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International Urogynecology Journal Jan 2022Family and twin studies demonstrate that pelvic organ prolapse (POP) is heritable, but the genetic etiology is poorly understood. This review aimed to identify genetic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND HYPOTHESIS
Family and twin studies demonstrate that pelvic organ prolapse (POP) is heritable, but the genetic etiology is poorly understood. This review aimed to identify genetic loci and specific polymorphisms associated with POP, while assessing the strength, consistency, and risk of bias among reported associations.
METHODS
Updating an earlier systematic review, PubMed and HuGE Navigator as well as relevant conference abstracts were searched using genetic and phenotype keywords from 2015 to 2020. Screening and data extraction were performed in duplicate. Fixed and random effects meta-analyses were conducted using co-dominant models of inheritance. We assessed credibility of pooled associations using interim Venice criteria.
RESULTS
We screened 504 new abstracts and included 46 published and 7 unpublished studies. In pooled analyses we found significant associations for four polymorphisms: rs2228480 at the ESR1 gene (OR 0.67 95% CI 0.46-0.98, I = 0.0%, Venice rating BAB), rs12589592 at the FBLN5 gene (OR 1.46 95% CI 1.11-1.82, I = 36.3%, Venice rating BBB), rs484389 in the PGR gene (OR 0.61 95% CI 0.39-0.96, I = 32.4%, Venice rating CBB), and rs1800012 at the COL1A1 gene (OR 0.80 95% CI 0.66-0.96, I = 0.0%, Venice rating BAB). Further credible novel variants have also been recently identified in genome-wide association studies.
CONCLUSION
The genetic contributions to POP remain poorly understood. Several biologically plausible variants have been identified, but much work is required to establish the role of these genes in the pathogenesis of POP or to establish a role for genetic testing in clinical practice.
Topics: Genetic Association Studies; Genome-Wide Association Study; Humans; Pelvic Organ Prolapse; Polymorphism, Genetic
PubMed: 33893823
DOI: 10.1007/s00192-021-04782-2 -
British Journal of Anaesthesia Apr 2023Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome...
BACKGROUND
Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials.
METHODS
Three domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process.
RESULTS
A high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien-Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien-Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus.
CONCLUSIONS
Both 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien-Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area.
Topics: Humans; Perioperative Care; Consensus; Reproducibility of Results; Perioperative Medicine; Morbidity; Delphi Technique
PubMed: 36697275
DOI: 10.1016/j.bja.2022.12.012 -
Veterinary Sciences Feb 2023Due to the limited information and lack of studies on neoplasms in domestic ruminants, i.e., cattle, sheep, and goats, and domestic swine, the objective of the present... (Review)
Review
BACKGROUND
Due to the limited information and lack of studies on neoplasms in domestic ruminants, i.e., cattle, sheep, and goats, and domestic swine, the objective of the present study was to systematically review the scientific literature to verify the occurrence, type, organ system, and organs most affected by neoplasms in these animals.
METHODS
The recommendations of the PRISMA methodology were followed for the elaboration of this study. The research consisted of a systematic review of neoplasms in domestic cattle, sheep, goats, and swine.
RESULTS
The number of neoplasms found was 1873. The most affected organ system was the integumentary system with 35.0%, followed in descending order by the alimentary system with 16.90%, the hematopoietic system with 13.50%, the special senses (i.e., eyes and ears) with 10.51%, the female and male genital systems with 7.31%, the urinary system with 4.38%, the liver and biliary system with 3.152%, the endocrine glands with 3.91%, the respiratory system with 2.67%, the nervous system with 2.35%, bones and joints with 0.43%, muscles and tendons with 0.37%, the cardiovascular system with 0.21%, and the pancreas with 0.16%. Of the animals with neoplasms studied, cattle were affected in 69.80% of cases, goats in 10.52%, sheep in 10.46%, and swine in 9.18%. In all species, the most frequent neoplasms were squamous cell carcinomas in ruminants, while melanoma was the most frequent in swine. Few studies carried out in slaughterhouses were found, and the existing ones referred to cattle and swine. No data were found on economic losses with carcass condemnation.
