Impact of the COVID-19 pandemic on corticosteroid injection services: A National Survey of Members of the British Society of Skeletal Radiologists (BSSR)

ObjectiveTo describe the restructuring of services by British radiologists in response to evolving national guidelines and highlight the impact of the COVID-19 pandemic on the treatment of musculoskeletal (MSK) conditions.MethodsAn online anonymised survey was distributed via the British Society of Skeletal Radiology (BSSR) members forum in November 2020. Responses were collated using a standardised Google form including 21 questions.Results135 members of the BSSR completed the survey. 85% of respondents stopped performing corticosteroid injections (CSI) during the initial lockdown of the pandemic. This was primarily influenced by national guidelines. The majority of respondents initially abstained from offered CSI procedures, then by November 2020, 69% of respondents were providing CSI for high and low risk patients, 23% were only providing CSI for low-risk patients with 8% still not performing any CSI. 40% of respondents reported routinely obtaining specific written consent regarding the risk of COVID-19. Approximately, 11,000 CSI were performed by respondents between March and November 2020 with no reported significant COVID-19-related complications. Over 80% of BSSR members reported that the number of CSI procedures that they performed dropped by more than 80% compared to usual. 73% of respondents reported an increased backlog of patients awaiting treatment. The average waiting time for routine outpatient CSI treatment was > 12 weeks in 53% of responses, compared to 34% the previous year.ConclusionThe COVID-19 pandemic has had a significant impact on the clinical practices of MSK radiologists in the UK. Our survey highlights the rapid response of BSSR members as national guidelines evolved. Currently, the majority of respondents are performing CSI for musculoskeletal conditions when clinically indicated, with enhanced consent. However, the pandemic has resulted in increased waiting times – delaying the treatment of patients who may be suffering with significant pain and disability. Further research is warranted to provide guidance around both service recovery and provision of CSI around COVID-19 vaccination schedules.Advances in knowledgeBSSR members responded rapidly to changing guidelines during the COVID-19 pandemic. The majority of respondents are currently performing CSI when clinically indicated. The pandemic has resulted in a significant increase in waiting times which will have a significant impact on UK musculoskeletal services.     

Effective ways of restoring muscular imbalances of the rotator cuff muscle group: a comparative study of various training methods

Background: Many studies have compared different training methods for improving muscular performance, but more investigations need to be directed to the restoration of muscular imbalances.

Objective: To determine the most effective training for altering strength ratios in the shoulder rotator cuff.

Methods: Forty eight physical education students were randomly assigned to four groups (12 per group): (a) experimental group who carried out multijoint dynamic resistance training for shoulder internal and external rotation movement (pull ups or lat pull downs, overhead press, reverse pull ups, push ups) (MJDR group); (b) experimental group who exercised the same muscle group using dumbbells weighing 2 kg (isolated group); (c) experimental group who followed an isokinetic strengthening programme for the rotator cuff muscle group (isokinetic group); (d) control group who had no strength training. Testing was performed in the supine position with the glenohumeral joint in 90° of abduction in the coronal plane, with a range of motion of 0–90° of external rotation and 0–65° of internal rotation at angular velocities of 60, 120, and 180°/s. The test procedure was performed before and after the exercise period of six weeks.

Results: One way analysis of variance found no differences between the groups for the initial tests. Analysis of variance with repeated measures showed that the strength ratios in all the experimental groups had altered after the exercise period, with the isokinetic group showing the most significant improvement.

Conclusions: Isokinetic strengthening is the most effective method of altering strength ratios of the rotator cuff muscle.

     

Mitochondria Distinguish Granule-Stored from de novo Synthesized Tumor Necrosis Factor Secretion in Human Mast Cells

Background: Mast cells are immune cells derived from hematopoietic precursors that mature in the tissue microenvironment. Mast cells are critical for allergic, immune and inflammatory processes, many of which involve tumor necrosis factor (TNF). These cells uniquely store TNF in their secretory granules. Upon stimulation, mast cells rapidly (30 min) secrete β-hexosaminidase and granule-stored TNF through degranulation, but also increase TNF mRNA and release de novo synthesized TNF 24 h later. The regulation of these two distinct pathways is poorly understood. Methods: Human LAD2 leukemic mast cells are stimulated by substance P. TNF secretion and gene expression were measured by ELISA and real-time PCR, and mitochondrial dynamics was observed in live cells under confocal microscopy. Cell energy consumption was measured in terms of oxygen consumption rate. Results: Here, we show that granule-stored TNF is preformed, and its secretion from LAD2 mast cells stimulated by substance P (1) exhibits higher energy consumption and is inhibited by the mitochondrial ATP pump blocker oligomycin, (2) shows rapid increase in intracellular calcium levels, and (3) exhibits reversible mitochondrial translocation, from a perinuclear distribution to the cell surface, as compared to de novo synthesized TNF release induced by lipopolysaccharide. This mitochondrial translocation is confirmed using primary human umbilical cord blood-derived mast cells stimulated by an allergic trigger (IgE/streptavidin). Conclusion: Our findings indicate that unique mitochondrial functions distinguish granule-stored from newly synthesized TNF release from human mast cells, thus permitting the versatile involvement of mast cells in different biological processes.     

