fold upregulation of interleukin (IL)-6, IL-8 mRNA, increased secretion of tumor necrosis factor-α (TNF-α) and IL-6, all P < 0.05) associated with impaired kinetics of myotube differentiation. The HSE biopsy samples showed satellite cell activation (Pax7, P < 0.05) compared with HMC. However, no significant upregulation of the early myogenesis (MyoD and Myf5) markers was evident; only the late myogenesis marker myogenin was upregulated (P < 0.05). Higher activation of the oxidative stress pathway was found in HENS compared with the HSE group. In contrast, there was 10-fold higher upregulation of HSPA1A a stress-induced chaperone acting upon misfolded proteins in HSE compared with the HENS group. CONCLUSIONS: Both pathological and adaptive processes are active in skeletal muscle during healthy ageing. Muscle regeneration pathways are activated during healthy ageing, but there is evidence of dysregulation in sarcopenia. In addition, increased cellular stress, with an impaired oxidative-stress and mis-folded protein response (HSPA1A), may be associated with the development of sarcopenia. The in vitro system of young and old myoblasts replicated some of the differences between young and old muscle.

Current margin practice and effect on re-excision rates following the publication of the SSO-ASTRO consensus and ABS consensus guidelines: a national prospective study of 2858 women undergoing breast-conserving therapy in the UK and Ireland.

INTRODUCTION: There is variation in margin policy for breast conserving therapy (BCT) in the UK and Ireland. In response to the Society of Surgical Oncology and American Society for Radiation Oncology (SSO-ASTRO) margin consensus ('no ink on tumour' for invasive and 2 mm for ductal carcinoma in situ [DCIS]) and the Association of Breast Surgery (ABS) consensus (1 mm for invasive and DCIS), we report on current margin practice and unit infrastructure in the UK and Ireland and describe how these factors impact on re-excision rates. METHODS: A trainee collaborative-led multicentre prospective study was conducted in the UK and Ireland between 1st February and 31st May 2016. Data were collected on consecutive BCT patients and on local infrastructure and policies. RESULTS: A total of 79 sites participated in the data collection (75% screening units; average 372 cancers annually, range 70-900). For DCIS, 53.2% of units accept 1 mm and 38% accept 2-mm margins. For invasive disease 77.2% accept 1 mm and 13.9% accept 'no ink on tumour'. A total of 2858 patients underwent BCT with a mean re-excision rate of 17.2% across units (range 0-41%). The re-excision rate would be reduced to 15% if all units applied SSO-ASTRO guidelines and to 14.8% if all units followed ABS guidelines. Of those who required re-operation, 65% had disease present at margin. CONCLUSION: There continues to be large variation in margin policy and re-excision rates across units. Altering margin policies to follow either SSO-ASTRO or ABS guidelines would result in a modest reduction in the national re-excision rate. Most re-excisions are for involved margins rather than close margins.

A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer.

BACKGROUND: Cancer cachexia is a syndrome of weight loss (including muscle and fat), anorexia, and decreased physical function. It has been suggested that the optimal treatment for cachexia should be a multimodal intervention. The primary aim of this study was to examine the feasibility and safety of a multimodal intervention (n-3 polyunsaturated fatty acid nutritional supplements, exercise, and anti-inflammatory medication: celecoxib) for cancer cachexia in patients with incurable lung or pancreatic cancer, undergoing chemotherapy. METHODS: Patients receiving two cycles of standard chemotherapy were randomized to either the multimodal cachexia intervention or standard care. Primary outcome measures were feasibility assessed by recruitment, attrition, and compliance with intervention (>50% of components in >50% of patients). Key secondary outcomes were change in weight, muscle mass, physical activity, safety, and survival. RESULTS: Three hundred and ninety-nine were screened resulting in 46 patients recruited (11.5%). Twenty five patients were randomized to the treatment and 21 as controls. Forty-one completed the study (attrition rate 11%). Compliance to the individual components of the intervention was 76% for celecoxib, 60% for exercise, and 48% for nutritional supplements. As expected from the sample size, there was no statistically significant effect on physical activity or muscle mass. There were no intervention-related Serious Adverse Events and survival was similar between the groups. CONCLUSIONS: A multimodal cachexia intervention is feasible and safe in patients with incurable lung or pancreatic cancer; however, compliance to nutritional supplements was suboptimal. A phase III study is now underway to assess fully the effect of the intervention.

