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American Journal of Obstetrics and... Aug 2022To update a previously published systematic review and perform a meta-analysis on the risk factors for primary pelvic organ prolapse and prolapse recurrence. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To update a previously published systematic review and perform a meta-analysis on the risk factors for primary pelvic organ prolapse and prolapse recurrence.
DATA SOURCES
PubMed and Embase were systematically searched. We searched from July 1, 2014 until July 5, 2021. The previous search was from inception until August 4, 2014.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials and cross-sectional and cohort studies conducted in the Western developed countries that reported on multivariable analysis of risk factors for primary prolapse or prolapse recurrence were included. The definition of prolapse was based on anatomic references, and prolapse recurrence was defined as anatomic recurrence after native tissue repair. Studies on prolapse recurrence with a median follow-up of ≥1 year after surgery were included.
METHODS
Quality assessment was performed with the Newcastle-Ottawa Scale. Data from the previous review and this review were combined into forest plots, and meta-analyses were performed where possible. If the data could not be pooled, "confirmed risk factors" were identified if ≥2 studies reported a significant association in multivariable analysis.
RESULTS
After screening, 14 additional studies were selected-8 on the risk factors for primary prolapse and 6 on prolapse recurrence. Combined with the results from the previous review, 27 studies met the inclusion criteria, representing the data of 47,429 women. Not all studies could be pooled because of heterogeneity. Meta-analyses showed that birthweight (n=3, odds ratio, 1.04; 95% confidence interval, 1.02-1.06), age (n=3, odds ratio, 1.34; 95% confidence interval, 1.23-1.47), body mass index (n=2, odds ratio, 1.75; 95% confidence interval, 1.17-2.62), and levator defect (n=2, odds ratio, 3.99; 95% confidence interval, 2.57-6.18) are statistically significant risk factors, and cesarean delivery (n=2, pooled odds ratio, 0.08; 95% confidence interval, 0.03-0.20) and smoking (n=3, odds ratio, 0.59; 95% confidence interval, 0.46-0.75) are protective factors for primary prolapse. Parity, vaginal delivery, and levator hiatal area are identified as "confirmed risk factors." For prolapse recurrence, preoperative prolapse stage (n=5, odds ratio, 2.68; 95% confidence interval, 1.93-3.73) and age (n=2, odds ratio, 3.48; 95% confidence interval, 1.99-6.08) are statistically significant risk factors.
CONCLUSION
Vaginal delivery, parity, birthweight, age, body mass index, levator defect, and levator hiatal area are risk factors, and cesarean delivery and smoking are protective factors for primary prolapse. Preoperative prolapse stage and younger age are risk factors for prolapse recurrence after native tissue surgery.
Topics: Birth Weight; Cross-Sectional Studies; Delivery, Obstetric; Female; Humans; Pelvic Organ Prolapse; Pregnancy; Risk Factors
PubMed: 35500611
DOI: 10.1016/j.ajog.2022.04.046 -
Journal of Clinical Nursing Mar 2018To examine the role of healthcare professionals in the organ donation and transplantation process. (Review)
Review
AIMS AND OBJECTIVES
To examine the role of healthcare professionals in the organ donation and transplantation process.
BACKGROUND
Globally, there remains a perennial disequilibrium between organ donation and organ transplantation. Several factors account for this disequilibrium; however, as healthcare professionals are not only strategically positioned as the primary intermediaries between organ donors and transplant recipients, but also professionally situated as the implementers of organ donation and transplantation processes, they are often blamed for the global organ shortage.
DESIGN
Mixed-method systematic review using the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols 2015 checklist.
METHODS
Databases were searched including CINAHL, MEDLINE, Web of Science and EMBASE using the search terms "organ donation," "healthcare professionals," "awareness" and "roles" to retrieve relevant publications.
RESULTS
Thirteen publications met the inclusion criteria. The global organ shortage is neither contingent upon unavailability of suitable organs nor exclusively dependent upon healthcare professionals. Instead, the existence of disequilibrium between organ donation and transplantation is necessitated by a web of factors. These include the following: healthcare professionals' attitudes towards, and experience of, the organ donation and transplantation process, underpinned by professional education, specialist clinical area and duration of professional practice; conflicts of interests; ethical dilemmas; altruistic values towards organ donation; and varied organ donation legislations in different legal jurisdictions.
CONCLUSION
This review maintains that if this web of factors is to be adequately addressed by healthcare systems in different global and legal jurisdictions, there should be sufficient organs voluntarily donated to meet all transplantation needs.
