Optimal management of preschool asthma Calogero, Claudia; Sly, Peter D
Expert review of respiratory medicine,
12/1/2007, 2007-Dec, 2007-12-00, 20071201, Letnik:
1, Številka:
3
Journal Article
Recenzirano
Asthma is common in most parts of the world and remains the most common single reason preschool aged children are admitted to hospital in developed countries. In determining what the optimal ...management of preschool asthma is, several factors must be considered, including: the aims of treating preschool asthma; which children require treatment; and what treatment is effective. The most controversial aspects of treating preschool asthma relate to maintenance treatment. Guidelines for managing asthma in children have been developed; however, the relative lack of appropriate clinical trials in preschool children is a problem. Prolonged treatment with inhaled corticosteroids controls asthma during treatment but has no disease-modifying effects. Intermittent treatment with inhaled corticosteroids initiated at the onset of asthma-like symptoms and continued for short periods is ineffective. Short-term treatment with leukotriene receptor antagonists provides symptomatic relief but evidence for long-term efficacy is lacking. Further data are needed to determine optimal asthma management in preschool children.
We aimed to assess the diagnostic accuracy of AGILE 3+, a recently developed score based on the combination of aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes ...status, sex, age, and liver stiffness measurement (LSM) by transient elastography, when compared with Fibrosis-4 (FIB-4) and LSM, for the diagnosis of advanced fibrosis and for the prediction of liver-related events (LREs) occurrence in patients with NAFLD.
A total of 614 consecutive patients with biopsy-proven NAFLD or clinical diagnosis of NAFLD-related compensated cirrhosis were enrolled. LREs were recorded during follow-up. FIB-4, LSM by transient elastography (FibroScan device), and AGILE 3+ were measured. The diagnostic performance of noninvasive criteria for advanced fibrosis and for the prediction of LREs was assessed using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis.
In patients with biopsy-proven NAFLD (n = 520), LSM and AGILE 3+ had higher AUROC than FIB-4 (0.88 for LSM and AGILE 3+ vs 0.78 for FIB-4; P < .001) for advanced fibrosis, and AGILE 3+ exhibited a smaller indeterminate area in the test (25.2% for FIB-4 vs 13.1% for LSM vs 8.3% for AGILE 3+). Within the entire cohort of patients, AGILE 3+ had significantly higher AUROC for predicting LREs with respect to LSM (AUROC 36 months 0.95 vs 0.93; P =.008; 60 months 0.95 vs 0.92; P = .006; 96 months 0.97 vs 0.95; P = .001). Decision curve analysis showed that all scores had modest net benefit for ruling-out advanced fibrosis at the risk threshold of 5% to 10% where advanced fibrosis was absent. At the risk threshold of 5% of false negatives or false positives in LRE at 36, 60, 96, and 120 months, AGILE 3+ outperformed both FIB-4 and LSM for ruling out LRE.
Depending on resource availability, clinical setting, and the risk scenarios, AGILE 3+ is an accurate and valid alternative to FIB-4 and LSM for the noninvasive assessment of disease severity and prognosis in patients with NAFLD.
To evaluate the relationship between testosterone replacement therapy (TRT) and arterial and/or venous thrombosis in patients with pre-treatment total testosterone (TT) <12 nmol l-1, we performed a ...meta-analysis following the Population Intervention Comparison Outcome model. Population: men with TT <12 nmol l-1 or clear mention of hypogonadism in the inclusion criteria of patients; intervention: TRT; comparison: placebo or no therapy; outcomes: arterial thrombotic events (stroke, myocardial infarction MI, upper limbs, and lower limbs), VTE (deep vein thrombosis DVT, portal vein thrombosis, splenic thrombosis, and pulmonary embolism), and mortality. A total of 2423 abstracts were assessed for eligibility. Twenty-four studies, including 14 randomized controlled trials (RCTs), were finally included, with a total of 4027 and 310 288 hypotestosteronemic male patients, from RCTs and from observational studies, respectively. Based on RCT-derived data, TRT did not influence the risk of arterial thrombosis (odds ratio OR = 1.27, 95% confidence interval CI: 0.47-3.43, P = 0.64), stroke (OR = 1.34, 95% CI: 0.09-18.97, P = 0.83), MI (OR = 0.51, 95% CI: 0.11-2.31, P = 0.39), VTE (OR = 1.42, 95% CI: 0.22-9.03, P = 0.71), pulmonary embolism (OR = 1.38, 95% CI: 0.27-7.04, P = 0.70), and mortality (OR = 0.70, 95% CI: 0.20-2.38, P = 0.56). Meanwhile, when only observational studies are considered, a significant reduction in the risk of developing arterial thrombotic events, MI, venous thromboembolism, and mortality was observed. The risk for DVT remains uncertain, due to the paucity of RCT-based data. TRT in men with TT <12 nmol l-1 is safe from the risk of adverse cardiovascular events. Further studies specifically assessing the risk of DVT in men on TRT are needed.
Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies ...have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.
Rotator cuff (RC) injuries include a wide range of pathologic states. Athletes are perhaps the most susceptible to RC injuries ranging from tendinopathy to partial or full-thickness tears, due to ...functional overload and repetitive movements, causing abstention from sports for long periods. Regenerative medicine keeps giving us multiple choices to fight the disability caused by these pathologies. A literature search was performed, and findings related to the structure-function of rotator cuff units, pathophysiology of injuries, regenerative medicine treatments, and future strategies were outlined. Platelet-rich plasma (PRP) has a greater number of articles and clinical trials, accompanied by stem cells progenitor, prolotherapy, and new approaches such as microfragmented adipose tissue and exosomes. RC injuries in athletes can cause pain, functional impotence, and the risk of recurrence, and can lead them to stop playing sports. Regenerative medicine offers a range of treatments, but some of them need further studies to underline their actual validity.