CONCLUSIONS
In view of the above, it is necessary to carry out extensive and detailed studies that provide knowledge about the impact of neoplasms on the production and condemnation of carcasses in domestic cattle, sheep, goats, and swine and the respective risk factors.
PubMed: 36851467
DOI: 10.3390/vetsci10020163 -
Environmental Research Feb 2023Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumourigenic chemicals. Studies show that even EDCs which were long abolished are... (Review)
Review
INTRODUCTION
Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumourigenic chemicals. Studies show that even EDCs which were long abolished are still contributing to the increasing incidence of neoplasia.
AIM
To investigate the association between human exposure to EDCs and the risk of endocrine-related tumours: breast, prostate, thyroid, uterus, testis, and ovary.
METHODS
A systematic review using PubMed, Scopus, and Embase was conducted, searching for original observational studies published between 1980 and 2020, approaching EDCs exposure and endocrine tumourigenic risk in humans. We comprised neoplasia of six endocrine organs. We included all the studies on EDCs reporting tumour odds ratio, risk ratio, or hazard ratio. Study levels of confidence and risk of bias were accessed applying accredited guidelines. Human-made accidents and natural EDCs were not considered in the present study.
RESULTS
Our search returned 3271 papers. After duplicate removal and screening, only 237 papers were included (corresponding to 268 records). EDCs were grouped from the most frequently (pesticides) to the least frequently studied (salts). The most tumourigenic EDC groups were phthalates (63%), heavy metals (54%), particulate matter (47%), and pesticides (46%). Pesticides group comprised the highest number of retrieved studies (n = 133). Increased neoplasia risk was found in 43-67% of the studies, with a lower value for ovary (43%) and a higher value for thyroid (67%).
CONCLUSIONS
The innovative nature of our review comes from including human studies of six endocrine-related neoplasia aiming to understand the contribution of specific EDCs groups to each organ's tumourigenesis. Thyroid was the organ presenting the highest cancer risk after EDC exposure which may explain the increasing thyroid cancer incidence. However, detailed and controlled works reporting the effects of EDCs are scarce, probably justifying conflicting results. Multinational and multicentric human studies with biochemical analysis are needed to achieve stronger and concordant evidence.
Topics: Male; Female; Humans; Endocrine Disruptors; Endocrine System; Pesticides; Testis; Metals, Heavy
PubMed: 36460069
DOI: 10.1016/j.envres.2022.114869 -
Genes Aug 2021SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene family. It plays important roles in the maintenance of self-renewal and...
SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene family. It plays important roles in the maintenance of self-renewal and pluripotency of embryonic stem cells, and its expression is repressed in most adult organs. SALL4 re-expression has been observed in different types of human cancers, and dysregulation of SALL4 contributes to the pathogenesis, metastasis, and even drug resistance of multiple cancer types. Surprisingly, little is known regarding how SALL4 expression is controlled, but recently microRNAs (miRNAs) have emerged as important regulators of SALL4. Due to the ability of regulating targets differentially in specific tissues, and recent advances in systemic and organ specific miRNA delivery mechanisms, miRNAs have emerged as promising therapeutic targets for cancer treatment. In this review, we summarize current knowledge of the interaction between SALL4 and miRNAs in mammalian development and cancer, paying particular attention to the emerging roles of the Let-7/Lin28 axis. In addition, we discuss the therapeutic prospects of targeting SALL4 using miRNA-based strategies, with a focus on the Let-7/LIN28 axis.
Topics: Animals; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Lung Neoplasms; MicroRNAs; Transcription Factors
PubMed: 34573282
DOI: 10.3390/genes12091301 -
Annals of Translational Medicine Mar 2021Sacrocolpopexy is the gold standard procedure for treating pelvic organ prolapse (POP) patients with apical defects. Different surgical approaches have emerged and been...
