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Frontiers in Oncology 2022Tumors can survive environmental and metabolic stress by triggering homeostatic responses that re-establish the pre-stress status and permit them to grow and thrive. The...
Tumors can survive environmental and metabolic stress by triggering homeostatic responses that re-establish the pre-stress status and permit them to grow and thrive. The endoplasmic reticulum (ER) is the organelle where proteins undergo post-translational modifications and are folded and exported to the secretory pathway. Its environment and activity are therefore fundamental for proteostasis, i.e., the plethora of mechanisms controlling protein formation, folding, degradation, and secretion, needed to assure protein balance and cellular health. In different tumor-related conditions, such as after the activation of oncogenes or under hypoxia and nutrient deprivation, the ER experiences stress, triggered by a high load of proteins to be folded compared to the limited folding capacity of the organelle. As a consequence, three ER membrane sensors and the related unfolded protein response (UPR) are activated. The UPR comprises a complex interconnection between signal transduction pathways that promote a homeostatic response that acts by increasing the amount of protein chaperones and of proteins involved in ER-associated protein degradation (ERAD) on one hand and attenuating protein translation on the other. ER-phagy, literally "eating" the ER, is part of another homeostatic response consisting of the clearance of non-functional ER portions including misfolded proteins. This response is also activated by a set of dedicated ER-phagy receptors after ER stimuli, which overlap the stimuli generating ER stress. Thus, the UPR and ER-phagy are two closely related homeostatic mechanisms that cooperate in re-establishing ER homeostasis. However, while the role of the UPR in favoring cancer growth and thriving by promoting angiogenesis, metastasis, chemotherapy resistance, and epithelial-to-mesenchymal transition is consolidated, that of ER-phagy is still in its infancy. This essay provides an overview of emerging concepts on ER stress, the UPR, and ER-phagy and their crosstalk in tumorigenesis. We also critically review new findings on their pharmacological targeting in cancer.
PubMed: 36408145
DOI: 10.3389/fonc.2022.997235 -
ASAIO Journal (American Society For... 2014The aim of the study was to systematically evaluate effect of CentriMag heart pump (Thoratec Corporation) as temporary ventricular assist device (VAD) and part of... (Meta-Analysis)
Meta-Analysis Review
Thoratec CentriMag for temporary treatment of refractory cardiogenic shock or severe cardiopulmonary insufficiency: a systematic literature review and meta-analysis of observational studies.
The aim of the study was to systematically evaluate effect of CentriMag heart pump (Thoratec Corporation) as temporary ventricular assist device (VAD) and part of extracorporeal membrane oxygenation (ECMO) system on outcomes in patients with cardiac or cardiac-respiratory failure. A systematic search was conducted in five databases for the period 2003 to 2012. Fifty-three publications with data for 999 patients, supported with CentriMag, were included. In 72% studies, CentriMag was used as a VAD and in 25% as part of ECMO circuit. Mean duration of VAD support was 25.0 days in precardiotomy group, 10.9 days in postcardiac surgery cardiogenic shock group, 8.8 days in post-transplant graft failure and rejection group, and 16.0 days in post-LVAD placement right ventricular failure group. Survival on support was 82% (95% CI 70-92) for VAD support in precardiotomy cardiogenic shock indication, 63% (95% CI 46-78) in VAD support in postcardiac surgery cardiogenic shock indication, 62% (95% CI 46-76) in VAD support in post-transplant graft rejection or failure indication, and 83% (95% CI 73-92) in VAD support in post-LVAD placement right ventricular failure indication. CentriMag is an effective technology for temporary support of patients with cardiac and cardiorespiratory failure.
Topics: Extracorporeal Membrane Oxygenation; Female; Heart Failure; Heart-Assist Devices; Humans; Male; Observational Studies as Topic; Respiratory Insufficiency; Shock, Cardiogenic
PubMed: 25010916
DOI: 10.1097/MAT.0000000000000117 -
Annals of Medicine and Surgery (2012) Jul 2023Despite the significant research and development of COVID-19 diagnostic and therapeutic approaches, the virus still poses a concern, particularly to groups that are...
UNLABELLED
Despite the significant research and development of COVID-19 diagnostic and therapeutic approaches, the virus still poses a concern, particularly to groups that are already vulnerable. Several individuals experienced cardiac problems like myocardial infarction, arrhythmia, heart failure, cardiomyopathy, myocarditis, and pericarditis after they had recovered from the infection. Early diagnosis and timely management of sequelae are part of the therapy. However, there are gaps in the knowledge of the diagnostic and definitive treatment options for COVID-19 myocarditis. This review focuses on myocarditis associated with COVID-19.
