Oral digoxin effects on exercise performance, K+ regulation and skeletal muscle Na+ ,K+ -ATPase in healthy humans.

We investigated whether digoxin lowered muscle Na+ ,K+ -ATPase (NKA), impaired muscle performance and exacerbated exercise K+ disturbances. Ten healthy adults ingested digoxin (0.25 mg; DIG) or placebo (CON) for 14 days and performed quadriceps strength and fatiguability, finger flexion (FF, 105%peak-workrate , 3 × 1 min, fourth bout to fatigue) and leg cycling (LC, 10 min at 33% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ and 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ , 90% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ to fatigue) trials using a double-blind, crossover, randomised, counter-balanced design. Arterial (a) and antecubital venous (v) blood was sampled (FF, LC) and muscle biopsied (LC, rest, 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ , fatigue, 3 h after exercise). In DIG, in resting muscle, [3 H]-ouabain binding site content (OB-Fab ) was unchanged; however, bound-digoxin removal with Digibind revealed total ouabain binding (OB+Fab ) increased (8.2%, P = 0.047), indicating 7.6% NKA-digoxin occupancy. Quadriceps muscle strength declined in DIG (-4.3%, P = 0.010) but fatiguability was unchanged. During LC, in DIG (main effects), time to fatigue and [K+ ]a were unchanged, whilst [K+ ]v was lower (P = 0.042) and [K+ ]a-v greater (P = 0.004) than in CON; with exercise (main effects), muscle OB-Fab was increased at 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ (per wet-weight, P = 0.005; per protein P = 0.001) and at fatigue (per protein, P = 0.003), whilst [K+ ]a , [K+ ]v and [K+ ]a-v were each increased at fatigue (P = 0.001). During FF, in DIG (main effects), time to fatigue, [K+ ]a , [K+ ]v and [K+ ]a-v were unchanged; with exercise (main effects), plasma [K+ ]a , [K+ ]v , [K+ ]a-v and muscle K+ efflux were all increased at fatigue (P = 0.001). Thus, muscle strength declined, but functional muscle NKA content was preserved during DIG, despite elevated plasma digoxin and muscle NKA-digoxin occupancy, with K+ disturbances and fatiguability unchanged. KEY POINTS: The Na+ ,K+ -ATPase (NKA) is vital in regulating skeletal muscle extracellular potassium concentration ([K+ ]), excitability and plasma [K+ ] and thereby also in modulating fatigue during intense contractions. NKA is inhibited by digoxin, which in cardiac patients lowers muscle functional NKA content ([3 H]-ouabain binding) and exacerbates K+ disturbances during exercise. In healthy adults, we found that digoxin at clinical levels surprisingly did not reduce functional muscle NKA content, whilst digoxin removal by Digibind antibody revealed an ∼8% increased muscle total NKA content. Accordingly, digoxin did not exacerbate arterial plasma [K+ ] disturbances or worsen fatigue during intense exercise, although quadriceps muscle strength was reduced. Thus, digoxin treatment in healthy participants elevated serum digoxin, but muscle functional NKA content was preserved, whilst K+ disturbances and fatigue with intense exercise were unchanged. This resilience to digoxin NKA inhibition is consistent with the importance of NKA in preserving K+ regulation and muscle function.

High-intensity training elicits greater improvements in cardio-metabolic and reproductive outcomes than moderate-intensity training in women with polycystic ovary syndrome: a randomized clinical trial.

