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American Journal of Obstetrics and... May 2023Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard.... (Review)
Review
Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard. The condition has been attributed to the passage of fetal colonic content (meconium), intraamniotic bleeding with the presence of heme catabolic products, or both. The frequency of green-stained amniotic fluid increases as a function of gestational age, reaching approximately 27% in post-term gestation. Green-stained amniotic fluid during labor has been associated with fetal acidemia (umbilical artery pH <7.00), neonatal respiratory distress, and seizures as well as cerebral palsy. Hypoxia is widely considered a mechanism responsible for fetal defecation and meconium-stained amniotic fluid; however, most fetuses with meconium-stained amniotic fluid do not have fetal acidemia. Intraamniotic infection/inflammation has emerged as an important factor in meconium-stained amniotic fluid in term and preterm gestations, as patients with these conditions have a higher rate of clinical chorioamnionitis and neonatal sepsis. The precise mechanisms linking intraamniotic inflammation to green-stained amniotic fluid have not been determined, but the effects of oxidative stress in heme catabolism have been implicated. Two randomized clinical trials suggest that antibiotic administration decreases the rate of clinical chorioamnionitis in patients with meconium-stained amniotic fluid. A serious complication of meconium-stained amniotic fluid is meconium aspiration syndrome. This condition develops in 5% of cases presenting with meconium-stained amniotic fluid and is a severe complication typical of term newborns. Meconium aspiration syndrome is attributed to the mechanical and chemical effects of aspirated meconium coupled with local and systemic fetal inflammation. Routine naso/oropharyngeal suctioning and tracheal intubation in cases of meconium-stained amniotic fluid have not been shown to be beneficial and are no longer recommended in obstetrical practice. A systematic review of randomized controlled trials suggested that amnioinfusion may decrease the rate of meconium aspiration syndrome. Histologic examination of the fetal membranes for meconium has been invoked in medical legal litigation to time the occurrence of fetal injury. However, inferences have been largely based on the results of in vitro experiments, and extrapolation of such findings to the clinical setting warrants caution. Fetal defecation throughout gestation appears to be a physiologic phenomenon based on ultrasound as well as in observations in animals.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Meconium Aspiration Syndrome; Meconium; Amniotic Fluid; Chorioamnionitis; Pregnancy Complications; Inflammation; Heme
PubMed: 37012128
DOI: 10.1016/j.ajog.2022.11.1283 -
The Cochrane Database of Systematic... Aug 2021Traditionally, amalgam has been used for filling cavities in posterior teeth, and it continues to be the restorative material of choice in some low- and middle-income... (Review)
Review
BACKGROUND
Traditionally, amalgam has been used for filling cavities in posterior teeth, and it continues to be the restorative material of choice in some low- and middle-income countries due to its effectiveness and relatively low cost. However, there are concerns over the use of amalgam restorations (fillings) with regard to mercury release in the body and the environmental impact of mercury disposal. Dental composite resin materials are an aesthetic alternative to amalgam, and their mechanical properties have developed sufficiently to make them suitable for restoring posterior teeth. Nevertheless, composite resin materials may have potential for toxicity to human health and the environment. The United Nations Environment Programme has established the Minamata Convention on Mercury, which is an international treaty that aims "to protect the [sic] human health and the environment from anthropogenic emissions and releases of mercury and mercury compounds". It entered into force in August 2017, and as of February 2021 had been ratified by 127 governments. Ratification involves committing to the adoption of at least two of nine proposed measures to phase down the use of mercury, including amalgam in dentistry. In light of this, we have updated a review originally published in 2014, expanding the scope of the review by undertaking an additional search for harms outcomes. Our review synthesises the results of studies that evaluate the long-term effectiveness and safety of amalgam versus composite resin restorations, and evaluates the level of certainty we can have in that evidence.
OBJECTIVES
To examine the effects (i.e. efficacy and safety) of direct composite resin fillings versus amalgam fillings.
