Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post-COVID-19 condition

BACKGROUND: The post‐COVID‐19 condition (PCC) consists of a wide array of symptoms including fatigue and impaired daily living. People seek a wide variety of approaches to help them recover. A new belief, arising from a few laboratory studies, is that 'microclots' cause the symptoms of PCC. This belief has been extended outside these studies, suggesting that to recover people need plasmapheresis (an expensive process where blood is filtered outside the body). We appraised the laboratory studies, and it was clear that the term 'microclots' is incorrect to describe the phenomenon being described. The particles are amyloid and include fibrin(ogen); amyloid is not a part of a thrombus which is a mix of fibrin mesh and platelets. Initial acute COVID‐19 infection is associated with clotting abnormalities; this review concerns amyloid fibrin(ogen) particles in PCC only. We have reported here our appraisal of laboratory studies investigating the presence of amyloid fibrin(ogen) particles in PCC, and of evidence that plasmapheresis may be an effective therapy to remove amyloid fibrin(ogen) particles for treating PCC. OBJECTIVES: Laboratory studies review: To summarize and appraise the research reports on amyloid fibrin(ogen) particles related to PCC. / Randomized controlled trials review: To assess the evidence of the safety and efficacy of plasmapheresis to remove amyloid fibrin(ogen) particles in individuals with PCC from randomized controlled trials. SEARCH METHODS: Laboratory studies review: We searched for all relevant laboratory studies up to 27 October 2022 using a comprehensive search strategy which included the search terms ‘COVID’, ‘amyloid’, ‘fibrin’, ‘fibrinogen’. / Randomized controlled trials review We searched the following databases on 21 October 2022: Cochrane COVID‐19 Study Register; MEDLINE (Ovid); Embase (Ovid); and BIOSIS Previews (Web of Science). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress. SELECTION CRITERIA: Laboratory studies review: Laboratory studies that investigate the presence of amyloid fibrin(ogen) particles in plasma samples from patients with PCC were eligible. This included studies with or without controls. / Randomized controlled trials review: Studies were eligible if they were of randomized controlled design and investigated the effectiveness or safety of plasmapheresis for removing amyloid fibrin(ogen) particles for treating PCC. DATA COLLECTION AND ANALYSIS: Two review authors applied study inclusion criteria to identify eligible studies and extracted data. / Laboratory studies review: We assessed the risk of bias of included studies using pre‐developed methods for laboratory studies. We planned to perform synthesis without meta‐analysis (SWiM) as described in our protocol. / Randomized controlled trials review: We planned that if we identified any eligible studies, we would assess risk of bias and report results with 95% confidence intervals. The primary outcome was recovery, measured using the Post‐COVID‐19 Functional Status Scale (absence of symptoms related to the illness, ability to do usual daily activities, and a return to a previous state of health and mind). MAIN RESULTS: Laboratory studies review: We identified five laboratory studies. Amyloid fibrin(ogen) particles were identified in participants across all studies, including those with PCC, healthy individuals, and those with diabetes. The results of three studies were based on visual images of amyloid fibrin(ogen) particles, which did not quantify the amount or size of the particles identified. Formal risk of bias assessment showed concerns in how the studies were conducted and reported. This means the results were insufficient to support the belief that amyloid fibrin(ogen) particles are associated with PCC, or to determine whether there is a difference in the amount or size of amyloid fibrin(ogen) particles in the plasma of people with PCC compared to healthy controls. / Randomized controlled trials review: We identified no trials meeting our inclusion criteria. AUTHORS' CONCLUSIONS: In the absence of reliable research showing that amyloid fibrin(ogen) particles contribute to the pathophysiology of PCC, there is no rationale for plasmapheresis to remove amyloid fibrin(ogen) particles in PCC. Plasmapheresis for this indication should not be used outside the context of a well‐conducted randomized controlled trial

Cross-sectional associations between occupational factors and musculoskeletal pain in women teachers, nurses and sonographers

A. Technical measurements of the physical workload. (DOCX 18 kb

Mixtures of four organochlorines enhance human breast cancer cell proliferation.

In view of the large differences between the concentrations of estrogenic chemicals needed to elicit effects in in vitro assays and their levels in human tissues, it is hard to explain possible health risks in terms of exposure to individual compounds. Human populations, however, are exposed to mixtures of estrogenic and estrogen-like agents and it is necessary to consider the impact of combined effects. We assessed the combined effects of 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2,2-trichloroethane (o,p'-DDT), 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (p,p'-DDT) on the induction of cell proliferation in MCF-7 cells. All four compounds are persistent organochlorines that can be found in human tissues. We performed extensive concentration-response analyses with the single agents to predict the effects of two mixtures of all four compounds with different mixture ratios. We calculated the predictions by using the pharmacologically well-founded models of concentration addition and independent action and then tested them experimentally. o,p'-DDT, p,p'-DDE, beta-HCH, and p,p'-DDT acted together to produce proliferative effects in MCF-7 cells. The combined effect of the four agents could be predicted on the basis of data about single agent concentration-response relationships. Regression analysis demonstrated that there were combination effects even when each mixture component was present at levels at or below its individual no-observed-effect-concentration. We assessed combination effects in two ways: First, evaluations in relation to the proliferative responses induced by single mixture components revealed that the combination effects were stronger than the effects of the most potent constituent. Thus, according to this method of evaluation, the combined effects may be termed synergistic. Second, comparisons with the expected effects, as predicted by concentration addition and independent action, showed excellent agreement between prediction and observation. With this approach, the combined effect of all four compounds can be termed additive

