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Πέμπτη 17 Μαρτίου 2022

Propensity Score Analysis of Outcomes Following Laparoscopic or Open Radical Resection for Gallbladder Cancer in T2 and T3 Stages

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Abstract

Background

Although laparoscopic radical resection (LRR) has long been contraindicated in gallbladder cancer (GBC), recent studies have demonstrated laparoscopic surgery did not adversely affect the perioperative and survival outcomes of GBC patients. However, these literatures are mainly focused on GBC of relatively early stages or incidental GBC. This study aimed to investigate the perioperative and long-term outcomes of LRR versus open radical resection (ORR) for GBCs in T2 and T3 stages.

Methods

A retrospective study was conducted on 99 patients with GBC of T2 and T3 stages who underwent radical resection at Zhejiang Provincial People's Hospital from January 2010 to December 2020. A 1:1 propensity score matching (PSM), which is widely used to reduce selection bias, was performed to compare the surgical outcomes and long-term prognosis between LRR and ORR. A logistic regression analysis was implemented to identify the predictive risk factors of postoperative overall survival.

Results

By using PSM, the baseline characteristics of two groups (with 30 patients in each group) were generally well balanced. In the LRR group, the length of operation was significantly longer than the ORR group, but the intraoperative bleeding and postoperative days of hospital stay were significantly decreased compared to the ORR group. The two groups showed comparable outcomes regarding the incidence of biliary reconstruction, lymph node yield, the incidence of postoperative morbidities, the incidence of Clavien–Dindo (C–D) grades III–IV, the days of drainage tubes indwelling, mortality at 30 postoperative days and 90 postoperative days, and the incidence of port-site metastasis. The 1-, 2-, and 3-year overall survival rates were 61.2, 40.1, and 30.1%, respectively, in the LRR group, and 53.3, 40.1, and 40.1%, respectively, in the OLR group (P = 0.644). On multivariate analysis, T stage, vascular invasion, and tumor differentiation were found to be the independent risk factors for overall survival of GBC in T2 and T3 stages.

Conclusions

For GBC in T2 and T3 stages, LRR can achieve comparable perioperative outcomes and similar long-term survival benefit compared to ORR. LRR tends to show advantages over ORR regarding intraoperative bleeding and postoperative days of hospital stay.

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Quantum description of the moving magnetic quadrupole moment interacting with electric field configurations under the rotating background with the screw dislocation

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Abstract

In this paper, we present the quantum description that arose from the interaction of a moving magnetic quadrupole moment with electric field configurations in the background having a rotating frame of the presence of screw dislocation in the nonrelativistic regime. Interacting a moving particle involving a magnetic quadrupole moment with the chosen electric field configuration in a rotating frame can produce a kind of static scalar potential for the geometric background. We solve the relevant Schrödinger equation and acquire the exact solutions for that system by applying an analytical method. Besides, based on this interaction, owing to one of the choices for the electric field, we can see an Aharonov–Anandan quantum phase in the corresponding solutions.

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Hepatocellular Carcinoma Metastasising to Anterior Chest Wall: a Rare Occurrence

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Pregnancy, Fetal, and Infant Outcomes Following Maternal Exposure to Glatiramer Acetate During Pregnancy and Breastfeeding

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Abstract

Introduction

Published data support the safety of glatiramer acetate in patients with multiple sclerosis who are pregnant or breastfeeding, but long-term data are limited.

Objective

We aimed to assess pregnancy, fetal, and infant outcomes following maternal exposure to glatiramer acetate.

Methods

In-utero glatiramer acetate-exposed postmarketing pregnancy reports from 2019 to 2021 were extracted from Teva's pharmacovigilance database. Pregnancy data acquired prior to knowledge of pregnancy outcome or detection of congenital malformation (prospective reports) were used to estimate pregnancy and infant outcome rates for glatiramer acetate 20- and 40-mg/mL exposure. A subgroup of cases completed follow-up questionnaires and were analyzed separately.

