Global prevalence of cefiderocol non-susceptibility in Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia: a systematic review and meta-analysis.

BACKGROUND: Cefiderocol is a last resort option for carbapenem-resistant (CR) Gram-negative bacteria, especially metallo-ß-lactamase-producing Pseudomonas aeruginosa and CR Acinetobacter baumannii. Monitoring global levels of cefiderocol non-susceptibility (CFDC-NS) is important. OBJECTIVES: To systematically collate and examine studies investigating in vitro CFDC-NS and estimate the global prevalence of CFDC-NS against major Gram-negative pathogens. DATA SOURCES: PubMed and Scopus, up to May 2023. STUDY ELIGIBILITY CRITERIA: Eligible were studies reporting CFDC-NS in Enterobacterales, P. aeruginosa, A. baumannii, or Stenotrophomonas maltophilia clinical isolates. RISK-OF-BIAS ASSESSMENT: Two independent reviewers extracted study data and assessed the risk of bias on the population, setting, and measurement (susceptibility testing) domains. DATA SYNTHESIS: Binomial-Normal mixed-effects models were applied to estimate CFDC-NS prevalence by species, coresistance phenotype, and breakpoint definition (EUCAST, CLSI, and FDA). Sources of heterogeneity were investigated by subgroup and meta-regression analyses. RESULTS: In all, 78 studies reporting 82 035 clinical isolates were analysed (87% published between 2020 and 2023). CFDC-NS prevalence (EUCAST breakpoints) was low overall but varied by species (S. maltophilia 0.4% [95% CI 0.2-0.7%], Enterobacterales 3.0% [95% CI 1.5-6.0%], P. aeruginosa 1.4% [95% CI 0.5-4.0%]) and was highest for A. baumannii (8.8%, 95% CI 4.9-15.2%). CFDC-NS was much higher in CR Enterobacterales (12.4%, 95% CI 7.3-20.0%) and CR A. baumannii (13.2%, 95% CI 7.8-21.5%), but relatively low for CR P. aeruginosa (3.5%, 95% CI 1.6-7.8%). CFDC-NS was exceedingly high in New Delhi metallo-ß-lactamase-producing Enterobacterales (38.8%, 95% CI 22.6-58.0%), New Delhi metallo-ß-lactamase-producing A. baumannii (44.7%, 95% CI 34.5-55.4%), and ceftazidime/avibactam-resistant Enterobacterales (36.6%, 95% CI 22.7-53.1%). CFDC-NS varied considerably with breakpoint definition, predominantly among CR bacteria. Additional sources of heterogeneity were single-centre investigations and geographical regions. CONCLUSIONS: CFDC-NS prevalence is low overall, but alarmingly high for specific CR phenotypes circulating in some institutions or regions. Continuous surveillance and updating of global CFDC-NS estimates are imperative while cefiderocol is increasingly introduced into clinical practice. The need to harmonize EUCAST and CLSI breakpoints was evident.

Effectiveness of probiotics and synbiotics in reducing duration of acute infectious diarrhea in pediatric patients in developed countries: a systematic review and meta-analysis.