STUDY QUESTION: Does 12 weeks of high-intensity interval training (HIIT) result in greater improvements in cardio-metabolic and reproductive outcomes compared to standard moderate-intensity continuous training (MICT) in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: HIIT offers greater improvements in aerobic capacity, insulin sensitivity and menstrual cyclicity, and larger reductions in hyperandrogenism compared to MICT. WHAT IS KNOWN ALREADY: Exercise training is recognized to improve clinical outcomes in women with PCOS, but little is known about whether HIIT results in greater health outcomes compared to standard MICT. STUDY DESIGN, SIZE, DURATION: This was a two-armed randomized clinical trial enrolling a total of 29 overweight women with PCOS between May 2016 and November 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS aged 18-45 years were randomly assigned to 12 weeks of either MICT (60-75% peak heart rate, N = 14) or HIIT (>90% peak heart rate, N = 15), each completed three times per week. The primary clinical outcomes were aerobic capacity (VO2peak) and insulin sensitivity (euglycaemic-hyperinsulinaemic clamp). Secondary outcomes included hormonal profiles, menstrual cyclicity and body composition. MAIN RESULTS AND THE ROLE OF CHANCE: Both HIIT and MICT improved VO2peak (HIIT; Δ 5.8 ± 2.6 ml/kg/min, P < 0.001 and MICT; Δ 3.2 ± 2 ml/kg/min, P < 0.001), however, the HIIT group had a greater improvement in aerobic capacity compared to MICT (ß = 2.73 ml/kg/min, P = 0.015). HIIT increased the insulin sensitivity index compared to baseline (Δ 2.3 ± 4.4 AU, P = 0.007) and MICT (ß = 0.36 AU, P = 0.030), and caused higher increases in sex hormone-binding globulin compared to MICT (ß = 0.25 nmol/l, P = 0.002). HIIT participants were 7.8 times more likely to report improved menstrual cyclicity than those in the MICT group (odds ratio 7.8, P = 0.04). LIMITATIONS, REASONS FOR CAUTION: This study has a small sample size and the findings of the effect of the exercise interventions are limited to overweight reproductive-aged women, who do not have any co-existing co-morbidities that require medication. WIDER IMPLICATIONS OF THE FINDINGS: Exercise, regardless of intensity, has clear health benefits for women with PCOS. HIIT appears to be a more beneficial strategy and should be considered for promoting health and reducing cardio-metabolic risk in overweight women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a Project Support Grant from the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in PCOS. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: ACTRN12615000242527. TRIAL REGISTRATION DATE: 19 February 2015. DATE OF FIRST PATIENT'S ENROLMENT: 27 May 2016.

Interpretation of exercise-induced changes in human skeletal muscle mRNA expression depends on the timing of the post-exercise biopsies.

BACKGROUND: Exercise elicits a range of adaptive responses in skeletal muscle, which include changes in mRNA expression. To better understand the health benefits of exercise training, it is important to investigate the underlying molecular mechanisms of skeletal muscle adaptation to exercise. However, most studies have assessed the molecular events at only a few time-points within a short time frame post-exercise, and the variations of gene expression kinetics have not been addressed systematically. METHODS: We assessed the mRNA expression of 23 gene isoforms implicated in the adaptive response to exercise at six time-points (0, 3, 9, 24, 48, and 72 h post exercise) over a 3-day period following a single session of high-intensity interval exercise. RESULTS: The temporal patterns of target gene expression were highly variable and the expression of mRNA transcripts detected was largely dependent on the timing of muscle sampling. The largest fold change in mRNA expression of each tested target gene was observed between 3 and 72 h post-exercise. DISCUSSION AND CONCLUSIONS: Our findings highlight an important gap in knowledge regarding the molecular response to exercise, where the use of limited time-points within a short period post-exercise has led to an incomplete understanding of the molecular response to exercise. Muscle sampling timing for individual studies needs to be carefully chosen based on existing literature and preliminary analysis of the molecular targets of interest. We propose that a comprehensive time-course analysis on the exercise-induced transcriptional response in humans will significantly benefit the field of exercise molecular biology.

Individual physiological and mitochondrial responses during 12 weeks of intensified exercise.

