Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma.

BACKGROUND: Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines. OBJECTIVE: We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma. METHODS: IgE to 112 allergenic molecules (components, c-sIgE) was measured using multiplex array among 509 adults and 140 school-age and 131 preschool children with asthma/wheeze from the Unbiased BIOmarkers for the PREDiction of respiratory diseases outcomes cohort, of whom 595 had severe disease. We applied clustering methods to identify co-occurrence patterns of components (component clusters) and patterns of sensitization among participants (sensitization clusters). Network analysis techniques explored the connectivity structure of c-sIgE, and differential network analysis looked for differences in c-sIgE interactions between severe and mild/moderate asthma. RESULTS: Four sensitization clusters were identified, but with no difference between disease severity groups. Similarly, component clusters were not associated with asthma severity. None of the c-sIgE were identified as associates of severe asthma. The key difference between school children and adults with mild/moderate compared with those with severe asthma was in the network of connections between c-sIgE. Participants with severe asthma had higher connectivity among components, but these connections were weaker. The mild/moderate network had fewer connections, but the connections were stronger. Connectivity between components with no structural homology tended to co-occur among participants with severe asthma. Results were independent from the different sample sizes of mild/moderate and severe groups. CONCLUSIONS: The patterns of interactions between IgE to multiple allergenic proteins are predictors of asthma severity among school children and adults with allergic asthma.

Prevalence estimates and risk factors for early childhood wheeze across Europe: the EuroPrevall birth cohort.

BACKGROUND: Preschool wheeze is an important problem worldwide. No comparative population-based studies covering different countries have previously been undertaken. OBJECTIVE: To assess the prevalence of early childhood wheeze across Europe and evaluate risk factors focusing on food allergy, breast feeding and smoke exposure. METHODS: Infants from nine countries were recruited into the EuroPrevall birth cohort. At 12 and 24 months, data on wheeze, allergic signs/symptoms, feeding, smoke exposure, infections and day care attendance were collected using questionnaires. Poisson regression was used to assess risk factors for wheeze. RESULTS: 12 049 infants were recruited. Data from the second year of life were available in 8805 (73.1%). The prevalence of wheeze in the second year of life ranged from <2% in Lodz (Poland) and Vilnius (Lithuania) to 13.1% (95% CI 10.7% to 15.5%) in Southampton (UK) and 17.2% (95% CI 15.0% 19.5%) in Reykjavik (Iceland). In multivariable analysis, frequent lower respiratory tract infections in the first and second years of life (incidence rate ratio (IRR) 1.9 (95% CI 1.3 to 2.6) and 2.5 (95% CI 1.9 to3.4), respectively), postnatal maternal smoking (IRR 1.6, 95% CI 1.1 to 2.4), day care attendance (IRR 1.6, 95% CI 1.1 to 2.5) and male gender (IRR 1.3, 95% CI 1.0 to 1.7) were associated with wheeze. The strength of their association with wheeze differed between countries. Food allergy and breast feeding were not independently associated with wheeze. CONCLUSION: The prevalence of early childhood wheeze varied considerably across Europe. Lower respiratory tract infections, day care attendance, postnatal smoke exposure and male gender are important risk factors. Further research is needed to identify additional modifiable risk factors that may differ between countries.

Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression.

Statins are associated with muscle myalgia and myopathy, which probably reduce habitual physical activity. This is particularly relevant to older people who are less active, sarcopaenic and at increased risk of statin myalgia. We hypothesised that statin myalgia would be allied to impaired strength and work capacity in older people, and determined whether differences aligned with divergences in lean mass, protein turnover, insulin sensitivity and the molecular regulation of these processes. Knee extensor strength and work output during 30 maximal isokinetic contractions were assessed in healthy male volunteers, nine with no statin use (control 70.4 ± 0.7 years) and nine with statin myalgia (71.5 ± 0.9 years). Whole body and leg glucose disposal, muscle myofibrillar protein synthesis (MPS) and leg protein breakdown (LPB) were measured during fasting (≈5 mU l(-1) insulin) and fed (≈40 mU l(-1) insulin + hyperaminoacidaemia) euglyceamic clamps. Muscle biopsies were taken before and after each clamp. Lean mass, MPS, LPB and strength were not different but work output during the initial three isokinetic contractions was 19% lower (P < 0.05) in statin myalgic subjects due to a delay in time to reach peak power output. Statin myalgic subjects had reduced whole body (P = 0.05) and leg (P < 0.01) glucose disposal, greater abdominal adiposity (P < 0.05) and differential expression of 33 muscle mRNAs (5% false discovery rate (FDR)), six of which, linked to mitochondrial dysfunction and apoptosis, increased at 1% FDR. Statin myalgia was associated with impaired muscle function, increased abdominal adiposity, whole body and leg insulin resistance, and evidence of mitochondrial dysfunction and apoptosis.