Results

Prospective cases with 702 fetuses had known outcomes with 647 (92.2%) live births, 47 (6.7%) spontaneous abortions, 4 (0.6%) induced abortions, 2 (0.3%) ectopic pregnancies, and 2 (0.3%) fetal deaths. Rates of major congenital malformation (1.1%), preterm births (7.2%), and low/very low birth weight (4.8%), and parameters of growth were within background rates. No infant developmental delay was reported. Overall, pregnancy and infant outcomes were similar across glatiramer acetate doses.

Conclusions

Maternal exposure to glatiramer acetate does not appear to be related to adverse pregnancy, fetal, or infant outcomes. These data further support the safety of both glatiramer acetate 20-mg/mL and 40-mg/mL treatments during pregnancy and breastfeeding.

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Experimental and computational characterization of dynamic biomolecular interaction systems involving glycolipid glycans

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Abstract

On cell surfaces, carbohydrate chains that modify proteins and lipids mediate various biological functions, which are exerted not only through carbohydrate–protein interactions but also through carbohydrate–carbohydrate interactions. These glycans exhibit considerable degrees of conformational variability and often form clusters providing multiple binding sites. The integration of nuclear magnetic resonance spectroscopy and molecular dynamics simulation has made it possible to delineate the dynamical structures of carbohydrate chains. This approach has facilitated the remodeling of oligosaccharide conformational space in the prebound state to improve protein-binding affinity and has been applied to visualize dynamic carbohydrate–carbohydrate interactions that control glycoprotein–glycoprotein complex formation. Functional glycoclusters have been characterized by experimental and computational approaches applied to various model membranes and artificial se lf-assembling systems. This line of investigation has provided dynamic views of molecular assembling on glycoclusters, giving mechanistic insights into physiological and pathological molecular events on cell surfaces as well as clues for the design and creation of molecular systems exerting improved glycofunctions. Further development and accumulation of such studies will allow detailed understanding and artificial control of the "glycosynapse" foreseen by Dr. Sen-itiroh Hakomori.

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Characteristics and outcomes of carbapenemase harbouring carbapenem-resistant Klebsiella spp. bloodstream infections: a multicentre prospective cohort study in an OXA-48 endemic setting

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Abstract

A prospective, multicentre observational cohort study of carbapenem-resistant Klebsiella spp. (CRK) bloodstream infections was conducted in Turkey from June 2018 to June 2019. One hundred eighty-seven patients were recruited. Single OXA-48-like carbapenemases predominated (75%), followed by OXA-48-like/NDM coproducers (16%). OXA-232 constituted 31% of all OXA-48-like carbapenemases and was mainly carried on ST2096. Thirty-day mortality was 44% overall and 51% for ST2096. In the multivariate cox regression analysis, SOFA score and immunosuppression were significant predictors of 30-day mortality and ST2096 had a non-significant effect. All OXA-48-like producers remained susceptible to ceftazidime-avibactam.

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Covered Transjugular Intrahepatic Portosystemic Shunt Improves Hypersplenism-Associated Cytopenia in Cirrhosis

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Abstract

Background

Patients with cirrhosis often develop portal hypertension-associated splenomegaly and hypersplenism, potentially causing severe cytopenia.

AIMS

Systematic assessment on the impact of transjugular intrahepatic portosystemic shunt (TIPS) implantation on platelet count (PLT), hemoglobin (Hb), and white blood cell count (WBC).

Methods

Patients with cirrhosis undergoing covered TIPS implantation were retrospectively included. Patients with malignancies or hematologic disorders were excluded. Hematology lab work was recorded at baseline (pre-TIPS) and at regular intervals after TIPS.

