Fatigue in Children and Adolescents: A Population-Based Longitudinal Study on Fatigue and Chronic Pain

Abstract:

Objective: There are limited data on the prevalence and stability of fatigue in pediatrics, particularly among youth with chronic pain. Little is known about longitudinal effects of fatigue on health outcomes such as sleep quality, psychological distress, Health-Related Quality of Life, and chronic pain.

Methods: A community-based sample of N = 1276 students (9-17 years; 52% female; 30.3% with chronic pain) from 3 schools was screened at 2 measurement points 3 months apart. Prevalence and stability of fatigue were examined. Longitudinal analyses regarding fatigue and health outcomes were run using repeated measures correlations. The impact of change in fatigue on pain progression was analyzed using multilevel linear models.

Results: In the total community sample, 4.4% reported severe fatigue symptoms. The prevalence of severe fatigue was significantly higher in students with chronic pain (11.4%) compared to those without (1.3%). Fatigue symptoms persisted for several months, worsening of symptoms was more common and improvement less common in children with chronic pain. Sleep, psychological distress, and Health-Related Quality of Life were significantly associated with fatigue across both measurement points (rs = |0.16-0.44|), with no significant differences in the strength of correlations between children with and without chronic pain (ps > .05). There was a significant interaction between change in fatigue and courses of pain intensity and functional impairment.

Conclusions: Fatigue is highly prevalent, particularly in youth with chronic pain. The negative association of fatigue with health outcomes, and its impact on the course of pain, require early identification and treatment of those affected to prevent negative long-term consequences.

Source: Sommer A, Grothus S, Claus BB, Stahlschmidt L, Wager J. Fatigue in Children and Adolescents: A Population-Based Longitudinal Study on Fatigue and Chronic Pain. J Pediatr Psychol. 2023 May 10:jsad026. doi: 10.1093/jpepsy/jsad026. Epub ahead of print. PMID: 37164626. https://pubmed.ncbi.nlm.nih.gov/37164626/

Bamboo-based medicinal moxibustion for chronic fatigue syndrome: a randomized controlled trial

Abstract:

in English, Chinese

Objective: To observe the clinical efficacy of bamboo-based medicinal moxibustion for chronic fatigue syndrome (CFS), and to preliminarily explore its action mechanism.

Methods: Sixty-four patients with CFS were randomly divided into a moxibustion group (32 cases, 1 case dropped off, 1 case excluded) and an acupuncture group (32 cases, 2 cases dropped off). The patients in the moxibustion group were treated with bamboo-based medicinal moxibustion, while the patients in the acupuncture group were treated with routine acupuncture. Both groups were treated once a day, 6 days as a course of treatment with 1 day interval, for a total of 2 courses of treatment. Before treatment, 1 and 2 courses into treatment and in the follow-up of 14 days after treatment, the fatigue scale-14 (FS-14) and somatic and psychological health report (SPHERE) scores were observed in the two groups. Before and after treatment, the contents of CD+3, CD+4, CD+8 of peripheral blood T lymphocyte subsets were measured and CD+4/CD+8 ratio was calculated; the clinical efficacy of the two groups was compared.

Results: Compared before treatment, the FS-14 and SPHERE scores in the two groups were decreased 1 and 2 courses into treatment and in the follow-up (P<0.01), and the FS-14 and SPHERE scores in the moxibustion group were lower than those in the acupuncture group (P<0.01, P<0.05). Compared before treatment, the contents of CD+3, CD+4 and CD+4/CD+8 ratio in the moxibustion group were increased after treatment (P<0.01). There was no significant difference of CD+3, CD+4, CD+8 and CD+4/CD+8 ratio between before and after treatment in the acupuncture group (P>0.05). After treatment, the contents of CD+3 and CD+4 in the moxibustion group were higher than those in the acupuncture group (P<0.05). The total effective rate was 93.3% (28/30) in the moxibustion group, which was higher than 73.3% (22/30) in the acupuncture group (P<0.05).