OBJECTIVE
This systemic review provides the most recent overview of myocarditis caused by COVID-19, including clinical manifestations, diagnostic techniques, available treatments, and outcomes.
METHODS
The PubMed, Google Scholar, and ScienceDirect servers were used to conduct a systematic search in compliance with the PRISMA guidelines. Boolean search terms included "(COVID-19)" OR "(COVID19)" OR "(COVID-19 VIRUS INFECTION)" AND "(MYOCARDITIS)". The results were tabulated and analyzed.
RESULTS
A total of 32 studies, including 26 case reports and 6 case series, were included in the final analysis, and 38 cases of COVID-19-associated myocarditis were analyzed. Middle-aged men constituted the most affected population (60.52%). Dyspnoea (63.15%), chest pain or discomfort (44.73%), and fever (42.10%) were the prevalent presentations. ST-segment abnormalities were reported in 48.38% of cases on electrocardiography testing. Leucocytic infiltration (60%) was the frequent finding obtained on endomyocardial biopsy. Cardiac magnetic resonance imaging yielded myocardial oedema (63.63%), and late gadolinium enhancement (54.54%) as the most common findings. Reduced ejection fraction (75%) was the frequent result obtained on echocardiography. Corticosteroids (76.31%) and immunomodulators (42.10%) were the well-established in-hospital medications. Veno-arterial extracorporeal membrane oxygenation (35%) was the most common intervention used to support the treatment. The frequent in-hospital complications were cardiogenic shock (30.76%), followed by pneumonia (23.07%). The mortality rate was 7.9%.
CONCLUSION
Early detection and timely management of myocarditis are essential to reduce the risk of developing further complications. It is crucial to emphasize the need to evaluate COVID-19 as a possible cause of myocarditis in populations that are young and healthy to avoid fatal consequences.
PubMed: 37427189
DOI: 10.1097/MS9.0000000000000964 -
Critical Care (London, England) Jan 2015Patients with acute respiratory failure requiring respiratory support with invasive mechanical ventilation while awaiting lung transplantation are at a high risk of... (Review)
Review
INTRODUCTION
Patients with acute respiratory failure requiring respiratory support with invasive mechanical ventilation while awaiting lung transplantation are at a high risk of death. Extracorporeal membrane oxygenation (ECMO) has been proposed as an alternative bridging strategy to mechanical ventilation. The aim of this study was to assess the current evidence regarding how the ECMO bridge influences patients' survival and length of hospital stay.
METHODS
We performed a systematic review by searching PubMed, EMBASE and the bibliographies of retrieved articles. Three reviewers independently screened citation titles and abstracts and agreement was reached by consensus. We selected studies enrolling patients who received ECMO with the intention to bridge lung transplant. We included randomized controlled trials (RCTs), case-control studies and case series with ten or more patients. Outcomes of interest included survival and length of hospital stay. Quantitative data summaries were made when feasible.
RESULTS
We identified 82 studies, of which 14 were included in the final analysis. All 14 were retrospective studies which enrolled 441 patients in total. Because of the broad heterogeneity among the studies we did not perform a meta-analysis. The mortality rate of patients on ECMO before lung transplant and the one-year survival ranged from 10% to 50% and 50% to 90%, respectively. The intensive care and hospital length of stay ranged between a median of 15 to 47 days and 22 to 47 days, respectively. There was a general paucity of high-quality data and significant heterogeneity among studies in the enrolled patients and technology used, which confounded analysis.
CONCLUSIONS
In most of the studies, patients on ECMO while awaiting lung transplantation also received invasive mechanical ventilation. Therefore, whether ECMO as an alternative, rather than an adjunction, to invasive mechanical ventilation is a better bridging strategy to lung transplantation still remains an unresolved issue. ECMO support as a bridge for these patients could provide acceptable one-year survival. Future studies are needed to investigate ECMO as part of an algorithm of care for patients with end-stage lung disease.