Results

One hundred ninety-two patients (male: 72.4%, age: 56 ± 10 years; MELD: 12.1 ± 3.6) underwent TIPS implantation. Higher-grade (≥ G2) thrombocytopenia (PLT < 100 G/L) was present in 54 (28.7%),  ≥ G2 anemia (Hb < 10 g/dL) in 57 (29.7%), and  ≥ G2 leukopenia (WBC < 2 G/L) in 3 (1.6%) patients pre-TIPS, respectively. Resolution of ≥ G2 thrombocytopenia, anemia, and leukopenia occurred in 24/55 (43.6%), 23/57 (40.4%), and 2/3 (66.7%), respectively. Similar results were also observed in the subgroup of patients without 'bleeding' TIPS-indication, with improvements of G ≥ 2 thrombocytopenia and of G ≥ 2 anemia in 19.8% and 10.2% of patients after TIPS, respectively.

Conclusions

Thrombocytopenia, anemia, and leukopenia frequently improved after TIPS. Therefore, moderate- to higher-grade thrombocytopenia should not be regarded as a contraindication against TIPS, but rather be considered in case of severe thrombocytopenia—particularly prior to surgery or interventions.

Graphical Abstract

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Comprehensive analysis of cytokine adsorption properties of polymethyl methacrylate (PMMA) membrane material

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Abstract

In acute kidney injury caused by sepsis (septic AKI), excessive production of inflammatory mediators is believed to be involved in deterioration of the disease. Renal replacement therapy using a polymethyl methacrylate (PMMA) membrane hemofilter improves the pathological condition of septic AKI by adsorbing and removing inflammatory cytokines. However, the adsorption properties of the PMMA membrane are unclear. In this study, we comprehensively analyzed the adsorption of 48 different cytokines in human plasma to PMMA and polysulfone (PS) membranes. Seventy-nine percent (38/48) of the cytokines were adsorbed more efficiently to the PMMA membrane than the PS membrane, which indicates that the PMMA membrane has high cytokine adsorption ability. The adsorption rate tended to be higher for the cytokines with lower molecular weight, and there was a significant correlation between the molecular weight of the cytokines and the adsorption rates. Electron microscopy showed that the PMMA hollow fiber membrane had a uniform internal structure from the inner to the outer layers of the membrane and had nano-pores inside the membrane that may have contributed to the adsorption of proteins with a specific molecular weight range. The clinical efficacy of a PMMA membrane hemofilter with cytokine adsorption properties against septic AKI needs further investigation including the evaluation of filtration performance of the hemofilters.

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CEBPβ regulation of endogenous IGF-1 in adult sensory neurons can be mobilized to overcome diabetes-induced deficits in bioenergetics and axonal outgrowth

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Abstract

Aberrant insulin-like growth factor 1 (IGF-1) signaling has been proposed as a contributing factor to the development of neurodegenerative disorders including diabetic neuropathy, and delivery of exogenous IGF-1 has been explored as a treatment for Alzheimer's disease and amyotrophic lateral sclerosis. However, the role of autocrine/paracrine IGF-1 in neuroprotection has not been well established. We therefore used in vitro cell culture systems and animal models of diabetic neuropathy to characterize endogenous IGF-1 in sensory neurons and determine the factors regulating IGF-1 expression and/or affecting neuronal health. Single-cell RNA sequencing (scRNA-Seq) and in situ hybridization analyses revealed high expression of endogenous IGF-1 in non-peptidergic neurons and satellite glial cells (SGCs) of dorsal root ganglia (DRG). Brain cortex and DRG had higher IGF-1 gene expression than sciatic nerve. Bidirectional transport of IGF-1 along sensory nerves was ob served. Despite no difference in IGF-1 receptor levels, IGF-1 gene expression was significantly (P < 0.05) reduced in liver and DRG from streptozotocin (STZ)-induced type 1 diabetic rats, Zucker diabetic fatty (ZDF) rats, mice on a high-fat/ high-sugar diet and db/db type 2 diabetic mice. Hyperglycemia suppressed IGF-1 gene expression in cultured DRG neurons and this was reversed by exogenous IGF-1 or the aldose reductase inhibitor sorbinil. Transcription factors, such as NFAT1 and CEBPβ, were also less enriched at the IGF-1 promoter in DRG from diabetic rats vs control rats. CEBPβ overexpression promoted neurite outgrowth and mitochondrial respiration, both of which were blunted by knocking down or blocking IGF-1. Suppression of endogenous IGF-1 in diabetes may contribute to neuropathy and its upregulation at the transcriptional level by CEBPβ can be a promising therapeutic approach.