A COMPARISON OF CHOLINESTERASE DISTRIBUTION IN THE CEREBELLUM OF SEVERAL SPECIES *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65142/1/j.1471-4159.1964.tb06717.x.pd

Inhibition of plasmin-mediated TAFI activation may affect development but not progression of abdominal aortic aneurysms

Objective: Thrombin-activatable fibrinolysis inhibitor (TAFI) reduces the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Studies in TAFI-deficient mice have implicated a potential role for TAFI in Abdominal Aortic Aneurysm (AAA) disease. The role of TAFI inhibition on AAA formation in adult ApoE-/- mice is unknown. The aim of this paper was to investigate the effects of TAFI inhibition on AAA development and progression. Methods: Using the Angiotensin II model of AAA, male ApoE-/- mice were infused with Angiotensin II 750ng/kg/min with or without a monoclonal antibody inhibitor of plasmin-mediated activation of TAFI, MA-TCK26D6, or a competitive small molecule inhibitor of TAFI, UK-396082. Results: Inhibition of TAFI in the Angiotensin II model resulted in a decrease in the mortality associated with AAA rupture (from 40.0% to 16.6% with MA-TCK26D6 (log-rank Mantel Cox test p = 0.16), and 8.3% with UK-396082 (log-rank Mantel Cox test p = 0.05)). Inhibition of plasmin-mediated TAFI activation reduced the incidence of AAA from 52.4% to 30.0%. However, late treatment with MA-TCK26D6 once AAA were already established had no effect on the progression of AAA in this model. Conclusions: The formation of intra-mural thrombus is responsible for the dissection and early rupture in the angiotensin II model of AAA, and this process can be prevented through inhibition of TAFI. Late treatment with a TAFI inhibitor does not prevent AAA progression. These data may indicate a role for inhibition of plasmin-mediated TAFI activation in the early stages of AAA development, but not in its progression

Hemostasis and ageing

On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related Diseases was held in Palermo, Italy. The lecture of D. Mari on Hemostasis and ageing is summarized herein. Physiological ageing is associated with increased plasma levels of many proteins of blood coagulation together with fibrinolysis impairment. This may be of great concern in view of the known association between vascular and thromboembolic diseases and ageing. On the other hand, centenarians are characterized by a state of hypercoagulability and possession of several high-risk alleles and well-known atherothrombotic risk markers but this appears to be compatible with longevity and/or health. Parameters considered risk factors for atherosclerotic vascular diseases in young people may lose their biological significance in advanced age and assume a different role

Associations between neck musculoskeletal complaints and work related factors among public service computer workers in Kaunas

Objectives:Information technologies have been developing very rapidly, also in the case of occupational activities. Epidemiological studies have shown that employees, who work with computers, are more likely to complain of musculoskeletal disorders (MSD). The aim of this study was to evaluate associations between neck MSD and individual and work related factors. Materials and Methods: The investigation which consisted of two parts - a questionnaire study (using Nordic Musculoskeletal questionnaire and Copenhagen Psychosocial Questionnaire) and a direct observation (to evaluate ergonomic work environment using RULA method) was carried out in three randomly selected public sector companies of Kaunas. The study population consisted of 513 public service office workers. Results: The survey showed that neck MSDs were very common in the investigated population. The prevalence rate amounted to 65.7%. According to our survey neck MSDs were significantly associated with older age, bigger work experience, high quantitative and cognitive job demands, working for longer than 2 h without taking a break as well as with higher ergonomic risk score. The fully adjusted model working for longer than 2 h without taking a break had the strongest associations with neck complaints. Conclusion: It was confirmed, that neck MSDs were significantly associated with individual factors as well as conditions of work, therefore, preventive acions against neck complaints should be oriented at psychosocial and ergonomic work environment as well as at individual factors

Genes influencing coagulation and the risk of aneurysmal subarachnoid hemorrhage, and subsequent complications of secondary cerebral ischemia and rebleeding

