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Frontiers in Bioscience (Scholar... Jun 2024Several inherited metabolic fatty acid disorders present with myopathies. Skeletal muscle accounts for 40% of the body and is important for metabolism, exercise, and... (Review)
Review
Several inherited metabolic fatty acid disorders present with myopathies. Skeletal muscle accounts for 40% of the body and is important for metabolism, exercise, and movement. Muscle energy failure is manifested by metabolic crises with muscle weakness, sometimes associated with muscle fatigue and failure resulting in acute necrosis or rhabdomyolysis/myoglobinuria episodes. Lack of energy leads to muscle necrosis. Other presentations are weakness and myalgias with lipid storage myopathies in the biopsy. The biomarkers of such disorders are acyl-carnitine with various profiles and need to be carefully evaluated to plan supplementary therapy and specific diets. If red flags are not distinctly followed and diagnosed in time they might lead to a metabolic or cardiac failure.
Topics: Humans; Muscular Diseases; Carnitine; Lipid Metabolism, Inborn Errors; Muscle, Skeletal; Muscular Dystrophies
PubMed: 38939976
DOI: 10.31083/j.fbs1602012 -
Cureus May 2024The novel SARS-CoV-2 introduced several new inflammatory conditions including SARS-CoV-2-associated rhabdomyolysis and viral myositis. We present a 22-year-old man who...
The novel SARS-CoV-2 introduced several new inflammatory conditions including SARS-CoV-2-associated rhabdomyolysis and viral myositis. We present a 22-year-old man who noted a week of cough followed by myalgias, dark-colored urine, and decreased oral intake. He was found to have acute nontraumatic rhabdomyolysis after an acutely positive SARS-CoV-2 test. Initial creatine kinase (CK) level was above the reference range as were liver enzymes reflective of muscle breakdown. Treatment involved fluid resuscitation and pain control, with close monitoring of kidney, liver, and skeletal markers over five days of hospitalization till there was clinical and symptomatic improvement.
PubMed: 38933630
DOI: 10.7759/cureus.61172 -
Vaccines Jun 2024Enhancing our comprehension of mRNA vaccines may facilitate the future design of novel vaccines aimed at augmenting immune protection while minimising reactogenic...
Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Analysis on Immunology Aspects of a Prospective Cohort Study.
Enhancing our comprehension of mRNA vaccines may facilitate the future design of novel vaccines aimed at augmenting immune protection while minimising reactogenic responses. Before this design is carried out, it is important to determine whether adaptive immunity correlates with the reactogenicity profile of vaccines. We studied a large cohort that was vaccinated with mRNA vaccines to answer this question. This was an observational study with real-world data. Reactogenicity data were obtained from the VigilVacCOVID study. Immunogenicity (humoral and cellular) data were retrieved from health records. One main population (n = 215) and two subpopulations were defined (subpopulation 1, n = 3563; subpopulation 2, n = 597). Sensitivity analyses were performed with subpopulations 1 and 2 to explore the consistency of results. We analysed the association of the intensity and types of adverse reactions with the development and quantity of elicited antibody titres. As an exploratory analysis in subpopulation 1, we assessed the association between reactogenicity and cellular immunogenicity. A higher incidence of fever, malaise, and myalgia including severe cases was significantly associated with the development and quantity of positive antibody titres. No significant findings were observed with cellular immunity. We observed a positive association between immunogenicity and reactogenicity. These findings can be relevant for the future development of our understanding of how mRNA vaccines function.
PubMed: 38932394
DOI: 10.3390/vaccines12060665 -
Journal of Clinical Medicine Jun 2024SARS-CoV-2 continually mutates, with five identified variants. Many neurological manifestations were observed during the COVID-19 pandemic, with differences between...