AIM: Observed effects of exercise are highly variable between individuals, and subject-by-training interaction (i.e., individual response variability) is often not estimated. Here, we measured mitochondrial (citrate synthetase, cytochrome-c oxidase, succinate dehydrogenase, and mitochondrial copy-number), performance markers (Wpeak , lactate threshold [LT], and VO2peak ), and fiber type proportions/expression (type I, type IIa, and type IIx) in multiple time points during 12-week of high-intensity interval training (HIIT) to investigate effects of exercise at the individual level. METHODS: Sixteen young (age: 33.1 ± 9.0 years), healthy men (VO2peak 35-60 ml/min/kg and BMI: 26.4 ± 4.2) from the Gene SMART study completed 12-week of progressive HIIT. Performance markers and muscle biopsies were collected every 4 weeks. We used mixed-models and bivariate growth models to quantify individual response and to estimate correlations between variables. RESULTS: All performance markers exhibited significant (Wpeak 0.56 ± 0.33 p = 0.003, LT 0.37 ± 0.35 p = 0.007, VO2peak 3.81 ± 6.13 p = 0.02) increases overtime, with subject-by-training interaction being present (95% CI: Wpeak 0.09-0.24, LT 0.06-0.18, VO2peak 0.27-2.32). All other measurements did not exhibit significant changes. Fiber type IIa proportions at baseline was significantly associated with all physiological variables (p < 0.05), and citrate synthetase and cytochrome-c oxidase levels at baseline and overtime (i.e., intercept and slope) presented significant covariance (p < 0.05). Finally, low correlations between performance and mitochondrial markers were observed. CONCLUSION: We identified a significant subject-by-training interaction for the performance markers. While for all other measures within-subject variability was too large and interindividual differences in training efficacy could not be verified. Changes in measurements in response to exercise were not correlated, and such disconnection should be further investigated by future studies.

The Effects of an Acute "Train-Low" Nutritional Protocol on Markers of Recovery Optimization in Endurance-Trained Male Athletes.

PURPOSE: This study aimed to determine the effects of an acute "train-low" nutritional protocol on markers of recovery optimization compared to standard recovery nutrition protocol. METHODS: After completing a 2-hour high-intensity interval running protocol, 8 male endurance athletes consumed a standard dairy milk recovery beverage (CHO; 1.2 g/kg body mass [BM] of carbohydrate and 0.4 g/kg BM of protein) and a low-carbohydrate (L-CHO; isovolumetric with 0.35 g/kg BM of carbohydrate and 0.5 g/kg BM of protein) dairy milk beverage in a double-blind randomized crossover design. Venous blood and breath samples, nude BM, body water, and gastrointestinal symptom measurements were collected preexercise and during recovery. Muscle biopsy was performed at 0 hour and 2 hours of recovery. Participants returned to the laboratory the following morning to measure energy substrate oxidation and perform a 1-hour distance test. RESULTS: The exercise protocol resulted in depletion of muscle glycogen stores (250 mmol/kg dry weight) and mild body-water losses (BM loss = 1.8%). Neither recovery beverage replenished muscle glycogen stores (279 mmol/kg dry weight) or prevented a decrease in bacterially stimulated neutrophil function (-21%). Both recovery beverages increased phosphorylation of mTORSer2448 (main effect of time = P < .001) and returned hydration status to baseline. A greater fold increase in p-GSK-3ßSer9/total-GSK-3ß occurred on CHO (P = .012). Blood glucose (P = .005) and insulin (P = .012) responses were significantly greater on CHO (618 mmol/L per 2 h and 3507 µIU/mL per 2 h, respectively) compared to L-CHO (559 mmol/L per 2 h and 1147 µIU/mL per 2 h, respectively). Rates of total fat oxidation were greater on CHO, but performance was not affected. CONCLUSION: A lower-carbohydrate recovery beverage consumed after exercise in a "train-low" nutritional protocol does not negatively impact recovery optimization outcomes.

Recurrent primary hyperparathyroidism: a diagnostic and management dilemma.