The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts.

U-BIOPRED aims to characterise paediatric and adult severe asthma using conventional and innovative systems biology approaches. A total of 99 school-age children with severe asthma and 81 preschoolers with severe wheeze were compared with 49 school-age children with mild/moderate asthma and 53 preschoolers with mild/moderate wheeze in a cross-sectional study. Despite high-dose treatment, the severe cohorts had more severe exacerbations compared with the mild/moderate ones (annual medians: school-aged 3.0 versus 1.1, preschool 3.9 versus 1.8; p<0.001). Exhaled tobacco exposure was common in the severe wheeze cohort. Almost all participants in each cohort were atopic and had a normal body mass index. Asthma-related quality of life, as assessed by the Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), was worse in the severe cohorts (mean±se school-age PAQLQ: 4.77±0.15 versus 5.80±0.19; preschool PACQLQ: 4.27±0.18 versus 6.04±0.18; both p≤0.001); however, mild/moderate cohorts also had significant morbidity. Impaired quality of life was associated with poor control and airway obstruction. Otherwise, the severe and mild/moderate cohorts were clinically very similar. Children with severe preschool wheeze or severe asthma are usually atopic and have impaired quality of life that is associated with poor control and airflow limitation: a very different phenotype from adult severe asthma. In-depth phenotyping of these children, integrating clinical data with high-dimensional biomarkers, may help to improve and tailor their clinical management.

Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions.

Skeletal muscle anabolism associated with postprandial plasma aminoacidemia and insulinemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this study, we hypothesized that increasing muscle microvascular blood volume (flow) would enhance fed-state anabolic responses in muscle protein turnover. We studied 10 young men (23.2 ± 2.1 yr) under postabsorptive and fed [iv Glamin (∼10 g AA), glucose ∼7.5 mmol/l] conditions. Methacholine was infused into the femoral artery of one leg to determine, via bilateral comparison, the effects of feeding alone vs. feeding plus pharmacological vasodilation. We measured leg blood flow (LBF; femoral artery) by Doppler ultrasound, muscle microvascular blood volume (MBV) by contrast-enhanced ultrasound (CEUS), muscle protein synthesis (MPS) and breakdown (MPB; a-v balance modeling), and net protein balance (NPB) using [1,2-(13)C2]leucine and [(2)H5]phenylalanine tracers via gas chromatography-mass spectrometry (GC-MS). Indexes of anabolic signaling/endothelial activation (e.g., Akt/mTORC1/NOS) were assessed using immunoblotting techniques. Under fed conditions, LBF (+12 ± 5%, P < 0.05), MBV (+25 ± 10%, P < 0.05), and MPS (+129 ± 33%, P < 0.05) increased. Infusion of methacholine further enhanced LBF (+126 ± 12%, P < 0.05) and MBV (+79 ± 30%, P < 0.05). Despite these radically different blood flow conditions, neither increases in MPS in response to feeding (0.04 ± 0.004 vs. 0.08 ± 0.01%/h, P < 0.05) nor improvements in NPB (-4.4 ± 2.4 vs. 16.4 ± 5.7 nmol Phe·100 ml leg(-1)·min(-1), P < 0.05) were affected by methacholine infusion (MPS 0.07 ± 0.01%/h; NPB 24.0 ± 7.7 nmol Phe·100 ml leg(-1)·min(-1)), whereas MPB was unaltered by either feeding or infusion of methacholine. Thus, enhancing LBF/MBV above that occurring naturally with feeding alone does not improve muscle anabolism.