SEARCH METHODS
An information specialist searched five bibliographic databases up to 16 February 2021 and used additional search methods to identify published, unpublished and ongoing studies SELECTION CRITERIA: To assess efficacy, we included randomised controlled trials (RCTs) comparing dental composite resin with amalgam restorations in permanent posterior teeth that assessed restoration failure or survival at follow-up of at least three years. To assess safety, we sought non-randomised studies in addition to RCTs that directly compared composite resin and amalgam restorative materials and measured toxicity, sensitivity, allergy, or injury.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included a total of eight studies in this updated review, all of which were RCTs. Two studies used a parallel-group design, and six used a split-mouth design. We judged all of the included studies to be at high risk of bias due to lack of blinding and issues related to unit of analysis. We identified one new trial since the previous version of this review (2014), as well as eight additional papers that assessed safety, all of which related to the two parallel-group studies that were already included in the review. For our primary meta-analyses, we combined data from the two parallel-group trials, which involved 1645 composite restorations and 1365 amalgam restorations in 921 children. We found low-certainty evidence that composite resin restorations had almost double the risk of failure compared to amalgam restorations (risk ratio (RR) 1.89, 95% confidence interval (CI) 1.52 to 2.35; P < 0.001), and were at much higher risk of secondary caries (RR 2.14, 95% CI 1.67 to 2.74; P < 0.001). We found low-certainty evidence that composite resin restorations were not more likely to result in restoration fracture (RR 0.87, 95% CI 0.46 to 1.64; P = 0.66). Six trials used a split-mouth design. We considered these studies separately, as their reliability was compromised due to poor reporting, unit of analysis errors, and variability in methods and findings. Subgroup analysis showed that the findings were consistent with the results of the parallel-group studies. Three trials investigated possible harms of dental restorations. Higher urinary mercury levels were reported amongst children with amalgam restorations in two trials, but the levels were lower than what is known to be toxic. Some differences between amalgam and composite resin groups were observed on certain measures of renal, neuropsychological, and psychosocial function, physical development, and postoperative sensitivity; however, no consistent or clinically important harms were found. We considered that the vast number of comparisons made false-positive results likely. There was no evidence of differences between the amalgam and composite resin groups in neurological symptoms, immune function, and urinary porphyrin excretion. The evidence is of very low certainty, with most harms outcomes reported in only one trial.
AUTHORS' CONCLUSIONS
Low-certainty evidence suggests that composite resin restorations may have almost double the failure rate of amalgam restorations. The risk of restoration fracture does not seem to be higher with composite resin restorations, but there is a much higher risk of developing secondary caries. Very low-certainty evidence suggests that there may be no clinically important differences in the safety profile of amalgam compared with composite resin dental restorations. This review supports the utility of amalgam restorations, and the results may be particularly useful in parts of the world where amalgam is still the material of choice to restore posterior teeth with proximal caries. Of note, however, is that composite resin materials have undergone important improvements in the years since the trials informing the primary analyses for this review were conducted. The global phase-down of dental amalgam via the Minamata Convention on Mercury is an important consideration when deciding between amalgam and composite resin dental materials. The choice of which dental material to use will depend on shared decision-making between dental providers and patients in the clinic setting, and local directives and protocols.