Comprehensive proteome analysis of human skeletal muscle in cachexia and sarcopenia: a pilot study.

BACKGROUND: Cancer cachexia (cancer-induced muscle wasting) is found in a subgroup of cancer patients leaving the patients with a poor prognosis for survival due to a lower tolerance of the chemotherapeutic drug. The cause of the muscle wasting in these patients is not fully understood, and no predictive biomarker exists to identify these patients early on. Skeletal muscle loss is an inevitable consequence of advancing age. As cancer frequently occurs in old age, identifying and differentiating the molecular mechanisms mediating muscle wasting in cancer cachexia vs. age-related sarcopenia are a challenge. However, the ability to distinguish between them is critical for early intervention, and simple measures of body weight may not be sufficiently sensitive to detect cachexia early. METHODS: We used a range of omics approaches: (i) undepleted proteome was quantified using advanced high mass accuracy mass spectrometers in SWATH-MS acquisition mode; (ii) phospho epitopes were quantified using protein arrays; and (iii) morphology was assessed using fluorescent microscopy. RESULTS: We quantified the soluble proteome of muscle biopsies from cancer cachexia patients and compared them with cohorts of cancer patients and healthy individuals with and without age-related muscle loss (aka age-related sarcopenia). Comparing the proteomes of these cohorts, we quantified changes in muscle contractile myosins and energy metabolism allowing for a clear identification of cachexia patients. In an in vitro time lapse experiment, we mimicked cancer cachexia and identified signal transduction pathways governing cell fusion to play a pivotal role in preventing muscle regeneration. CONCLUSIONS: The work presented here lays the foundation for further understanding of muscle wasting diseases and holds the promise of overcoming ambiguous weight loss as a measure for defining cachexia to be replaced by a precise protein signature.

New genetic signatures associated with cancer cachexia as defined by low skeletal muscle index and weight loss.

BACKGROUND: Cachexia affects the majority with advanced cancer. Based on current demographic and clinical factors, it is not possible to predict who will develop cachexia or not. Such variation may, in part, be due to genotype. It has recently been proposed to extend the diagnostic criteria for cachexia to include a direct measure of low skeletal muscle index (LSMI) in addition to weight loss (WL). We aimed to explore our panel of candidate single nucleotide polymorphism (SNPs) for association with WL +/- computerized tomography-defined LSMI. We also explored whether the transcription in muscle of identified genes was altered according to such cachexia phenotype METHODS: A retrospective cohort study design was used. Analysis explored associations of candidate SNPs with WL (n = 1276) and WL + LSMI (n = 943). Human muscle transcriptome (n = 134) was analysed using an Agilent platform. RESULTS: Single nucleotide polymorphisms in the following genes showed association with WL alone: GCKR, LEPR, SELP, ACVR2B, TLR4, FOXO3, IGF1, CPN1, APOE, FOXO1, and GHRL. SNPs in LEPR, ACVR2B, TNF, and ACE were associated with concurrent WL + LSMI. There was concordance between muscle-specific expression for ACVR2B, FOXO1 and 3, LEPR, GCKR, and TLR4 genes and LSMI and/or WL (P < 0.05). CONCLUSIONS: The rs1799964 in the TNF gene and rs4291 in the ACE gene are new associations when the definition of cachexia is based on a combination of WL and LSMI. These findings focus attention on pro-inflammatory cytokines and the renin-angiotensin system as biomarkers/mediators of muscle wasting in cachexia.

Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not in the healthy elderly.