Flexor Injury Rehabilitation Splint Trial (FIRST): protocol for a pragmatic randomised controlled trial comparing three splints for finger flexor tendon repairs.

BACKGROUND: Without surgical repair, flexor tendon injuries do not heal and patients' ability to bend fingers and grip objects is impaired. However, flexor tendon repair surgery also requires optimal rehabilitation. There are currently three custom-made splints used in the rehabilitation of zone I/II flexor tendon repairs, each with different assumed harm/benefit profiles: the dorsal forearm and hand-based splint (long), the Manchester short splint (short), and the relative motion flexion splint (mini). There is, however, no robust evidence as to which splint, if any, is most clinical or cost effective. The Flexor Injury Rehabilitation Splint Trial (FIRST) was designed to address this evidence gap. METHODS: FIRST is a parallel group, superiority, analyst-blind, multi-centre, individual participant-randomised controlled trial. Participants will be assigned 1:1:1 to receive either the long, short, or mini splint. We aim to recruit 429 participants undergoing rehabilitation following zone I/II flexor tendon repair surgery. Potential participants will initially be identified prior to surgery, in NHS hand clinics across the UK, and consented and randomised at their splint fitting appointment post-surgery. The primary outcome will be the mean post-randomisation score on the patient-reported wrist and hand evaluation measure (PRWHE), assessed at 6, 12, 26, and 52 weeks post randomisation. Secondary outcome measures include blinded grip strength and active range of movement (AROM) assessments, adverse events, adherence to the splinting protocol (measured via temperature sensors inserted into the splints), quality of life assessment, and further patient-reported outcomes. An economic evaluation will assess the cost-effectiveness of each splint, and a qualitative sub-study will evaluate participants' preferences for, and experiences of wearing, the splints. Furthermore, a mediation analysis will determine the relationship between patient preferences, splint adherence, and splint effectiveness. DISCUSSION: FIRST will compare the three splints with respect to clinical efficacy, complications, quality of life and cost-effectiveness. FIRST is a pragmatic trial which will recruit from 26 NHS sites to allow findings to be generalisable to current clinical practice in the UK. It will also provide significant insights into patient experiences of splint wear and how adherence to splinting may impact outcomes. TRIAL REGISTRATION: ISRCTN: 10236011.

Role of overnight oximetry in assessing the severity of obstructive sleep apnoea in typically developing children: a multicentre study.

BACKGROUND AND OBJECTIVE: Cardiorespiratory polygraphy (CRP) is the predominant technology used to diagnose obstructive sleep apnoea (OSA) in tertiary centres in the UK. Nocturnal pulse oximetry (NPO) is, however, cheaper and more accessible. This study evaluated the ability of NPO indices to predict OSA in typically developing (TD) children. METHODS: Indices from simultaneous NPO and CRP recordings were compared in TD children (aged 1-16 years) referred to evaluate OSA in three tertiary centres. OSA was defined as an obstructive apnoea-hypopnoea index (OAHI) ≥1 event/hour. Receiver operating characteristic curves assessed the diagnostic accuracy of NPO indices including ODI3 (3% Oxygen Desaturation Index, ODI4 (4% Oxygen Desaturation Index), delta 12 s index and minimum oxygen saturation. Two-by-two tables were generated to determine the sensitivities and specificities of whole number cut-off values for predicting OAHIs ≥1, 5 and 10 events/hour. RESULTS: Recordings from 322 TD children, 197 male (61.2%), median age 4.9 years (range 1.1-15.6), were reviewed. OAHI was ≥1/hour in 144 (44.7%), ≥5/hour in 61 (18.9%) and ≥10/hour in 28 (8.7%) cases. ODI3 and ODI4 had the best diagnostic accuracy. ODI3 ≥7/hour and ODI4 ≥4/hour predicted OSA in TD children with sensitivities/specificities of 57.6%/85.4% and 46.2%/91.6%, respectively. ODI3 ≥8/hour was the best predictor of OAHI ≥5/hour (sensitivity 82.0%, specificity 84.3%). CONCLUSION: Raised ODI3 and ODI4 predict OSA in TD children with high specificity but variable sensitivity. NPO may be an alternative to diagnose moderate-severe OSA if access to CRP is limited. Low sensitivities to detect mild OSA mean that confirmatory CRP is needed if NPO is normal.