Topics: Bias; Child; Composite Resins; Dental Amalgam; Dental Caries; Dentition, Permanent; Humans; Randomized Controlled Trials as Topic
PubMed: 34387873
DOI: 10.1002/14651858.CD005620.pub3 -
Experimental Biology and Medicine... Apr 2017A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in... (Review)
Review
A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in those populations consuming a westernized diet. Determination of causation specifically by red or processed meat is contingent upon identification of plausible mechanisms that lead to colorectal cancer. We conducted a systematic review of the available evidence to determine the availability of plausible mechanistic data linking red and processed meat consumption to colorectal cancer risk. Forty studies using animal models or cell cultures met specified inclusion criteria, most of which were designed to examine the role of heme iron or heterocyclic amines in relation to colon carcinogenesis. Most studies used levels of meat or meat components well in excess of those found in human diets. Although many of the experiments used semi-purified diets designed to mimic the nutrient loads in current westernized diets, most did not include potential biologically active protective compounds present in whole foods. Because of these limitations in the existing literature, there is currently insufficient evidence to confirm a mechanistic link between the intake of red meat as part of a healthy dietary pattern and colorectal cancer risk. Impact statement Current recommendations to reduce colon cancer include the reduction or elimination of red or processed meats. These recommendations are based on data from epidemiological studies conducted among cultures where meat consumption is elevated and consumption of fruits, vegetables, and whole grains are reduced. This review evaluated experimental data exploring the putative mechanisms whereby red or processed meats may contribute to colon cancer. Most studies used levels of meat or meat-derived compounds that were in excess of those in human diets, even in cultures where meat intake is elevated. Experiments where protective dietary compounds were used to mitigate the extreme levels of meat and meat-derived compounds showed protection against colon cancer, with some essentially negating the impact of meat in the diet. It is essential that better-designed studies be conducted that use relevant concentrations of meat or meat-derived compounds in complex diets representative of the foods consumed by humans.
Topics: Animals; Colonic Neoplasms; Cooking; Diet, Western; Heme; Humans; Iron; Meat; Mutagens; Observational Studies as Topic
PubMed: 28205448
DOI: 10.1177/1535370217693117 -
International Journal For Vitamin and... Jun 2024Animal models have suggested the carcinogenic effect of iron due to its oxidative potential. The lung is particularly vulnerable to oxidative stress. However,... (Meta-Analysis)
Meta-Analysis Review
Animal models have suggested the carcinogenic effect of iron due to its oxidative potential. The lung is particularly vulnerable to oxidative stress. However, epidemiological studies investigating the association between dietary iron and the risk of lung cancer have reported inconclusive results. In this systematic review and meta-analysis, we aimed to clarify this association. We searched PubMed, Web of Science, Scopus and Google scholar for eligible articles published through May 2023 reporting the Relative Risk (RR), Hazard Ratio (HR) or Odds Ratio (OR) with 95% confidence interval (95% CI). Case-control and cohort studies that examined the relationship between dietary iron and lung cancer risk were included and review and meta-analyses articles, experimental studies, abstracts, letters to editor and studies with insufficient data were excluded. Finally, three case-control studies and 6 cohort studies were included. Random effect models were used to calculate the pooled results. Nine studies (cases =21,943, participants =1,542,993) were included. There were no significant associations between the highest dietary total iron (heme and non-heme) (RR: 1.09, 95% CI: 0.78 to 1.51) or heme iron (RR: 1.01, 95% CI: 0.73 to 1.38) intake compared to the lowest intake with lung cancer risk. Null-associations were also observed in the subgroup analysis based on smoking status and lung cancer histology. However, in the subgroup of women (cases =5074), heme iron was associated with a 14% increase in the risk of lung cancer (RR: 1.14, 95% CI: 1.01 to 1.29). The current results demonstrated that there is no significant relationship between dietary iron intake and the risk of lung cancer. However, a positive association was observed between dietary heme iron and the risk of lung cancer in women, which may require further investigation.
