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Τρίτη 12 Ιουλίου 2022

Understanding Etiologic Pathways Through Multiple Sequential Mediators: An Application in Perinatal Epidemiology

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Background: Causal mediation analysis facilitates decomposing the total effect into a direct effect and an indirect effect that operates through an intermediate variable. Recent developments in causal mediation analysis have clarified the process of evaluating how – and to what extent – different pathways via multiple causally ordered mediators link the exposure to the outcome. Methods: Through an application of natural effect models for multiple mediators, we show how placental abruption might affect perinatal mortality using small-for-gestational-age (SGA) birth and preterm delivery as two sequential mediators. We describe methods to disentangle the total effect into the proportions mediated via each of the sequential mediators, when evaluating natural direct and natural indirect effects. Results: Under the assumption that SGA births causally precedes preterm delivery, an analysis of 16.7 million singleton pregnancies is consistent with the hypothesis that abruption exerts powerful effects on perinatal mortality (adjusted risk ratio=11.9; 95% confidence interval 11.6, 12.1). The proportions of the estimated total effect mediated through SGA birth and preterm delivery were 2% and 58%, respectively. The proportion unmediated via either SGA or preterm delivery was 41%. Conclusions: Through an application of causal mediation analysis with sequential mediators, we uncovered new insights into the pathways along which abruption impacts perinatal mortality. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Resistance-Guided Therapy for Neisseria gonorrhoeae

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Abstract
Antimicrobial-resis tant Neisseria gonorrhoeae infections are a threat to public health. Novel strategies for combating such resistance include the development of molecular assays to facilitate real-time prediction of antimicrobial susceptibility. Resistance to ciprofloxacin is determined by the presence of a single mutation at codon 91 of the gyrase A gene; molecular assays to guide therapy are commercially available. Resistance to cefixime is conferred via 1 of 6 critical mutations in either the mosaic penA gene or specific loci in the nonmosaic region. Resistance to ceftriaxone is conferred through mutations in 1 of 4 genes: penA, ponA, penB, and mtr; however, the ability to predict reduced susceptibility based on those genes varies by geographic region. Here, we highlight the work done toward the development of 3 such assays for ciprofloxacin, cefixime, and ceftriaxone, discuss the status of our current understanding and ongoing challenges, and suggest future directions.
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Arthroscopic discopexy versus natural course of temporomandibular joint anterior disc displacement: a longitudinal study of clinical and radiological outcomes

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The aim of this study was to assess the various outcomes of arthroscopic discopexy compared to the natural course of anterior disc displacement (ADD) longitudinally in the same patients. A retrospective review was performed of 108 patients (152 joints) who experienced the natural course of ADD for a period of time and then underwent arthroscopic discopexy. The outcome was evaluated clinically and by magnetic resonance imaging. The natural course of ADD showed significant deterioration in pain, diet, and quality of life, and also a significant reduction in inter-incisal opening (all P   (Source: International Journal of Oral and Maxillofacial Surgery)
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Histamine H1‐ and H2‐receptors participate to provide metabolic energy differently

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Abstract

Histamine participates in a variety of physiological functions. The local effects of histamine have a role to provide metabolic energy for the tissues. The objective of this work is to study the mechanism whereby histamine affects serum glucose and liver glycogen fractions. Six groups of 10 male rats received two injections with histamine, H1-agonist (dipyridylethylamine), H2-agonist (dimaprit), H1-agonist plus H1-antagonist (cetirizine), or H2-agonist plus H2-antagonist (famotidine). Serum glucose and liver glycogen fractions were measured. Histamine caused a significant increase in serum glucose (163.7 ± 5.4 vs. 153.2 ± 3.3 mg/dl, p = 0.023). The effect of histamine was mimicked by selective H1-agonist (164.2 ± 3.5 vs. 152.8 ± 2.9 mg/dl, p = 0.005) but not with H2-agonist (159.3 ± 3.7 vs. 156.3 ± 4.8 mg/dl, p = 0.281). The effect of H1-agonist was abolished in the presence of selective H1-antagonist. Treatment by H1- but not H2-agonist decreased total glycogen by about 35% (30.6 ± 0.5 vs. 47.3 ± 2.8 mg/g wet weight of liver, p = 0.003). The decrease happened wholly in ASG fraction (26.8 ± 1.2 vs. 43.7 ± 3.2 mg/g wet weight of liver, p = 0.004), while AIG did not change significantly (4.2 ± 0.5 vs. 4.5 ± 0.4 mg/g wet weight of liver, p = 0.724). Histamine causes to decrease glycogen in the liver and increased serum glucose. The effects of histamine were mediated via H1-receptors. ASG was metabolically active fraction of liver glycogen in this process. The results confirm the role of histamine in providing metabolic energy of the tissues.
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Identification of Putative Causal Relationships Between Type 2 Diabetes and Blood-Based Biomarkers in East Asians by Mendelian Randomization