Conclusion: Bamboo-based medicinal moxibustion could improve the physical and mental fatigue symptoms and psychological status in patients with CFS. Its effect may be related to regulating the contents of CD+3, CD+4 of peripheral blood T lymphocyte subsets and CD+4/CD+8 ratio.

Source: Xue KY, Quan F, Tang JX, Xiao CH, Lu CX, Cui J. [Bamboo-based medicinal moxibustion for chronic fatigue syndrome: a randomized controlled trial]. Zhongguo Zhen Jiu. 2023 May 12;43(5):493-8. Chinese. PMID: 37161800. https://pubmed.ncbi.nlm.nih.gov/37161800/

Astragalus polysaccharide ameliorated complex factor-induced chronic fatigue syndrome by modulating the gut microbiota and metabolites in mice

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating disease with no symptomatic treatment. Astragalus polysaccharide (APS), a component derived from the traditional Chinese medicine A. membranaceus, has significant anti-fatigue activity. However, the mechanisms underlying the potential beneficial effects of APS on CFS remain poorly understood.

A CFS model of 6-week-old C57BL/6 male mice was established using the multiple-factor method. These mice underwent examinations for behavior, oxidative stress and inflammatory indicators in brain and intestinal tissues, and ileum histomorphology. 16 S rDNA sequencing analysis indicated that APS regulated the abundance of gut microbiota and increased production of short chain fatty acids (SCFAs) and anti-inflammatory bacteria.

In addition, APS reversed the abnormal expression of Nrf2, NF-κB, and their downstream factors in the brain-gut axis and alleviated the reduction in SCFAs in the cecal content caused by CFS. Further, APS modulated the changes in serum metabolic pathways induced by CFS.

Finally, it was verified that butyrate exerted antioxidant and anti-inflammatory effects in neuronal cells. In conclusion, APS could increase the SCFAs content by regulating the gut microbiota, and SCFAs (especially butyrate) can further regulate the oxidative stress and inflammation in the brain, thus alleviating CFS.

This study explored the efficacy and mechanism of APS for CFS from the perspective of gut-brain axis and provides a reference to further explore the efficacy of APS and the role of SCFAs in the central nervous system.

Source: Wei X, Xin J, Chen W, Wang J, Lv Y, Wei Y, Li Z, Ding Q, Shen Y, Xu X, Zhang X, Zhang W, Zu X. Astragalus polysaccharide ameliorated complex factor-induced chronic fatigue syndrome by modulating the gut microbiota and metabolites in mice. Biomed Pharmacother. 2023 May 9;163:114862. doi: 10.1016/j.biopha.2023.114862. Epub ahead of print. PMID: 37167729. https://www.sciencedirect.com/science/article/pii/S0753332223006522?via%3Dihub (Full study)

Whole-body cryotherapy as a treatment for chronic medical conditions?

Abstract:

Introduction: Whole-body cryotherapy (WBC) is a controlled exposure of the whole body to cold to gain health benefits. In recent years, data on potential applications of WBC in multiple clinical settings have emerged.

Sources of data: PubMed, EBSCO and Clinical Key search using keywords including terms ‘whole body’, ‘cryotherapy’ and ‘cryostimulation’.

Areas of agreement: WBC could be applied as adjuvant therapy in multiple conditions involving chronic inflammation because of its potent anti-inflammatory effects. Those might include systemic inflammation as in rheumatoid arthritis. In addition, WBC could serve as adjuvant therapy for chronic inflammation in some patients with obesity.

Areas of controversy: WBC probably might be applied as an adjuvant treatment in patients with chronic brain disorders including mild cognitive impairment and general anxiety disorder and in patients with depressive episodes and neuroinflammation reduction as in multiple sclerosis. WBC effects in metabolic disorder treatment are yet to be determined. WBC presumably exerts pleiotropic effects and therefore might serve as adjuvant therapy in multi-systemic disorders, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Growing points: The quality of studies on the effects of WBC in the clinical setting is in general low; hence, randomized controlled trials with adequate sample size and longer follow-up periods are needed.