Topics: Lung Neoplasms; Humans; Iron, Dietary; Risk Factors; Diet; Female; Heme; Male
PubMed: 37469109
DOI: 10.1024/0300-9831/a000789 -
Cancers Jun 2022Acute porphyrias are a group of metabolic disorders resulting in defective porphyrin synthesis and reduced heme production, which carries a risk of malignancy.... (Review)
Review
Acute porphyrias are a group of metabolic disorders resulting in defective porphyrin synthesis and reduced heme production, which carries a risk of malignancy. Porphyrias are inborn defects in the heme biosynthesis pathway resulting in neurovisceral manifestations and cutaneous photosensitivity attacks with multi-systemic involvement. Its estimated prevalence nears 5 per 100,000 patients worldwide. Subclinical liver disease is common, which can progress into transaminitis, fibrosis, cirrhosis, and malignancy. However, data on the incidence of primary liver cancer are lacking. We aim to determine the risk of hepatocellular carcinoma (HCC) in patients with porphyria. A systematic review and pooled analysis were conducted through 2021 on studies assessing blood tests, imaging, cancer development, liver transplant, surgical resection, and outcomes in porphyria. In total, 19 studies, which included 7381 patients with porphyria (3476 females), were considered for the final review. In eight studies, alpha-fetoprotein levels were elevated between 200 and 1000 IU/mL. Of the total cohort of patients with porphyria, primary liver cancer was diagnosed in 351 patients (4.8%), of whom 243 (3.3% of the total) were found to have HCC. A subset of patients was found to have cholangiocarcinoma ( = 18; 0.3% of the total). Interestingly, advanced liver disease or cirrhosis was not a prerequisite for the formation of HCC in a small group of patients. Of the total cohort, 30 patients underwent liver resection, 48 patients underwent liver transplantation, and 327 patients died. Patients with porphyria are at risk of developing primary liver malignancy. Further studies should aim to develop diagnostic and prognostic models aimed at the early detection of HCC in porphyria.
PubMed: 35740611
DOI: 10.3390/cancers14122947 -
Brain Communications 2024New treatments are needed to improve the prognosis of pneumococcal meningitis. We performed a systematic review on adjunctive treatments in animal models of pneumococcal... (Review)
Review
New treatments are needed to improve the prognosis of pneumococcal meningitis. We performed a systematic review on adjunctive treatments in animal models of pneumococcal meningitis in order to identify treatments with the most potential to progress to clinical trials. Studies testing therapy adjunctive to antibiotics in animal models of pneumococcal meningitis were included. A literature search was performed using Medline, Embase and Scopus for studies published from 1990 up to 17 February 2023. Two investigators screened studies for inclusion and independently extracted data. Treatment effect was assessed on the clinical parameters disease severity, hearing loss and cognitive impairment and the biological parameters inflammation, brain injury and bacterial load. Adjunctive treatments were evaluated by their effect on these outcomes and the quality, number and size of studies that investigated the treatments. Risk of bias was assessed with the SYRCLE risk of bias tool. A total of 58 of 2462 identified studies were included, which used 2703 experimental animals. Disease modelling was performed in rats (29 studies), rabbits (13 studies), mice (12 studies), gerbils (3 studies) or both rats and mice (1 study). Meningitis was induced by injection of into the subarachnoid space. Randomization of experimental groups was performed in 37 of 58 studies (64%) and 12 studies (12%) were investigator-blinded. Overall, 54 treatment regimens using 46 adjunctive drugs were evaluated: most commonly dexamethasone (16 studies), daptomycin (5 studies), complement component 5 (C5; 3 studies) antibody and Mn(III)tetrakis(4-benzoicacid)porphyrin chloride (MnTBAP; 3 studies). The most frequently evaluated outcome parameters were inflammation [32 studies (55%)] and brain injury [32 studies (55%)], followed by disease severity [30 studies (52%)], hearing loss [24 studies (41%)], bacterial load [18 studies (31%)] and cognitive impairment [9 studies (16%)]. Adjunctive therapy that improved clinical outcomes in multiple studies was dexamethasone (6 studies), C5 antibodies (3 studies) and daptomycin (3 studies). HMGB1 inhibitors, matrix metalloproteinase inhibitors, neurotrophins, antioxidants and paquinimod also improved clinical parameters but only in single or small studies. Evaluating the treatment effect of adjunctive therapy was complicated by study heterogeneity regarding the animal models used and outcomes reported. In conclusion, 24 of 54 treatment regimens (44%) tested improved clinically relevant outcomes in experimental pneumococcal meningitis but few were tested in multiple well-designed studies. The most promising new adjunctive treatments are with C5 antibodies or daptomycin, suggesting that these drugs could be tested in clinical trials.