Acute skeletal muscle wasting in critical illness.

IMPORTANCE: Survivors of critical illness demonstrate skeletal muscle wasting with associated functional impairment. OBJECTIVE: To perform a comprehensive prospective characterization of skeletal muscle wasting, defining the pathogenic roles of altered protein synthesis and breakdown. DESIGN, SETTING, AND PARTICIPANTS: Sixty-three critically ill patients (59% male; mean age: 54.7 years [95% CI, 50.0-59.6 years]) with an Acute Physiology and Chronic Health Evaluation II score of 23.5 (95% CI, 21.9-25.2) were prospectively recruited within 24 hours following intensive care unit (ICU) admission from August 2009 to April 2011 at a university teaching and a community hospital in England. Patients were recruited if older than 18 years and were anticipated to be intubated for longer than 48 hours, to spend more than 7 days in critical care, and to survive ICU stay. MAIN OUTCOMES AND MEASURES: Muscle loss was determined through serial ultrasound measurement of the rectus femoris cross-sectional area (CSA) on days 1, 3, 7, and 10. In a subset of patients, the fiber CSA area was quantified along with the ratio of protein to DNA on days 1 and 7. Histopathological analysis was performed. In addition, muscle protein synthesis, breakdown rates, and respective signaling pathways were characterized. RESULTS: There were significant reductions in the rectus femoris CSA observed at day 10 (−17.7% [95% CI, −25.9% to 8.1%]; P < .001). In the 28 patients assessed by all 3 measurement methods on days 1 and 7, the rectus femoris CSA decreased by 10.3% (95% CI, 6.1% to 14.5%), the fiber CSA by 17.5% (95% CI, 5.8% to 29.3%), and the ratio of protein to DNA by 29.5% (95% CI, 13.4% to 45.6%). Decrease in the rectus femoris CSA was greater in patients who experienced multiorgan failure by day 7 (−15.7%; 95% CI, −27.7% to 11.4%) compared with single organ failure (−3.0%; 95% CI, −5.3% to 2.1%) (P < .001), even by day 3 (−8.7% [95% CI, −59.3% to 50.6%] vs −1.8% [95% CI, −12.3% to 10.5%], respectively; P = .03). Myofiber necrosis occurred in 20 of 37 patients (54.1%). Protein synthesis measured by the muscle protein fractional synthetic rate was depressed in patients on day 1 (0.035%/hour; 95% CI, 0.023% to 0.047%/hour) compared with rates observed in fasted healthy controls (0.039%/hour; 95% CI, 0.029% to 0.048%/hour) (P = .57) and increased by day 7 (0.076% [95% CI, 0.032%-0.120%/hour]; P = .03) to rates associated with fed controls (0.065%/hour [95% CI, 0.049% to 0.080%/hour]; P = .30), independent of nutritional load. Leg protein breakdown remained elevated throughout the study (8.5 [95% CI, 4.7 to 12.3] to 10.6 [95% CI, 6.8 to 14.4] µmol of phenylalanine/min/ideal body weight × 100; P = .40). The pattern of intracellular signaling supported increased breakdown (n = 9, r = −0.83, P = .005) and decreased synthesis (n = 9, r = −0.69, P = .04). CONCLUSIONS AND RELEVANCE: Among these critically ill patients, muscle wasting occurred early and rapidly during the first week of critical illness and was more severe among those with multiorgan failure compared with single organ failure. These findings may provide insights into skeletal muscle wasting in critical illness.

The effectiveness of cognitive behavioural therapy for patients with concurrent hand and psychological disorders.