Areas are timely for developing research: Further studies should examine the mechanism underlying the clinical efficacy of WBC. Multiple conditions might involve chronic inflammation, which in turn could be a potential target of WBC. Further research on the application of WBC in neurodegenerative disorders, neuropsychiatric disorders and ME/CFS should be conducted.

Source: Tabisz H, Modlinska A, Kujawski S, Słomko J, Zalewski P. Whole-body cryotherapy as a treatment for chronic medical conditions? Br Med Bull. 2023 May 12:ldad007. doi: 10.1093/bmb/ldad007. Epub ahead of print. PMID: 37170956. https://pubmed.ncbi.nlm.nih.gov/37170956/

Can we Reduce the Symptoms of Chronic Fatigue Syndrome by Regulating Micronutrients? A Review

Abstract:

Introduction: Deficiencies of some micronutrients have been observed in chronic fatigue syndrome patients, but the underlying cause has not been fully understood. The aim of this study was to investigate whether there is a relationship between CFS and micronutrients.

Methods: Related articles searched the combinations of the following terms which were used for the search in the Web of Science database: “Chronic Fatigue Syndrome” OR “Chronic Fatigue- Fibromyalgia Syndrome” OR “Postviral Fatigue Syndrome” AND “vitamins” OR “minerals” OR “micronutrients”. Articles that met the inclusion criteria were included.

Results: The initial search resulted in 225 studies, with 11 studies fully meeting the inclusion criteria. In these studies, it has been shown that micronutrients may play a role in the etiology of CFS, and that supplemented micronutrients can positively affect the symptoms of CFS.

Conclusion: Although there seems to be a close relationship between CFS-related syndromes and nutritional status, the literature on this subject remains limited. The results of the studies were not compatible with each other due to differences in the studies. Therefore, new studies are needed to fully explain the relationship between CFS and micronutrients.

Source: Akduman, GUl; Kurtbeyoglu, Emine; Gunes, Fatma E. Can we Reduce the Symptoms of Chronic Fatigue Syndrome by Regulating Micronutrients? A Review. Current Nutrition & Food Science, Volume 19, Number 5, 2023, pp. 509-518(10). https://www.ingentaconnect.com/content/ben/cnf/2023/00000019/00000005/art00005

The fatal trajectory of pulmonary COVID-19 is driven by lobular ischemia and fibrotic remodelling

Abstract:

Background: COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response.

Methods: We studied a total of 85 lungs (n = 31 COVID autopsy samples; n = 7 influenza A autopsy samples; n = 18 interstitial lung disease explants; n = 24 healthy controls) using the highest resolution Synchrotron radiation-based hierarchical phase-contrast tomography, scanning electron microscopy of microvascular corrosion casts, immunohistochemistry, matrix-assisted laser desorption ionization mass spectrometry imaging, and analysis of mRNA expression and biological pathways. Plasma samples from all disease groups were used for liquid biomarker determination using ELISA. The anatomic/molecular data were analyzed as a function of patients’ hospitalization time.

Findings: The observed patchy/mosaic appearance of COVID-19 in conventional lung imaging resulted from microvascular occlusion and secondary lobular ischemia. The length of hospitalization was associated with increased intussusceptive angiogenesis. This was associated with enhanced angiogenic, and fibrotic gene expression demonstrated by molecular profiling and metabolomic analysis. Increased plasma fibrosis markers correlated with their pulmonary tissue transcript levels and predicted disease severity. Plasma analysis confirmed distinct fibrosis biomarkers (TSP2, GDF15, IGFBP7, Pro-C3) that predicted the fatal trajectory in COVID-19.

Interpretation: Pulmonary severe COVID-19 is a consequence of secondary lobular microischemia and fibrotic remodelling, resulting in a distinctive form of fibrotic interstitial lung disease that contributes to long-COVID.