Mast cells in allergic and inflammatory diseases

Mast cells are important in the development of allergic and anaphylactic reactions, but also in acquired and innate immunity. There is also increasing evidence that mast cells participate in inflammatory diseases, where they can be activated by non-allergic triggers, such as neuropeptides and cytokines, often having synergistic effects as in the case of substance P (SP) and IL-33. Secretion of vasoactive mediators, cytokines and proteinases contribute to the development of coronary artery disease (CAD), as well as to diet-induced obesity and the metabolic syndrome. Mast cells may be able to orchestrate such different biological processes through their ability to release pro-inflammatory mediators selectively without the degranulation typical of allergic reactions. Recent evidence suggests that mitochondrial uncoupling protein 2 (UCP2) and mitochondrial translocation regulate mast cell degranulation, but not selective mediator release. Better understanding of these two processes and how mast cells exert both immunostimulatory and immunosuppressive actions could lead to the development of inhibitors of release of specific mediators with novel therapeutic applications.     

Brief Report: “Allergic Symptoms” in Children with Autism Spectrum Disorders. More than Meets the Eye?

Many children with Autism Spectrum Disorders (ASD) have either family and/or personal history of “allergic symptomatology”, often in the absence of positive skin or RAST tests. These symptoms may suggest mast cell activation by non-allergic triggers. Moreover, children with mastocytosis or mast cell activation syndrome (MCAS), a spectrum of rare diseases characterized by increased number of activated mast cells in many organs, appear to have ASD at a rate tenfold higher (1/10 children) than that of the general population (1/100 children). Mast cell activation by allergic, infectious, environmental and stress-related triggers, especially perinatally, would release pro-inflammatory and neurotoxic molecules. We speculate these could disrupt the gut–blood–brain barriers, thus contributing to brain inflammation and ASD pathogenesis. Increased mast cell responsiveness may define at least a subgroup of ASD subjects, who could benefit from inhibition of mast cell activation.     

Substance P (SP) induces expression of functional corticotropin-releasing hormone receptor-1 (CRHR-1) in human mast cells

Corticotropin-releasing hormone (CRH) is secreted under stress and regulates the hypothalamic-pituitary-adrenal axis. However, CRH is also secreted outside the brain where it exerts proinflammatory effects through activation of mast cells, which are increasingly implicated in immunity and inflammation. Substance P (SP) is also involved in inflammatory diseases. Human LAD2 leukemic mast cells express only CRHR-1 mRNA weakly. Treatment of LAD2 cells with SP (0.5-2?μM) for 6?hours significantly increases corticotropin-releasing hormone receptor-1 (CRHR-1) mRNA and protein expression. Addition of CRH (1?μM) to LAD2 cells, which are "primed" with SP for 48?hours and then washed, induces synthesis and release of IL-8, tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) 24?hours later. These effects are blocked by pretreatment with an NK-1 receptor antagonist. Treatment of LAD2 cells with CRH (1?μM) for 6?hours induces gene expression of NK-1 as compared with controls. However, repeated stimulation of mast cells with CRH (1?μM) leads to downregulation of CRHR-1 and upregulation in NK-1 gene expression. These results indicate that SP can stimulate mast cells and also increase expression of functional CRHR-1, whereas CRH induces NK-1 gene expression. These results may explain CRHR-1 and NK-1 expression in lesional skin of psoriatic patients.     

IL-33 augments substance P–induced VEGF secretion from human mast cells and is increased in psoriatic skin

The peptide substance P (SP) has been implicated in inflammatory conditions, such as psoriasis, where mast cells and VEGF are increased. A relationship between SP and VEGF has not been well studied, nor has any interaction with the proinflammatory cytokines, especially IL-33. Here we report that SP (0.1–10 μM) induces gene expression and secretion of VEGF from human LAD2 mast cells and human umbilical core blood-derived cultured mast cells (hCBMCs). This effect is significantly increased by coadministration of IL-33 (5–100 ng/mL) in both cell types. The effect of SP on VEGF release is inhibited by treatment with the NK-1 receptor antagonist 733,060. SP rapidly increases cytosolic calcium, and so does IL-33 to a smaller extent; the addition of IL-33 augments the calcium increase. SP-induced VEGF production involves calcium-dependent PKC isoforms, as well as the ERK and JNK MAPKs. Gene expression of IL-33 and histidine decarboxylase (HDC), an indicator of mast cell presence/activation, is significantly increased in affected and unaffected (at least 15 cm away from the lesion) psoriatic skin, as compared with normal control skin. Immunohistochemistry indicates that IL-33 is associated with endothelial cells in both the unaffected and affected sites, but is stronger and also associated with immune cells in the affected site. These results imply that functional interactions among SP, IL-33, and mast cells leading to VEGF release contribute to inflammatory conditions, such as the psoriasis, a nonallergic hyperproliferative skin inflammatory disorder with a neurogenic component.     

Resistance training effects on muscular strength of elderly are related to intensity and gender

The purpose of this study was to determine whether a high intensity (HI) versus a moderate (MI) or low-intensity (LI) training program would be more effective in improving the isokinetic knee extension muscular performance in healthy inactive men and women. Sixty-four participants, men and women, were randomly assigned to one of four groups: control group (C), LI (50% of 1RM), the MI group (70% of 1RM) and the HI (90% of 1RM). Participants exercised on three resistance exercise machines: leg extension, leg curls and leg press. The isokinetic testing method (concentric mode) applied prior to and at the end of the training period (16 weeks, three 3 times per week) to assess the knee muscular performance. MANOVA repeated measures revealed that the HI group demonstrated the most strength gains following a speed specificity pattern (most considerable improvement occurred at or near slow speeds from 7.3% to 11.2% for male and from 2.3% to 15.2% for female). In addition, males demonstrated a greater improvement of knee extension power output than females. In conclusion, HI strength training is proposed for elderly men and women as the most effective protocol. Furthermore only at low-velocity testing, women of the HI showed a greater change than men (p < 0.05). Regarding strength increase in relation to various testing velocities, a greater increase was found in HI at low velocities, with the other training groups exhibiting almost similar strength increase at all tested speeds.