Early cholecystectomy for acute cholecystitis has proved to reduce hospital length of stay but with no benefit in morbidity when compared to delayed surgery. However, in the literature, early timing ...refers to cholecystectomy performed up to 96 h of admission or up to 1 week of the onset of symptoms. Considering the natural history of acute cholecystitis, the analysis based on such a range of early timings may have missed a potential advantage that could be hypothesized with an early timing of cholecystectomy limited to the initial phase of the disease. The review aimed to explore the hypothesis that adopting immediate cholecystectomy performed within 24 h of admission as early timing could reduce post-operative complications when compared to delayed cholecystectomy.
The literature search was conducted based on the Patient Intervention Comparison Outcome Study (PICOS) strategy. Randomized trials comparing post-operative complication rate after early and delayed cholecystectomy for acute cholecystitis were included. Studies were grouped based on the timing of cholecystectomy. The hypothesis that immediate cholecystectomy performed within 24 h of admission could reduce post-operative complications was explored by comparing early timing of cholecystectomy performed within and 24 h of admission and early timing of cholecystectomy performed over 24 h of admission both to delayed timing of cholecystectomy within a sub-group analysis. The literature finding allowed the performance of a second analysis in which early timing of cholecystectomy did not refer to admission but to the onset of symptoms.
Immediate cholecystectomy performed within 24 h of admission did not prove to reduce post-operative complications with relative risk (RR) of 1.89 and its 95% confidence interval (CI) 0.76; 4.71. When the timing was based on the onset of symptoms, cholecystectomy performed within 72 h of symptoms was found to significantly reduce post-operative complications compared to delayed cholecystectomy with RR = 0.60 95% CI 0.39;0.92.
The present study failed to confirm the hypothesis that immediate cholecystectomy performed within 24 h of admission may reduce post- operative complications unless surgery could be performed within 72 h of the onset of symptoms.
Neural tube (NT) morphogenesis is reliant on the proper temporospatial expression of numerous genes and synchronized crosstalk between diverse signaling cascades and gene regulatory networks ...governing key cellular processes. MicroRNAs (miRNAs), a group of small non-coding regulatory RNAs, execute defining roles in directing key canonical pathways during embryogenesis.
In order to comprehend the mechanistic underpinnings of miRNA regulation of NT morphogenesis, we have identified in the current study various miRNAs and their target mRNAs associated with BMP signaling during critical stages of neurulation.
We previously demonstrated the expression of several miRNAs during the critical stages of neurulation (gestational days (GD) 8.5, 9.0, and 9.5) employing high-sensitivity, high-coverage microarrays. In the present study, bioinformatic analyses were used to identify miRNAs differentially expressed (DE) in the embryonic NT that target messenger RNAs (mRNAs) associated with the bone morphogenetic protein (BMP) signaling pathway. RNAs extracted from the developing NT were hybridized to both miRNA and mRNA arrays to evaluate miRNA-mRNA interactions.
Bioinformatic analysis identified several DE miRNAs that targeted mRNAs encoding members of (and proteins associated with) the BMP signaling pathway - a signaling cascade central to normal NT development.
Identification of the miRNAs and their mRNA targets associated with BMP signaling facilitates a better understanding of the crucial epigenetic mechanisms underlying normal NT development as well as the pathogenesis of NT defects. The current study supports the notion that miRNAs function as key regulators of neural tube morphogenesis via modulation of the BMP signaling cascade. Altered expression of these miRNAs during neurulation may therefore result in NT defects.
► Failure of embryonic neural crest cell (NCC) migration can cause orofacial clefts. ► We examine the role of SDF-1/CXCR4 signaling in mesencephalic NCC migration. ► Transwell culture and bead ...implantation in avian embryos provide quantitative data. ► The CXCR4 antagonists, AMD3100 and TN14003, inhibit NCC migration. ► SDF-1/CXCR4 signaling is, thus, required for the migration of mesencephalic NCCs.
Clefts of the lip and/or palate are among the most prevalent birth defects affecting approximately 7000 newborns in the United States annually. Disruption of the developmentally programmed migration of neural crest cells (NCCs) into the orofacial region is thought to be one of the major causes of orofacial clefting. Signaling of the chemokine SDF-1 (Stromal Derived Factor-1) through its specific receptor, CXCR4, is required for the migration of many stem cell and progenitor cell populations from their respective sites of emergence to the regions where they differentiate into complex cell types, tissues and organs. In the present study, “transwell” assays of chick embryo mesencephalic (cranial) NCC migration and ex ovo whole embryo “bead implantation” assays were utilized to determine whether SDF-1/CXCR4 signaling mediates mesencephalic NCC migration. Results from this study demonstrate that attenuation of SDF-1 signaling, through the use of specific CXCR4 antagonists (AMD3100 and TN14003), disrupts the migration of mesencephalic NCCs into the orofacial region, suggesting a novel role for SDF-1/CXCR4 signaling in the directed migration of mesencephalic NCCs in the early stage embryo.