Source: Ackermann M, Kamp JC, Werlein C, Walsh CL, Stark H, Prade V, Surabattula R, Wagner WL, Disney C, Bodey AJ, Illig T, Leeming DJ, Karsdal MA, Tzankov A, Boor P, Kühnel MP, Länger FP, Verleden SE, Kvasnicka HM, Kreipe HH, Haverich A, Black SM, Walch A, Tafforeau P, Lee PD, Hoeper MM, Welte T, Seeliger B, David S, Schuppan D, Mentzer SJ, Jonigk DD. The fatal trajectory of pulmonary COVID-19 is driven by lobular ischemia and fibrotic remodelling. EBioMedicine. 2022 Nov;85:104296. doi: 10.1016/j.ebiom.2022.104296. Epub 2022 Oct 4. PMID: 36206625; PMCID: PMC9535314. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535314/ (Full text)

Trajectory of Gastrointestinal Symptoms in Previously Hospitalized COVID-19 Survivors: The Long COVID Experience Multicenter Study

Abstract:

This multicenter cohort study used Sankey plots and exponential bar plots to visualize the fluctuating evolution and the trajectory of gastrointestinal symptoms in previously hospitalized COVID-19 survivors during the first 18 months after acute SARS-CoV-2 infection. A total of 1266 previously hospitalized COVID-19 survivors were assessed at four points: hospital admission (T0), at 8.4 months (T1), at 13.2 months (T2), and at 18.3 months (T3) after hospitalization.
Participants were asked about their overall gastrointestinal symptoms and particularly diarrhea. Clinical and hospitalization data were collected from hospital medical records. The prevalence of overall gastrointestinal post-COVID symptomatology was 6.3% (n = 80) at T1, 3.99% (n = 50) at T2 and 2.39% (n = 32) at T3. The prevalence of diarrhea decreased from 10.69% (n = 135) at hospital admission (T0), to 2.55% (n = 32) at T1, to 1.04% (n = 14) at T2, and to 0.64% (n = 8) at T3. The Sankey plots revealed that just 20 (1.59%) and 4 (0.32%) patients exhibited overall gastrointestinal post-COVID symptoms or diarrhea, respectively, throughout the whole follow-up period.
The recovery fitted exponential curves revealed a decreasing prevalence trend, showing that diarrhea and gastrointestinal symptoms recover during the first two or three years after COVID-19 in previously hospitalized COVID-19 survivors. The regression models did not reveal any symptoms to be associated with the presence of gastrointestinal post-COVID symptomatology or post-COVID diarrhea at hospital admission or at T1. The use of Sankey plots revealed the fluctuating evolution of gastrointestinal post-COVID symptoms during the first two years after infection. In addition, exponential bar plots revealed the decreased prevalence of gastrointestinal post-COVID symptomatology during the first three years after infection.
Source: Fernández-de-las-Peñas C, Torres-Macho J, Guijarro C, Martín-Guerrero JD, Pellicer-Valero OJ, Plaza-Manzano G. Trajectory of Gastrointestinal Symptoms in Previously Hospitalized COVID-19 Survivors: The Long COVID Experience Multicenter Study. Viruses. 2023; 15(5):1134. https://doi.org/10.3390/v15051134 https://www.mdpi.com/1999-4915/15/5/1134 (Full text)

Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+β7 integrin+ T cells and anti-SARS-CoV-2 IgA response

Abstract:

Several millions of individuals are estimated to develop post-acute sequelae SARS-CoV-2 condition (PASC) that persists for months after infection. Here we evaluate the immune response in convalescent individuals with PASC compared to convalescent asymptomatic and uninfected participants, six months following their COVID-19 diagnosis.

Both convalescent asymptomatic and PASC cases are characterised by higher CD8+ T cell percentages, however, the proportion of blood CD8+ T cells expressing the mucosal homing receptor β7 is low in PASC patients. CD8 T cells show increased expression of PD-1, perforin and granzyme B in PASC, and the plasma levels of type I and type III (mucosal) interferons are elevated. The humoral response is characterized by higher levels of IgA against the N and S viral proteins, particularly in those individuals who had severe acute disease.  Our results also show that consistently elevated levels of IL-6, IL-8/CXCL8 and IP-10/CXCL10 during acute disease increase the risk to develop PASC.