The
(
) gene is a paternally expressed imprinted gene, whose abnormal methylation appears to be associated with syndromes associated with the use of assisted reproductive techniques (ART), such as ...Angelman and Prader-Willi. Data present in the literature suggest the association between aberrant sperm
gene methylation and abnormal sperm parameters. The latest meta-analysis on the methylation pattern of this gene in spermatozoa of infertile patients published in 2017 reported a higher degree of methylation in the spermatozoa of infertile patients compared to fertile controls.
Here we provide an updated and comprehensive systematic review and meta-analysis of the sperm methylation pattern of the
gene in patients with abnormal sperm parameters/infertility compared to men with normal sperm parameters/fertile. For the first time in the literature, we performed a meta-regression analysis to evaluate whether age or sperm concentration could influence the methylation status of this gene at the sperm level.
This meta-analysis was registered in PROSPERO (n. CRD42023397056). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the MOOSE guidelines for meta-analyses and systematic reviews of observational studies were strictly followed in our meta-analysis. According to our Population Exposure Comparison Outcome (PECO) question, we included data from original articles assessing the levels of
gene methylation at the sperm level in infertile patients or patients with abnormalities in one or more sperm parameters compared to fertile or normozoospermic men.
Only six of 354 screened studies were included in the quantitative synthesis. Our analysis showed significantly higher levels of
gene methylation in patients compared to controls. However, significant heterogeneity was found between studies. In sensitivity analysis, no studies were sensitive enough to skew the results. The Egger test showed no publication bias. In the meta-regression analysis, the results were independent of age and sperm concentration in the overall population. The same results were found in the control group. However, when analyzing the patient group, a direct correlation was found between
methylation and age, indicating that the degree of methylation of the
gene increases with advancing age.
Fertility status or abnormality of sperm parameters is associated with a change in the methylation pattern of the
gene, with higher levels found in infertile patients or those with abnormal sperm parameters compared to fertile men or men with normal sperm parameters. In the group of infertile patients/patients with abnormal sperm parameters, age was directly correlated to the degree of
methylation, highlighting the presence of a mechanism that explains the age-related altered sperm quality and the risk of ART. Despite some limitations present in the analyzed studies, our results support the inclusion of
methylation in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to analyze in couples who want to undergo ART.
Electrospinning is gaining increasing interest in the biomedical field as an eco-friendly and economic technique for production of random and oriented polymeric fibers. The aim of this review was to ...give an overview of electrospinning potentialities in the production of fibers for biomedical applications with a focus on the possibility to combine biomechanical and topographical stimuli. In fact, selection of the polymer and the eventual surface modification of the fibers allow selection of the proper chemical/biological signal to be administered to the cells. Moreover, a proper design of fiber orientation, dimension, and topography can give the opportunity to drive cell growth also from a spatial standpoint. At this purpose, the review contains a first introduction on potentialities of electrospinning for the obtainment of random and oriented fibers both with synthetic and natural polymers. The biological phenomena which can be guided and promoted by fibers composition and topography are in depth investigated and discussed in the second section of the paper. Finally, the recent strategies developed in the scientific community for the realization of electrospun fibers and for their surface modification for biomedical application are presented and discussed in the last section.
Summary
Background & Aim
Non‐alcoholic fatty liver disease (NAFLD), and especially fibrotic non‐alcoholic steatohepatitis, is associated with high risks of liver‐related events (LRE) and extrahepatic ...events (EHE). We evaluated the competitive risk occurrence of LRE and EHE in a large cohort of biopsy‐proven NAFLD stratified according to baseline severity of fibrosis.
Methods
Two thousand one hundred thirty‐five patients with biopsy‐proven NAFLD were enrolled. Observed cumulative incidence functions (CIFs) were used to evaluate the risk of LRE and EHE; cause‐specific Cox model and predicted CIFs were fitted to identify predictors of LRE and EHE. A replication cohort of NAFLD patients with liver fibrosis severity estimated by liver stiffness measurement by transient elastography was also enrolled.
Results
Observed CIFs indicated that the 60‐month probabilities of LRE and EHE were 0.2% and 3% in F0‐F1, 2% and 3.8% in F2 and 9.7% and 6.4% in F3‐F4 patients, respectively. The cause‐specific Cox model indicated that in F0‐F1 and F2 patients, age > 50 years (HR 2.7) was the only predictor of LRE, while age > 50 years (HR 2.96), previous cardiovascular events (CVE, HR 2.07), and previous extra‐hepatic cancer (HR 2.36) were independent risk factors for EHE. In F3‐F4 patients, age > 55 years (HR 1.73), obesity (HR 1.52), PLT < 150 000/mmc (HR 3.66) and log(GGT) (HR 1.77) were associated with LRE, while age > 55 years (HR 1.74) and previous CVE (HR 2.51) were independent predictors of EHE. Predicted CIFs for HE and EHE in F0‐F1, F2 and F3‐F4 patients stratified the risk of events. The results were externally replicated.
Conclusion
The likelihood of EHE in NAFLD patients is relevant and increases according to the severity of liver fibrosis, while the risk of LRE is negligible in F0‐F1, low but clinically relevant in F2 and high in F3‐F4 patients.
Liver‐related events and extrahepatic events by competing risks analyses in 2135 patients with histological diagnosis of NAFLD, and 2790 patients with clinical diagnosis of NAFLD where fibrosis was estimated by liver stiffness by transient elastography.
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