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Abstract
Observational studies revealed phenotypic associations between type 2 diabetes (T2D) and many biomarkers. However, causality between these conditions in East Asians is unclear. We leveraged genome-wide association study (GWAS) summary statistics of T2D (Ncase = 77,418; Ncontrol = 356,122) from the Asian Genetic Epidemiology Network (sample recruited during 2001-2011), and the GWAS summary statistics of 42 biomarkers (N = 12,303 to 143,658) from BioBank Japan (sample recruited during 2003-2008) to investigate causal relationships between T2D and biomarkers. Applications of Mendelian randomization (MR) approaches consistently revealed the genetically instrumented T2D associated with increased blood potassium (liability-scale β = [0.04, 0.10], p-value = [6.41×10-1 7, 9.85×10-5]) and decreased blood chloride (liability-scale β = [-0.16, -0.06], p-value = [5.22×10-27, 3.14×10-5]) whereas these two biomarkers showed no causal effects on T2D. Heritability estimation using summary statistics (ρ-HESS) and summary data-based Mendelian randomization (SMR) highlighted 27 genomic regions and three genes (MGAT1, TLE1, and HMGCR) interactively associated with the shared genetics underlying T2D and the two biomarkers. Thus, T2D may causally affect potassium and chloride in blood for East Asians. In contrast, the relationships from the potassium or chloride to T2D are not causal, suggesting the importance of monitoring the electrolyte disorder for T2D patients.
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SIRT3-mediated deacetylation protects inner hair cell synapses in a H2O2-induced oxidative stress model in vitro

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Publication date: Available online 11 July 2022

Source: Experimental Cell Research

Author(s): Chunli Zhao, Wenqi Liang, Zijing Yang, Zhongrui Chen, Zhengde Du, Shusheng Gong
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Circular Stapled Technique Versus Modified Collard Technique for Cervical Esophagogastric Anastomosis After Esophagectomy: A Randomized Controlled Trial

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imageObjective: This study was performed to investigate the efficacy of the modified Collard (MC) technique for reducing anastomotic stricture after esophagectomy compared with the circular stapled (CS) technique. Summary Background Data: The currently available techniques of anastomosis after esophagectomy are associated with a significant risk of anasto-motic complications. However, the optimal anastomotic technique after esophagectomy has not yet been established. Methods: We randomly allocated patients to either the CS group or the MC group. The primary endpoint was the incidence of anastomotic stricture. The secondary endpoints included the incidence of postoperative complications (including anastomotic leakage) and quality of life (QoL). All anastomoses were performed after indocyanine green evaluation for objective homogeni-zation of blood flow to the gastric conduit between the 2 techniques. Results: Among 100 randomized patients (CS group, n = 50; MC group, n = 50), anastomotic strictures were observed in 18 (42%) patients in the CS group and in no patients in the MC group. There were no significant between-group differences in anastomotic leakage (CS group, 7% vs MC group, 8%; P = 0.94). Quality of life domains of dysphagia and choking when swallowing at 3 months after surgery were significantly better in the MC group than in the CS group. Conclusions: The MC technique reduces the incidence of anastomotic stricture and improves postoperative quality of life. Furthermore, the incidence of anastomotic leakage is comparable between the 2 techniques based on accurate comparison under objective homogenization of the gastric conduit condition.
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The Efficacy of Liposomal Bupivacaine on Postoperative Pain Following Abdominal Wall Reconstruction: A Randomized, Double-blind, Placebo-controlled Trial

