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Article ; Online: Immunesenescence

Jon Hazeldine / Janet M. Lord

Frontiers in Immunology, Vol

A Predisposing Risk Factor for the Development of COVID-19?

2020 Volume 11

Abstract: Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of ... ...

Abstract	Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), is characterized by an expansion of inflammatory monocytes, functional exhaustion of lymphocytes, dysregulated myeloid responses and the presence of highly activated senescent T cells. Alongside advanced age, male gender and pre-existing co-morbidities [e.g., obesity and type 2 diabetes (T2D)] are emerging as significant risk factors for COVID-19. Interestingly, immunesenescence is more profound in males when compared to females, whilst accelerated aging of the immune system, termed premature immunesenescence, has been described in obese subjects and T2D patients. Thus, as three distinct demographic groups with an increased susceptibility to COVID-19 share a common immune profile, could immunesenescence be a generic contributory factor in the development of severe COVID-19? Here, by focussing on three key aspects of an immune response, namely pathogen recognition, elimination and resolution, we address this question by discussing how immunesenescence may weaken or exacerbate the immune response to SARS-CoV-2. We also highlight how aspects of immunesenescence could render potential COVID-19 treatments less effective in older adults and draw attention to certain therapeutic options, which by reversing or circumventing certain features of immunesenescence may prove to be beneficial for the treatment of groups at high risk of severe COVID-19.
Keywords	aging ; COVID-19 ; immunesenescence ; immune dysfunction ; inflammaging ; SARS-Cov_2 ; Immunologic diseases. Allergy ; RC581-607 ; covid19
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Influence of scar age, laser type and laser treatment intervals on adult burn scars

Yangmyung Ma / Sabrina P Barnes / Yung-Yi Chen / Naiem S Moiemen / Janet M Lord / Amanda V Sardeli

PLoS ONE, Vol 18, Iss 9, p e

A systematic review and meta-analysis.

2023 Volume 0292097

Abstract: Aim The study aims to identify whether factors such as time to initiation of laser therapy following scar formation, type of laser used, laser treatment interval and presence of complications influence burn scar outcomes in adults, by meta-analysis of ... ...

Abstract	Aim The study aims to identify whether factors such as time to initiation of laser therapy following scar formation, type of laser used, laser treatment interval and presence of complications influence burn scar outcomes in adults, by meta-analysis of previous studies. Methods A literature search was conducted in May 2022 in seven databases to select studies on the effects of laser therapy in adult hypertrophic burn scars. The study protocol was registered with PROSPERO (CRD42022347836). Results Eleven studies were included in the meta-analysis, with a total of 491 patients. Laser therapy significantly improved overall VSS/POSAS, vascularity, pliability, pigmentation and scar height of burn scars. Vascularity improvement was greater when laser therapy was performed >12 months (-1.50 [95%CI = -2.58;-0.42], p = 0.01) compared to <12 months after injury (-0.39 [95%CI = -0.68; -0.10], p = 0.01), the same was true for scar height ((-1.36 [95%CI = -2.07; -0.66], p<0.001) vs (-0.56 [95%CI = -0.70; -0.42], p<0.001)). Pulse dye laser (-4.35 [95%CI = -6.83; -1.86], p<0.001) gave a greater reduction in VSS/POSAS scores compared to non-ablative (-1.52 [95%CI = -2.24; -0.83], p<0.001) and ablative lasers (-0.95 [95%CI = -1.31; -0.59], p<0.001). Conclusion Efficacy of laser therapy is influenced by the time lapse after injury, the type of laser used and the interval between laser treatments. Significant heterogeneity was observed among studies, suggesting the need to explore other factors that may affect scar outcomes.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Incidence of immune-mediated inflammatory diseases following COVID-19

Umer Syed / Anuradhaa Subramanian / David C. Wraith / Janet M. Lord / Kirsty McGee / Krishna Ghokale / Krishnarajah Nirantharakumar / Shamil Haroon

BMC Medicine, Vol 21, Iss 1, Pp 1-

a matched cohort study in UK primary care

2023 Volume 9

Abstract: Abstract Background Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part ... ...