Acute diarrhea is one of the most frequent causes of doctor visits and hospital admissions for children. Our objective was to evaluate the association between probiotics administration and reduction of acute infectious diarrhea duration in children dwelling in developed countries. Bibliographic databases, gray literature, and reference lists were searched up to September 29, 2019. Double-blind, randomized controlled trials that examined probiotics efficacy in children with acute infectious diarrhea residing in developed countries were included. Data were synthesized by generic inverse variance method using fixed- and random-effects model. Twenty trials met the eligibility criteria (n = 3469 patients) and were included in the qualitative synthesis, and 19 studies in meta-analysis. Twelve trials (n = 840) were assessed as high/unclear risk of bias and eight (n = 2629) as low risk of bias. Comparisons revealed a moderate effectiveness of probiotics in low risk of bias studies (MD = - 13.45 h; 95% CI - 24.26, - 2.62; p = 0.02, Bayesian meta-analysis pooled effect MD = - 0.38, 95% CrI - 2.3, 1.58) and a notable effect in studies with high/unclear risk for bias (MD = - 19.70 h; 95% CI - 28.09, - 11.31; p = 0.0004). In trials of optimal methodological quality (n = 1989), probiotics effect was absent (MD = - 3.32 h; 95% CI - 8.78, 2.13, p = 0.23).Conclusion: Outcomes suggest that probiotics do not demonstrate sufficient clinical impact in reducing diarrhea duration in children in the developed countries.Systematic Review Registration: This review is registered at PROSPERO (ID: CRD42020152966). What is Known: • Probiotics, due to the conflicting study results, are administered without adequate evidence as an adjuvant therapeutic agent for eliminating duration of acute infectious diarrhea in pediatric patients. What is New: • In developed countries, probiotics are demonstrated as ineffective in reducing the duration of acute infectious diarrhea in children.

Defining the genetic profile of endometriosis.

Endometriosis is a pathological condition which has been extensively studied, since its pathophysiology stems from a broad spectrum of environmental influences and genetic factors. Familial studies aim at defining inheritance trends, while linkage analysis studies focus on the identification of genetic sites related to endometriosis susceptibility. Genetic association studies take into account candidate genes and single nucleotide polymorphisms, and hence target at unraveling the association between disease severity and genetic variation. The common goal of various types of studies is, through genetic mapping methods, the timely identification of therapeutic strategies for disease symptoms, including pelvic pain and infertility, as well as efficient counselling. While genome-wide association studies (GWAS) play a primary role in depicting genetic contributions to disease development, they entail a certain bias as regards the case-control nature of their design and the reproducibility of the results. Nevertheless, genetic-oriented studies and the implementation of the results through clinical tests, hold a considerable advantage in proper disease management. In this review article, we present information about gene-gene and gene-environment interactions involved in endometriosis and discuss the effectiveness of GWAS in identitying novel potential therapeutic targets in an attempt to develop novel therapeutic strategies for a better management and treatment of patients with endometriosis.

Endometriosis and in vitro fertilisation.

The aim of the present review was to discuss a matter of concern in the clinical field of obstetrics/gynecology, namely the potency of in vitro fertilization (IVF) in the management of endometriosis-associated infertility. Endometriosis is a medical condition affecting one tenth of women in their fertile years, and accounts for up to 50% of infertile women. Thus, such high prevalence has established the necessity for investigating the effectiveness of available techniques in eradicating the disease and constraining infertility as well as the accompanying pain symptoms of endometriosis. The underlying mechanisms connecting endometriosis with low fecundity have been extensively studied, both in terms of genetic alterations and epigenetic events that contribute to the manifestation of an infertility phenotype in women with the disease. Several studies have dealt with the impact of IVF in pregnancy rates (PRs) on patients with endometriosis, particularly regarding women who wish to conceive. Results retrieved from studies and meta-analyses depict a diverse pattern of IVF success, underlining the involvement of individual parameters in the configuration of the final outcome. The ultimate decision on undergoing IVF treatment should be based on objective criteria and clinicians' experience, customized according to patients' individual needs.

Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review).

Colorectal cancer (CRC) is among the most common cancers. In fact, it is placed in the third place among the most diagnosed cancer in men, after lung and prostate cancer, and in the second one for the most diagnosed cancer in women, following breast cancer. Moreover, its high mortality rates classifies it among the leading causes of cancer­related death worldwide. Thus, in order to help clinicians to optimize their practice, it is crucial to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. In that way, they will be able to decrease both morbidity and mortality of their patients. In accordance with that, colon cancer research has described numerous biomarkers for diagnostic, prognostic and predictive purposes that either alone or as part of a panel would help improve patient's clinical management. This review aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, faeces or blood) along with their restrictions. Lastly, new insight in CRC monitoring will be discussed presenting promising emerging biomarkers (telomerase activity, telomere length and micronuclei frequency).