We investigated the effectiveness of cognitive behavioural therapy (CBT) for patients with psychological disorders thought to be influencing recovery from elective and traumatic hand conditions. Demographic data and psychological assessment scores (Primary Health Questionnaire 9 (PHQ9), General Anxiety Disorder Assessment (GAD7), Impact of Event Scale (IES)) were prospectively collected before and after CBT treatment. One hundred and fourteen patients underwent CBT with 81 completing treatment. Full data was available for 78 (68%) patients. Mean age was 43 (range 13-84) and 63% were women. Sixty-one per cent had sustained a traumatic hand injury. PHQ9, GAD7 and IES scores decreased significantly following treatment. Many patients with hand conditions have associated psychological problems that may influence outcome. CBT in a hand unit setting appears to be an effective treatment. Further research with a control group should investigate whether CBT improves psychological health or if this may occur as patients recover from their physical hand disorder regardless of CBT.Level of evidence: IV.

Improvement in the Appearance and Function of the Hand at 2 Weeks after Percutaneous Needle Fasciotomy for Dupuytren Disease.

Background: Percutaneous needle fasciotomy (PNF) has been successfully used for the treatment of contracture bands in the hand in patients with Dupuytren disease. The aim of this study is to determine aesthetic and functional outcomes at 2 weeks following PNF in patients with Dupuytren contracture. Methods: Seventy-five patients undergoing PNF for Dupuytren disease during a 4-month period were included. Patients completed the Visual Analogue Appearance Score (VAAS), Derriford Appearance Score (DAS), and the quick Disabilities of the Arm, Shoulder and Hand score (QuickDASH) preoperatively and at 2 weeks after surgery. In addition, VAAS was done in the immediate postoperative period as well. Results: Seventy-four (99%) patients completed the immediate postoperative VAAS scores and 51 (68%) completed the VAAS, DAS, and QuickDASH at 2 weeks. Preoperative VAAS fell from 6.01 to 1.53 (p < 0.0001) immediately post operation. Two weeks later, VAAS increased to 2.91 but was still significantly lower than preoperatively (p < 0.0001). DAS was unchanged. QuickDASH decreased from 22.4 preoperatively to 12.1 2 weeks later (p = 0.001). Conclusion: PNF for Dupuytren contracture resulted in improvement in both aesthetic and functional outcomes at 2 weeks. Longer term follow-up is required to determine whether these improvements are sustained. Level of Evidence: Level IV (Therapeutic).

Impact of COVID-19 pandemic on emergency department attendances for young people.

INTRODUCTION: There are concerns that the COVID-19 pandemic is having an indirect negative impact on young people. We aimed to assess the impact of the pandemic on emergency department (ED) presentations and admissions. DESIGN: We analysed ED presentations and admissions from a 5-year period (April 2016-February 2021). An interrupted time series analysis was used to estimate the presentations and admissions that would have been seen in year 5 without the pandemic using the data from years 1 to 4. These estimations were used to calculate the difference between the expected and the observed presentations and admissions during the pandemic year. RESULTS: There were 166 459 presentations over 5 years. There was a 38.1% (95% CI 33.9% to 42.3%) reduction in presentations during the pandemic with no variation by sex, age, deprivation or ethnicity. Largest reductions were associated with children being home schooled rather than with lockdowns. For admissions, there was a 23.4% (17.4% to 29.4%) reduction, less for 5-17 year age group. Infection and asthma/wheeze presentations reduced by around 60% with smaller reductions for mental health and trauma. There was no change for surgical presentations, burns/scolds or allergic reactions. There was an increase in females aged 11-17 years presenting with mental health issues during the pandemic. CONCLUSIONS: During the pandemic, there was a substantial reduction in both ED presentations and admissions. The differential impact on specific presentations suggests this was due to the impact of social distancing and reduced social mixing rather than widening of health inequality or increased barriers to care. TRIAL REGISTRATION NUMBER: NCT04893122.

A Review of Outcome Reporting Practices after Flexor Tendon Repair in Zones 1 and 2.