Abstract	Abstract Background Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs). Methods Matched cohort study using primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS-CoV-2 infection and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults with no diagnosis of confirmed or suspected SARS-CoV-2 infection. The primary outcome was a composite of any of the following IMIDs: autoimmune thyroiditis, coeliac disease, inflammatory bowel disease (IBD), myasthenia gravis, pernicious anaemia, psoriasis, rheumatoid arthritis (RA), Sjogren’s syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo. The secondary outcomes were each of these conditions separately. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes, adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications. Results Six hundred and nighty six (0.15%) and 2230 (0.12%) patients in the exposed and unexposed cohort developed an IMID during the follow-up period over 0.29 person-years, giving a crude incidence rate of 4.59 and 3.65 per 1000 person-years, respectively. Patients in the exposed cohort had a 22% increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.12 to 1.33). The incidence of three IMIDs was significantly associated with SARS-CoV-2 infection. These were T1DM (aHR 1.56, 1.09 to 2.23), IBD (aHR ...
Keywords	COVID-19 ; SARS-CoV-2 ; Cohort study ; Immune-mediated inflammatory diseases ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Assessing the feasibility and impact of an adapted resistance training intervention, aimed at improving the multi-dimensional health and functional capacity of frail older adults in residential care settings

Paul Doody / Janet M. Lord / Anna C. Whittaker

Pilot and Feasibility Studies, Vol 5, Iss 1, Pp 1-

protocol for a feasibility study

2019 Volume 12

Abstract: Abstract Background Frailty is a common and clinically significant condition in older adults, predominantly due to its association with adverse health outcomes such as hospitalisation, disability and mortality. Exercise interventions have been shown to ... ...

Abstract	Abstract Background Frailty is a common and clinically significant condition in older adults, predominantly due to its association with adverse health outcomes such as hospitalisation, disability and mortality. Exercise interventions have been shown to be a beneficial treatment for frail older adults. However, more high-quality studies are needed within this area to assess the feasibility and impact of these interventions in frail geriatric populations within different settings, and with regards to their impact on broader aspects of health and wellbeing. Methods This study will utilise an interventional, randomised, controlled research design in order to assess the feasibility (acceptability, demand, implementation, practicality, adaptation, integration, expansion) and potential impact (limited-efficacy testing) of a specially adapted resistance training intervention; aimed at improving the multi-dimensional health and functional capacity of frail geriatric care home residents. Discussion The most immediate implication of this research from a scientific perspective is informing the feasibility, and potential efficacy, of a proposed future clinical trial within this setting. Additionally, if the study proves feasible, and the limited-efficacy testing proves positive, this study also has the potential to lead to advancement in the care for frail geriatric populations within residential care settings; and the ability to measurably improve various aspects of health and functional capacity within this population. This study has been granted a favourable ethical opinion by the London Harrow NHS Research Ethics Committee and is sponsored by the University of Birmingham. The findings of this study will be disseminated through publication in open access scientific journals, public engagement events, online via social media, conference presentations and directly to study participants. Trial registration ClinicalTrials.gov: NCT03141879. Registered 5 May 2017.
Keywords	Care home ; Elderly ; Exercise ; Feasibility study ; Frail ; Functional capacity ; Medicine (General) ; R5-920
Subject code	360
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Vitamin D status and its influence on outcomes following major burn injury and critical illness

Khaled Al-Tarrah / Martin Hewison / Naiem Moiemen / Janet M. Lord

Burns & Trauma, Vol 6, Iss 1, Pp 1-

2018 Volume 11

Abstract: Abstract Vitamin D deficiency is common among the general population. It is also observed in up to 76% of critically ill patients. Despite the high prevalence of hypovitaminosis D in critical illness, vitamin D is often overlooked by medical staff as the ...