BACKGROUND
Sacrocolpopexy is the gold standard procedure for treating pelvic organ prolapse (POP) patients with apical defects. Different surgical approaches have emerged and been utilized successively, including traditional laparoscopy, single-hole laparoscopy, robotic laparoscopy, vaginal-assisted laparoscopy, and transvaginal approaches. Robotic sacrocolpopexy (RSC) has attracted increasing attention as an emerging surgical technique and has unique advantages, such as a "simulated wrist" mechanical arm and high-definition three-dimensional (3D) visual field, which has gradually begun to be utilized in the clinical setting.
METHODS
We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) reporting checklist, and a systematic literature search was conducted on six databases from their inception to 1st March 2020. We evaluated patients with POP who underwent RSC or laparoscopic sacrocolpopexy (LSC), outcomes (including perioperative outcomes: blood loss, operating times, blood transfusion, and hospital stay), surgery-related complications, as well as cure and recurrence rates.
RESULTS
A total of 49 articles were available, including 3,014 patients, among which 18 were comparative studies on LSC RSC, and 31 were non-comparative single-arm studies on RSC. For RSC, median operative time was 226 [90-604] minutes, estimated blood loss was 56 [5-1,500] mL, and hospital stay was 1.55 [1-16] days. Intraoperative complications and postoperative complications occurred in 74 (2.7%) and 360 (13.0%) patients, respectively. Of 2,768 RSC patients, 40 had been converted from a robot-assisted approach to other approaches, and 134 of 1,852 patients (7.2%) have recurrent prolapses of any compartment. Compared to LSC, RSC was associated with significantly lower blood loss and lower conversion rate. However, more operative time was observed in RSC. No significant differences were observed in perioperative transfusion, intraoperative and postoperative complications, or objective recurrence between RSC and LSC.
CONCLUSIONS
RSC's application seems to contribute some advantages compared to conventional laparoscopic surgery, although both approaches appear to promote equivalent clinical outcomes. Notably, heterogeneity among studies might have affected the outcome of the study. Consequently, high-quality and large-sample randomized trials comparing both techniques are necessitated.
PubMed: 33850846
DOI: 10.21037/atm-20-4347 -
International Journal of Molecular... Aug 2022Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to... (Review)
Review
Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to microbial pathogens. Such processes lead to an abnormal inflammatory response and multi-organ failure. MicroRNAs (miRNA) are single-stranded non-coding RNAs with the function of gene regulation. This means that miRNAs are involved in multiple intracellular pathways and thus contribute to or inhibit inflammation. As a result, their variable expression in different tissues and organs may play a key role in regulating the pathophysiological events of sepsis. Thanks to this property, miRNAs may serve as potential diagnostic and prognostic biomarkers in such life-threatening events. In this narrative review, we collect the results of recent studies on the expression of miRNAs in heart, blood, lung, liver, brain, and kidney during sepsis and the molecular processes in which they are involved. In reviewing the literature, we find at least 122 miRNAs and signaling pathways involved in sepsis-related organ dysfunction. This may help clinicians to detect, prevent, and treat sepsis-related organ failures early, although further studies are needed to deepen the knowledge of their potential contribution.
Topics: Gene Expression Regulation; Humans; Macrophages; MicroRNAs; Multiple Organ Failure; Sepsis
PubMed: 36012630
DOI: 10.3390/ijms23169354 -
Pharmaceutics Feb 2023Microneedles (MNs) have been widely used in biomedical applications for drug delivery and biomarker detection purposes. Furthermore, MNs can also be used as a... (Review)
Review
Microneedles (MNs) have been widely used in biomedical applications for drug delivery and biomarker detection purposes. Furthermore, MNs can also be used as a stand-alone tool to be combined with microfluidic devices. For that purpose, lab- or organ-on-a-chip are being developed. This systematic review aims to summarize the most recent progress in these emerging systems, to identify their advantages and limitations, and discuss promising potential applications of MNs in microfluidics. Therefore, three databases were used to search papers of interest, and their selection was made following the guidelines for systematic reviews proposed by PRISMA. In the selected studies, the MNs type, fabrication strategy, materials, and function/application were evaluated. The literature reviewed showed that although the use of MNs for lab-on-a-chip has been more explored than for organ-on-a-chip, some recent studies have explored this applicability with great potential for the monitoring of organ models. Overall, it is shown that the presence of MNs in advanced microfluidic devices can simplify drug delivery and microinjection, as well as fluid extraction for biomarker detection by using integrated biosensors, which is a promising tool to precisely monitor, in real-time, different kinds of biomarkers in lab- and organ-on-a-chip platforms.