In summary, our study indicates that PASC is defined by persisting immunological dysfunction as late as six months following SARS-CoV-2 infection, including alterations in mucosal immune parameters, redistribution of mucosal CD8+β7Integrin+ T cells and IgA, indicative of potential viral persistence and mucosal involvement in the etiopathology of PASC.

Source: Santa Cruz A, Mendes-Frias A, Azarias-da-Silva M, André S, Oliveira AI, Pires O, Mendes M, Oliveira B, Braga M, Lopes JR, Domingues R, Costa R, Silva LN, Matos AR, Ângela C, Costa P, Carvalho A, Capela C, Pedrosa J, Castro AG, Estaquier J, Silvestre R. Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+β7 integrin+ T cells and anti-SARS-CoV-2 IgA response. Nat Commun. 2023 Mar 30;14(1):1772. doi: 10.1038/s41467-023-37368-1. PMID: 36997530; PMCID: PMC10061413. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061413/ (Full text)

An Exercise Immune Fitness test to unravel mechanisms of post-acute sequelae of COVID-19

Abstract:

The Post-Acute Sequelae of COVID-19 (PASC) Syndrome is a debilitating syndrome with onset three months post COVID-19 infection, marked by the presence of fatigue, headache, cognitive dysfunction, post-exertional malaise, orthostatic intolerance, and dyspnea that is clinically relevant and is at least as severe as fatigue in several other clinical conditions, including cancer. The onset, progression, and symptom profile of PASC patients have considerable overlap with Myalgic-Encephalopathy/Chronic Fatigue Syndrome (ME/CFS).

In people with ME/CFS, exercise (and other types of exertion) can cause serious setbacks and deterioration in function. Post-exertional malaise (PEM) appears to be a common and a significant challenge for the majority of this patient group. Of the nearly 24 million adults in the U.S. who currently have long COVID, more than 80% are having some trouble carrying out daily activities. Mechanisms of PACS remain poorly understood.

While multi-omic information gathered at the time of acute COVID-19 onset may help predict long COVID outcomes, we here propose to test the hypothesis that additional molecular immunological information collected during standardized exercise-testing for cardio-respiratory fitness after recovery from acute COVID-19 can be used to improve the understanding of mechanisms of PASC.

Source: Deng MC. An Exercise Immune Fitness test to unravel mechanisms of post-acute sequelae of COVID-19. Expert Rev Clin Immunol. 2023 May 16. doi: 10.1080/1744666X.2023.2214364. Epub ahead of print. PMID: 37190994. https://www.tandfonline.com/doi/full/10.1080/1744666X.2023.2214364 (Full text)

Contesting misrecognition online: Experiences of epistemic in/justice by vloggers with contested illnesses

Abstract:

Contested illnesses, such as fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and chronic Lyme disease (CLD), are surrounded by polemic debates regarding their etiology, symptomology, treatment, and even their existence. People who suffer from these contested illnesses arguably also suffer from “epistemic injustice.” This concept, coined by the philosopher Miranda Fricker, captures how people’s knowledge may be discredited because of identity prejudices. In our paper, this concept is used to understand how seven Dutch women with contested illnesses experience the emancipatory potential of their vlogging practices.

Our findings show how these women understood their vlogging as a means to break with epistemic smothering, understood as the propensity to cater ones testimony to one’s audience (Dotson, 2011), and as a means to attain and enhance epistemic justice. However, our findings also show how vlogging about contested illnesses did not seem to allow these women to fully break with their epistemic smothering practices, and that the ableist design and gendered norms of YouTube were experienced as obstacles to attaining epistemic justice. We conclude that, even though social media do seem to hold emancipatory potential for these women, the experiences of individual users are diverse and ambiguous.

Source: Groenevelt IPI, de Boer MLM. Contesting misrecognition online: Experiences of epistemic in/justice by vloggers with contested illnesses. Soc Sci Med. 2023 May 7;327:115951. doi: 10.1016/j.socscimed.2023.115951. Epub ahead of print. PMID: 37182295. https://www.sciencedirect.com/science/article/pii/S0277953623003088?via%3Dihub (Full text)