SARS-CoV-2 continually mutates, with five identified variants. Many neurological manifestations were observed during the COVID-19 pandemic, with differences between virus variants. The aim of this study is to assess the frequency and characteristics of neurological manifestations during COVID-19 in hospitalized patients over three waves in Poland with comparison and analysis correlation with the course of infection. This retrospective single-center study included 600 consecutive adults with confirmed COVID-19, hospitalized during 3 waves (pre-Delta, Delta and Omicron) in Poland. Demographic and clinical information and neurological manifestations were collected and compared across three periods. The median age of the study group was 68, lower during the Delta wave. In the Omicron period, the disease severity at admission and inflammatory markers concentration were the lowest. Neurological manifestations were observed in 49%. The most common were altered mentation, headache, myalgia, mood disorder, ischemic stroke and encephalopathy. Smell and taste disturbances (STDs) were less frequent in the Omicron period. Neurological complications were predominant in the pre-Delta and Omicron periods. Ischemic stroke was observed more often in pre-Delta period. Altered mentation was related to higher severity at admission, worse lab test results, higher admission to ICU and mortality, while headache reduced mortality. Pre-existing dementia was related to higher mortality. Neurological manifestations of COVID-19 are frequent, with a lower rate of STDs in the Omicron period and more often cerebrovascular diseases in the pre-Delta period. Headache improves the course of COVID-19, while altered mentation, stroke and neurological comorbidities increase severity and mortality.
PubMed: 38930003
DOI: 10.3390/jcm13123477 -
Medicina (Kaunas, Lithuania) Jun 2024Medical and public recognition of "long-COVID or post-COVID syndrome", as well as its impact on the quality of life (QoL), is required to better address the disease... (Observational Study)
Observational Study
Medical and public recognition of "long-COVID or post-COVID syndrome", as well as its impact on the quality of life (QoL), is required to better address the disease burden. Objectives: We aimed to describe the persistence of COVID-19 symptoms and QoL among patients at three and twelve months after their discharge from the hospital. We conducted an observational, prospective, and longitudinal analytic study from September 2021 to April 2022. To measure QoL, we used a validated version of the 36-item Short-Form Health Survey (SF-36). We included 68 patients in the study. A total of 54 (79.4%) patients reported at least one persistent symptom at three months vs. 52 (76.4%) at twelve months ( = 0.804). Some persistent symptoms (myalgia, alopecia, and cough) decreased significantly at twelve months (50% vs. 30.9%, 29.4% vs. 13.2%, and 23.5% vs. 7.4%; respectively, = 0.007); in contrast, other persistent symptoms (sleep-wake and memory disorders) were more frequent (5.9% vs. 32.4% and 4.4% vs. 20.6%; respectively, = ≤0.001). Regarding QoL, a statistically significant improvement was observed in some scores over time, = ≤0.037. At twelve months, dyspnea, myalgia, and depression were risk factors associated with a poor physical component summary (PCS), = ≤0.027, whereas anxiety, depression, and fatigue were associated with a poor mental component summary (MCS), = ≤0.015. As the proportion of persistent symptoms at twelve months is high, we suggest that patients must continue under long-term follow up to reclassify, diagnose, and treat new onset symptoms/diseases.
Topics: Humans; COVID-19; Quality of Life; Female; Male; Middle Aged; Prospective Studies; Patient Discharge; Longitudinal Studies; Aged; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Adult; Myalgia; Time Factors; Cough; Alopecia
PubMed: 38929561
DOI: 10.3390/medicina60060944 -
Biomedicines May 2024The SARS-CoV-2 virus has spread rapidly despite implementing strategies to reduce its transmission. The disease caused by this virus has been associated with a diverse... (Review)
Review
The SARS-CoV-2 virus has spread rapidly despite implementing strategies to reduce its transmission. The disease caused by this virus has been associated with a diverse range of symptoms, including common neurological manifestations such as dysgeusia, anosmia, and myalgias. Additionally, numerous cases of severe neurological complications associated with this disease have been reported, including encephalitis, stroke, seizures, and Guillain-Barré syndrome, among others. Given the high prevalence of neurological manifestations in this disease, the objective of this review is to analyze the mechanisms by which this virus can affect the nervous system, from its direct invasion to aberrant activation of the immune system and other mechanisms involved in the symptoms, including neuropsychiatric manifestations, to gain a better understanding of the disease and thus facilitate the search for effective therapeutic strategies.