Background: Outcome reporting following flexor tendon repair has historically concentrated on range of movement. Recently, there has been an increase in the use of patient-reported outcome measures (PROMs). At present, there is no agreed set of outcomes to report following flexor tendon repair. The aim of this study is to review outcome reporting practices after flexor tendon repair in zones 1 and 2. Methods: A search of Ovid MEDLINE, Ovid EMBASE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) between 1 January 1980 and 31 December 2019 was performed to identify the studies that reported outcomes following the repair of flexor tendons in zones 1 and 2. Study characteristics and data with regard to the reporting of eight outcome domains was extracted: functional outcome (quantitative), functional outcome (subjective), activities of daily living (ADL), satisfaction/quality of life, post-treatment recovery, resources, aesthetics and safety. Results: A total of 94 out of 4,118 articles identified were included in the review. All studies reported range of motion using 17 different methods of measurement. Eleven studies defined measurement methods incorrectly or unclearly. Only 16 studies reported PROMs, with only one reporting data on assessment of quality of life. Eighteen studies reported time away from employment. Minimal data on resource utilisation and aesthetics were included. Conclusion: This review highlights wide heterogeneity and paucity of data reporting clinical outcomes of flexor tendon surgery. The development of a core outcome set that would ensure essential outcomes are correctly defined, measured and reported is required. Level of Evidence: Level IV (Prognostic).

The influence of carbohydrate-protein co-ingestion following endurance exercise on myofibrillar and mitochondrial protein synthesis.

The aim of the present study was to determine mitochondrial and myofibrillar muscle protein synthesis (MPS) when carbohydrate (CHO) or carbohydrate plus protein (C+P) beverages were ingested following prolonged cycling exercise. The intracellular mechanisms thought to regulate MPS were also investigated. In a single-blind, cross-over study, 10 trained cyclists (age 29 ± 6 years, VO2max 66.5 ± 5.1 ml kg(−1) min(−1)) completed two trials in a randomized order. Subjects cycled for 90 min at 77 ± 1% VO2max before ingesting a CHO (25 g of carbohydrate) or C+P (25 g carbohydrate + 10 g whey protein) beverage immediately and 30 min post-exercise. A primed constant infusion of L-[ring-(13)C6]phenylalanine began 1.5 h prior to exercise and continued until 4 h post-exercise. Muscle biopsy samples were obtained to determine myofibrillar and mitochondrial MPS and the phosphorylation of intracellular signalling proteins. Arterialized blood samples were obtained throughout the protocol. Plasma amino acid and urea concentrations increased following ingestion of C+P only. Serum insulin concentration increased more for C+P than CHO. Myofibrillar MPS was ∼35% greater for C+P compared with CHO (0.087 ± 0.007 and 0.057 ± 0.006% h(−1), respectively; P = 0.025). Mitochondrial MPS rates were similar for C+P and CHO (0.082 ± 0.011 and 0.086 ± 0.018% h(−1), respectively). mTOR(Ser2448) phosphorylation was greater for C+P compared with CHO at 4 h post-exercise (P < 0.05). p70S6K(Thr389) phosphorylation increased at 4 h post-exercise for C+P (P < 0.05), whilst eEF2(Thr56) phosphorylation increased by ∼40% at 4 h post-exercise for CHO only (P < 0.01). The present study demonstrates that the ingestion of protein in addition to carbohydrate stimulates an increase in myofibrillar, but not mitochondrial, MPS following prolonged cycling. These data indicate that the increase in myofibrillar MPS for C+P could, potentially, be mediated through p70S6K, downstream of mTOR, which in turn may suppress the rise in eEF2 on translation elongation.

Effects of hypoxia on muscle protein synthesis and anabolic signaling at rest and in response to acute resistance exercise.