Abstract	Abstract Vitamin D deficiency is common among the general population. It is also observed in up to 76% of critically ill patients. Despite the high prevalence of hypovitaminosis D in critical illness, vitamin D is often overlooked by medical staff as the clinical implications and consequences of vitamin D deficiency in acute contexts remain to be fully understood. Vitamin D has a broad range of pleotropic effects on various processes and systems including the immune-inflammatory response. 1α,25-dihydroxyvitamin D (1,25(OH)2D), has been shown to promote a tolerogenic immune response limiting deleterious inflammatory effects, modulation of the innate immune system, and enhancement of anti-microbial peptides. Vitamin D deficiency is frequently observed in critically ill patients and has been related to extrinsic causes (i.e., limited sunlight exposure), magnitude of injury/illness, or the treatment started by medical doctors including fluid resuscitation. Low levels of vitamin D in critically ill patients have been associated with sepsis, organ failure, and mortality. Despite this, there are subpopulations of critical illness, such as burn patients, where the literature regarding vitamin D status and its influence on outcomes remain insufficient. Thermal injury results in damage to both burned and non-burned tissues, as well as induces an exaggerated and persistent immune-inflammatory and hypermetabolic response. In this review, we propose potential mechanisms in which burn injury affects the vitamin D status and summarizes current literature investigating the influence of vitamin D status on outcomes. In addition, we reviewed the literature and trials investigating vitamin D supplementation in critically ill patients and discuss the therapeutic potential of vitamin D supplementation in burn and critically ill patients. We also highlight current limitations of studies that have investigated vitamin D status and supplementation in critical illness. Thermal injury influences vitamin D status. More studies ...
Keywords	Vitamin D ; Critical care ; Burns ; Trauma ; Thermal injury ; Critically ill ; Medicine ; R
Subject code	610
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	Oxford University Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The challenges of muscle biopsy in a community based geriatric population

Daisy Wilson / Leigh Breen / Janet M. Lord / Elizabeth Sapey

BMC Research Notes, Vol 11, Iss 1, Pp 1-

2018 Volume 6

Abstract: Abstract Objectives To describe the difficulties of obtaining muscle samples using a Bergstrom needle technique in a frail older adult population. The data were obtained from a study primarily investigating immunosenescence in frailty. An intended ... ...

Abstract	Abstract Objectives To describe the difficulties of obtaining muscle samples using a Bergstrom needle technique in a frail older adult population. The data were obtained from a study primarily investigating immunosenescence in frailty. An intended research technique was skeletal muscle biopsy in a small subset of participants to investigate muscle morphology and local inflammatory factors. Results Forty healthy older adults and 37 frail older adults were considered for a Bergstrom needle muscle biopsy. Of these, 17.5% of healthy older adults and 94.6% of the frail older adults had single or multiple participant factors resulting in a contra-indication to muscle biopsy. 40.7% of healthy older female participants were at risk of a failed muscle biopsy due to low muscle mass. Considering only muscle mass muscle biopsy would have been successful in 18.7% of the frail older women and 21.4% of the frail older men. In this population, muscle biopsy was not feasible because of contra-indications in the majority of participants. This questions whether a biopsy sample obtained from frail older individuals, is actually representative of this population and supports the need to disclose biopsy failure rate in this population.
Keywords	Sarcopenia ; Frailty ; Bergstrom needle ; Percutaneous muscle biopsy ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
Subject code	610
Language	English
Publishing date	2018-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Impact of Slice Interval and Equation on the Accuracy of Magnetic Resonance Image Estimation of Quadriceps Muscle Volume in End Stage Liver Disease

Jonathan I. Quinlan / Clare Jones / Emma Bissonnette / Amritpal Dhaliwal / Felicity Williams / Surabhi Choudhary / Leigh Breen / Gareth G. Lavery / Matthew J. Armstrong / Ahmed M. Elsharkawy / Janet M. Lord / Carolyn A. Greig

Frontiers in Rehabilitation Sciences, Vol

2022 Volume 3

Abstract: IntroductionEnd stage liver disease (ESLD) is associated with loss of muscle mass and function, known as sarcopenia, which can increase the risk of complications of ESLD, hospitalization and mortality. Therefore, the accurate assessment of muscle mass is ...