Muscle wasting in old age or cancer may result from failed myofiber regeneration and/or accelerated atrophy. This study aimed to determine from transcriptomic analysis of human muscle the integrity of the cellular stress response system in relation to satellite cell differentiation or apoptosis in patients with cancer (weight-stable (CWS) or weight-losing (CWL)) or healthy elderly (HE) when compared with healthy middle-aged controls (HMA). 28 patients with cancer (CWS: 18 and CWL: 10), HE: 21 and HMA: 20 underwent biopsy of quadriceps muscle. The expression of transcription factors for muscle regeneration (Pax3, Pax7 and MyoD) was increased in CWS and HE compared with HMA (p≤0.001). In contrast, the expression of the late myogenic differentiation marker MyoG was reduced in CWS and CWL but increased in HE (p≤0.0001). Bax was significantly increased in CWS, CWL and HE (p≤0.0001). Expression of the oxidative defense genes SOD2, GCLM, and Nrf2 was decreased in CWS and CWL but increased in HE (p≤0.0001). There is evidence for blockade of satellite cell maturation, upregulation of apoptosis and reduced oxidative defense in the muscle of cancer patients. In the healthy elderly the potential for differentiation and oxidative defense is maintained.

Skeletal Muscle Changes After Elective Colorectal Cancer Resection: A Longitudinal Study.

BACKGROUND: Muscle depletion is a poor prognostic indicator in colorectal cancer (CRC) patients, but there were no data assessing comparative temporal body composition changes following elective CRC surgery. We examined patient skeletal muscle index trajectories over time after surgery and determined factors that may contribute to those alterations. METHODS: Patients diagnosed with CRC undergoing elective surgical resection between 2006 and 2013 were included in this study. Image analysis of serial computed tomography (CT) scans was used to calculate lumbar skeletal muscle index (LSMI). A multilevel mixed-effect linear regression model was applied using STATA (version 12.0) using the xtmixed command to fit growth curve models (GCM) for LSMI and time. RESULTS: In 856 patients, a total of 2136 CT images were analyzed; 856 (38.2 %) were preoperative. A quadratic GCM with random intercept and random slope for patients' LSMI was identified that demonstrated laparoscopy produces a positive change on the LSMI curve [estimate = 0.17 cm(2)/m(2), standard error (SE) 0.06 cm(2)/m(2); p = 0.03], whereas Union for International Cancer Control (UICC) stage III + IV disease contributed to a negative curve change (estimate = -0.19 cm(2)/m(2), SE 0.09 cm(2)/m(2); p = 0.03). Older age (p < 0.01), female gender (p < 0.01), higher American Society of Anesthesiologists (ASA) score (p < 0.01), and altered systemic inflammatory response [SIR] (p = 0.03) were factors significantly associated with lower values of LSMI over time. CONCLUSION: In patients undergoing CRC surgery, laparoscopy and the absence of a significantly elevated SIR favored preservation and restoration of skeletal muscle, postoperatively. These emerging data may permit the development of new treatment protocols whereby monitoring and modification of body composition has therapeutic potential.

Low Muscularity and Myosteatosis Is Related to the Host Systemic Inflammatory Response in Patients Undergoing Surgery for Colorectal Cancer.