SUMMARY: Primary hyperparathyroidism requires a surgical approach to achieve a long-term cure. However, post-surgical recurrence significantly complicates the management of this condition. A number of causes for recurrent disease are well understood and several diagnostic modalities exist to localise the culprit parathyroid adenoma although none of them is efficacious in localisation of the recurrent lesion. In this case report, we highlight a novel causative mechanism and describe a unique diagnostic sequence that enabled curative treatment to be delivered. LEARNING POINTS: In the case described herein, we describe a novel location for a parathyroid adenoma causing recurrent PHPT. The case elucidates well the difficulties presented by such cases in terms of surgical planning and show the utility of PVS in such cases. Based on this case, we make the following recommendations: Meticulous care must be taken to prevent seeding of adenomatous tissue during primary excision. To consider the use of PVS in patients with discordant imaging in the setting of recurrent/persistent PHPT as a method to localise the causative adenoma. Same day PVS and surgery is a viable option for patients who either represent an anaesthetic risk or who are extremely anxious about the prospect of two separate procedures. Disordered calcium homeostasis is an important but forgotten cause of dysphagia which can be extremely debilitating for affected patients.

Resistance training upregulates skeletal muscle Na+, K+-ATPase content, with elevations in both α1 and α2, but not ß isoforms.

PURPOSE: The Na+, K+-ATPase (NKA) is important in regulating trans-membrane ion gradients, cellular excitability and muscle function. We investigated the effects of resistance training in healthy young adults on the adaptability of NKA content and of the specific α and ß isoforms in human skeletal muscle. METHODS: Twenty-one healthy young males (22.9 ± 4.6 year; 1.80 ± 0.70 m, 85.1 ± 17.8 kg, mean ± SD) underwent 7 weeks of resistance training, training three times per week (RT, n = 16) or control (CON, n = 5). The training program was effective with a 39% gain in leg press muscle strength (p = 0.001). A resting vastus lateralis muscle biopsy was taken before and following RT or CON and assayed for NKA content ([3H]ouabain binding site content) and NKA isoform (α1, α2, ß1, ß2) abundances. RESULTS: After RT, each of NKA content (12%, 311 ± 76 vs 349 ± 76 pmol g wet weight-1, p = 0.01), NKA α1 (32%, p = 0.01) and α2 (10%, p < 0.01) isoforms were increased, whereas ß1 (p = 0.18) and ß2 (p = 0.22) isoforms were unchanged. NKA content and isoform abundances were unchanged during CON. CONCLUSIONS: Resistance training increased muscle NKA content through upregulation of both α1 and α2 isoforms, which were independent of ß isoform changes. In animal models, modulations in α1 and α2 isoform abundances in skeletal muscle may affect fatigue resistance during exercise, muscle hypertrophy and strength. Whether similar in-vivo functional benefits of these NKA isoform adaptations occurs in human muscle with resistance training remains to be determined.

Meta-analysis of direct surgical versus endovascular revascularization for aortoiliac occlusive disease.

OBJECTIVE: There is a paucity of good-quality evidence comparing direct surgical (DS) with endovascular/hybrid (EVH) revascularization for aortoiliac occlusive disease (AIOD). We aimed to perform a meta-analysis of studies comparing DS and EVH revascularization for AIOD. METHODS: PubMed, Ovid MEDLINE, Cochrane, and Embase databases were searched for studies comparing DS and EVH revascularization for AIOD from 2000 to 2018. Risk of bias assessment was performed using the Methodological Index for Non-Randomized Studies. Demographics, clinical presentation, and comorbidities of the two groups were compared. Kaplan-Meier curves from selected studies were digitized with WebPlotDigitizer. Meta-analysis was conducted using Review Manager, and outcome measures were compared. Subgroup analysis was performed for primary patency in the EVH group. RESULTS: Eleven observational studies were identified comparing a sample of 4030 patients. The median Methodological Index for Non-Randomized Studies score was 19 of 24. A total of 1679 and 2351 patients underwent DS and EVH techniques, respectively. No significant difference was found between means for sex, claudication, rest pain, tissue loss, preoperative ankle-brachial pressure index, and TransAtlantic Inter-Society Consensus C and D lesions in the two groups averaged across studies. However, the DS group had significantly younger patients (average age, 61.83 vs 66.77; P = .0011). The risk factors of the two groups, such as smoking, diabetes, ischemic heart disease, hypertension, hyperlipidemia, renal failure, and chronic lung disease, were comparable. Average hospital stay was significantly higher for the DS group (7.76 days vs 3.12 days; P = .025). Change in ankle-brachial pressure index, 30-day mortality, and 30-day graft/stent thrombosis were not significantly different for the groups. Overall, primary patency for a median follow-up of 50 months favored the DS group (hazard ratio [HR], 0.51; confidence interval [CI], 0.36-0.73; P = .0002). There was moderate heterogeneity among studies (I2 = 46%). The HR for the subgroup for which endovascular procedures were combined with common femoral endarterectomy was 0.43 compared with 0.88 for endovascular revascularization alone. Limb salvage was similar in both groups (HR, 1.10; CI, 0.74-1.64; P = .63), but overall survival after the procedure favored the DS group (HR, 0.75; CI, 0.60-0.94; P = .01; I2 = 0%). CONCLUSIONS: Moderate-quality studies showed that DS revascularization had significantly better primary patency than EVH revascularization for AIOD, although DS patients were younger and may have differed on other confounding variables. Both techniques had similar limb salvage rates, and the primary patency was better for endovascular revascularization combined with common femoral endarterectomy than for endovascular revascularization alone.