RELEVANCE TO CLINICAL PRACTICE
There is a suggestion that healthcare professionals partly account for the global shortage in organ donation, but there is a need to examine how healthcare professionals' roles, knowledge, awareness, skills and competencies might impact upon the organ donation and transplantation process.
Topics: Attitude of Health Personnel; Awareness; Education, Professional; Health Personnel; Humans; Organ Transplantation; Tissue Donors; Tissue Preservation; Tissue and Organ Procurement
PubMed: 29098739
DOI: 10.1111/jocn.14154 -
Human Reproduction Update Nov 2022To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones...
BACKGROUND
To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field.
OBJECTIVE AND RATIONALE
This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman's syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases.
OUTCOMES
Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather than by meta-analysis. Hydrogels and scaffolds were commonly applied in various bioengineering-related studies of the female reproductive tract. Emerging technologies, such as organoids and bioprinting, offered personalized diagnoses and alternative treatment options, respectively. Promising microfluidic systems combining various bioengineering approaches have also shown translational value.
WIDER IMPLICATIONS
The complexity of the molecular, endocrine and tissue-level interactions regulating female reproduction present challenges for bioengineering approaches to replace female reproductive organs. However, interdisciplinary work is providing valuable insight into the physicochemical properties necessary for reproductive biological processes to occur. Defining the landscape of reproductive bioengineering technologies currently available and under development for women can provide alternative models for toxicology/drug testing, ex vivo fertility options, clinical therapies and a basis for future organ regeneration studies.
Topics: Animals; Female; Humans; Pregnancy; Bioengineering; Embryo Implantation; Genitalia, Female; Reproduction; Uterus
PubMed: 35652272
DOI: 10.1093/humupd/dmac025 -
Journal of Assisted Reproduction and... Apr 2016The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural... (Review)
Review
The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural process comprising of irreversible changes due to a myriad of endogenous and environmental factors at the level of all organs and systems. In modern life, as more couples choose to postpone having a child due to various socioeconomic reasons, research for understanding the effects of aging on the reproductive system has gained an increased importance. Paternal aging also causes genetic and epigenetic changes in spermatozoa, which impair male reproductive functions through their adverse effects on sperm quality and count as, well as, on sexual organs and the hypothalamic-pituitary-gonadal axis. Hormone production, spermatogenesis, and testes undergo changes as a man ages. These small changes lead to decrease in both the quality and quantity of spermatozoa. The offspring of older fathers show high prevalence of genetic abnormalities, childhood cancers, and several neuropsychiatric disorders. In addition, the latest advances in assisted reproductive techniques give older men a chance to have a child even with poor semen parameters. Further studies should investigate the onset of gonadal senesce and its effects on aging men.
Topics: Aging; Cellular Senescence; Epigenesis, Genetic; Gonads; Humans; Male; Reproduction; Reproductive Techniques, Assisted; Spermatogenesis; Spermatozoa; Testis
PubMed: 26867640
DOI: 10.1007/s10815-016-0663-y -
Journal of Neurology Dec 2021Down syndrome (DS) is one of the most well-recognized genetic disorders. Persons with DS are known to have a variety of co-morbid medical problems, affecting nearly all... (Review)
Review
Down syndrome (DS) is one of the most well-recognized genetic disorders. Persons with DS are known to have a variety of co-morbid medical problems, affecting nearly all organ systems. Improved healthcare interventions and research have allowed for increased life span of persons with DS, although disorders of the neurologic system remain underexplored. The purpose of this systematic review is to provide clinically pertinent information on the neurological phenotypes of frequently occurring or clinically relevant conditions. A retrospective review of MEDLINE, Scopus, and Pubmed were used to identify sources among seventeen, clinically relevant, search categories. MeSH terms all contained the phrase "Down Syndrome" in conjunction with the topic of interest. 'Frequently-occurring' was defined as prevalent in more than 10% of persons with DS across their lifespan, whereas 'clinically-relevant' was defined as a disease condition where early diagnosis or intervention can augment the disease course. In total, 4896 sources were identified with 159 sources meeting criteria for inclusion. Seventeen clinical conditions were grouped under the following subjects: hypotonia, intellectual and learning disability, cervical instability, autism spectrum disorder, epilepsy, cerebrovascular disease, Alzheimer's disease and neuropsychiatric disease. The results of this review provide a blueprint for the clinical neurologist taking care of persons with DS across the age spectrum and indicate that there are many underrecognized and misdiagnosed co-occurring conditions in DS, highlighting the need for further research.