PubMed: 38927354
DOI: 10.3390/biomedicines12061147 -
Communicable Diseases Intelligence... Jun 2024This report summarises Australia's spontaneous (passive) surveillance data for adverse events following immunisation (AEFI) for coronavirus disease 2019 (COVID-19)...
This report summarises Australia's spontaneous (passive) surveillance data for adverse events following immunisation (AEFI) for coronavirus disease 2019 (COVID-19) vaccines in 2021 reported to the Therapeutic Goods Administration (TGA). The TGA strongly promoted and facilitated adverse event reporting in preparation for, and during, the COVID-19 vaccine rollout as a core component of the most intensive vaccine safety monitoring ever conducted in Australia. There were 111,348 AEFI reports for COVID-19 vaccines administered in 2021, an annual AEFI reporting rate of 271.4 per 100,000 doses of COVID-19 vaccines administered to people aged ≥ 12 years. The annual AEFI reporting rate for non-COVID-19 vaccines in 2021 was 30.6 per 100,000 doses administered to people of all ages. Overall, the most frequently reported symptoms were headache, adverse events classified as 'gastrointestinal nonspecific symptoms and therapeutic procedures', myalgia, pyrexia and fatigue, which were consistent with common expected adverse events following COVID-19 vaccines used in Australia. The most commonly reported adverse events of special interest were myocarditis and/or pericarditis, followed by thrombosis and thromboembolism, and anaphylaxis. Of all COVID-19 vaccine AEFI reports, 762 (0.7%) included a fatal outcome, of which over 80% were in people aged ≥ 60 years. Thirteen deaths reported in 2021 were assessed as likely to be causally linked to vaccination. This report confirms the value of spontaneous post-marketing vaccine pharmacovigilance, especially in the context of new vaccines using novel vaccine technologies and near whole-of-population pandemic vaccination programs. The most frequently reported AEFI for COVID-19 vaccines were common, mild and temporary (lasting 1 or 2 days), and consistent with clinical trial and active surveillance data. Ongoing safety monitoring detected rare, unexpected conditions, such as myocarditis/pericarditis and thrombosis with thrombocytopenia syndrome (TTS), which were investigated and confirmed as safety signals, resulting in changes to vaccine recommendations and product information. The outcomes of TGA monitoring were published in weekly vaccine safety reports. Overall, COVID-19 vaccine safety monitoring provided critical information on the risks of vaccine related adverse events that enabled decisionmakers to undertake informed risk-benefit assessments.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Male; Middle Aged; Young Adult; Adverse Drug Reaction Reporting Systems; Australia; COVID-19; COVID-19 Vaccines; Vaccination
PubMed: 38926650
DOI: 10.33321/cdi.2024.48.2 -
Brain, Behavior, and Immunity Jun 2024Activity-induced muscle pain increases interleukin-1β (IL-1β) release from muscle macrophages and the development of hyperalgesia is prevented by blockade of IL-1β in...
Activity-induced muscle pain increases interleukin-1β (IL-1β) release from muscle macrophages and the development of hyperalgesia is prevented by blockade of IL-1β in muscle. Brain derived neurotrophic factor (BDNF) is released from sensory neurons in response to IL-1β and mediates both inflammatory and neuropathic pain. Thus, we hypothesize that in activity-induced pain, fatigue metabolites combined with IL-1β activate sensory neurons to increase BDNF release, peripherally in muscle and centrally in the spinal dorsal horn, to produce hyperalgesia. We tested the effect of intrathecal or intramuscular injection of BDNF-Tropomyosin receptor kinase B (TrkB) inhibitors, ANA-12 or TrkB-Fc, on development of activity-induced pain. Both inhibitors prevented the hyperalgesia when given before or 24hr after induction of the model in male but not female mice. BDNF messenger ribonucleic acid (mRNA) and protein were significantly increased in dorsal root ganglion (DRG) 24hr after induction of the model in both male and female mice. Blockade of IL-1β in muscle had no effect on the increased BNDF mRNA observed in the activity-induced pain model, while IL-1β applied to cultured DRG significantly induced BDNF expression, suggesting IL-1β is sufficient but not necessary to induce BNDF. Thus, fatigue metabolites, combined with IL-1β, upregulate BDNF in primary DRG neurons in both male and female mice, but contribute to activity-induced pain only in males.