PubMed: 38707710
DOI: 10.1093/braincomms/fcae131 -
American Journal of Reproductive... Feb 2018Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory... (Review)
Review
Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory biomarkers linked to labor, a comprehensive profile of them in each of the uterine compartments is not available to better understand their mechanistic contributions to labor. This systematic review investigated the pro- and anti-inflammatory biomarkers reported in intra-uterine tissues (amnion, chorion, decidua, placenta, and myometrium) at term labor. We conducted a systematic review of studies on pro- and anti-inflammatory biomarkers (mRNA and/or protein) reported in feto-maternal tissues during normal human term labor, published in English (1980-2016), in 3 electronic data bases. From a total of 3712 citations, 172 were included for final review. Each tissue expresses a unique set of biomarkers at the time of term labor, but there is significant overlap between tissues. All tissues had IL-6, IL-8, IL-1β, COX-2, PGE-2, TNF-α, and hCAP18 in common at term labor. Common and unique inflammatory biomarkers are expressed in various feto-maternal compartments at term labor. Increase in pro-inflammatory markers in all gestational tissue signifies their harmonious functional role in promoting labor. Anti-inflammatory markers at term labor are hardly reported.
Topics: Animals; Antimicrobial Cationic Peptides; Biomarkers; Cathelicidins; Cyclooxygenase 2; Female; Humans; Inflammation; Inflammation Mediators; Metalloporphyrins; Parturition; Pregnancy; Uterus
PubMed: 29076197
DOI: 10.1111/aji.12776 -
Acta Ophthalmologica May 2024Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical... (Meta-Analysis)
Meta-Analysis Review
Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical non-steroidal anti-inflammatory drugs (NSAID) have previously been proposed as a treatment for CSC, although its exact efficacy remains unclear. In this systematic review and meta-analysis, we outlined the efficacy of topical NSAIDs for the treatment of CSC. We searched 11 literature databases on 13 December 2022, for any study describing topical NSAID treatment for CSC. Thirteen eligible studies were included with a total of 1001 eyes of 994 patients with CSC. Six studies were case reports, two were cohort studies and five were non-randomized comparative studies. Where specified, topical NSAIDs used were bromfenac 0.09%, diclofenac 0.1%, ketorolac 0.4% and 0.5%, pranoprofen 0.1%, and nepafenac 0.1% and 0.3%. Studies were predominantly of cases with acute CSC and several case studies reported treatment outcomes simultaneously with discontinuation of corticosteroid use, which complicated treatment evaluation. Meta-analyses of comparative studies revealed a statistically significant but clinically irrelevant best-corrected visual acuity improvement of -0.04 logMAR (95% CI: -0.07 to -0.01 logMAR; p = 0.01) at 1-month follow-up, which became statistically insignificant at 3-month follow-up (-0.03 logMAR; 95% CI: -0.06 to 0.003 logMAR; p = 0.08). Further, we found no benefit in complete subretinal fluid resolution at 1-month follow-up (OR: 1.20; 95% CI: 0.81-1.76; p = 0.37) or 3-month follow-up (OR: 1.17; 95% CI: 0.86 to 1.59; p = 0.33). Taken together, available evidence does not support the use of topical NSAIDs for the treatment of CSC.
Topics: Humans; Central Serous Chorioretinopathy; Treatment Outcome; Verteporfin; Photochemotherapy; Anti-Inflammatory Agents, Non-Steroidal; Tomography, Optical Coherence; Fluorescein Angiography
PubMed: 37551858
DOI: 10.1111/aos.15743 -
PloS One 2022Heme-oxygenase 1 (HMOX1) is a critical stress response gene that catalyzes the multistep oxidation of heme. A GT(n) repeat of variable length in the promoter in has been...
INTRODUCTION
Heme-oxygenase 1 (HMOX1) is a critical stress response gene that catalyzes the multistep oxidation of heme. A GT(n) repeat of variable length in the promoter in has been associated with a wide range of human diseases, including infections. This paper aims to summarise and systematically review associations between the length of the HMOX1 GT(n) promoter and infectious disease in humans.