Topics: Extracorporeal Membrane Oxygenation; Humans; Length of Stay; Life Support Systems; Lung Transplantation; Retrospective Studies; Survival Rate; Treatment Outcome
PubMed: 25774818
DOI: 10.1186/s13054-014-0686-7 -
European Urology Oncology Jun 2021Management of newly diagnosed prostate cancer (PCa) is guided in part by accurate clinical staging. The role of imaging, including magnetic resonance imaging (MRI) and... (Review)
Review
The Role of Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Primary Staging of Newly Diagnosed Prostate Cancer: A Systematic Review of the Literature.
CONTEXT
Management of newly diagnosed prostate cancer (PCa) is guided in part by accurate clinical staging. The role of imaging, including magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT), in initial staging remains controversial.
OBJECTIVE
To systematically review the studies of MRI and/or PET/CT in the staging of newly diagnosed PCa with respect to tumor (T), nodal (N), and metastatic (M) staging (TNM staging).
EVIDENCE ACQUISITION
We performed a systematic review of the literature using MEDLINE and Web of Science databases between 2012 and 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines.
EVIDENCE SYNTHESIS
A total of 139 studies (83 on T, 47 on N, and 24 on M status) were included. Ninety-nine (71%) were retrospective, 39 (28%) were prospective, and one was a randomized controlled trial (RCT). Most studies on T staging examined MRI, while PET/CT was used primarily for N and M staging. Sensitivity for the detection of extraprostatic extension, seminal vesicle invasion, or lymph node invasion ranged widely. When imaging was incorporated into existing risk tools, gain in accuracy was observed in some studies, although these findings have not been replicated. For M staging, most favorable results were reported for prostate-specific membrane antigen (PSMA) PET/CT, which demonstrated significantly better performance than conventional imaging.
CONCLUSIONS
A variety of studies on modern imaging techniques for TNM staging in newly diagnosed PCa exist. For T and N staging, reported sensitivity of imaging modalities such as MRI or PET/CT varied widely due to data heterogeneity, small sample size, and low event rates resulting in large confidence intervals and a high level of uncertainty. Therefore, uniformity in data presentation and standardization on this topic are needed. The most promising technique for M staging, which was evaluated recently in an RCT, is PSMA-PET/CT.
PATIENT SUMMARY
We performed a systematic review of currently available imaging modalities to stage newly diagnosed prostate cancer. With respect to local tumor and lymph node assessment, performance of imaging ranged widely. However, prostate-specific membrane antigen positron emission tomography/computed tomography showed favorable results for the detection of distant metastases.
Topics: Humans; Lymph Nodes; Magnetic Resonance Imaging; Male; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 33272865
DOI: 10.1016/j.euo.2020.11.002 -
The Annals of Otology, Rhinology, and... Apr 2021In tissue engineering, biomaterials create a 3D scaffold for cell-to-cell adhesion, proliferation and tissue formation. Because of their similarity to extracellular...
OBJECTIVE
In tissue engineering, biomaterials create a 3D scaffold for cell-to-cell adhesion, proliferation and tissue formation. Because of their similarity to extracellular matrix and architectural adaptability, nanofibers are of particular interest in tissue engineering. Electrospinning is a well-documented technique for nanofiber production for tissue engineering scaffolds. Here we present literature on the applications of electrospinning in the field of otolaryngology.
REVIEW METHODS
A PubMed database search was performed to isolate articles published about applications of electrospun nanofibers for tissue engineering in otolaryngology. Study design, size, material tested, site of application within the head and neck, and outcomes were obtained for each study.
RESULTS
Almost all data on electrospinning in otolaryngology was published in the last 6 years (84%), highlighting its novelty. A total of 25 pre-clinical studies were identified: 9 in vitro studies, 5 in vivo animal studies, and 11 combination studies. Sites of application included: tracheal reconstruction (n = 16), tympanic membrane repair (n = 3), cranial nerve regeneration (n = 3), mastoid osteogenesis (n = 1) and ear/nose chondrogenesis (n = 2).
IMPLICATIONS FOR PRACTICE
Tissue engineering is a burgeoning field, with recent innovative applications in the field of otolaryngology. Electrospun nanofibers specifically have relevant applications in the field of otolaryngology, due in part to their similarity to native extracellular matrix, with emerging areas of interest being tympanic membrane repair, cranial nerve regeneration and tracheal reconstruction.