Topics: Alzheimer Disease; Autism Spectrum Disorder; Comorbidity; Down Syndrome; Humans; Retrospective Studies
PubMed: 32920658
DOI: 10.1007/s00415-020-10179-w -
The Cochrane Database of Systematic... Apr 2017In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure.
OBJECTIVES
To assess the effects of different pharmacological interventions in people with acute pancreatitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials.
SELECTION CRITERIA
We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model.
MAIN RESULTS
We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials.
SOURCE OF FUNDING
seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life.
AUTHORS' CONCLUSIONS
Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).
Topics: Acute Disease; Anti-Bacterial Agents; Antioxidants; Confidence Intervals; Gastrointestinal Agents; Humans; Pancreatitis; Pancreatitis, Acute Necrotizing; Probiotics; Randomized Controlled Trials as Topic
PubMed: 28431202
DOI: 10.1002/14651858.CD011384.pub2 -
Sports Medicine (Auckland, N.Z.) Sep 2017Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance. Anabolic androgenic steroids use may have serious and potentially irreversible adverse effects on different organs and systems, including the reproductive system.
OBJECTIVE
This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes and recreational users.
METHODS
An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes or recreational users of any age, sex, level or type of sport; AAS use of any type, dose, form or duration; AAS effects on the reproductive system were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects meta-analysis was performed to assess the weighted mean difference (WMD) of serum gonadotropin (luteinizing hormone, follicle-stimulating hormone) and testosterone levels compared with baseline, during the period of AAS use, as well as following AAS discontinuation.
RESULTS
Thirty-three studies (three randomized clinical trials, 11 cohort, 18 cross-sectional, and one non-randomized parallel clinical trial) were included in the systematic review (3879 participants; 1766 AAS users and 2113 non-AAS users). The majority of the participants were men; only six studies provided data for female athletes. A meta-analysis (11 studies) was conducted of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (six studies, n = 65 AAS users; seven studies, n = 59, evaluating gonadotropin and testosterone levels respectively); (2) during AAS use and following AAS discontinuation (four studies, n = 35; six studies, n = 39, respectively); as well as (3) prior to AAS use and following AAS discontinuation (three studies, n = 17; five studies, n = 27, respectively). During AAS intake, significant reductions in luteinizing hormone [weighted mean difference (WMD) -3.37 IU/L, 95% confidence interval (CI) -5.05 to -1.70, p < 0.001], follicle-stimulating hormone (WMD -1.73 IU/L, 95% CI -2.67 to -0.79, p < 0.001), and endogenous testosterone levels (WMD -10.75 nmol/L, 95% CI -15.01 to -6.49, p < 0.001) were reported. Following AAS discontinuation, serum gonadotropin levels gradually returned to baseline values within 13-24 weeks, whereas serum testosterone levels remained lower as compared with baseline (WMD -9.40 nmol/L, 95% CI -14.38 to -4.42, p < 0.001). Serum testosterone levels remained reduced at 16 weeks following discontinuation of AAS. In addition, AAS abuse resulted in structural and functional sperm changes, a reduction in testicular volume, gynecomastia, as well as clitoromegaly, menstrual irregularities, and subfertility.
CONCLUSION
The majority of AAS users demonstrated hypogonadism with persistently low gonadotropin and testosterone levels, lasting for several weeks to months after AAS withdrawal. Anabolic androgenic steroid use results in profound and prolonged effects on the reproductive system of athletes and recreational users and potentially on fertility.
Topics: Anabolic Agents; Androgens; Athletes; Female; Genitalia; Gonadotropins; Humans; Hypogonadism; Male; Steroids; Testosterone; Testosterone Congeners
PubMed: 28258581
DOI: 10.1007/s40279-017-0709-z -
Nutrients Dec 2022The microbiota, as a complex of microorganisms in a particular ecosystem, is part of the wider term-microbiome, which is defined as the set of all genetic content in the... (Review)
Review
The microbiota, as a complex of microorganisms in a particular ecosystem, is part of the wider term-microbiome, which is defined as the set of all genetic content in the microbial community. Imbalanced gut microbiota has a great impact on the homeostasis of the organism. Dysbiosis, as a disturbance in bacterial balance, might trigger or exacerbate the course of different pathologies. Small intestinal bacterial overgrowth (SIBO) is a disorder characterized by differences in quantity, quality, and location of the small intestine microbiota. SIBO underlies symptoms associated with functional gastrointestinal disorders (FGD) as well as may alter the presentation of chronic diseases such as heart failure, diabetes, etc. In recent years there has been growing interest in the influence of SIBO and its impact on the whole human body as well as individual systems. Therefore, we aimed to investigate the co-existence of SIBO with different medical conditions. The PubMed database was searched up to July 2022 and we found 580 original studies; inclusion and exclusion criteria let us identify 112 eligible articles, which are quoted in this paper. The present SIBO diagnostic methods could be divided into two groups-invasive, the gold standard-small intestine aspirate culture, and non-invasive, breath tests (BT). Over the years scientists have explored SIBO and its associations with other diseases. Its role has been confirmed not only in gastroenterology but also in cardiology, endocrinology, neurology, rheumatology, and nephrology. Antibiotic therapy could reduce SIBO occurrence resulting not only in the relief of FGD symptoms but also manifestations of comorbid diseases. Although more research is needed, the link between SIBO and other diseases is an important pathway for scientists to follow.