Artery Ligation for Infected Femoral Pseudoaneurysms Does Carry a High Risk of Major Amputation.

BACKGROUND: Arterial ligation has been described in the literature as a safe and effective procedure with a relatively low number of patients requiring major amputations. METHODS: We performed a retrospective analysis of a prospectively held database of all patients who underwent arterial ligation for infected femoral pseudoaneurysms due to chronic intravenous drug abuse from January 2012 to March 2018. Information recorded for each patient included age, gender, blood investigations, microbiologic results, diagnostic modality, operative details, outcome of surgery, postoperative complications, and follow-up. RESULTS: There were 25 patients identified, with 2 of them undergoing bilateral ligations. It was more common in men (4:1), and the mean age at presentation was 39.7 years (standard deviation 8.2 y). Nine patients underwent major limb amputation for severe limb ischemia (7 transfemoral amputations and two 53 hip disarticulation). Average hospital stay was 24 days, and there was no mortality. We found a trend with a higher level of arterial ligation, leading to a higher rate of amputation. CONCLUSIONS: Our study is the first to show that there is a trend toward a higher risk of amputation with a higher level of ligation in this cohort of patients, and therefore, we suggest avoidance of external iliac artery ligation even at the most distal part just under the ligament, leaving the circumflex iliac vessel in circuit. Arterial ligation also carries a higher risk of major amputation than previously reported.

Short-term Mortality, Morbidity and Recovery Milestones after Major Lower Limb Amputation: a Prospective Evaluation of Outcomes in a Tertiary Center.

BACKGROUND: Major lower limb amputation (MLLA) is well recognized to carry a high rate of mortality; however, little evidence explores the reasons for this. Even fewer studies look at other outcomes after MLLA such as major morbidity and functional and social recovery. This study aims to provide a contemporary analysis of these outcomes to contextualize the current state of care for MLLA in the United Kingdom. METHODS: All index MLLAs conducted in a single tertiary vascular center over a 1-year period were entered into the study. Data including demographic details, preoperative biochemical markers, and functional and social status were collected by a multidisciplinary team . Postoperative functional recovery milestones, and mortality and major morbidity data were collected prospectively from the date of amputation. Descriptive, univariate and multivariate analysis was used to present the results. RESULTS: Seventy-nine amputations were performed. The median total length of stay was 28.0 days (interquartile range [IQR] 14.0-48.0), and postoperative length was 18.0 days (IQR 9.5-36.0). Thirty-day mortality was 5.1% (n = 4), and 90-day mortality was 8.9% (n = 7). Thirty-day major morbidity was 32.4% (n = 24). After controlling for age and gender, preoperative serum white cell count was an independent predictor of 30-day mortality (odds ratio [OR] 1.375 [95% confidence interval [CI] 1.080-1.751]), 90-day mortality (OR 1.258 [95% CI 1.078-1.469]), and 30-day major morbidity (OR 1.228 [95% CI 1.070-1.409]. The proportion of the population living independently reduced from 56.7% to 13.7%, with 23.3% requiring further rehabilitation. The number needing either social care at home or permanent care placement rose by 12.8%. CONCLUSIONS: MLLA carries clinically significant risk of short-term mortality and morbidity. The only factor found to be consistently influential was preoperative serum white cell count. MLLA requires a significant in-hospital stay, and there is a significant deterioration in functional and social status after discharge from hospital.