Abstract Maternal/fetal genetic constitution and environmental factors are vital to delivery of a healthy baby. In the United States (US), a low birth weight (LBW) baby is born every minute and a ...half. LBW, defined as weighing less than 5.5 lbs at birth, affects nearly 1 in 12 infants born in the US with resultant costs for the nation of more than 15 billion dollars annually. Infant birth weight is the single most important factor affecting neonatal mortality. Various environmental and genetic risk factors for LBW have been identified. Several risks are preventable, such as cigarette smoking during pregnancy. Over one million babies are exposed prenatally to cigarette smoke accounting for over 20% of the LBW incidence in the US. Cigarette smoke exposure in utero results in a variety of adverse developmental outcomes with intrauterine growth restriction and infant LBW being the most well documented. However, the mechanisms underlying the causes of LBW remain poorly understood. The purpose of this study was: (1) to establish an animal model of cigarette smoke-induced in utero growth retardation and LBW using physiologically relevant inhalation exposure conditions which simulate “active” and “passive” tobacco smoke exposures, and (2) to determine whether particular stages of development are more susceptible than others to the adverse effects of in utero smoke exposure on embryo/fetal growth. Pregnant C57BL/6J mice were exposed to cigarette smoke during three periods of gestation: pre-/peri-implantation (gestational days gds 1–5), post-implantation (gds 6–18), and throughout gestation (gds 1–17). Reproductive and fetal outcomes were assessed on gd 18.5. Exposure of dams to mainstream/sidestream cigarette smoke, simulating “active” maternal smoking, resulted in decreases in fetal weight and crown–rump length when exposed throughout gestation (gds 1–17). Similar results were seen when dams were exposed only during the first 5 days of gestation (pre-/peri-implantation period gds 1–5). Exposure of dams from the post-implantation period through gestation (gds 6–18) did not result in reduced fetal weight, although a significant reduction in crown–rump length remained evident. Interestingly, maternal sidestream smoke exposure, simulating exposure to environmental tobacco smoke (ETS), during the pre-/peri-implantation period of development also produced significant decreases in fetal weight and crown–rump length. Collectively, results from the present study confirm an association between prenatal exposure to either “active” or “passive” cigarette smoke and in utero growth retardation. The data also identify a period of susceptibility to in utero cigarette smoke exposure-induced growth retardation and LBW during pre-/peri-implantation embryonic development.
Gallstone disease is very common afflicting 20 million people in the USA. In Europe, the overall incidence of gallstone disease is 18.8% in women and 9.5% in men. The frequency of gallstones related ...disease increases by age. The elderly population is increasing worldwide.
The present guidelines aims to report the results of the World Society of Emergency Surgery (WSES) and Italian Surgical Society for Elderly (SICG) consensus conference on acute calcolous cholecystitis (ACC) focused on elderly population.
The 2016 WSES guidelines on ACC were used as baseline; six questions have been used to investigate the particularities in elderly population; the answers have been developed in terms of differences compared to the general population and to statements of the 2016 WSES Guidelines. The Consensus Conference discusses, voted, and modified the statements. International experts contributed in the elaboration of final statements and evaluation of the level of scientific evidences.
The quality of the studies available decreases when we approach ACC in elderly. Same admission laparoscopic cholecystectomy should be suggested for elderly people with ACC; frailty scores as well as clinical and surgical risk scores could be adopted but no general consensus exist. The role of cholecystostomy is uncertain.
The evaluation of pro and cons for surgery or for alternative treatments in elderly suffering of ACC is more complex than in young people; also, the oldest old age is not a contraindication for surgery; however, a larger use of frailty and surgical risk scores could contribute to reach the best clinical judgment by the surgeon. The present guidelines offer the opportunity to share with the scientific community a baseline for future researches and discussion.
A multidisciplinary group, mainly from Bergamo region - the epicenter of the COVID-19 pandemic crisis in Italy on march 2020- has developed concept of creating intermediate care facilities and ...proposes a three-tier model of community-based care, with the goal of reducing hospital admissions, contagion and mortality related to hospital overloading and optimizing human resources.
Cigarette smoke is composed of over 4000 chemicals many of which are strong oxidizing agents and chemical carcinogens. Chronic cigarette smoke exposure (CSE) induces mild alterations in liver ...histology indicative of toxicity though the molecular pathways underlying these alterations remain to be explored. Utilizing a mouse model of ‘active’ developmental CSE (gestational day (GD) 1 through postnatal day (PD) 21; cotinine >50ng/mL) characterized by low birth weight offspring, the impact of developmental CSE on liver protein abundances was determined. On PD21, liver tissue was collected from pups for 2D SDS-PAGE based proteome analysis with statistical analysis by Partial Least Squares-Discriminant Analysis (PLS-DA). Protein spots of interest were identified by ESI-MS/MS with impacted molecular pathways identified by Ingenuity Pathway Analysis. Developmental CSE decreased the abundance of proteins associated with the small molecule biochemistry (includes glucose metabolism), lipid metabolism, amino acid metabolism, and inflammatory response pathways. Decreased gluconeogenic enzyme activity and lysophosphatidylcholine availability following developmental CSE were found and supports the impact of CSE on these pathways. Proteins with increased abundance belonged to the cell death and drug metabolism networks. Liver antioxidant enzyme abundances glutathione-S-transferase (GST) and peroxiredoxins were also altered by CSE, but GST enzymatic activity was unchanged. In summary, cigarette smoke exposure spanning pre- and post-natal development resulted in persistent decreased offspring weights, decreased abundances of liver metabolic proteins, decreased gluconeogenic activity, and altered lipid metabolism. The companion paper details the kidney proteome alterations in the same offspring.