PubMed: 36986653
DOI: 10.3390/pharmaceutics15030792 -
Frontiers in Immunology 2023Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even... (Review)
Review
Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even endanger life. Acupuncture is widely accepted and applied in the treatment of sepsis, and breakthroughs have been made regarding its mechanism of action in recent years. In this review, we systematically discuss the current clinical applications of acupuncture in the treatment of sepsis and focus on the mechanisms of acupuncture in animal models of systemic inflammation. In clinical research, acupuncture can not only effectively inhibit excessive inflammatory reactions but also improve the immunosuppressive state of patients with sepsis, thus maintaining immune homeostasis. Mechanistically, a change in the acupoint microenvironment is the initial response link for acupuncture to take effect, whereas PROKR2 neurons, high-threshold thin nerve fibres, cannabinoid CB2 receptor (CB2R) activation, and Ca influx are the key material bases. The cholinergic anti-inflammatory pathway of the vagus nervous system, the adrenal dopamine anti-inflammatory pathway, and the sympathetic nervous system are key to the transmission of acupuncture information and the inhibition of systemic inflammation. In MODS, acupuncture protects against septic organ damage by inhibiting excessive inflammatory reactions, resisting oxidative stress, protecting mitochondrial function, and reducing apoptosis and tissue or organ damage.
Topics: Animals; Humans; Sepsis; Acupuncture Therapy; Inflammation; Vagus Nerve
PubMed: 37753078
DOI: 10.3389/fimmu.2023.1242640 -
Reviews in Medical Virology Jan 2023Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic... (Meta-Analysis)
Meta-Analysis Review
Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic virus, has been proposed as marker of functional immunity: higher loads correspond to over-immunosuppression, and lower loads to under-immunosuppression. This review offers an overview of the current evidence of the association between TTV-load and infection and rejection after SOT. A systematic literature search strategy, deposited in the PROSPERO registry, resulted in 548 records. After screening, 23 original and peer-reviewed articles were assessed investigating the association between TTV-load, infection and/or rejection in SOT. The Quality in Prognostic Studies (QUIPS)-tool was used to assess the risk of bias. Meta-analysis with random-effects was performed on results with similar outcomes and exposure measures. Most of the included studies involved retrospective cohorts in which the TTV-load was measured longitudinally, within the first 2 years post-transplantation. Infection outcomes differed between studies and included viral, bacterial, parasitic and fungal infections. Rejection was defined by biopsy confirmation or initiation of rejection treatment. Twelve out of 16 studies reported an association between high TTV-load and infections, whereas 13 out of 15 reported an association between low TTV-load and rejection. Meta-analysis showed an increased risk of infection (OR: 1.16, 95% CI: 1.03-1.32; HR: 1.05, 95% CI: 0.97-1.14) and a decreased risk of rejection (OR: 0.90, 95% CI: 0.87-0.94; HR: 0.74, 95% CI: 0.71-0.76) per 1 log TTV-load increase. The qualitative assessment showed varying risks of bias in the included studies. This systematic review and meta-analysis indicates that blood TTV-load measured within the first 2 years after SOT is associated with the risk of infection or allograft rejection, although substantial risk of bias in the studies included warrant cautious interpretation. The results in this review provide a rationale for larger, prospective, studies into TTV as marker of infection and rejection after SOT.
Topics: Humans; Torque teno virus; Retrospective Studies; Prospective Studies; Organ Transplantation; Immunosuppression Therapy; Viral Load; DNA, Viral
PubMed: 36056751
DOI: 10.1002/rmv.2393