Influence of Perioperative Serum Magnesium for Cardiac and Noncardiac Morbidity and Mortality Following Emergency Peripheral Vascular Surgery.

OBJECTIVES: To examine the influence of serum magnesium on 30-day mortality and cardiac and noncardiac morbidity. DESIGN: Retrospective cross-sectional observational study of routinely collected prospective data. SETTING: Single-center tertiary vascular center in the United Kingdom. PARTICIPANTS: All patients undergoing arterial peripheral vascular surgery during an unplanned admission. INTERVENTIONS: Observational, no interventions implemented. MEASUREMENTS AND MAIN RESULTS: In the study, n = 197. One hundred thirty-eight were male (70.1%). Median age at procedure was 70.0 years (interquartile range 20.0). Of those with a documented history, 37.9% had diabetes, 81.7% had a smoking history, 63.7% had hypertension, and 26.5% had known ischemic heart disease or heart failure. There was a significant perioperative change in magnesium (p < 0.001), calcium (p < 0.001), and creatinine (p = 0.004), with no significant alteration in potassium (p = 0.096). Thirty-day mortality was 4.6%. Thirty-day cardiac morbidity was 4.1%. Thirty-day noncardiac morbidity was 32.3%. Postoperative magnesium was independently predictive for 30-day mortality (p = 0.02, odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94-0.99) and cardiac morbidity (p = 0.03, OR 0.97, 95% CI 0.95-1.00). Only a previous smoking history was independently predictive of noncardiac morbidity (p = 0.03, OR 9.67, 95% CI 1.20-78.15). CONCLUSION: Perioperative changes in serum magnesium may have an influence on short-term mortality and cardiac complications. This should be considered in the management of patients undergoing unplanned peripheral vascular surgery; however, further research is needed to examine the benefit of supplementation perioperatively and to explore the exact mechanisms.

No evidence of direct association between GLUT4 and glycogen in human skeletal muscle.

Previous studies have demonstrated that exercise increases whole body and skeletal muscle insulin sensitivity that is linked with increased GLUT4 at the plasma membrane following insulin stimulation and associated with muscle glycogen depletion. To assess the potential direct association between muscle glycogen and GLUT4, seven untrained, male subjects exercised for 60 min at ~75% VO2 peak, with muscle samples obtained by percutaneous needle biopsy immediately before and after exercise. Exercise reduced muscle glycogen content by ~43%. An ultracentrifugation protocol resulted in a ~2-3-fold enriched glycogen fraction from muscle samples for analysis. Total GLUT4 content was unaltered by exercise and we were unable to detect any GLUT4 in glycogen fractions, either with or without amylase treatment. In skinned muscle fiber segments, there was very little, if any, GLUT4 detected in wash solutions, except following exposure to 1% Triton X-100. Amylase treatment of single fibers did not increase GLUT4 in the wash solution and there were no differences in GLUT4 content between fibers obtained before or after exercise for any of the wash treatments. Our results indicate no direct association between GLUT4 and glycogen in human skeletal muscle, before or after exercise, and suggest that alterations in GLUT4 translocation associated with exercise-induced muscle glycogen depletion are mediated via other mechanisms.

The role of compression after endovenous ablation of varicose veins.

OBJECTIVE: The aim of this review was to identify the evidence regarding the optimal duration of compression therapy after endovenous ablation of varicose veins. METHODS: Electronic databases were searched for studies assessing the use of compression after endovenous ablation in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The primary outcomes for this study were pain score and complications. Secondary outcomes were time to full recovery, quality of life score, leg circumference, bruising score, and compliance rates. RESULTS: Following strict inclusion and exclusion criteria, five studies were included in our review, including a total of 734 patients. The short-duration compression therapy ranged from 4 hours to 2 days, whereas the longer duration ranged from 3 to 15 days. A single study showed a better outcome in terms of complications with a short compression therapy. A single study showed a benefit to pain and quality of life with extended compression therapy, whereas the others did not. There was no significant difference in terms of bruising, recovery time, and leg swelling. CONCLUSIONS: Our review showed that there is no evidence for the extended use of compression after endovenous ablation of varicose veins.