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Th17 cells and their related cytokines: vital players in progression of malignant pleural effusion

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Abstract

Malignant pleural effusion (MPE) is an exudative effusion caused by primary or metastatic pleural carcinosis. Th17 cells and their cytokines are critical components in various disease including MPE. In this review, we summarize current published articles regarding the multifunctional roles of Th17 cells and their related cytokines in MPE. Th17 cells are accumulated in MPE compared with paired serum via certain manners. The upregulation of Th17 cells and the interactions between Th17 cells and other immune cells, such as Th1 cells, Th9 cells, regulatory T cells and B cells, are reported to be involved in the formation and development of MPE. In addition, cytokines, which are elaborated by Th17 cells, including IL-17A, IL-17F, IL-21, IL-22, IL-26, GM-CSF, or associated with Th17 cells differentiation, including IL-1β, IL-6, IL-23, TGF-β, are linked to the pathogenesis of MPE through exerting pro- or anti-tumorigenic functions on their own as well as regulating the generation and differentiation of Th17 cells in MPE. Based on these findings, we proposed that Th17 cells and their cytokines might be diagnostic or prognostic tools and potential therapeutic targets for MPE.

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Sugemalimab: First Approval

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Abstract

Sugemalimab (Cejemly® in China) is a fully human, full length, anti-programmed death ligand 1 (PD-L1) immunoglobulin G4 (IgG4) monoclonal antibody (mAb) that is being developed by CStone Pharmaceuticals for the treatment of advanced solid tumours and lymphoma. In December 2021, sugemalimab was approved in China for the first-line treatment of epidermal growth factor receptor (EGFR) gene mutation and anaplastic lymphoma kinase (ALK) negative metastatic non-small cell lung cancer (NSCLC) administered in combination with pemetrexed and carboplatin for non-squamous NSCLC and in combination with paclitaxel and carboplatin for squamous NSCLC. Sugemalimab is under regulatory review as consolidation treatment in patients with stage III NSCLC in China. Clinical studies assessing sugemalimab for the treatment of several other cancers, including liver cancer, gastric cancer, oesophageal cancer, Hodgkin lymphoma and extranodal natural killer/T cell lymphoma are u nderway in China, the US and Australia. This article summarizes the milestones in the development of sugemalimab leading to this first approval for the first-line treatment of EGFR gene mutation and ALK-negative metastatic NSCLC.

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Τετάρτη 16 Μαρτίου 2022

An enhanced recovery after surgery pathway: LOS reduction, rapid discharge and minimal complications after anterior cervical spine surgery

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Abstract

Background

Enhance recovery after surgery (ERAS) is a new and promising paradigm for spine surgery. The purpose of this study is to investigate the effectiveness and safety of a multimodal and evidence-based ERAS pathway to the patients undergoing anterior cervical discectomy and fusion (ACDF).

Methods

The patients treated with the ACDF-ERAS pathway were compared with a historical cohort of patients who underwent ACDF before ERAS pathway implementation. Primary outcome was length of stay (LOS). Secondary outcomes included cost, MacNab grading, complication rates and 90-day readmission and reoperation. And perioperative factors and postoperative complications were reviewed.

Results

The ERAS protocol was composed of 21 components. More patients undergoing multi-level surgery (n ≥ 3) were included in the ERAS group. The ERAS group showed a shorter LOS and a lower cost than the conventional group. The postoperative satisfaction of patients in ERAS group was better than that in conventional group. In addition, the rate of overall complications was significantly higher in the conventional group than that in the ERAS group. There were no significant differences in operative time, postoperative drainage, or 90-day readmission and reoperation.

Conclusions

The ACDF-tailored ERAS pathway can reduce LOS, cost and postoperative complications, and improve patient satisfaction without increasing 90-day readmission and reoperation.

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