OBJECTIVE: We examined the relationships between computed tomography (CT)-defined skeletal muscle parameters and the systemic inflammatory response (SIR) in patients with operable primary colorectal cancer (CRC). BACKGROUND: Muscle depletion is characterized by a reduced muscle mass (myopenia) and increased infiltration by inter- and intramuscular fat (myosteatosis). It is recognized as a poor prognostic indicator in patients with cancer, but the underlying factors remain unclear. METHODS: A total of 763 patients diagnosed with CRC undergoing elective surgical resection between 2006 and 2013 were included. Image analysis of CT scans was used to calculate Lumbar skeletal muscle index (LSMI), and mean muscle attenuation (MA). The SIR was quantified by the preoperative neutrophil to lymphocyte ratio (NLR) and albumin levels. Correlation and multivariate regression analysis was performed to identify independent relationships between patient SIR and muscle characteristics. RESULTS: Patients with NLR > 3 had significantly lower LSMI and lower MA than those with NLR < 3 [LSMI = 42.07 cmm vs 44.27 cmm (P = 0.002) and MA = 30.04 Hounsfield unit (HU) vs 28.36 HU (P = 0.016)]. Multivariate logistic regression analysis showed that high NLR [odds ratio (OR) = 1.78 (95% confidence interval [CI]: 1.29-2.45), P < 0.001] and low albumin [OR = 1.80 (95% CI: 1.17-2.74), P = 0.007] were independent predictors of reduced muscle mass. High NLR was significantly related with a low mean MA and hence myosteatosis [OR = 1.60 (95% CI: 1.03-2.49), P = 0.038]. CONCLUSIONS: These results highlight a direct association between myopenia, myosteatosis, and the host SIR in patients with operable CRC. A better understanding of factors that regulate muscle changes such as myopenia and myosteatosis may lead to the development of novel therapies that influence a more metabolically "healthy" skeletal muscle and potentially alter cancer outcomes.

Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia.

PURPOSE: Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity, and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in patients with cancer compared with healthy controls. EXPERIMENTAL DESIGN: An oral heavy water (87.5 g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine, and alanine in the myofibrillar component of muscle using gas chromatography-pyrolysis-isotope ratio mass spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown. RESULTS: Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (≥5% weight loss) patients undergoing surgery for upper gastrointestinal cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight-stable, and weight-losing patients, respectively. Weight-losing patients had higher synthetic rates than controls (P = 0.03). CONCLUSION: Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting.

Contemporary outcomes of open repair of thoracoabdominal aortic aneurysm in young patients.

BACKGROUND: Endovascular technology now permits total endovascular thoracoabdominal aortic aneurysm (TAAA) repair with high volume centres reporting encouraging results. The long-term durability of such stent grafts is unknown, leading to concerns regarding their use in younger patients. This study reports contemporary outcomes of open repair in young patients. METHODS: Outcomes for patients age 60 or younger undergoing open TAAA repair between June 1999 and August 2013 with prospective collected data were analysed retrospectively. RESULTS: Thirty-seven patients (31 men, 84%) with a median age of 56 (range 22-60) were identified with a median TAAA diameter of 6.9 cm (range 5.6-11). Aneurysm aetiology included degenerative change (18), dilation of chronic dissection (10), connective tissue disease (7) and mycotic degeneration (2). Crawford Type IV TAAA were most commonly treated (17), followed by Type II (10), Type III (7) and Type I (3). Two (5%) patients died in hospital, one from multiple organ failure and one from respiratory failure. Three patients (8%) developed temporary paraplegia, all of whom made a complete recovery and 4 (11%) patients required temporary renal replacement therapy. Median critical care stay was 5 days (range 2-28) with an in-hospital stay of 14 days (range 7-83). During a median follow-up of 72 months (range 13-171), no patient subsequently required any further aneurysm related surgical or radiological intervention. The mean (SEM) survival time was 138.5 (11) months. The 5 year survival was 79.7% (8.3) including early deaths, with no aneurysm related complications. CONCLUSIONS: The outcome of open TAAA repair in patients aged less than 60 years is favorable. It is against these results that evolving endovascular interventions must be compared.

Confirmed Bacillus anthracis infection among persons who inject drugs, Scotland, 2009-2010.

In Scotland, the 2009 outbreak of Bacillus anthracis infection among persons who inject drugs resulted in a 28% death rate. To compare nonsurvivors and survivors, we obtained data on 11 nonsurvivors and 16 survivors. Time from B. anthracis exposure to symptoms or hospitalization and skin and limb findings at presentation did not differ between nonsurvivors and survivors. Proportionately more nonsurvivors had histories of excessive alcohol use (p = 0.05) and required vasopressors and/or mechanical ventilation (p≤0.01 for each individually). Nonsurvivors also had higher sequential organ failure assessment scores (mean ± SEM) (7.3 ± 0.9 vs. 1.2 ± 0.4, p<0.0001). Antibacterial drug administration, surgery, and anthrax polyclonal immune globulin treatments did not differ between nonsurvivors and survivors. Of the 14 patients who required vasopressors during hospitalization, 11 died. Sequential organ failure assessment score or vasopressor requirement during hospitalization might identify patients with injectional anthrax for whom limited adjunctive therapies might be beneficial.