Actin alpha cardiac muscle 1 gene expression is upregulated in the skeletal muscle of men undergoing androgen deprivation therapy for prostate cancer.

Androgen deprivation therapy (ADT) decreases muscle mass and function but no human studies have investigated the underlying genetic or cellular effects. We tested the hypothesis that ADT will lead to changes in skeletal muscle gene expression, which may explain the adverse muscle phenotype seen clinically. We conducted a prospective cohort study of 9 men with localised prostate cancer who underwent a vastus lateralis biopsy before and after 4 weeks of ADT. Next-generation RNA sequencing was performed and genes differentially expressed following ADT underwent gene ontology mining using Ingenuity Pathway Analysis. Differential expression of genes of interest was confirmed by quantitative PCR (Q-PCR) on gastrocnemius muscle of orchidectomised mice and sham controls (n=11/group). We found that in men, circulating total testosterone decreased from 16.5±4.3nmol/L at baseline to 0.4±0.15nmol/L post-ADT (p<0.001). RNA sequencing identified 19 differentially expressed genes post-ADT (all p<0.05 after adjusting for multiple testing). Gene ontology mining identified 8 genes to be of particular interest due to known roles in androgen-mediated signalling; ABCG1, ACTC1, ANKRD1, DMPK, THY1, DCLK1, CST3 were upregulated and SLC38A3 was downregulated post-ADT. Q-PCR in mouse gastrocnemius muscle confirmed that only one gene, Actc1 was concordantly upregulated (p<0.01) in orchidectomised mice compared with controls. In conclusion, given that ACTC1 upregulation is associated with improved muscle function in certain myopathies, we hypothesise that upregulation of ACTC1 may represent a compensatory response to ADT-induced muscle loss. Further studies will be required to evaluate the role and function of ACTC1.

Isolated Peripheral Nerve Palsies in Thoracic Outlet Syndrome.

Thoracic outlet syndrome (TOS) poses a difficult diagnostic entity with varied etiology and clinical presentation. We present a 35-year-old gentleman with unilateral long thoracic nerve palsy and contralateral subscapular paralysis caused by aberrant scalenus medius anatomy. TOS ought to be considered in patients presenting with isolated nerve palsies.

Bony morphology of the hip in professional ballet dancers compared to athletes.

OBJECTIVES: To compare hip bony morphology between ballet dancers and a sporting control group and to determine the relationship with hip pain. METHODS: Thirty-three professional ballet dancers and 33 age- and sex-matched athletes completed questionnaires, including the Copenhagen Hip and Groin Outcome Score (HAGOS), and underwent clinical testing and 3.0-T magnetic resonance imaging to measure acetabular coverage with lateral centre edge angles, femoral head-neck junction concavity with alpha angles at anterior and superior positions, femoral neck-shaft angles, and acetabular version angles. RESULTS: Bony morphological measures fell within normal ranges. Dancers had higher neck-shaft angles (dancers 134.6 ± 4.6°/athletes130.8 ± 4.7°, p = 0.002), lower acetabular version angles (13.5 ± 4.7°/17.1 ± 4.7°, p = 0.003), lower superior alpha angles (38.9 ± 6.9°/46.7 ± 10.6°, p < 0.001), similar anterior alpha angles (43.6 ± 8.1/46 ± 7°, p = 0.2), and similar lateral centre edge angles (28.8 ± 4.6°/30.8 ± 4.5°, p = 0.07) compared to athletes. Abnormal morphology was detected in dancers: 3% acetabular dysplasia (athletes 0), 15% borderline dysplasia (6%), 24% cam morphology (33%), 24% coxa valga (6%), and 21% acetabular retroversion (18%). The HAGOS pain scores correlated moderately with acetabular version (r = -0.43, p = 0.02) in dancers, with no other correlation between pain and morphological parameters in either group. CONCLUSIONS: Professional ballet dancers have hip bony morphology that differentiates them from athletes. Hip pain correlated poorly with bony morphology. KEY POINTS: • Ballet dancers have hip bony morphology that may allow extreme hip motion. • Morphological parameter means fell within normal reference intervals in dancers. • Bony morphology correlates poorly with hip pain. • The risk of hip injury due to abnormal morphology requires prospective studies.