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imageObjective: To study the efficacy of liposomal bupivacaine on postoperative opioid requirement and pain following abdominal wall reconstruction. Summary Background Data: Despite the widespread use of liposomal bupivacaine in transversus abdominis plane block, there is inadequate evidence demonstrating its efficacy in open abdominal wall reconstruction. We hypothesized that liposomal bupivacaine plane block would result in decreased opioid requirements compared with placebo in the first 72 hours after surgery. Methods: This was a single-center double-blind, placebo-controlled prospective study conducted between July 2018 and November 2019. Adult patients (at least 18 yrs of age) undergoing open, elective, ventral hernia repairs with mesh placed in the retromuscular position were enrolled. Patients were randomized to surgeon-performed transversus abdominis plane block with liposomal bupivacaine, simple bupivacaine, or normal saline (placebo). The main outcome was opioid requirements in the first 72 hours after surgery. Secondary outcomes included total inpatient opioid use, pain scores determined using a 100 mm visual analog scale, length of hospital stay, and patientreported quality of life. Results: Of the 164 patients who were included in the analysis, 57 patients received liposomal bupivacaine, 55 patients received simple bupivacaine, and 52 received placebo. There were no differences in the total opioid used in the first 72 hours after surgery as measured by morphine milligram equivalents when liposomal bupivacaine was compared with simple bupivacaine and placebo (325 ± 225 vs 350 ± 284 vs 310 ± 272, respectively, P = 0.725). Similarly, there were no differences in total inpatient opioid use, pain scores, length of stay, and patient-reported quality of life. Conclusions: There are no apparent clinical benefits to using liposomal bupivacaine transversus abdominis plane block when compared with simple bupivacaine and placebo for open abdominal wall reconstruction.
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The Problem of Appetite Loss After Major Abdominal Surgery: A Systematic Review

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imageObjective: To systematically review the problem of appetite loss after major abdominal surgery. Summary of Background Data: Appetite loss is a common problem after major abdominal surgery. Understanding of etiology and treatment options is limited. Methods: We searched Medline, Cochrane Central Register of Controlled Trials, and Web of Science for studies describing postoperative appetite loss. Data were extracted to clarify definition, etiology, measurement, surgical influence, pharmacological, and nonpharmacological treatment. PROSPERO registration ID: CRD42021224489. Results: Out of 6144 articles, we included 165 studies, 121 of which were also analyzed quantitatively. A total of 19.8% were randomized, controlled trials (n = 24) and 80.2% were nonrandomized studies (n = 97). The studies included 20,506 patients undergoing the following surgeries: esophageal (n = 33 studies), gastric (n = 48), small bowel (n = 6), colon (n = 27), rectal (n = 20), hepatobiliary (n = 6), and pancreatic (n = 13). Appetite was mostly measured with the Quality of Life Questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30, n = 54). In a meta-analysis of 4 randomized controlled trials gum chewing reduced time to first hunger by 21.2 hours among patients who had bowel surgery. Other reported treatment options with positive effects on appetite but lower levels of evidence include, among others, intravenous ghrelin administration, the oral Japanese herbal medicine Rikkunshito, oral mosapride citrate, multidisciplin-ary-counseling, and watchin g cooking shows. No studies investigated the effect of well-known appetite stimulants such as cannabinoids, steroids, or megestrol acetate on surgical patients. Conclusions: Appetite loss after major abdominal surgery is common and associated with increased morbidity and reduced quality of life. Recent studies demonstrate the influence of reduced gastric volume and ghrelin secretion, and increased satiety hormone secretion. There are various treatment options available including level IA evidence for postoperative gum chewing. In the future, surgical trials should include the assessment of appetite loss as a relevant outcome measure.
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