PubMed: 38925417
DOI: 10.1016/j.bbi.2024.06.019 -
Reumatismo Jun 2024The safety profile of baricitinib (BARI), a Janus kinase inhibitor broadly used for the treatment of rheumatoid arthritis (RA), includes asymptomatic laboratory...
The safety profile of baricitinib (BARI), a Janus kinase inhibitor broadly used for the treatment of rheumatoid arthritis (RA), includes asymptomatic laboratory abnormalities, such as an increase in creatine kinase (CK). Data from randomized controlled trials suggest that concomitant myalgia is rare in RA and does not lead to drug discontinuation. We describe the case of a 68-year-old Caucasian female with longstanding, multi-failure RA who started BARI and achieved disease remission. However, she developed a symptomatic CK increase, as well as a parallel increase in total cholesterol, low-density lipoprotein, and triglycerides. Dechallenge-rechallenge demonstrated a plausible relationship between the clinical/laboratory abnormalities and BARI. In fact, when the drug was withdrawn, CK returned to normal and myalgia disappeared, whereas symptoms returned and CK levels increased when BARI was restarted. BARI may be rarely associated with symptomatic CK elevation, and this may pose clinical challenges, particularly for patients with multi-failure RA who achieved good disease control with BARI but required drug discontinuation due to intolerance.
Topics: Humans; Arthritis, Rheumatoid; Female; Purines; Aged; Azetidines; Pyrazoles; Sulfonamides; Creatine Kinase; Myalgia; Antirheumatic Agents; Janus Kinase Inhibitors
PubMed: 38916168
DOI: 10.4081/reumatismo.2024.1620 -
Mayo Clinic Proceedings Jun 2024The guidelines for cholesterol management have been updated over the years from treat-to-target using any drug class to emphasis on statins without treatment targets to... (Review)
Review
The guidelines for cholesterol management have been updated over the years from treat-to-target using any drug class to emphasis on statins without treatment targets to a hybrid of the 2 approaches. The most recent guideline updates include newer nonstatin lipid-lowering therapies (LLTs), low-density lipoprotein cholesterol (LDL-C) reduction goals, and LDL-C thresholds considering secondary prevention and cardiovascular risk. Although statins have been the mainstay of LLT for years, newer pharmacological agents such as proprotein convertase subtilisin-kexin type 9 inhibitor(s) (PCSK9i) monoclonal antibodies, small interfering RNA PCSK9i, and bempedoic acid to optimize LDL-C levels may be underutilized in clinical practice. To provide an updated review for clinicians, we performed a literature search in PubMed for articles published from January 1, 2000, to August 31, 2023, that included the terms cholesterol, LLT, bempedoic acid, inclisiran, or PCSK9 inhibitor. Studies were selected for inclusion according to relatedness to cholesterol management and outcomes with novel LLT agents. Optimization of statins can improve the lipid profile and contribute to primary and secondary atherosclerotic cardiovascular disease (ASCVD) prevention. The newest guidance combines anticipated LDL-C reduction from statins and LDL-C thresholds for primary and secondary prevention. Nonstatin agents such as PCSK9i monoclonal antibodies, small interfering RNA PCSK9i, and bempedoic acid are safe and effective LLTs that can be used in addition to statin therapy for additional LDL-C lowering and prevention of ASCVD. Additionally, these nonstatin agents are reasonable to initiate in patients who have not been able to tolerate statins due to myalgias, rhabdomyolysis, or contraindications. Cost may be a barrier to initiating these agents for patients who are underinsured or uninsured. Clinicians should reference the most up-to-date guidance for LLT for primary and secondary prevention of ASCVD. Additionally, clinicians must diligently continue to optimize statin and nonstatin LLT to improve cardiovascular health outcomes.
PubMed: 38912991
DOI: 10.1016/j.mayocp.2024.03.001