METHODS
A search using relevant terms was performed in PubMED and EMBASE through to 15/01/21 identifying all research that studied an association between the HMOX1 GT(n) repeat polymorphism and the incidence and/or outcome of any human infectious disease. Citations were screened for additional studies. Potential studies were screened for inclusion by two authors. Data was extracted on allele frequency, genotype, strength of association, mechanism of genotyping, and potential biases. A narrative review was performed across each type of infection.
RESULTS
1,533 studies were identified in the search, and one via citation screening. Sixteen studies were ultimately included, seven in malaria, three in HIV, three in sepsis, and one each in pneumonia, hepatitis C, and acute respiratory distress syndrome (ARDS). Sample sizes for nearly all studies were small (biggest study, n = 1,646). Allelic definition was different across all included studies. All studies were at some risk of bias. In malaria, three studies suggested that longer alleles were associated with reduced risk of severe malaria, particularly malaria-induced renal dysfunction, with four studies identifying a null association. In sepsis, two studies suggested an association with longer alleles and better outcomes.
CONCLUSIONS
Despite the importance of HMOX1 in survival from infection, and the association between repeat length and gene expression, the clinical data supporting an association between repeat length and incidence and/or outcome of infection remain inconclusive.
Topics: Communicable Diseases; Genetic Predisposition to Disease; Heme; Heme Oxygenase-1; Humans; Polymorphism, Genetic; Sepsis
PubMed: 35551540
DOI: 10.1371/journal.pone.0267399 -
Retina (Philadelphia, Pa.) Aug 2015To evaluate the 3-year outcome in eyes with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy with verteporfin. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the 3-year outcome in eyes with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy with verteporfin.
METHODS
Retrospective study and review of the literature. We performed a retrospective study of patients with PCV who were treated with photodynamic therapy between January 2007 and December 2008. Patients were excluded if they had received photodynamic therapy before the study period, but those who received previous treatment with other modalities (thermal laser or intravitreal therapies) were allowed. The main outcome measures were best-corrected visual acuity, repeat photodynamic therapy, and recurrence of PCV at the end of Years 1, 2, and 3. We further conducted a systematic review of the literature using the terms "polypoidal choroidal vasculopathy" and "photodynamic therapy" and compared the visual outcome of studies over 3 years using meta-analytical methods.
RESULTS
The retrospective study included 68 eyes. The mean best-corrected visual acuity was 0.73 ± 0.56 logMAR (20/107, Snellen equivalent) at baseline, 0.73 ± 0.70 logMAR (20/107, Snellen equivalent) at 1 year, 0.96 ± 0.76 logMAR (20/182, Snellen equivalent) at 2 years, and 1.07 ± 0.81 logMAR (20/235, Snellen equivalent) at 3 years. The cumulative recurrence rates of PCV were 16.1% (1 year), 34.9% (2 years), and 52.7% (3 years) and eyes with recurrence were more likely to suffer ≥3 lines loss compared with eyes without recurrence (63.2 vs. 17.6%, P = 0.006). The systematic review summarized results from 48 published studies and our retrospective study. The pooled analysis from 29 studies (316 eyes reporting the 3-year visual outcome) reported mean best-corrected visual acuity improvement of 0.115 logMAR at 1 year (n = 1,669), 0.066 logMAR at 2 years (n = 701), and 0.027 logMAR at 3 years (n = 316). Reported recurrence rates were 5.9% to 50.0% after 1 year, 9.1% to 83.3% after 2 years, and 40.0% to 78.6% after 3 years or longer of follow-up.
CONCLUSION
The visual outcome in eyes with PCV was stable until 2 years, but the outcome at 3 years worsened, particularly in eyes that experienced recurrence.
Topics: Adult; Aged; Aged, 80 and over; Choroidal Neovascularization; Female; Follow-Up Studies; Humans; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Polyps; Porphyrins; Prognosis; Retrospective Studies; Risk Factors; Ultraviolet Rays; Verteporfin; Visual Acuity; Wet Macular Degeneration
PubMed: 25719986
DOI: 10.1097/IAE.0000000000000499