Erythropoietin Does Not Enhance Skeletal Muscle Protein Synthesis Following Exercise in Young and Older Adults.

PURPOSE: Erythropoietin (EPO) is a renal cytokine that is primarily involved in hematopoiesis while also playing a role in non-hematopoietic tissues expressing the EPO-receptor (EPOR). The EPOR is present in human skeletal muscle. In mouse skeletal muscle, EPO stimulation can activate the AKT serine/threonine kinase 1 (AKT) signaling pathway, the main positive regulator of muscle protein synthesis. We hypothesized that a single intravenous EPO injection combined with acute resistance exercise would have a synergistic effect on skeletal muscle protein synthesis via activation of the AKT pathway. METHODS: Ten young (24.2 ± 0.9 years) and 10 older (66.6 ± 1.1 years) healthy subjects received a primed, constant infusion of [ring-13C(6)] L-phenylalanine and a single injection of 10,000 IU epoetin-beta or placebo in a double-blind randomized, cross-over design. 2 h after the injection, the subjects completed an acute bout of leg extension resistance exercise to stimulate skeletal muscle protein synthesis. RESULTS: Significant interaction effects in the phosphorylation levels of the members of the AKT signaling pathway indicated a differential activation of protein synthesis signaling in older subjects when compared to young subjects. However, EPO offered no synergistic effect on vastus lateralis mixed muscle protein synthesis rate in young or older subjects. CONCLUSIONS: Despite its ability to activate the AKT pathway in skeletal muscle, an acute EPO injection had no additive or synergistic effect on the exercise-induced activation of muscle protein synthesis or muscle protein synthesis signaling pathways.

Cerebral oxygenation monitoring in patients with bilateral carotid stenosis undergoing urgent cardiac surgery: Observational case series.

BACKGROUND: Patients with significant bilateral carotid artery stenosis requiring urgent cardiac surgery have an increased risk of stroke and death. The optimal management strategy remains inconclusive, and the available evidence does not support the superiority of one strategy over another. MATERIALS AND METHODS: A number of noninvasive strategies have been developed for minimizing perioperative stroke including continuous real-time monitoring of cerebral oxygenation with near-infrared spectroscopy (NIRS). The number of patients presenting with this combination (bilateral significant carotid stenosis requiring urgent cardiac surgery) in any single institution will be small and hence there is a lack of large randomized studies. RESULTS: This case series describes our early experience with NIRS in a select group of patients with significant bilateral carotid stenosis undergoing urgent cardiac surgery (n = 8). In contrast to other studies, this series is a single surgeon, single center study, where the entire surgery (both distal ends and proximal ends) was performed during single aortic clamp technique, which effectively removes several confounding variables. NIRS monitoring led to the early recognition of decreased cerebral oxygenation, and corrective steps (increased cardiopulmonary bypass flow, increased pCO 2 , etc.,) were taken. CONCLUSION: The study shows good clinical outcome with the use of NIRS. This is our "work in progress," and we aim to conduct a larger study.

A new technique to explant an infected aortic endograft.

The management of an infected aortic endograft can be challenging both operatively and clinically. Although aortic endograft infection is rare, the incidence is likely to increase in the coming years because of ever rising numbers of endovascular aneurysm repairs. Definitive management involves the removal of the endograft through laparotomy. Removal of the graft is technically challenging; no manufacturer's device is available to assist in disengagement of barbed hooks that hold the endograft in position. We present a new technique using the disposable proctoscope as a device to facilitate safe removal of the endograft with minimal damage to the aortic wall.