Abstract	IntroductionEnd stage liver disease (ESLD) is associated with loss of muscle mass and function, known as sarcopenia, which can increase the risk of complications of ESLD, hospitalization and mortality. Therefore, the accurate assessment of muscle mass is essential to evaluate sarcopenia in ESLD. However, manual segmentation of muscle volume (MV) can be laborious on cross-sectional imaging, due to the number of slices that require analysis. This study aimed to investigate the impact of reducing the number of slices required for MV estimation. Further, we aimed to compare two equations utilized in estimating MV (cylindrical and truncated cone).MethodsThirty eight ESLD patients (23 males; 54.8 ± 10.7 years) were recruited from the Queen Elizabeth University Hospital Birmingham. A 3T MRI scan was completed of the lower limbs. Quadriceps MV was estimated utilizing 1-, 2-, 3-, and 4 cm slice intervals with both cylindrical and truncated cone equations. Absolute and relative error (compared to 1 cm slice interval) was generated for 2-, 3-, and 4 cm slice intervals. L3 skeletal muscle index (SMI) was also calculated in 30 patients.ResultsRelative error increased with slice interval using the cylindrical (0.45 vs. 1.06 vs. 1.72%) and truncated cone equation (0.27 vs. 0.58 vs. 0.74%) for 2, 3, and 4 cm, respectively. Significantly, the cylindrical equation produced approximately twice the error compared to truncated cone, with 3 cm (0.58 vs. 1.06%, P < 0.01) and 4 cm intervals (0.74 vs. 1.72%, P < 0.001). Finally, quadriceps MV was significantly correlated to L3 SMI (r2 = 0.44, P < 0.0001).ConclusionThe use of the truncated equation with a 4 cm slice interval on MRI offers an efficient but accurate estimation of quadricep muscle volume in ESLD patients.
Keywords	MRI ; muscle volume ; end stage liver disease ; muscle mass ; sarcopenia ; Other systems of medicine ; RZ201-999 ; Medical technology ; R855-855.5
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Innate and adaptive immune dysregulation in critically ill ICU patients

Niharika Arora Duggal / Catherine Snelson / Ulfath Shaheen / Victoria Pearce / Janet M. Lord

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 11

Abstract: Abstract This study aimed to evaluate whether ICU patients who developed persistent critical illness displayed an immune profile similar to an aged immune phenotype and any associations with patient outcomes. Twenty two critically ill ICU patients (27–76 ...

Abstract	Abstract This study aimed to evaluate whether ICU patients who developed persistent critical illness displayed an immune profile similar to an aged immune phenotype and any associations with patient outcomes. Twenty two critically ill ICU patients (27–76 years, 15 males), at day 5 of mechanical ventilation, and 22 healthy age-matched controls (27–77 years, 13 males) were recruited. Frequency and phenotype of innate and adaptive immune cells and telomere length in peripheral blood mononuclear cells (PBMCs) were measured. An elevated granulocyte count (p < 0.0001), increased numbers of immature granulocytes (p < 0.0001), increased CD16++ve monocytes (p = 0.003) and CD14+ve HLADRdim/low monocytes (p = 0.004) and lower NK cell numbers (p = 0.007) were observed in ICU patients compared to controls. Critically ill patients also had lower numbers of total T lymphocytes (p = 0.03), naïve CD4 T cells (p = 0.003) and PTK7+ve recent thymic emigrants (p = 0.002), and increased senescent CD28−ve CD57+ve CD4 T cells (p = 0.02), but there was no difference in PBMC telomere length. Regulatory immune cell frequency was affected with reduced circulating CD19+veCD24hiCD38hi regulatory B cells (p = 0.02). However, only a raised neutrophil:lymphocyte ratio and reduced frequency of CD14+ve HLADRdim/low monocytes were associated with poor outcomes. We conclude that persistent critical illness results in changes to immune cell phenotype only some of which are similar to that seen in physiological ageing of the immune system.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A pilot observational study measuring acute sarcopenia in older colorectal surgery patients