Endocrine Disruptors Leading to Obesity and Related Diseases.

The review aims to comprehensively present the impact of exposure to endocrine disruptors (EDs) in relation to the clinical manifestation of obesity and related diseases, including diabetes mellitus, metabolic syndrome, cardiovascular diseases, carcinogenesis and infertility. EDs are strong participants in the obesity epidemic scenery by interfering with cellular morphological and biochemical processes; by inducing inflammatory responses; and by presenting transcriptional and oncogenic activity. Obesity and lipotoxicity enhancement occur through reprogramming and/or remodeling of germline epigenome by exposure to EDs. Specific population groups are vulnerable to ED exposure due to current dietary and environmental conditions. Obesity, morbidity and carcinogenicity induced by ED exposure are an evolving reality. Therefore, a new collective strategic approach is deemed essential, for the reappraisal of current global conditions pertaining to energy management.

CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides.

The association between genetic variations in the cytochrome P450 (CYP) family genes and pathological conditions related to long-term exposure to organochlorine compounds (OCs) deserves further elucidation. OCs are persistent organic pollutants with bioaccumulative and lipophilic characteristics. They can act as endocrine disruptors and perturb cellular mechanisms. Prolonged exposure to OCs has been associated with different pathological manifestations. CYP genes are responsible for transcribing enzymes essential in xenobiotic metabolism. Therefore, polymorphisms in these genetic sequences a. alter the metabolic pathways, b. induce false cellular responses, and c. may provoke pathological conditions. The main aim of this review is to define the interaction between parameters a, b and c at a mechanistic/molecular level, with references in clinical cases.

Environmental exposure to organophosphorus nerve agents.

Exposure to organophosphorus nerve agents, the most deadly chemical warfare agents, is possible in a variety of situations, such as destruction of chemical warfare agents, terrorist attacks, armed conflicts or accidents in research laboratories and storage facilities. Hundreds of thousands of tons of chemical munitions were disposed of at the sea in the post World War II period, with European, Russian, Japanese and US coasts being the most affected. Sulfur mustard, Lewisite and nerve agents appear to be the most frequently chemical warfare agents disposed of at the sea. Addressing the overall environmental risk, it has been one of the priorities of the world community since that time. Aside from confirming exposure to nerve agents in the alleged use for forensic purposes, the detection and identification of biological markers of exposure are also needed for the diagnosis and treatment of poisoning, in addition to occupational health monitoring for specific profiles of workers. When estimating detrimental effects of acute or potential chronic sub-lethal doses of organophosphorus nerve agents, released accidentally or intentionally into the environment, it is necessary to understand the wide spectra of physical, chemical and toxicological properties of these agents, and predict their ultimate fate in environmental systems.

Obesity, Persistent Organic Pollutants and Related Health Problems.

The present review aims to delve into persistent organic pollutants (POPs) , as xenobiotics, in correlation to human health. POPs exhibit a group of common characteristics, including lipophilicity, persistence to decomposition and bioaccumulation in tissues. POPs have been thoroughly studied by former researchers, as they offer a particular interest in the elucidation of metabolic, endocrine and immune perturbation caused by their synergy with intracellular mechanisms. Herein particular focus is attributed to the relationship of POPs with obesity provocation. Obesity nowadays receives epidemic dimensions, as its prevalence elevates in an exponential degree. POPs-induced obesity rotates around interfering in metabolic and endocrinal procedures and interacting with peroxisome-proliferator and retinoic receptors. Moreover, polymorphisms in CYP gene families exert a negative result, as they incapacitate detoxification of POPs. Obesity could be deemed as a multidimensional condition, as various factors interact to lead to an obesogenic result. Therefore, concomitant disorders may occur, from mild to lethal, and get intensified due to POPs exposure. POPs exact function mechanisms remain rather enigmatic, thus further investigation should be prospectively performed, for a more lucid picture of this issue, and, consequently for the establishment of alternative solutions.