Evaluation of novel local anesthetic wound infiltration techniques for postoperative pain following colorectal resection surgery: a meta-analysis.

BACKGROUND: Novel local anesthetic blocks have become increasingly popular in the multimodal pain management following abdominal surgery, but have not been evaluated in a procedure-specific manner in colorectal surgery. OBJECTIVE: This study aims to evaluate the efficacy of novel local anesthetic techniques in colorectal surgery. DATA SOURCES: Electronic literature search of PubMed, EMBASE, and Cochrane databases (date range, January 1990 to February 2013) STUDY SELECTION: Randomized controlled trials comparing a novel local anesthetic technique with placebo/routine analgesia in adults undergoing open or laparoscopic colonic or rectal resection were selected. INTERVENTIONS: This is a meta-analysis of randomized controlled trials evaluating novel local anesthetic wound infiltration techniques such as wound catheter, transversus abdominis plane block, and intraperitoneal instillation in colorectal surgical procedures. The comparator group was defined as placebo/routine analgesia. OUTCOME MEASURES: The primary outcome was opiate requirement at 24 hours. Secondary outcomes included opiate requirements at 48 hours, pain numerical rating score at 24 and 48 hours at rest and on movement, recovery (length of stay, nausea and vomiting, time until bowel movement and diet resumption), and complications. Subgroup analysis was performed to evaluate specific local anesthetic techniques and open and laparoscopic surgery. RESULTS: Twelve randomized controlled trials compared local anesthetic techniques with placebo/routine analgesia. Local anesthetic techniques demonstrated a significant reduction in opiate requirement at 48 hours. Local anesthetic techniques were also associated with lower pain scores on movement at 24 and 48 hours, shorter length of stay, and earlier resumption of diet. LIMITATIONS: The diverse study design led to statistical heterogeneity in several analyses. CONCLUSIONS: Novel local anesthetic wound infiltration techniques in colorectal surgery appear to reduce opiate requirements, to reduce pain scores, and to improve recovery in comparison with placebo/routine analgesia.

Clinical classification of cancer cachexia: phenotypic correlates in human skeletal muscle.

BACKGROUND: Cachexia affects the majority of patients with advanced cancer and is associated with a reduction in treatment tolerance, response to therapy, and duration of survival. One impediment towards the effective treatment of cachexia is a validated classification system. METHODS: 41 patients with resectable upper gastrointestinal (GI) or pancreatic cancer underwent characterisation for cachexia based on weight-loss (WL) and/or low muscularity (LM). Four diagnostic criteria were used >5%WL, >10%WL, LM, and LM+>2%WL. All patients underwent biopsy of the rectus muscle. Analysis included immunohistochemistry for fibre size and type, protein and nucleic acid concentration, Western blots for markers of autophagy, SMAD signalling, and inflammation. FINDINGS: Compared with non-cachectic cancer patients, patients with LM or LM+>2%WL, mean muscle fibre diameter was reduced by about 25% (p = 0.02 and p = 0.001 respectively). No significant difference in fibre diameter was observed if patients had WL alone. Regardless of classification, there was no difference in fibre number or proportion of fibre type across all myosin heavy chain isoforms. Mean muscle protein content was reduced and the ratio of RNA/DNA decreased in patients with either >5%WL or LM+>2%WL. Compared with non-cachectic patients, SMAD3 protein levels were increased in patients with >5%WL (p = 0.022) and with >10%WL, beclin (p = 0.05) and ATG5 (p = 0.01) protein levels were increased. There were no differences in phospho-NFkB or phospho-STAT3 levels across any of the groups. CONCLUSION: Muscle fibre size, biochemical composition and pathway phenotype can vary according to whether the diagnostic criteria for cachexia are based on weight loss alone, a measure of low muscularity alone or a combination of the two. For intervention trials where the primary end-point is a change in muscle mass or function, use of combined diagnostic criteria may allow identification of a more homogeneous patient cohort, reduce the sample size required and enhance the time scale within which trials can be conducted.

