Πέμπτη 17 Μαρτίου 2022

Mycobacterium avium and Mycobacterium intracellulare in potable water in the USA

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Abstract

Nontuberculous mycobacterium (NTM) infections are increasing in the USA and have a high cost burden associated with treatment. Thus, it is necessary to understand what changes could be contributing to this increase in NTM disease rate. Water samples from 40 sites were collected from around the USA. They represented three water types: groundwater disinfected with chlorine and surface water disinfected with chlorine or monochloramine. Two methods, culture and qPCR, were used to measure M. avium and M. intracellulare. Heterotrophic bacteria and NTM counts were also measured. M. avium and M. intracellulare were molecularly detected in 25% (73/292) and 35% (102/292) of samples. The mean concentrations of M. avium and M. intracellulare were 2.8 × 103 and 4.0 × 103 genomic units (GU) L−1. The Northeast sites had the highest sample positively rate for both M. avium and M. intracellulare. The highest NTM counts and M. avium concentrations were observed in the surface water treated with chloramine. Geographic location and source water/disinfectant type were observed to significantly influence M. avium and M. intracellulare occurrence rates. These studies can help improve public health risk management by balancing disinfectant treatments and diverse microbial loads in drinking water.

Key points

• M. avium (MA) culture rate increased significantly: 1% (1999) to 13%.

• Culture versus qPCR method: 13% vs 31% for MA and 6% vs 35% for MI.

• The results of each method type tell two different stories of MA and MI occurrence.

Graphical abstract

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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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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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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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