Topics: Humans; Intestine, Small; Anti-Bacterial Agents; Blind Loop Syndrome; Irritable Bowel Syndrome; Microbiota; Breath Tests
PubMed: 36615748
DOI: 10.3390/nu15010090 -
Birth Defects Research. Part C, Embryo... Jun 2016Review of published manuscripts on fetal alcohol exposure on several body systems. (Review)
Review
UNLABELLED
Review of published manuscripts on fetal alcohol exposure on several body systems.
METHOD
Articles in this review were found online using databases such as Medline, Medline Complete, PubMed, and Health Source: Nursing/Academic Edition. The following terms were searched: fetal alcohol spectrum disorders, fetal alcohol syndrome, prenatal alcohol exposure, and alcohol related birth defects.
RESULTS
Thirteen articles were gathered, five original investigations and eight reviews. This review identified several abnormalities in the body systems discussed and their associations to fetal alcohol syndrome.
CONCLUSIONS
Evidence shows that the brain was the most severely impacted organ of the body systems discussed. However, prenatal alcohol exposure causes several abnormalities within the heart, kidney, liver, gastrointestinal tract, and the endocrine systems. In addition, preventative measures need to be taken by mothers during pregnancy. Birth Defects Research (Part C), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part C) 108:174-180, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Abnormalities, Multiple; Alcohol Drinking; Brain; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Fetal Development; Fetus; Human Body; Humans; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 27297122
DOI: 10.1002/bdrc.21129 -
Pharmacological Reviews Apr 2021The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the...
The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the name "complement." Complement is also part of the innate immune system, protecting the host by recognition of pathogen-associated molecular patterns. However, complement is multifunctional far beyond infectious defense. It contributes to organ development, such as sculpting neuron synapses, promoting tissue regeneration and repair, and rapidly engaging and synergizing with a number of processes, including hemostasis leading to thromboinflammation. Complement is a double-edged sword. Although it usually protects the host, it may cause tissue damage when dysregulated or overactivated, such as in the systemic inflammatory reaction seen in trauma and sepsis and severe coronavirus disease 2019 (COVID-19). Damage-associated molecular patterns generated during ischemia-reperfusion injuries (myocardial infarction, stroke, and transplant dysfunction) and in chronic neurologic and rheumatic disease activate complement, thereby increasing damaging inflammation. Despite the long list of diseases with potential for ameliorating complement modulation, only a few rare diseases are approved for clinical treatment targeting complement. Those currently being efficiently treated include paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, myasthenia gravis, and neuromyelitis optica spectrum disorders. Rare diseases, unfortunately, preclude robust clinical trials. The increasing evidence for complement as a pathogenetic driver in many more common diseases suggests an opportunity for future complement therapy, which, however, requires robust clinical trials; one ongoing example is COVID-19 disease. The current review aims to discuss complement in disease pathogenesis and discuss future pharmacological strategies to treat these diseases with complement-targeted therapies. SIGNIFICANCE STATEMENT: The complement system is the host's defense friend by protecting it from invading pathogens, promoting tissue repair, and maintaining homeostasis. Complement is a double-edged sword, since when dysregulated or overactivated it becomes the host's enemy, leading to tissue damage, organ failure, and, in worst case, death. A number of acute and chronic diseases are candidates for pharmacological treatment to avoid complement-dependent damage, ranging from the well established treatment for rare diseases to possible future treatment of large patient groups like the pandemic coronavirus disease 2019.
Topics: COVID-19; Collectins; Complement Activating Enzymes; Complement C3; Complement Inactivating Agents; Complement System Proteins; Genetic Therapy; Humans; Inflammation Mediators; Lectins; Mannose-Binding Protein-Associated Serine Proteases; Pandemics; Rare Diseases; SARS-CoV-2; Synapses; Ficolins
PubMed: 33687995
DOI: 10.1124/pharmrev.120.000072