Topics: Biocompatible Materials; Electrochemical Techniques; Humans; Materials Testing; Nanofibers; Otolaryngology; Tissue Engineering; Tissue Scaffolds
PubMed: 32975429
DOI: 10.1177/0003489420959692 -
The Cochrane Database of Systematic... Sep 2017Genital Chlamydia trachomatis (C.trachomatis) infection may lead to pregnancy complications such as miscarriage, preterm labour, low birthweight, preterm rupture of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genital Chlamydia trachomatis (C.trachomatis) infection may lead to pregnancy complications such as miscarriage, preterm labour, low birthweight, preterm rupture of membranes, increased perinatal mortality, postpartum endometritis, chlamydial conjunctivitis and C.trachomatis pneumonia.This review supersedes a previous review on this topic.
OBJECTIVES
To establish the most efficacious and best-tolerated therapy for treatment of genital chlamydial infection in preventing maternal infection and adverse neonatal outcomes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (26 June 2017) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) as well as studies published in abstract form assessing interventions for treating genital C.trachomatis infection in pregnancy. Cluster-RCTs were also eligible for inclusion but none were identified. Quasi-randomised trials and trials using cross-over design are not eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, assessed trial quality and extracted the data using the agreed form. Data were checked for accuracy. Evidence was assessed using the GRADE approach.
MAIN RESULTS
We included 15 trials (involving 1754 women) although our meta-analyses were based on fewer numbers of studies/women. All of the included studies were undertaken in North America from 1982 to 2001. Two studies were low risk of bias in all domains, all other studies had varying risk of bias. Four other studies were excluded and one study is ongoing.Eight comparisons were included in this review; three compared antibiotic (erythromycin, clindamycin, amoxicillin) versus placebo; five compared an antibiotic versus another antibiotic (erythromycin, clindamycin, amoxicillin, azithromycin). No study reported different antibiotic regimens. Microbiological cure (primary outcome) Antibiotics versus placebo: Erythromycin (average risk ratio (RR) 2.64, 95% confidence interval (CI) 1.60 to 4.38; two trials, 495 women; I = 68%; moderate-certainty evidence), and clindamycin (RR 4.08, 95% CI 2.35 to 7.08; one trial, 85 women;low-certainty evidence) were associated with improved microbiological cure compared to a placebo control. In one very small trial comparing amoxicillin and placebo, the results were unclear, but the evidence was graded very low (RR 2.00, 95% CI 0.59 to 6.79; 15 women). One antibiotic versus another antibiotic: Amoxicillin made little or no difference in microbiological cure in comparison to erythromycin (RR 0.97, 95% CI 0.93 to 1.01; four trials, 466 women; high-certainty evidence), probably no difference compared to clindamycin (RR 0.96, 95% CI 0.89 to 1.04; one trial, 101 women; moderate-quality evidence), and evidence is very low certainty when compared to azithromycin so the effect is not certain (RR 0.89, 95% CI 0.71 to 1.12; two trials, 144 women; very low-certainty evidence). Azithromycin versus erythromycin (average RR 1.11, 95% CI 1.00 to 1.23; six trials, 374 women; I = 53%; moderate-certainty evidence) probably have similar efficacy though results appear to favour azithromycin. Clindamycin versus erythromycin (RR 1.06, 95% CI 0.97 to 1.15; two trials, 173 women; low-certainty evidence) may have similar numbers of women with a microbiological cure between groups.Evidence was downgraded for design limitations, inconsistency, and imprecision in effect estimates. Side effects of the treatment (maternal) (secondary outcome) Antibiotics versus placebo: side effects including nausea, vomiting, and abdominal pain, were reported in two studies (495 women) but there was no clear evidence whether erythromycin was associated with more side effects than placebo and a high level of heterogeneity (I = 78%) was observed (average RR 2.93, 95% CI 0.36 to 23.76). There was no clear difference in the number of women experiencing side effects when clindamycin was compared to placebo in one small study (5/41 versus 1/44) (RR 6.35, 95% CI 0.38 to 107.45, 62 women). The side effects reported were mostly gastrointestinal and also included resolving skin rashes. One antibiotic versus another antibiotic: There was no clear difference in incidence of side effects (including nausea, vomiting, diarrhoea and abdominal pain) when amoxicillin was compared to azithromycin based on data from one small study (36 women) (RR 0.56, 95% CI 0.24 to 1.31).However, amoxicillin was associated with fewer side effects compared to erythromycin with data from four trials (513 women) (RR 0.31, 95% CI 0.21 to 0.46; I = 27%). Side effects included nausea, vomiting, diarrhoea, abdominal cramping, rash, and allergic reaction.Both azithromycin (RR 0.24, 95% CI 0.17 to 0.34; six trials, 374 women) and clindamycin (RR 0.44, 95% CI 0.22 to 0.87; two trials, 183 women) were associated with a lower incidence of side effects compared to erythromycin. These side effects included nausea, vomiting, diarrhoea and abdominal cramping.One small study (101 women) reported there was no clear difference in the number of women with side effects when amoxicillin was compared with clindamycin (RR 0.57, 95% CI 0.14 to 2.26; 107 women). The side effects reported included rash and gastrointestinal complaints. Other secondary outcomes Single trials reported data on repeated infections, preterm birth, preterm rupture of membranes, perinatal mortality and low birthweight and found no clear differences between treatments.Many of this review's secondary outcomes were not reported in the included studies.