Carly Welch / Carolyn A. Greig / Zaki K. Hassan-Smith / Thomas D. Pinkney / Janet M. Lord / Thomas A. Jackson

BMC Research Notes, Vol 12, Iss 1, Pp 1-

2019 Volume 7

Abstract: Abstract Objective To explore variability in acute changes in muscle mass and function in older patients undergoing elective colorectal surgery, as well as feasibility of measures, in order to refine study processes to inform the protocol for a larger ... ...

Abstract	Abstract Objective To explore variability in acute changes in muscle mass and function in older patients undergoing elective colorectal surgery, as well as feasibility of measures, in order to refine study processes to inform the protocol for a larger study. Results Results are presented for seven participants recruited to this pilot study. It is possible to perform serial measurements of bilateral anterior thigh thickness (BATT) and handgrip strength prior to, within 24 h of surgery, and 1 week postoperatively. Gait speed can be reliably measured preoperatively and at 1 week postoperatively. In this pilot study, BATT and gait speed declined at 1 week postoperatively (median BATT 4.17 cm, 3.47 cm, p = 0.028; median gait speed 0.89 m/s, 0.83 m/s, p = 0.043). Baseline hsCRP correlated with change in BATT (τb = 0.73, p = 0.04) and baseline DHEA-S correlated with change in gait speed (τb = 0.87, p = 0.02). This pilot study has assisted to refine the protocol for our larger study, which will further characterise these changes.
Keywords	Acute sarcopenia ; Inflammation ; Biomarkers ; Aged ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth

Sophie L. Allen / Alex P. Seabright / Jonathan I. Quinlan / Amritpal Dhaliwal / Felicity R. Williams / Nicholas H. F. Fine / David J. Hodson / Matthew J. Armstrong / Ahmed M. Elsharkaway / Carolyn A. Greig / Yu-Chiang Lai / Janet M. Lord / Gareth G. Lavery / Leigh Breen

Cells, Vol 11, Iss 1098, p

2022 Volume 1098

Abstract: Sarcopenia is a common complication affecting liver disease patients, yet the underlying mechanisms remain unclear. We aimed to elucidate the cellular mechanisms that drive sarcopenia progression using an in vitro model of liver disease. C2C12 myotubes ... ...

Abstract	Sarcopenia is a common complication affecting liver disease patients, yet the underlying mechanisms remain unclear. We aimed to elucidate the cellular mechanisms that drive sarcopenia progression using an in vitro model of liver disease. C2C12 myotubes were serum and amino acid starved for 1-h and subsequently conditioned with fasted ex vivo serum from four non-cirrhotic non-alcoholic fatty liver disease patients (NAFLD), four decompensated end-stage liver disease patients (ESLD) and four age-matched healthy controls (CON) for 4- or 24-h. After 4-h C2C12 myotubes were treated with an anabolic stimulus (5 mM leucine) for 30-min. Myotube diameter was reduced following treatment with serum from ESLD compared with CON (−45%) and NAFLD (−35%; p < 0.001 for both). A reduction in maximal mitochondrial respiration (24% and 29%, respectively), coupling efficiency (~12%) and mitophagy (~13%) was identified in myotubes conditioned with NAFLD and ESLD serum compared with CON ( p < 0.05 for both). Myostatin (43%, p = 0.04) and MuRF-1 (41%, p = 0.03) protein content was elevated in myotubes treated with ESLD serum compared with CON. Here we highlight a novel, experimental platform to further probe changes in circulating markers associated with liver disease that may drive sarcopenia and develop targeted therapeutic interventions.
Keywords	chronic liver disease ; sarcopenia ; leucine ; mitochondria ; protein breakdown ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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