Contemporary vascular smartphone medical applications.

BACKGROUND: Use of smartphones and medical mHealth applications (apps) within the clinical environment provides a potential means for delivering elements of vascular care. This article reviews the contemporary availability of apps specifically themed to major vascular diseases and the opportunities and concerns regarding their integration into practice. METHODS: Smartphone apps relating to major vascular diseases were identified from the app stores for the 6 most popular smartphone platforms, including iPhone, Android, Blackberry, Nokia, Windows, and Samsung. Search terms included peripheral artery (arterial) disease, varicose veins, aortic aneurysm, carotid artery disease, amputation, ulcers, hyperhydrosis, thoracic outlet syndrome, vascular malformation, and lymphatic disorders. RESULTS: Forty-nine vascular-themed apps were identified. Sixteen (33%) were free of charge. Fifteen apps (31%) had customer satisfaction ratings, but only 3 (6%) had greater than 100. Only 13 apps (27%) had documented medical professional involvement in their design or content. CONCLUSIONS: The integration of apps into the delivery of care has the potential to benefit vascular health care workers and patients. However, high-quality apps designed by clinicians with vascular expertise are currently lacking and represent an area of concern in the mHealth market. Improvement in the quality and reliability of these apps will require the development of robust regulation.

Muscle protein kinetics in cancer cachexia.

PURPOSE OF REVIEW: Skeletal muscle loss appears to be the most significant event in cancer cachexia and is associated with a poor outcome. The balance between mechanisms that control synthesis and degradation is fundamental when designing new therapies. This review aims to highlight the molecular mechanisms that are associated with protein kinetics. RECENT FINDINGS: The mechanisms that promote muscle synthesis have been explored in detail recently but moreover they have been the mechanisms behind degradation. Specific advances in cellular signalling molecules related to autophagy pathways including signal transducer and activators of transcription-3, activin type-2 receptor, TRAF6, and transcriptomic research have been given special attention in this review to highlight their roles in degradation and as potential targets for therapeutics. Ways to quantify muscle loss are badly needed for outcome measures; recent research using radiolabelled amino acids has also been discussed in this review. SUMMARY: Only by having an appreciation of the complex regulation of muscle protein synthesis and degradation, will potential new therapeutics be able to be developed. This review identifies known targets in molecular pathways of current interest, explores methods used to find novel genes which may be involved in muscle kinetics and also highlights ways in which muscle kinetics may be measured to assess the efficacy of such interventions.

Is tissue cross-talk important in cancer cachexia?

Recent work suggests molecular cross-talk between adipose tissue and muscle that occurs through adipokines and myokines. These molecules act in an endocrine fashion to play an intricate role in regulating body composition in both health and disease. Studies in exercise physiology have focused on the molecular cross-talk between adipose tissue and muscle that occurs through adipokines and myokines and on the role these molecules may play in chronic diseases. Similarly, integrative physiology in obesity and diabetes has long emphasised the importance of chronic inflammation, increased adipocyte lipolysis, and increased levels of circulating free fatty acids in the adipose-muscle cross-talk that contributes to lipotoxicity and insulin resistance in muscle. Cachexia affects the majority of patients with advanced cancer and is associated with a reduction in treatment tolerance, response to therapy, quality of life, and duration of survival. Although cachexia in patients with cancer is characterized by systemic inflammation, increased lipolysis, insulin resistance, and reduced physical activity, there has been little effort to manipulate the integrative physiology of adipose tissue and muscle tissue for therapeutic gain.