Chronic reductions in tissue O(2) tension (hypoxia) are associated with muscle atrophy and blunted hypertrophic responses to resistance exercise (RE) training. However, the effect of hypoxia on muscle protein synthesis (MPS) at rest and after RE is unknown. In a crossover study, seven healthy men (21.4 ± 0.7 yr) performed unilateral leg RE (6 × 8 repetitions at 70% 1-repetition maximum) under normoxic (20.9% inspired O(2)) and normobaric hypoxic (12% inspired O(2) for 3.5 h) postabsorptive conditions. Immediately after RE the rested leg was biopsied, and a primed continuous infusion of [1,2-(13)C(2)]leucine was maintained for 2.5 h before final biopsies from both legs to measure tracer incorporation and signaling responses (i.e., ribosomal S6 kinase 1). After 3.5 h of hypoxia, MPS was not different from normoxia in the rested leg (normoxia 0.033 ± 0.016 vs. hypoxia 0.043 ± 0.016%/h). MPS increased significantly from baseline 2.5 h after RE in normoxia (0.033 ± 0.016 vs. 0.104 ± 0.038%/h) but not hypoxia (0.043 ± 0.016 vs. 0.060 ± 0.063%/h). A significant linear relationship existed between MPS 2.5 h after RE in hypoxia and mean arterial blood O(2) saturation during hypoxia (r(2) = 0.49, P = 0.04). Phosphorylation of p70S6K(Thr389) remained unchanged in hypoxia at rest but increased after RE in both normoxia and hypoxia (2.6 ± 1.2-fold and 3.4 ± 1.1-fold, respectively). Concentrations of the hypoxia-responsive mTOR inhibitor regulated in development and DNA damage-1 were unaltered by hypoxia or RE. We conclude that normobaric hypoxia does not reduce MPS over 3.5 h at rest but blunts the increased MPS response to acute RE to a degree dependent on extant SpO(2).

The case for skin camouflage in the management of upper limb scarring - A case series.

Introduction: For some people the appearance of their hands is as important as function. Upper limb scarring can cause some patients distress. Skin camouflage is an intervention that can be used to reduce the visual impact of a scar but there is limited published evidence for its use for hand scarring. Methods: This is a case series study with a primary objective to determine whether skin camouflage reduces distress in patients with an upper limb scar and to evaluate this new service. Patients experiencing distress from an upper limb scar were recruited from a hand therapy outpatient clinic. The intervention delivered was a one hour skin camouflage session. Photographs of the upper limb pre and post skin camouflage intervention were taken. The patient-rated Michigan Hand Questionnaire (MHQ) and Derriford Appearance Scale (DAS24) were completed before treatment, at 1 week and 1 month after treatment. Results: Six participants reporting distress from an upper limb scar received skin camouflage intervention. Only three out of six participants completed all follow-up. All three showed improvement in at least two domains of the MHQ (function and aesthetics) at one month post treatment. Increased confidence during functional and work-based activities was also reported on the DAS24. Participants reported increased engagement in daily activities as a result of being able to camouflage their scars. Conclusions: This small case series shows that skin camouflage intervention may be beneficial for some patients who are experiencing distress related to an upper limb scar by increasing function and self-confidence.

The association between surgery for carpal and cubital tunnel syndrome: analysis of incidence and risk factors within a geographical area.

The relationship between surgery for cubital tunnel and carpal tunnel syndrome was examined in this retrospective study. Between 1997 and 2018, data from consecutive patients who underwent carpal tunnel release (8352 patients), cubital tunnel release (1681 patients) or both procedures (692 patients) were analysed. The relative risk of undergoing cubital tunnel release in the population who had carpal tunnel release compared with those with no carpal tunnel release was 15.3 (male 20.3; female 12.5). The relative risk of undergoing carpal tunnel release in the population who had cubital tunnel release compared with those who did not undergo carpal tunnel release was 11.5 (male 16.5; female 9.1). Our study showed that men and women who undergo carpal tunnel release are over 20 times and 10 times more likely to have cubital tunnel release than those who did not undergo carpal tunnel release, respectively. These findings suggest that the two conditions may share a similar aetiology.Level of evidence: IV.

The effect of social deprivation on the incidence rate of carpal and cubital tunnel syndrome surgery.