AUTHORS' CONCLUSIONS
Treatment with antibacterial agents achieves microbiological cure from C.trachomatis infection during pregnancy. There was no apparent difference between assessed agents (amoxicillin, erythromycin, clindamycin, azithromycin) in terms of efficacy (microbiological cure and repeat infection) and pregnancy complications (preterm birth, preterm rupture of membranes, low birthweight). Azithromycin and clindamycin appear to result in fewer side effects than erythromycin.All of the studies in this review were conducted in North America, which may limit the generalisability of the results. In addition, study populations may differ in low-resource settings and these results are therefore only applicable to well-resourced settings. Furthermore, the trials in this review mainly took place in the nineties and early 2000's and antibiotic resistance may have changed since then.Further well-designed studies, with appropriate sample sizes and set in a variety of settings, are required to further evaluate interventions for treating C.trachomatis infection in pregnancy and determine which agents achieve the best microbiological cure with the least side effects. Such studies could report on the outcomes listed in this review.
Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Clindamycin; Erythromycin; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic; Reproductive Tract Infections
PubMed: 28937705
DOI: 10.1002/14651858.CD010485.pub2 -
Frontiers in Plant Science 2022Vegetables are a distinct collection of plant-based foods that vary in nutritional diversity and form an important part of the healthy diet of the human being. Besides...
Vegetables are a distinct collection of plant-based foods that vary in nutritional diversity and form an important part of the healthy diet of the human being. Besides providing basic nutrition, they have great potential for boosting human health. The balanced consumption of vegetables is highly recommended for supplementing the human body with better nutrition density, dietary fiber, minerals, vitamins, and bioactive compounds. However, the production and quality of fresh vegetables are influenced directly or indirectly by exposure to high temperatures or heat stress (HS). A decline in quality traits and harvestable yield are the most common effects of HS among vegetable crops. Heat-induced morphological damage, such as poor vegetative growth, leaf tip burning, and rib discoloration in leafy vegetables and sunburn, decreased fruit size, fruit/pod abortion, and unfilled fruit/pods in beans, are common, often rendering vegetable cultivation unprofitable. Further studies to trace down the possible physiological and biochemical effects associated with crop failure reveal that the key factors include membrane damage, photosynthetic inhibition, oxidative stress, and damage to reproductive tissues, which may be the key factors governing heat-induced crop failure. The reproductive stage of plants has extensively been studied for HS-induced abnormalities. Plant reproduction is more sensitive to HS than the vegetative stages, and affects various reproductive processes like pollen germination, pollen load, pollen tube growth, stigma receptivity, ovule fertility and, seed filling, resulting in poorer yields. Hence, sound and robust adaptation and mitigation strategies are needed to overcome the adverse impacts of HS at the morphological, physiological, and biochemical levels to ensure the productivity and quality of vegetable crops. Physiological traits such as the stay-green trait, canopy temperature depression, cell membrane thermostability, chlorophyll fluorescence, relative water content, increased reproductive fertility, fruit numbers, and fruit size are important for developing better yielding heat-tolerant varieties/cultivars. Moreover, various molecular approaches such as omics, molecular breeding, and transgenics, have been proved to be useful in enhancing/incorporating tolerance and can be potential tools for developing heat-tolerant varieties/cultivars. Further, these approaches will provide insights into the physiological and molecular mechanisms that govern thermotolerance and pave the way for engineering "designer" vegetable crops for better health and nutritional security. Besides these approaches, agronomic methods are also important for adaptation, escape and mitigation of HS protect and improve yields.