We investigated whether genes influencing coagulation are associated with the occurrence of aneurysmal subarachnoid hemorrhage (SAH) and with secondary cerebral ischemia and rebleeding in patients with aneurysmal SAH. Genotyping for factor V Leiden (G1691A), prothrombin G20210A, methylenetetetrahydrofolate reductase (MTHFR) C677T, factor XIII subunit A Val34Leu, Tyr204Phe and Pro564Leu, and factor XIII subunit B His95Arg was performed in 208 patients with aneurysmal SAH and in 925 controls. Secondary cerebral ischemia occurred in 49 (24%) patients and rebleeding in 28 (14%) during their clinical course of 3 months after the aneurysmal SAH. The risk of aneurysmal SAH was assessed as odds ratio (OR) with 95% confidence interval (95% CI). The risk of secondary cerebral ischemia and rebleeding was assessed as hazard ratio (HR) with 95% CI using Cox regression. Carriers of the subunit B His95Arg factor XIII polymorphism had an increased risk of aneurysmal SAH with 23% of the patients homozygous or heterozygous for the variant allele compared to 17% of control subjects (OR 1.5, 95% CI 1.0-2.2). For the remaining genetic variants no effect on the risk of aneurysmal SAH could be demonstrated. A clear relation with the risk of secondary cerebral ischemia and of rebleeding could not be established for any of the genetic variants. We found that aneurysmal SAH patients are more often carriers of the subunit B His95Arg factor XIII polymorphism compared to controls. This suggests that carriers of the subunit B His95Arg factor XIII polymorphism have an increased risk of aneurysmal SAH. Larger studies should confirm our results. As aneurysmal SAH patients who died soon after admission could not be included in the present study, our results only apply to a population of patients who survived the initial hours after the hemorrhage. For the other studied genetic factors involved in coagulation, no association with the occurrence of aneurysmal SAH or with the occurrence of secondary cerebral ischemia or rebleeding after aneurysmal SAH could be demonstrated

Interventions to improve work outcomes in work-related PTSD: a systematic review

<p>Abstract</p> <p>Background</p> <p>Posttraumatic stress disorder acquired at work can be debilitating both for workers and their employers. The disorder can result in increased sick leave, reduced productivity, and even unemployment. Furthermore, workers are especially unlikely to return to their previous place of employment after a traumatic incident at work because of the traumatic memories and symptoms of avoidance that typically accompany the disorder. Therefore, intervening in work-related PTSD becomes especially important in order to get workers back to the workplace.</p> <p>Methods</p> <p>A systematic literature search was conducted using Medline, PsycINFO, Embase, and Web of Science. The articles were independently screened based on inclusion and exclusion criteria, followed by a quality assessment of all included articles.</p> <p>Results</p> <p>The systematic search identified seven articles for inclusion in the review. These consisted of six research articles and one systematic review. The review focused specifically on interventions using real exposure techniques for anxiety disorders in the workplace. In the research articles addressed in the current review, study populations included police officers, public transportation workers, and employees injured at work. The studies examined the effectiveness of EMDR, cognitive-behavioural techniques, and an integrative therapy approach called brief eclectic psychotherapy. Interestingly, 2 of the 6 research articles addressed add-on treatments for workplace PTSD, which were designed to treat workers with PTSD who failed to respond to traditional evidence-based psychotherapy.</p> <p>Conclusions</p> <p>Results of the current review suggest that work-related interventions show promise as effective strategies for promoting return to work in employees who acquired PTSD in the workplace. Further research is needed in this area to determine how different occupational groups with specific types of traumatic exposure might respond differently to work-tailored treatments.</p

Work related complaints of neck, shoulder and arm among computer office workers: a cross-sectional evaluation of prevalence and risk factors in a developing country

<p>Abstract</p> <p>Background</p> <p>Complaints of arms, neck and shoulders (CANS) is common among computer office workers. We evaluated an aetiological model with physical/psychosocial risk-factors.</p> <p>Methods</p> <p>We invited 2,500 computer office workers for the study. Data on prevalence and risk-factors of CANS were collected by validated Maastricht-Upper-extremity-Questionnaire. Workstations were evaluated by Occupational Safety and Health Administration (OSHA) Visual-Display-Terminal workstation-checklist. Participants' knowledge and awareness was evaluated by a set of expert-validated questions. A binary logistic regression analysis investigated relationships/correlations between risk-factors and symptoms.</p> <p>Results</p> <p>Sample size was 2,210. Mean age 30.8 ± 8.1 years, 50.8% were males. The 1-year prevalence of CANS was 56.9%, commonest region of complaint was forearm/hand (42.6%), followed by neck (36.7%) and shoulder/arm (32.0%). In those with CANS, 22.7% had taken treatment from a health care professional, only in 1.1% seeking medical advice an occupation-related injury had been suspected/diagnosed. In addition 9.3% reported CANS-related absenteeism from work, while 15.4% reported CANS causing disruption of normal activities. A majority of evaluated workstations in all participants (88.4%,) and in those with CANS (91.9%) had OSHA non-compliant workstations. In the binary logistic regression analyses female gender, daily computer usage, incorrect body posture, bad work-habits, work overload, poor social support and poor ergonomic knowledge were associated with CANS and its' severity In a multiple logistic regression analysis controlling for age, gender and duration of occupation, incorrect body posture, bad work-habits and daily computer usage were significant independent predictors of CANS</p> <p>Conclusions</p> <p>The prevalence of work-related CANS among computer office workers in Sri Lanka, a developing, South Asian country is high and comparable to prevalence in developed countries. Work-related physical factors, psychosocial factors and lack of awareness were all important associations of CANS and effective preventive strategies need to address all three areas.</p