We sought to establish whether carpal and cubital tunnel syndrome requiring surgery is associated with deprivation in England. Data from 10,496 adult patients who were treated in our hand unit over a 20-year period were reviewed. The Index of Multiple Deprivation was used to measure deprivation from the patients' postcode. The mean age at surgery in the most deprived three quintiles was significantly lower than in the least deprived two quintiles for carpal tunnel release (55 vs 59 years, respectively) and cubital tunnel release (52 vs 57 years, respectively). The incidence rate was significantly lower for the three least deprived quintiles when compared with the most deprived quintile for both conditions. The incidence rate ratio of the least deprived quintile compared with the most deprived quintile for carpal tunnel release was 0.70 for men and 0.76 for women. The incidence rate ratio of the least deprived quintile compared with the most deprived quintile for cubital tunnel release was 0.79 for men and 0.49 for women. Carpal tunnel and cubital tunnel syndrome requiring surgery is more common in deprived patients and occurs at an earlier age.Level of evidence: IV.

Increasing skeletal muscle carnitine content in older individuals increases whole-body fat oxidation during moderate-intensity exercise.

Intramyocellular lipid (IMCL) utilization is impaired in older individuals, and IMCL accumulation is associated with insulin resistance. We hypothesized that increasing muscle total carnitine content in older men would increase fat oxidation and IMCL utilization during exercise, and improve insulin sensitivity. Fourteen healthy older men (69 ± 1 year, BMI 26.5 ± 0.8 kg/m2 ) performed 1 h of cycling at 50% VO2 max and, on a separate occasion, underwent a 60 mU/m2 /min euglycaemic hyperinsulinaemic clamp before and after 25 weeks of daily ingestion of a 220 ml insulinogenic beverage (44.4 g carbohydrate, 13.8 g protein) containing 4.5 g placebo (n = 7) or L-carnitine L-tartrate (n = 7). During supplementation, participants performed twice-weekly cycling for 1 h at 50% VO2 max. Placebo ingestion had no effect on muscle carnitine content or total fat oxidation during exercise at 50% VO2 max. L-carnitine supplementation resulted in a 20% increase in muscle total carnitine content (20.1 ± 1.2 to 23.9 ± 1.7 mmol/kg/dm; p < 0.01) and a 20% increase in total fat oxidation (181.1 ± 15.0 to 220.4 ± 19.6 J/kg lbm/min; p < 0.01), predominantly due to increased IMCL utilization. These changes were associated with increased expression of genes involved in fat metabolism (ACAT1, DGKD & PLIN2; p < 0.05). There was no change in resting insulin-stimulated whole-body or skeletal muscle glucose disposal after supplementation. This is the first study to demonstrate that a carnitine-mediated increase in fat oxidation is achievable in older individuals. This warrants further investigation given reduced lipid turnover is associated with poor metabolic health in older adults.

Are exhaled nitric oxide measurements using the portable NIOX MINO repeatable?

BACKGROUND: Exhaled nitric oxide is a non-invasive marker of airway inflammation and a portable analyser, the NIOX MINO (Aerocrine AB, Solna, Sweden), is now available. This study aimed to assess the reproducibility of the NIOX MINO measurements across age, sex and lung function for both absolute and categorical exhaled nitric oxide values in two distinct groups of children and teenagers. METHODS: Paired exhaled nitric oxide readings were obtained from 494 teenagers, aged 16-18 years, enrolled in an unselected birth cohort and 65 young people, aged 6-17 years, with asthma enrolled in an interventional asthma management study. RESULTS: The birth cohort participants showed a high degree of variability between first and second exhaled nitric oxide readings (mean intra-participant difference 1.37 ppb, 95% limits of agreement -7.61 to 10.34 ppb), although there was very close agreement when values were categorised as low, normal, intermediate or high (kappa = 0.907, p < 0.001). Similar findings were seen in subgroup analyses by sex, lung function and asthma status. Similar findings were seen in the interventional study participants. CONCLUSIONS: The reproducibility of exhaled nitric oxide is poor for absolute values but acceptable when values are categorised as low, normal, intermediate or high in children and teenagers. One measurement is therefore sufficient when using categorical exhaled nitric oxide values to direct asthma management but a mean of at least two measurements is required for absolute values.