PubMed: 35837452
DOI: 10.3389/fpls.2022.878498 -
The Cochrane Database of Systematic... Nov 2017Observational evidence suggests a potential benefit with several anti-adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of an intrauterine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Observational evidence suggests a potential benefit with several anti-adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of an intrauterine device or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) for decreasing intrauterine adhesions (IUAs).
OBJECTIVES
To assess the effectiveness of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy, following operative hysteroscopy for treatment of female subfertility.
SEARCH METHODS
We searched the following databases from inception to June 2017: the Cochrane Gynaecology and Fertility Group Specialised Register; the Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; CINAHL and other electronic sources of trials, including trial registers, sources of unpublished literature and reference lists. We handsearched the Journal of Minimally Invasive Gynecology, and we contacted experts in the field. We also searched reference lists of appropriate papers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy in subfertile women. The primary outcome was live birth. Secondary outcomes were clinical pregnancy, miscarriage and IUAs present at second-look hysteroscopy, along with mean adhesion scores and severity of IUAs.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed risk of bias, extracted data and evaluated quality of evidence using the GRADE method.
MAIN RESULTS
The overall quality of the evidence was low to very low. The main limitations were serious risk of bias related to blinding of participants and personnel, indirectness and imprecision. We identified 16 RCTs comparing a device versus no treatment (two studies; 90 women), hormonal treatment versus no treatment or placebo (two studies; 136 women), device combined with hormonal treatment versus no treatment (one study; 20 women), barrier gel versus no treatment (five studies; 464 women), device with graft versus device without graft (three studies; 190 women), one type of device versus another device (one study; 201 women), gel combined with hormonal treatment and antibiotics versus hormonal treatment with antibiotics (one study; 52 women) and device combined with gel versus device (one study; 120 women). The total number of participants was 1273, but data on 1133 women were available for analysis. Only two of 16 studies included 100% infertile women; in all other studies, the proportion was variable or unknown.No study reported live birth, but some (five studies) reported outcomes that were used as surrogate outcomes for live birth (term delivery or ongoing pregnancy). Anti-adhesion therapy versus placebo or no treatment following operative hysteroscopy.There was insufficient evidence to determine whether there was a difference between the use of a device or hormonal treatment compared to no treatment or placebo with respect to term delivery or ongoing pregnancy rates (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.42 to 2.12; 107 women; 2 studies; I² = 0%; very-low-quality evidence).There were fewer IUAs at second-look hysteroscopy using a device with or without hormonal treatment or hormonal treatment or barrier gels compared with no treatment or placebo (OR 0.35, 95% CI 0.21 to 0.60; 560 women; 8 studies; I² = 0%; low-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) was 9 (95% CI 5 to 17). Comparisons of different anti-adhesion therapies following operative hysteroscopyIt was unclear whether there was a difference between the use of a device combined with graft versus device only for the outcome of ongoing pregnancy (OR 1.48, 95% CI 0.57 to 3.83; 180 women; 3 studies; I² = 0%; low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without graft/gel or gel combined with hormonal treatment and antibiotics compared with using a device only or hormonal treatment combined with antibiotics, but the findings of this meta-analysis were affected by evidence quality (OR 0.55, 95% CI 0.36 to 0.83; 451 women; 5 studies; I² = 0%; low-quality evidence).
AUTHORS' CONCLUSIONS
Implications for clinical practiceThe quality of the evidence ranged from very low to low. The effectiveness of anti-adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain. Implications for researchMore research is needed to assess the comparative safety and (cost-)effectiveness of different anti-adhesion treatments compared to no treatment or other interventions for improving key reproductive outcomes in subfertile women.
Topics: Amnion; Estrogens; Female; Gels; Humans; Hysteroscopy; Infertility, Female; Intrauterine Devices; Live Birth; Pregnancy; Randomized Controlled Trials as Topic; Second-Look Surgery; Tissue Adhesions; Uterine Diseases
PubMed: 29178172
DOI: 10.1002/14651858.CD011110.pub3 -
Alzheimer's Research & Therapy Mar 2024Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid...
BACKGROUND
Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.
METHODS
Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.
RESULTS
We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.
CONCLUSIONS
These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
Topics: Male; Humans; Female; Progranulins; Frontotemporal Dementia; Intercellular Signaling Peptides and Proteins; Virulence; Mutation; Membrane Proteins; Nerve Tissue Proteins
PubMed: 38539243
DOI: 10.1186/s13195-024-01420-z